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Sample records for root nerve signals

  1. Nerve root replantation.

    PubMed

    Carlstedt, Thomas

    2009-01-01

    Traumatic avulsion of nerve roots from the spinal cord is a devastating event that usually occurs in the brachial plexus of young adults following motor vehicle or sports accidents or in newborn children during difficult childbirth. A strategy to restore motor function in the affected arm by reimplanting into the spinal cord the avulsed ventral roots or autologous nerve grafts connected distally to the avulsed roots has been developed. Surgical outcome is good and useful recovery in shoulder and proximal arm muscles occurs. Pain is alleviated with motor recovery but sensory improvement is poor when only motor conduits have been reconstructed. In experimental studies, restoration of sensory connections with general improvement in the outcome from this surgery is pursued.

  2. Lumbosacral nerve root avulsion.

    PubMed

    Chin, C H; Chew, K C

    1997-01-01

    Lumbosacral nerve root avulsion is a rare clinical entity. Since the first description in 1955, only 35 cases have been reported. It is often associated with pelvic fractures and may be missed in the initial clinical examination as these patients usually present with multiple injuries. We present three such cases with clinical and radiological findings. These patients were involved in road traffic accidents. Two had fractures of the sacroiliac joint with diastasis of the symphysis pubis (Tile type C 1.2) and one had fractures of the public rami (Tile type B 2.1). All three had various degrees of sensory and motor deficit of the lower limbs. Lumbar myelogram shows characteristic pseudomeningoceles in the affected lumboscral region. Magnetic resonance (MR) imaging provides an additional non-invasive modality to diagnose this condition.

  3. Purely extradural spinal nerve root hemangioblastomas

    PubMed Central

    Aytar, Murat Hamit; Yener, Ulaş; Ekşi, Murat Şakir; Kaya, Behram; Özgen, Serdar; Sav, Aydin; Alanay, Ahmet

    2016-01-01

    Spinal nerve root hemangioblastomas present mostly as intradural-extradurally. Purely extradural spinal nerve root hemangioblastoma is a very rare entity. In this study, we aimed to analyze epidemiological perspectives of purely extradural spinal nerve root hemangioblastomas presented in English medical literature in addition to our own exemplary case. PubMed/MEDLINE was searched using the terms “hemangioblastoma,” “extradural,” “spinal,” and “nerve root.” Demographical variables of age, gender, concomitant presence of von Hippel–Lindau (VHL) disease; spinal imaging and/or intraoperative findings for tumor location were surveyed from retrieved articles. There are 38 patients with purely extradural spinal nerve root hemangioblastoma. The median age is 45 years (range = 24–72 years). Female:male ratio is 0.6. Spinal levels for purely extradural spinal nerve root hemangioblastomas, in order of decreasing frequency, are thoracic (48.6%), cervical (13.5%), lumbar (13.5%), lumbosacral (10.8%), sacral (8.1%), and thoracolumbar (5.4%). Concomitant presence of VHL disease is 45%. Purely extradural spinal nerve root hemangioblastomas are very rare and can be confused with other more common extradural spinal cord tumors. Concomitant presence of VHL disease is observed in less than half of the patients with purely extradural spinal nerve root hemangioblastomas. Surgery is the first-line treatment in these tumors. PMID:27891027

  4. Ultrasonography Evaluation of Vulnerable Vessels Around Cervical Nerve Roots During Selective Cervical Nerve Root Block

    PubMed Central

    2017-01-01

    Objective To evaluate the prevalence of vulnerable blood vessels around cervical nerve roots before cervical nerve root block in the clinical setting. Methods This retrospective study included 74 patients with cervical radiculopathy who received an ultrasonography-guided nerve block at an outpatient clinic from July 2012 to July 2014. Before actual injection of the steroid was performed, we evaluated the vulnerable blood vessels around each C5, C6, and C7 nerve root of each patient's painful side, with Doppler ultrasound. Results Out of 74 cases, the C5 level had 2 blood vessels (2.7%), the C6 level had 4 blood vessels (5.45%), and the C7 level had 6 blood vessels (8.11%) close to each targeted nerve root. Moreover, the C5 level had 2 blood vessels (2.7%), the C6 level 5 blood vessels (6.75%), and the C7 level had 4 blood vessels (5.45%) at the site of an imaginary needle's projected pathway to the targeted nerve root, as revealed by axial transverse ultrasound imaging with color Doppler imaging. In total, the C5 level had 4 blood vessels (5.45%), the C6 level 9 blood vessels (12.16%), and the C7 level 10 had blood vessels (13.51%) either at the targeted nerve root or at the site of the imaginary needle's projected pathway to the targeted nerve root. There was an unneglectable prevalence of vulnerable blood vessels either at the targeted nerve root or at the site of the needle' projected pathway to the nerve root. Also, it shows a higher prevalence of vulnerable blood vessels either at the targeted nerve root or at the site of an imaginary needle's projected pathway to the nerve root as the spinal nerve root level gets lower. Conclusion To prevent unexpected critical complications involving vulnerable blood vessel injury during cervical nerve root block, it is recommended to routinely evaluate for the presence of vulnerable blood vessels around each cervical nerve root using Doppler ultrasound imaging before the cervical nerve root block, especially for the lower

  5. Endoscopic decompression for intraforaminal and extraforaminal nerve root compression

    PubMed Central

    2011-01-01

    Objective The purpose of this study was to evaluate the outcome of endoscopic decompression surgery for intraforaminal and extraforaminal nerve root compression in the lumbar spine. Methods The records from seventeen consecutive patients treated with endoscopic posterior decompression without fusion for intaforaminal and extraforaminal nerve root compression in the lumbar spine (7 males and 10 females, mean age: 67.9 ± 10.7 years) were retrospectively reviewed. The surgical procedures consisted of lateral or translaminal decompression with or without discectomy. The following items were investigated: 1) the preoperative clinical findings; 2) the radiologic findings including MRI and computed tomography-discography; and 3) the surgical outcome as evaluated using the Japanese Orthopaedic Association scale for lower back pain (JOA score). Results All patients had neurological findings compatible with a radiculopathy, such as muscle weakness and sensory disturbance. MRI demonstrated the obliteration of the normal increased signal intensity fat in the intervertebral foramen. Ten patients out of 14 who underwent computed tomography-discography exhibited disc protrusion or herniation. Selective nerve root block was effective in all patients. During surgery, 12 patients were found to have a protruded disc or herniation that compressed the nerve root. Sixteen patients reported pain relief immediately after surgery. Conclusions Intraforaminal and extraforaminal nerve root compression is a rare but distinct pathological condition causing severe radiculopathy. Endoscopic decompression surgery is considered to be an appropriate and less invasive surgical option. PMID:21439083

  6. Reconstruction of nerve root sheaths for sacral extradural spinal meningeal cysts with spinal nerve root fibers.

    PubMed

    Sun, Jianjun; Wang, Zhenyu; Li, Zhendong; Wu, Haibo; Yen, Ruyu; Zheng, Mei; Chang, Qing; Liu, Isabelle Yisha

    2013-11-01

    This study analyzed the clinical characteristics and outcomes of sacral extradural spinal meningeal cysts with spinal nerve root fibers treated by reconstruction of the nerve root sheaths. The relationships between the cysts and spinal nerve root fibers were examined microscopically, the cysts were partially excised, and the defects were oversewn to reconstruct the nerve root sheaths. The Improved Japanese Orthopedic Association (IJOA) scoring system was used to evaluate preoperative and postoperative neurological function. Thirty-eight patients were included in this study, with a mean age of 41.4 ± 15.57 years. The mean IJOA score was 18.8 ± 1.32 preoperatively and 19.6 ± 0.65 postoperatively, which was a significant difference (t=-3.77, P=0.001). These results indicate a significant improvement in neurological function after surgery. The most significant improvement in neurological function was sensation (z=-2.86, P=0.004), followed by bowel/bladder function (z=-2.31, P=0.02).

  7. Chronic sciatic nerve compression induces fibrosis in dorsal root ganglia.

    PubMed

    Li, Qinwen; Chen, Jianghai; Chen, Yanhua; Cong, Xiaobin; Chen, Zhenbing

    2016-03-01

    In the present study, pathological alterations in neurons of the dorsal root ganglia (DRG) were investigated in a rat model of chronic sciatic nerve compression. The rat model of chronic sciatic nerve compression was established by placing a 1 cm Silastic tube around the right sciatic nerve. Histological examination was performed via Masson's trichrome staining. DRG injury was assessed using Fluoro Ruby (FR) or Fluoro Gold (FG). The expression levels of target genes were examined using reverse transcription‑quantitative polymerase chain reaction, western blot and immunohistochemical analyses. At 3 weeks post‑compression, collagen fiber accumulation was observed in the ipsilateral area and, at 8 weeks, excessive collagen formation with muscle atrophy was observed. The collagen volume fraction gradually and significantly increased following sciatic nerve compression. In the model rats, the numbers of FR‑labeled DRG neurons were significantly higher, relative to the sham‑operated group, however, the numbers of FG‑labeled neurons were similar. In the ipsilateral DRG neurons of the model group, the levels of transforming growth factor‑β1 (TGF‑β1) and connective tissue growth factor (CTGF) were elevated and, surrounding the neurons, the levels of collagen type I were increased, compared with those in the contralateral DRG. In the ipsilateral DRG, chronic nerve compression was associated with significantly higher levels of phosphorylated (p)‑extracellular signal‑regulated kinase 1/2, and significantly lower levels of p‑c‑Jun N‑terminal kinase and p‑p38, compared with those in the contralateral DRGs. Chronic sciatic nerve compression likely induced DRG pathology by upregulating the expression levels of TGF‑β1, CTGF and collagen type I, with involvement of the mitogen‑activated protein kinase signaling pathway.

  8. Study on lumbosacral nerve root compression using DTI

    PubMed Central

    Li, Jinfeng; Wang, Yonghao; Wang, Yueyi; Lv, Yang; Ma, Lin

    2016-01-01

    Diffusion tensor imaging (DTI) can objectively describe the distribution of nerve roots in morphology, and provide a set of objective reference data on the quantitative indicators. The present study aimed to investigate the value of DTI in lumbosacral nerve root compression in patients with lumbar intervertebral disc degeneration. DTI was performed in 45 patients with lumbar intervertebral disc degeneration. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured in compressed and normal nerve roots. Fiber tracking imaging was also applied to observe the lumbosacral nerve roots. ADC value was significantly lower in the compressed group (1.314±0.14 mm2/sec) compared to in the uncompressed group (1.794±0.11 mm2/sec) (P<0.05). The FA value was significantly lower in the compressed group (0.196±0.020) compared to the uncompressed group (0.272±0.016) (P<0.05). DTI can evidently reveal the compressed nerve roots. DTI could be used to evaluate the lumbosacral nerve injury in patients with lumbar intervertebral disc degeneration to quantitatively assess nerve roots. PMID:27602215

  9. Rare Intradural Cervical Nerve Root Metastasis of Follicular Thyroid Carcinoma

    PubMed Central

    Milosavljevic, Elena; Hanna, George; Gospodarev, Vadim; Raghavan, Ravi; Ghostine, Samer

    2016-01-01

    Intradural extramedullary nerve root metastasis is extremely unusual with only a handful of cases reported, and it presents most commonly in the thoracic and lumbosacral regions. We report the first case of metastasis to a ventral cervical nerve root in a patient with low-grade follicular thyroid carcinoma thought to be in remission for several years. Histopathology demonstrated malignant transformation and invasion of the nerve root. This case underscores that any history of malignancy regardless of staging, grading, or remission status should raise the suspicion of metastasis as it can mimic other spine and nerve sheath tumors and represent malignant transformation. Gross total resection can be safely achieved with intraoperative neuromonitoring and result in improved function; however, treatment is likely palliative. PMID:28018768

  10. Intraoperative conjoined lumbosacral nerve roots associated with spondylolisthesis.

    PubMed

    Popa, Iulian; Poenaru, Dan V; Oprea, Manuel D; Andrei, Diana

    2013-07-01

    Lumbosacral nerve roots anomalies may produce low back pain. These anomalies are reported to be a cause for failed back surgery. They are usually left undiagnosed, especially in endoscopic discectomy techniques. Any surgery for entrapment disorders, performed on a patient with undiagnosed lumbosacral nerve roots anomaly, may lead to serious neural injuries because of an improper surgical technique or decompression. In this report, we describe our experience with a case of L5-S1 spondylolisthesis and associated congenital lumbosacral nerve root anomalies discovered during the surgical intervention, and the difficulties raised by such a discovery. Careful examination of coronal and axial views obtained through high-quality Magnetic Resonance Imaging may lead to a proper diagnosis of this condition leading to an adequate surgical planning, minimizing the intraoperatory complications.

  11. Proposed Classification of Auriculotemporal Nerve, Based on the Root System

    PubMed Central

    Komarnitki, Iulian; Tomczyk, Jacek; Ciszek, Bogdan; Zalewska, Marta

    2015-01-01

    The topography of the auriculotemporal nerve (ATN) root system is the main criterion of this nerve classification. Previous publications indicate that ATN may have between one and five roots. Most common is a one- or two-root variant of the nerve structure. The problem of many publications is the inconsistency of nomenclature which concerns the terms “roots”, “connecting branches”, or “branches” that are used to identify the same structures. This study was performed on 80 specimens (40 adults and 40 fetuses) to propose a classification based on: (i) the number of roots, (ii) way of root division, and (iii) configuration of interradicular fibers that form the ATN trunk. This new classification is a remedy for inconsistency of nomenclature of ATN in the infratemporal fossa. This classification system has proven beneficial when organizing all ATN variants described in previous studies and could become a helpful tool for surgeons and dentists. Examination of ATN from the infratemporal fossa of fetuses (the youngest was at 18 weeks gestational age) showed that, at that stage, the nerve is fully developed. PMID:25856464

  12. Calcium Signaling in Intact Dorsal Root Ganglia

    PubMed Central

    Gemes, Geza; Rigaud, Marcel; Koopmeiners, Andrew S.; Poroli, Mark J.; Zoga, Vasiliki; Hogan, Quinn H.

    2013-01-01

    Background Ca2+ is the dominant second messenger in primary sensory neurons. In addition, disrupted Ca2+ signaling is a prominent feature in pain models involving peripheral nerve injury. Standard cytoplasmic Ca2+ recording techniques use high K+ or field stimulation and dissociated neurons. To compare findings in intact dorsal root ganglia, we used a method of simultaneous electrophysiologic and microfluorimetric recording. Methods Dissociated neurons were loaded by bath-applied Fura-2-AM and subjected to field stimulation. Alternatively, we adapted a technique in which neuronal somata of intact ganglia were loaded with Fura-2 through an intracellular microelectrode that provided simultaneous membrane potential recording during activation by action potentials (APs) conducted from attached dorsal roots. Results Field stimulation at levels necessary to activate neurons generated bath pH changes through electrolysis and failed to predictably drive neurons with AP trains. In the intact ganglion technique, single APs produced measurable Ca2+ transients that were fourfold larger in presumed nociceptive C-type neurons than in nonnociceptive Aβ-type neurons. Unitary Ca2+ transients summated during AP trains, forming transients with amplitudes that were highly dependent on stimulation frequency. Each neuron was tuned to a preferred frequency at which transient amplitude was maximal. Transients predominantly exhibited monoexponential recovery and had sustained plateaus during recovery only with trains of more than 100 APs. Nerve injury decreased Ca2+ transients in C-type neurons, but increased transients in Aβ-type neurons. Conclusions Refined observation of Ca2+ signaling is possible through natural activation by conducted APs in undissociated sensory neurons and reveals features distinct to neuronal types and injury state. PMID:20526180

  13. [Blood circulation of cauda equina and nerve root].

    PubMed

    Kobayashi, Shigeru; Baba, Hisatoshi; Uchida, Kenzo; Kokubo, Yasuo; Yayama, Takafumi; Takeno, Kenichi; Negoro, Kohei

    2005-03-01

    It is generally considered that the genesis of radiculopathy associated with pathologic conditions of the spine, such as lumbar disc herniaton and lumbarl canal stenosis, may result from both mechanical compression and vascular problems. In this article, we have reviewed about the blood circulation of cauda equina and nerve root under normal and pathologic conditions.

  14. Conjoined lumbosacral nerve roots: current aspects of diagnosis.

    PubMed

    Böttcher, J; Petrovitch, A; Sörös, P; Malich, A; Hussein, S; Kaiser, W A

    2004-03-01

    Conjoined lumbosacral nerve roots (CLNR) are the most common anomalies involving the lumbar nerve structures which can be one of the origins of failed back syndromes. They can cause sciatica even without the presence of a additional compressive impingement (such as disc herniation, spondylolisthesis or lateral recess stenosis), and often congenital lumbosacral spine anomalies (such as bony defects) are present at the "conjoined sheaths". This congenital anomaly has been reported in 14% of cadaver studies, but myelographic or computed tomographic studies have revealed an incidence of approximately 4% only. Diagnostic methods such as magnetic resonance imaging (MRI) are helpful for determination of the exact anatomical relations in this context. We present five typical cases of conjoined nerve roots observed during a 1 year period, equivalent to 6% of our out-patients without a history of surgical treatment on the lumbar spine. In all cases with suspicious radiological findings MRI or lumbar myelography combined with CT and multiplanar reconstructions is recommended.

  15. Infrared neural stimulation of human spinal nerve roots in vivo

    PubMed Central

    Cayce, Jonathan M.; Wells, Jonathon D.; Malphrus, Jonathan D.; Kao, Chris; Thomsen, Sharon; Tulipan, Noel B.; Konrad, Peter E.; Jansen, E. Duco; Mahadevan-Jansen, Anita

    2015-01-01

    Abstract. Infrared neural stimulation (INS) is a neurostimulation modality that uses pulsed infrared light to evoke artifact-free, spatially precise neural activity with a noncontact interface; however, the technique has not been demonstrated in humans. The objective of this study is to demonstrate the safety and efficacy of INS in humans in vivo. The feasibility of INS in humans was assessed in patients (n=7) undergoing selective dorsal root rhizotomy, where hyperactive dorsal roots, identified for transection, were stimulated in vivo with INS on two to three sites per nerve with electromyogram recordings acquired throughout the stimulation. The stimulated dorsal root was removed and histology was performed to determine thermal damage thresholds of INS. Threshold activation of human dorsal rootlets occurred in 63% of nerves for radiant exposures between 0.53 and 1.23  J/cm2. In all cases, only one or two monitored muscle groups were activated from INS stimulation of a hyperactive spinal root identified by electrical stimulation. Thermal damage was first noted at 1.09  J/cm2 and a 2∶1 safety ratio was identified. These findings demonstrate the success of INS as a fresh approach for activating human nerves in vivo and providing the necessary safety data needed to pursue clinically driven therapeutic and diagnostic applications of INS in humans. PMID:26157986

  16. Infrared neural stimulation of human spinal nerve roots in vivo.

    PubMed

    Cayce, Jonathan M; Wells, Jonathon D; Malphrus, Jonathan D; Kao, Chris; Thomsen, Sharon; Tulipan, Noel B; Konrad, Peter E; Jansen, E Duco; Mahadevan-Jansen, Anita

    2015-01-01

    Infrared neural stimulation (INS) is a neurostimulation modality that uses pulsed infrared light to evoke artifact-free, spatially precise neural activity with a noncontact interface; however, the technique has not been demonstrated in humans. The objective of this study is to demonstrate the safety and efficacy of INS in humans in vivo. The feasibility of INS in humans was assessed in patients ([Formula: see text]) undergoing selective dorsal root rhizotomy, where hyperactive dorsal roots, identified for transection, were stimulated in vivo with INS on two to three sites per nerve with electromyogram recordings acquired throughout the stimulation. The stimulated dorsal root was removed and histology was performed to determine thermal damage thresholds of INS. Threshold activation of human dorsal rootlets occurred in 63% of nerves for radiant exposures between 0.53 and [Formula: see text]. In all cases, only one or two monitored muscle groups were activated from INS stimulation of a hyperactive spinal root identified by electrical stimulation. Thermal damage was first noted at [Formula: see text] and a [Formula: see text] safety ratio was identified. These findings demonstrate the success of INS as a fresh approach for activating human nerves in vivo and providing the necessary safety data needed to pursue clinically driven therapeutic and diagnostic applications of INS in humans.

  17. Ultrasound and electrical nerve stimulation-guided S1 nerve root block.

    PubMed

    Sato, Masaki; Mikawa, Yasuhito; Matuda, Akiko

    2013-10-01

    A selective lumbosacral nerve root block is generally is performed under X-ray fluoroscopy, which has the disadvantage of radiation exposure and the need for fluoroscopy equipment. In this study, we assessed the effectiveness of ultrasound and nerve stimulation-guided S1 nerve root block on 37 patients with S1 radicular syndrome. With the patient in a prone position, an ultrasound scan was performed by placing the probe parallel to the body axis. The needle was pointed slightly medial from the lateral side of the probe and advanced toward a hyperechoic area in the sacral foramina with ultrasound guidance. Contrast medium was then injected and its dispersion confirmed by fluoroscopy. The acquired contrast images were classified into intraneural, perineural, and paraneural patterns. The significance of differences in the effect of the block among the contrast image patterns was analyzed. After nerve block, decreased sensation at the S1 innervated region and pain relief was achieved in all patients. No significant difference was noted in the effect of the block between perineural and paraneural patterns. In conclusion, this technique provided reliable S1 nerve root block in patients with S1 radicular syndrome and minimized radiation exposure.

  18. Traumatic Cervical Nerve Root Avulsion with Pseudomeningocele Formation

    PubMed Central

    Haider, Ali S; Watson, Ian T; Sulhan, Suraj; Arrey, Eliel N; Khan, Umair; Nguyen, Phu; Layton, Kennith F

    2017-01-01

    Cervical nerve root avulsion is a well-documented result of motor vehicle collision (MVC), especially when occurring at high velocities. These avulsions are commonly traction injuries of nerve roots that may be accompanied by a tear in the meninges through the vertebral foramina with associated collections of cerebrospinal fluid (CSF), thereby resulting in a pseudomeningocele. We present a case of a 19-year-old male who experienced an MVC and was brought to the emergency department (ED) with right arm paralysis and other injuries. A neurological examination demonstrated intact sensation but 0/5 muscle strength in the right upper extremity. A magnetic resonance imaging (MRI) of the spinal cord demonstrated massive epidural hematomas extending the length of the cervical spine caudally from C2. An MRI of the right brachial plexus showed C3-C7 anterior horn cell edema and associated traumatic nerve root avulsion with pseudomeningoceles on the right from C5-C8. The development of spinal cord hematoma with these injuries has rarely been documented in the literature and the multiple level avulsion described here with extensive hematoma is a rare clinical presentation. A literature review was conducted to determine the diagnostic requirements, treatment strategies, and complications of such an injury. Our patient received conservative treatment of the right brachial plexus injury and was transferred to an inpatient rehabilitation facility 13 days later.  PMID:28352498

  19. Autotaxin and lysophosphatidic acid1 receptor-mediated demyelination of dorsal root fibers by sciatic nerve injury and intrathecal lysophosphatidylcholine

    PubMed Central

    2010-01-01

    Background Although neuropathic pain is frequently observed in demyelinating diseases such as Guillain-Barré syndrome and multiple sclerosis, the molecular basis for the relationship between demyelination and neuropathic pain behaviors is poorly understood. Previously, we found that lysophosphatidic acid receptor (LPA1) signaling initiates sciatic nerve injury-induced neuropathic pain and demyelination. Results In the present study, we have demonstrated that sciatic nerve injury induces marked demyelination accompanied by myelin-associated glycoprotein (MAG) down-regulation and damage of Schwann cell partitioning of C-fiber-containing Remak bundles in the sciatic nerve and dorsal root, but not in the spinal nerve. Demyelination, MAG down-regulation and Remak bundle damage in the dorsal root were abolished in LPA1 receptor-deficient (Lpar1-/-) mice, but these alterations were not observed in sciatic nerve. However, LPA-induced demyelination in ex vivo experiments was observed in the sciatic nerve, spinal nerve and dorsal root, all which express LPA1 transcript and protein. Nerve injury-induced dorsal root demyelination was markedly attenuated in mice heterozygous for autotaxin (atx+/-), which converts lysophosphatidylcholine (LPC) to LPA. Although the addition of LPC to ex vivo cultures of dorsal root fibers in the presence of recombinant ATX caused potent demyelination, it had no significant effect in the absence of ATX. On the other hand, intrathecal injection of LPC caused potent dorsal root demyelination, which was markedly attenuated or abolished in atx+/- or Lpar1-/- mice. Conclusions These results suggest that LPA, which is converted from LPC by ATX, activates LPA1 receptors and induces dorsal root demyelination following nerve injury, which causes neuropathic pain. PMID:21062487

  20. Repair of multiple cervical root avulsion with sural nerve graft.

    PubMed

    Hsu, Sanford P C; Shih, Yang-Hsin; Huang, Ming-Chao; Chuang, Tien-Yow; Huang, Wen-Cheng; Wu, Hsiu-Mei; Lin, Pei-Hsin; Lee, Liang-Shong; Cheng, Henrich

    2004-09-01

    To obtain easier access to avulsed roots in the intradural space for patients suffering cervical root avulsion, the authors of this study developed a novel repair method. This involves using nerve grafts to bridge corresponding segments of the spinal cord and the trunk or cord level of the plexus, respectively, in two surgical stages. All eight patients admitted to this study received pre- and post-operative workups of electrophysiological evaluations and muscle power grading through Medical Research Council (MRC) scores. The degrees of impairment were also graded according to a modified version of Dumitru's and Wilbourn's scale (mild = 1; moderate = 2; severe = 3). The preoperative versus post-operative differences in the severity of the injuries and in the grading of the target muscle power were calculated according to the Wilcoxon signed-rank test. The preoperative degree of the severity of the injuries, as measured by electromyography (EMG), was 3.00 +/- 0.00 (mean +/- S.D.). The post-operative result was 2.125 +/- 0.641. Significant change took place after repair (P = 0.0313). Moreover, although little improvement was observed in the triceps, brachioradialis (BR), extensor carpi radialis (ECR), flexor digitorum profundus (FDP) and intrinsic hand muscles, the MRC grading showed significant yet not prominent motor recovery in the deltoid and biceps brachii (both P = 0.0313). We were impressed that the initial significant statistical results of differences in pre- and post-operative severity of the injuries and muscle power grading, demonstrated that regeneration does occur with this repair strategy.

  1. Activation of neurotrophins in lumbar dorsal root probably contributes to neuropathic pain after spinal nerve ligation

    PubMed Central

    Kazemi, Abdolreza; Rahmati, Masoud; Eslami, Rasoul; Sheibani, Vahid

    2017-01-01

    Objective(s): Neurotrophins (NTs) exert various effects on neuronal system. Growing evidence indicates that NTs are involved in the pathophysiology of neuropathic pain. However, the exact role of these proteins in modulating nociceptive signaling requires being defined. Thus, the aim of this study was to evaluate the effects of spinal nerve ligation (SNL) on NTs activation in the lumbar dorsal root. Materials and Methods: Ten male Wistar rats were randomly assigned to two groups: tight ligation of the L5 spinal nerve (SNL: n=5) and Sham (n=5). In order to produce neuropathic pain, the L5 spinal nerve was tightly ligated (SNL). Then, allodynia and hyperalgesia tests were conducted weekly. After 4 weeks, tissue samples were taken from the two groups for laboratory evaluations. Here, Real-Time PCR quantity method was used for measuring NTs gene expression levels. Results: SNL resulted in a significant weight loss in the soleus muscle (P<0.05), mechanical allodynia and thermal hyperalgesia thresholds (respectively, P<0.05; P<0.05). Also, NGF, NT-4, NT-3, TrkA, TrkB and TrkC expression were up-regulated following spinal nerve ligation group (respectively, P=0.025, P=0.013, P=0.001, P=0.002, P<0.001, P=001) (respectively, 4.7, 5.2, 7.5, 5.1, 7.2, 6.2 folds). Conclusion: The present study provides new evidence that neuropathic pain induced by spinal nerve ligation probably activates NTs and Trk receptors expression in DRG. However, further studies are needed to better elucidate the role of NTs in a neuropathic pain. PMID:28133521

  2. NERVE GROWTH FACTOR MAINTAINS POTASSIUM CONDUCTANCE AFTER NERVE INJURY IN ADULT CUTANEOUS AFFERENT DORSAL ROOT GANGLION NEURONS

    PubMed Central

    EVERILL, B.; KOCSIS, J. D.

    2008-01-01

    Whole-cell patch-clamp techniques were used to study the effects of nerve growth factor on voltage-dependent potassium conductance in normal and axotomized identified large cutaneous afferent dorsal root ganglion neurons (48–50 μm diameter) many of which probably give rise to myelinated Aβ fibers. K-currents were isolated by blocking Na- and Ca-currents with appropriate ion replacement and channel blockers. Separation of current components was achieved on the basis of response to variation in conditioning voltage. Cutaneous afferents were labeled by the retrograde marker hydroxy-stilbamide (FluoroGold) which was injected into the skin of the foot. The sciatic nerve was either ligated or crushed with fine forceps five to seven days later. Neurons were dissociated 14–17 days after injury. The cut ends of the sciatic nerves were positioned into polyethylene tubes, which were connected to mini-osmotic pumps filled with either nerve growth factor or sterile saline. Control neurons displayed a prominent sustained K-current and the transient potassium currents “A” and “D”. Nerve ligation, which blocks target reconnection resulted in near 50% reduction of total outward current; isolated sustained K-current and transient A-current were reduced by a comparable amount. Nerve crush, which allows regeneration to peripheral targets and exposure of the regenerating nerve to the distal nerve segment, resulted in a small reduction in sustained K-current but no reduction in transient A-current compared to controls. Levels of transient A-current and sustained K-current were maintained at control levels after nerve growth factor treatment. These results indicate that the large reduction in transient A-current, and in sustained K-current, observed in cutaneous afferent cell bodies after nerve ligation is prevented by application of nerve growth factor. PMID:11008179

  3. Implantable electrode for recording nerve signals in awake animals

    NASA Technical Reports Server (NTRS)

    Ninomiya, I.; Yonezawa, Y.; Wilson, M. F.

    1976-01-01

    An implantable electrode assembly consisting of collagen and metallic electrodes was constructed to measure simultaneously neural signals from the intact nerve and bioelectrical noises in awake animals. Mechanical artifacts, due to bodily movement, were negligibly small. The impedance of the collagen electrodes, measured in awake cats 6-7 days after implantation surgery, ranged from 39.8-11.5 k ohms at a frequency range of 20-5 kHz. Aortic nerve activity and renal nerve activity, measured in awake conditions using the collagen electrode, showed grouped activity synchronous with the cardiac cycle. Results indicate that most of the renal nerve activity was from postganglionic sympathetic fibers and was inhibited by the baroceptor reflex in the same cardiac cycle.

  4. Return of function after spinal cord implantation of avulsed spinal nerve roots.

    PubMed

    Carlstedt, T; Grane, P; Hallin, R G; Norén, G

    1995-11-18

    Avulsion of nerve roots from the spinal cord is widely regarded as an untreatable injury. However, a series of experiments in animals has shown that, if continuity is restored between spinal cord and ventral roots, axons from spinal motor neurons can regrow into the peripheral nerves with recovery of motor function. These observations were applied in the treatment of a man with avulsion of the 6th cervical (C6) to 1st thoracic roots due to brachial plexus injury. Two ventral roots were implanted into the spinal cord through slits in the pia mater, C6 directly and C7 via sural nerve grafts. Voluntary activity in proximal arm muscles was detected electromyographically after nine months and clinically after one year. After three years the patient had voluntary activity (with some co-contraction) in the deltoid, biceps, and triceps muscles. To determine whether the improvement was due to spontaneous recovery from C5, the C5 root was blocked pharmacologically, and the results indicated that the repaired roots were contributing substantially to motor function. Repair of spinal nerve roots deserves further exploration in management of brachial plexus injury.

  5. Reduction in nerve root compression by the nucleus pulposus after Feng's Spinal Manipulation.

    PubMed

    Feng, Yu; Gao, Yan; Yang, Wendong; Feng, Tianyou

    2013-04-25

    Ninety-four patients with lumbar intervertebral disc herniation were enrolled in this study. Of these, 48 were treated with Feng's Spinal Manipulation, hot fomentation, and bed rest (treatment group). The remaining 46 patients were treated with hot fomentation and bed rest only (control group). After 3 weeks of treatment, clinical parameters including the angle of straight-leg raising, visual analogue scale pain score, and Japanese Orthopaedic Association score for low back pain were improved. The treatment group had significantly better improvement in scores than the control group. Magnetic resonance myelography three-dimensional reconstruction imaging of the vertebral canal demonstrated that filling of the compressed nerve root sleeve with cerebrospinal fluid increased significantly in the treatment group. The diameter of the nerve root sleeve was significantly larger in the treatment group than in the control group. However, the sagittal diameter index of the herniated nucleus pulposus and the angle between the nerve root sleeve and the thecal sac did not change significantly in either the treatment or control groups. The effectiveness of Feng's Spinal Manipulation for the treatment of symptoms associated with lumbar intervertebral disc herniation may be attributable to the relief of nerve root compression, without affecting the herniated nucleus pulposus or changing the morphology or position of the nerve root.

  6. Deficient FGF signaling causes optic nerve dysgenesis and ocular coloboma.

    PubMed

    Cai, Zhigang; Tao, Chenqi; Li, Hongge; Ladher, Raj; Gotoh, Noriko; Feng, Gen-Sheng; Wang, Fen; Zhang, Xin

    2013-07-01

    FGF signaling plays a pivotal role in eye development. Previous studies using in vitro chick models and systemic zebrafish mutants have suggested that FGF signaling is required for the patterning and specification of the optic vesicle, but due to a lack of genetic models, its role in mammalian retinal development remains elusive. In this study, we show that specific deletion of Fgfr1 and Fgfr2 in the optic vesicle disrupts ERK signaling, which results in optic disc and nerve dysgenesis and, ultimately, ocular coloboma. Defective FGF signaling does not abrogate Shh or BMP signaling, nor does it affect axial patterning of the optic vesicle. Instead, FGF signaling regulates Mitf and Pax2 in coordinating the closure of the optic fissure and optic disc specification, which is necessary for the outgrowth of the optic nerve. Genetic evidence further supports that the formation of an Frs2α-Shp2 complex and its recruitment to FGF receptors are crucial for downstream ERK signaling in this process, whereas constitutively active Ras signaling can rescue ocular coloboma in the FGF signaling mutants. Our results thus reveal a previously unappreciated role of FGF-Frs2α-Shp2-Ras-ERK signaling axis in preventing ocular coloboma. These findings suggest that components of FGF signaling pathway may be novel targets in the diagnosis of and the therapeutic interventions for congenital ocular anomalies.

  7. More nerve root injuries occur with minimally invasive lumbar surgery: Let's tell someone

    PubMed Central

    Epstein, Nancy E.

    2016-01-01

    Background: In a recent study entitled: “More nerve root injuries occur with minimally invasive lumbar surgery, especially extreme lateral interbody fusion (XLIF): A review”, Epstein documented that more nerve root injuries occurred utilizing minimally invasive surgery (MIS) versus open lumbar surgery for diskectomy, decompression of stenosis (laminectomy), and/or fusion for instability. Methods: In large multicenter Spine Patient Outcomes Research Trial reviews performed by Desai et al., nerve root injury with open diskectomy occurred in 0.13–0.25% of cases, occurred in 0% of laminectomy/stenosis with/without fusion cases, and just 2% for open laminectomy/stenosis/degenerative spondylolisthesis with/without fusion. Results: In another MIS series performed largely for disc disease (often contained nonsurgical disc herniations, therefore unnecessary procedures) or spondylolisthesis, the risk of root injury was 2% for transforaminal lumbar interbody fusion (TLIF) versus 7.8% for posterior lumbar interbody fusion (PLIF). Furthermore, the high frequencies of radiculitis/nerve root/plexus injuries incurring during anterior lumbar interbody fusions (ALIF: 15.8%) versus extreme lumbar interbody fusions (XLIF: 23.8%), addressing disc disease, failed back surgery, and spondylolisthesis, were far from acceptable. Conclusions: The incidence of nerve root injuries following any of the multiple MIS lumbar surgical techniques (TLIF/PLIF/ALIF/XLIF) resulted in more nerve root injuries when compared with open conventional lumbar surgical techniques. Considering the majority of these procedures are unnecessarily being performed for degenerative disc disease alone, spine surgeons should be increasingly asked why they are offering these operations to their patients? PMID:26904373

  8. The radio-radial nerve transfer for elbow extension restoration in C5 to C7 nerve root injury.

    PubMed

    Flores, Leandro Pretto

    2012-01-01

    Extension of the elbow is required to oppose gravity; however, activation of the triceps brachii is frequently underestimated during the surgical planning for brachial plexus injuries. This report aims to describe a novel technique of distal nerve transfer designed for elbow extension reconstruction in patients sustaining a C5-C7 nerve root injury. We report a patient sustaining a brachial plexus injury with triceps palsy and preserved finger extension motion; after careful intraneural dissection of the radial nerve, a fascicle innervating the extensor digitorum communis muscle was sectioned, derouted and connected to a motor branch to the lateral head of the triceps. Eleven months after surgery, elbow extension strength scored MRC M4. No deficits on finger extension were observed.

  9. [Sciatica due to unusual causes: Tarlov cysts and nerve roots anomalies].

    PubMed

    Younes, M; Korbaa, W; Zrour, S; Bejia, I; Touzi, M; Bergaoui, N

    2009-03-01

    Tarlov cysts and nerve roots anomalies usually involve lumbosacral roots and are often asymptomatic. MRI has enabled recognition of many conditions that used to be missed by CT or myelography investigations performed for back and leg pain. However, even without additional compressive impingement (disc hernia, spondylolisthesis or lumbar canal stenosis) these anomalies can be responsible for sciatica, motor deficit and bladder sphincter dysfunction. Tarlov cysts are perinervous dilatations of the dorsal root ganglion. CT and especially MRI can reveal these cysts and their precise relations with the neighboring structures. Delayed filling of the cysts can be visualized on the myelogram. MRI is more sensitive than CT myelography for a positive diagnosis of nerve root anomalies, a differential diagnosis with disc hernia and classification of these anomalies. Surgical treatment is indicated for symptomatic Tarlov cysts and nerve root anomalies resistant to conservative treatment. Better outcome is observed in patients with an additional compressive impingement component. We report two cases of sciatica: one caused by Tarlov cysts diagnosed by MRI and the other by nerve root anomalies diagnosed by CT myelography. In both cases, conservative treatment was undertaken. The clinical, radiological and therapeutic aspects of these disorders are discussed.

  10. Cerebrospinal fluid infection after lumbar nerve root steroid injection: a case report

    PubMed Central

    Kim, Seong-Su; Shim, Sung Min; Cho, Hae Jun

    2017-01-01

    A 45-year-old woman was admitted due to severe headache and neck stiffness. She had visited a local clinic for back pain and received a lumbar nerve root steroid injection 10 days before admission. Computed tomography and magnetic resonance imaging showed psoas abscess, pneumocephalus, and subdural hygroma. She was diagnosed with psoas abscess and meningitis. The abscess and external ventricle were drained, and antibiotics were administered. Unfortunately, the patient died on hospital day 19 due to diffuse leptomeningitis. Lumbar nerve root steroid injections are commonly used to control back pain. Vigilance to "red flag signs" and a rapid diagnosis can prevent lethal outcomes produced by rare and unexpected complications related to infection. Here, we report a case of fatal meningitis after infection of the cerebrospinal fluid following a lumbar nerve root steroid injection. PMID:28184274

  11. Slit-Robo GTPase-activating proteins are differentially expressed in murine dorsal root ganglia: modulation by peripheral nerve injury.

    PubMed

    Chen, Zhi-Bing; Zhang, Hai-Ying; Zhao, Jiu-Hong; Zhao, Wei; Zhao, Dan; Zheng, Lin-Feng; Zhang, Xian-Fang; Liao, Xiao-Ping; Yi, Xi-Nan

    2012-04-01

    The Slit-Robo GTPase-activating proteins (srGAPs) play an important role in neurite outgrowth and axon guidance; however, little is known about its role in nerve regeneration after injury. Here, we studied the expression of srGAPs in mouse dorsal root ganglia (DRG) following sciatic nerve transection (SNT) using morphometric and immunohistochemical techniques. Reverse transcriptase polymerase chain reaction and Western blot analysis indicated that srGAP1 and srGAP3, but not srGAP2, were expressed in normal adult DRG. Following unilateral SNT, elevated mRNA and protein levels of srGAP1 and srGAP3 were detected in the ipsilateral relative to contralateral L(3-4) DRGs from day 3 to day 14. Immunohistochemical results showed that srGAP1 and srGAP3 were largely expressed in subpopulations of DRG neurons in naïve DRGs. However, after SNT, srGAP3 in neurons was significantly increased in the ipsilateral relative to contralateral DRGs, which peaked at day 7 to day 14. Interestingly, DRG neurons with strong srGAP3 labeling also coexpressed Robo2 after peripheral nerve injury. These results suggest that srGAPs are differentially expressed in murine DRG and srGAP3 are the predominant form. Moreover, srGAP3 may participate in Slit-Robo signaling in response to peripheral nerve injury or the course of nerve regeneration.

  12. Expression and regulation of redoxins at nociceptive signaling sites after sciatic nerve injury in mice

    PubMed Central

    Valek, Lucie; Kanngießer, Maike; Tegeder, Irmgard

    2015-01-01

    Injury of the sciatic nerve results in regulations of pro- and anti-oxidative enzymes at sites of nociceptive signaling including the injured nerve, dorsal root ganglia (DRGs), dorsal horn of the spinal cord, thalamus and somatosensory cortex (Valek et al., 2015) [1]. The present DiB paper shows immunohistochemistry of redoxins including peroxiredoxins (Prdx1–6), glutaredoxins (Glrx1, 2, 3, 5), thioredoxins (Txn1, 2) and thioredoxin reductases (Txnrd1, 2) in the DRGs, spinal cord and sciatic nerve and thalamus in naïve mice and 7 days after Spared sciatic Nerve Injury (SNI) in control mice (Hif1α-flfl) and in mice with a specific deletion of hypoxia inducible factor 1 alpha (SNS-HIF1α−/−) in DRG neurons. The sciatic nerves were immunostained for the respective redoxins and counterstained with hematoxylin. The redoxin immunoreactivity was quantified with ImageJ. For the DRGs and spinal cord the data show the quantitative assessment of the intensity of redoxin immunoreactivity transformed to rainbow pseudocolors. In addition, some redoxin examples of the ipsi and contralateral dorsal and ventral horns of the lumbar spinal cord and some redoxin examples of the thalamus are presented. PMID:26693520

  13. [Physiological approach to peripheral neuropathy. Conventional nerve conduction studies and magnetic motor root stimulation].

    PubMed

    Ugawa, Yoshikazu

    2004-11-01

    In this communication, I first show some points we should mind in the conventional peripheral nerve conduction studies and later present clinical usefulness of motor root stimulation for peripheral neuropathy. CONVENTIONAL NERVE CONDUCTION STUDIES (NCS): The most important point revealed by the conventional NCSs is whether neuropathy is due to axonal degeneration or demyelinating process. Precise clinical examination with this neurophysiological information leads us to a diagnosis and treatment. Poor clinical examination makes these findings useless. Long standing axonal degeneration sometimes induces secondary demyelination at the most distal part of involved nerves. On the other hand, severe segmental demyelination often provokes secondary axonal degeneration at distal parts to the site of demyelination. These secondary changes show the same abnormal neurophysiological findings as those of the primary involvement. We should be careful of this possibility when interpreting the results of NCS. NCS of sensory nerves is not good at revealing demyelinating process. Mild temporal dispersion of potentials often reduces an amplitude of SNAP or loss of responses, which usually suggests axonal degeneration, because of short duration of sensory nerve potentials. MOTOR ROOT STIMULATION IN PERIPHERAL NEUROPATHY: Magnetic stimulation with a coil placed over the spine activates motor roots and evokes EMG responses from upper and lower limb muscles. The site of activation with this method was determined to be where the motor roots exit from the spinal canal (intervertebral foramina) (J Neurol Neurosurg Psychiatry 52 (9): 1025-1032, 1989) because induced currents are very dense at such a foramen made by electric resistant bones. In several kinds of peripheral neuropathy, this method has been used to detect a lesion at a proximal part of the peripheral nerves which can not be detected by the conventional NCSs. I present a few cases in whom motor root stimulation had a clinical

  14. Role of Netrin-1 Signaling in Nerve Regeneration

    PubMed Central

    Dun, Xin-Peng; Parkinson, David B.

    2017-01-01

    Netrin-1 was the first axon guidance molecule to be discovered in vertebrates and has a strong chemotropic function for axonal guidance, cell migration, morphogenesis and angiogenesis. It is a secreted axon guidance cue that can trigger attraction by binding to its canonical receptors Deleted in Colorectal Cancer (DCC) and Neogenin or repulsion through binding the DCC/Uncoordinated (Unc5) A–D receptor complex. The crystal structures of Netrin-1/receptor complexes have recently been revealed. These studies have provided a structure based explanation of Netrin-1 bi-functionality. Netrin-1 and its receptor are continuously expressed in the adult nervous system and are differentially regulated after nerve injury. In the adult spinal cord and optic nerve, Netrin-1 has been considered as an inhibitor that contributes to axon regeneration failure after injury. In the peripheral nervous system, Netrin-1 receptors are expressed in Schwann cells, the cell bodies of sensory neurons and the axons of both motor and sensory neurons. Netrin-1 is expressed in Schwann cells and its expression is up-regulated after peripheral nerve transection injury. Recent studies indicated that Netrin-1 plays a positive role in promoting peripheral nerve regeneration, Schwann cell proliferation and migration. Targeting of the Netrin-1 signaling pathway could develop novel therapeutic strategies to promote peripheral nerve regeneration and functional recovery. PMID:28245592

  15. Scanning pattern of diffusion tensor tractography and an analysis of the morphology and function of spinal nerve roots.

    PubMed

    Tian, Xin; Liu, Huaijun; Geng, Zuojun; Yang, Hua; Wang, Guoshi; Yang, Jiping; Wang, Chunxia; Li, Cuining; Li, Ying

    2013-11-25

    Radiculopathy, commonly induced by intervertebral disk bulging or protrusion, is presently diagnosed in accordance with clinical symptoms because there is no objective quantitative diagnostic criterion. Diffusion tensor magnetic resonance imaging and diffusion tensor tractography revealed the characterization of anisotropic diffusion and displayed the anatomic form of nerve root fibers. This study included 18 cases with intervertebral disc degeneration-induced unilateral radiculopathy. Magnetic resonance diffusion tensor imaging was creatively used to reveal the scanning pattern of fiber tracking of the spinal nerve root. A scoring system of nerve root morphology was used to quantitatively assess nerve root morphology and functional alteration after intervertebral disc degeneration. Results showed that after fiber tracking, compared with unaffected nerve root, fiber bundles gathered together and interrupted at the affected side. No significant alteration was detected in the number of fiber bundles, but the cross-sectional area of nerve root fibers was reduced. These results suggest that diffusion tensor magnetic resonance imaging-based tractography can be used to quantitatively evaluate nerve root function according to the area and morphology of fiber bundles of nerve roots.

  16. Differences between Cervical Schwannomas of the Anterior and Posterior Nerve Roots in Relation to the Incidence of Postoperative Radicular Dysfunction

    PubMed Central

    Ohnishi, Yu-Ichiro; Ohkawa, Toshika; Ninomiya, Koshi; Moriwaki, Takashi; Yoshimine, Toshiki

    2015-01-01

    Study Design A retrospective study. Purpose To assess the case files of patients who underwent surgery for cervical dumbbell schwannoma for determining the differences between schwannomas of the anterior and posterior nerve roots with respect to the incidence of postoperative radicular dysfunction. Overview of Literature The spinal roots giving origin to schwannoma are frequently nonfunctional, but there is a risk of postoperative neurological deficit once these roots are resected during surgery. Methods Fifteen patients with cervical dumbbell schwannomas were treated surgically. Ten men and 5 women, who were 35-79 years old (mean age, 61.5 years), presented with neck pain (n=6), radiculopathy (n=10), and myelopathy (n=11). Results Fourteen patients underwent gross total resection and exhibited no recurrence. Follow-ups were performed for a period of 6-66 months (mean, 28 months). Preoperative symptoms resolved in 11 patients (73.3%) but they persisted partially in 4 patients (26.7%). Six patients had tumors of anterior nerve root origin, and 9 patients had tumors of posterior nerve root origin. Two patients who underwent total resection of anterior nerve root tumors (33.3%) displayed minor postoperative motor weakness. One patient who underwent total resection of a posterior nerve root tumor (11.1%) showed postoperative numbness. Conclusions Appropriate tumor removal improved the neurological symptoms. In this study, the incidence of radicular dysfunction was higher in patients who underwent resection of anterior nerve root tumors than in patients who underwent resection of posterior nerve root tumors. PMID:25901239

  17. A conduction block in sciatic nerves can be detected by magnetic motor root stimulation.

    PubMed

    Matsumoto, Hideyuki; Konoma, Yuko; Fujii, Kengo; Hanajima, Ritsuko; Terao, Yasuo; Ugawa, Yoshikazu

    2013-08-15

    Useful diagnostic techniques for the acute phase of sciatic nerve palsy, an entrapment neuropathy, are not well established. The aim of this paper is to demonstrate the diagnostic utility of magnetic sacral motor root stimulation for sciatic nerve palsy. We analyzed the peripheral nerves innervating the abductor hallucis muscle using both electrical stimulations at the ankle and knee and magnetic stimulations at the neuro-foramina and conus medullaris levels in a patient with sciatic nerve palsy at the level of the piriformis muscle due to gluteal compression related to alcohol consumption. On the fourth day after onset, magnetic sacral motor root stimulation using a MATS coil (the MATS coil stimulation method) clearly revealed a conduction block between the knee and the sacral neuro-foramina. Two weeks after onset, needle electromyography supported the existence of the focal lesion. The MATS coil stimulation method clearly revealed a conduction block in the sciatic nerve and is therefore a useful diagnostic tool for the abnormal neurophysiological findings associated with sciatic nerve palsy even at the acute phase.

  18. Dorsal root ganglion transcriptome analysis following peripheral nerve injury in mice

    PubMed Central

    Wu, Shaogen; Marie Lutz, Brianna; Miao, Xuerong; Liang, Lingli; Mo, Kai; Chang, Yun-Juan; Du, Peicheng; Soteropoulos, Patricia; Tian, Bin; Kaufman, Andrew G.; Bekker, Alex; Hu, Yali

    2016-01-01

    Background Peripheral nerve injury leads to changes in gene expression in primary sensory neurons of the injured dorsal root ganglia. These changes are believed to be involved in neuropathic pain genesis. Previously, these changes have been identified using gene microarrays or next generation RNA sequencing with poly-A tail selection, but these approaches cannot provide a more thorough analysis of gene expression alterations after nerve injury. Methods The present study chose to eliminate mRNA poly-A tail selection and perform strand-specific next generation RNA sequencing to analyze whole transcriptomes in the injured dorsal root ganglia following spinal nerve ligation. Quantitative real-time reverse transcriptase polymerase chain reaction assay was carried out to verify the changes of some differentially expressed RNAs in the injured dorsal root ganglia after spinal nerve ligation. Results Our results showed that more than 50 million (M) paired mapped sequences with strand information were yielded in each group (51.87 M–56.12 M in sham vs. 51.08 M–57.99 M in spinal nerve ligation). Six days after spinal nerve ligation, expression levels of 11,163 out of a total of 27,463 identified genes in the injured dorsal root ganglia significantly changed, of which 52.14% were upregulated and 47.86% downregulated. The largest transcriptional changes were observed in protein-coding genes (91.5%) followed by noncoding RNAs. Within 944 differentially expressed noncoding RNAs, the most significant changes were seen in long interspersed noncoding RNAs followed by antisense RNAs, processed transcripts, and pseudogenes. We observed a notable proportion of reads aligning to intronic regions in both groups (44.0% in sham vs. 49.6% in spinal nerve ligation). Using quantitative real-time polymerase chain reaction, we confirmed consistent differential expression of selected genes including Kcna2, Oprm1 as well as lncRNAs Gm21781 and 4732491K20Rik following spinal nerve

  19. The action of prostaglandin E2 and triamcinolone acetonide on the firing activity of lumbar nerve roots.

    PubMed

    Muramoto, T; Atsuta, Y; Iwahara, T; Sato, M; Takemitsu, Y

    1997-01-01

    Sciatica, due to lumbar disc herniation, is understood electrophysiogically to be an ectopic firing originating from a nerve root. The recent concept of chemical radiculitis implies the involvement, not only of mechanical compression, but also of chemical mediators which contribute to the generation of ectopic firing. The present study demonstrates that prostaglandin E2, a chemical mediator of inflammation, provoked the ectopic firing of nerve roots in a canine in vitro model which indicates that it may play a part in the irritation of nerve roots. In contrast, triamcinolone acetonide suppressed the firing induced by prostaglandin suggesting that steroids may be effective in the treatment of root symptoms.

  20. An Nfic-hedgehog signaling cascade regulates tooth root development

    PubMed Central

    Liu, Yang; Feng, Jifan; Li, Jingyuan; Zhao, Hu; Ho, Thach-Vu; Chai, Yang

    2015-01-01

    Coordination between the Hertwig's epithelial root sheath (HERS) and apical papilla (AP) is crucial for proper tooth root development. The hedgehog (Hh) signaling pathway and Nfic are both involved in tooth root development; however, their relationship has yet to be elucidated. Here, we establish a timecourse of mouse molar root development by histological staining of sections, and we demonstrate that Hh signaling is active before and during root development in the AP and HERS using Gli1 reporter mice. The proper pattern of Hh signaling activity in the AP is crucial for the proliferation of dental mesenchymal cells, because either inhibition with Hh inhibitors or constitutive activation of Hh signaling activity in transgenic mice leads to decreased proliferation in the AP and shorter roots. Moreover, Hh activity is elevated in Nfic−/− mice, a root defect model, whereas RNA sequencing and in situ hybridization show that the Hh attenuator Hhip is downregulated. ChIP and RNAscope analyses suggest that Nfic binds to the promoter region of Hhip. Treatment of Nfic−/− mice with Hh inhibitor partially restores cell proliferation, AP growth and root development. Taken together, our results demonstrate that an Nfic-Hhip-Hh signaling pathway is crucial for apical papilla growth and proper root formation. This discovery provides insight into the molecular mechanisms regulating tooth root development. PMID:26293299

  1. Lack of effectiveness of laser therapy applied to the nerve course and the correspondent medullary roots

    PubMed Central

    Sousa, Fausto Fernandes de Almeida; Ribeiro, Thaís Lopes; Fazan, Valéria Paula Sassoli; Barbieri, Claudio Henrique

    2013-01-01

    OBJECTIVE: To investigate the influence of low intensity laser irradiation on the regeneration of the fibular nerve of rats after crush injury. METHODS: Twenty-five rats were used, divided into three groups: 1) intact nerve, no treatment; 2) crushed nerve, no treatment; 3) crush injury, laser irradiation applied on the medullary region corresponding to the roots of the sciatic nerve and subsequently on the course of the damaged nerve. Laser irradiation was carried out for 14 consecutive days. RESULTS: Animals were evaluated by functional gait analysis with the peroneal functional index and by histomorphometric analysis using the total number of myelinated nerve fibers and their density, total number of Schwann cells, total number of blood vessels and the occupied area, minimum diameter of the fiber diameter and G-quotient. CONCLUSION: According to the statistical analysis there was no significant difference among groups and the authors conclude that low intensity laser irradiation has little or no influence on nerve regeneration and functional recovery. Laboratory investigation. PMID:24453650

  2. Ethylene signaling pathway modulates attractiveness of host roots to the root-knot nematode Meloidogyne hapla.

    PubMed

    Fudali, Sylwia L; Wang, Congli; Williamson, Valerie M

    2013-01-01

    Infective juveniles of the root-knot nematode Meloidogyne hapla are attracted to the zone of elongation of roots where they invade the host but little is known about what directs the nematode to this region of the root. We found that Arabidopsis roots exposed to an ethylene (ET)-synthesis inhibitor attracted significantly more nematodes than control roots and that ET-overproducing mutants were less attractive. Arabidopsis seedlings with ET-insensitive mutations were generally more attractive whereas mutations resulting in constitutive signaling were less attractive. Roots of the ET-insensitive tomato mutant Never ripe (Nr) were also more attractive, indicating that ET signaling also modulated attraction of root-knot nematodes to this host. ET-insensitive mutants have longer roots due to reduced basipetal auxin transport. However, assessments of Arabidopsis mutants that differ in various aspects of the ET response suggest that components of the ET-signaling pathway directly affecting root length are not responsible for modulating root attractiveness and that other components of downstream signaling result in changes in levels of attractants or repellents for M. hapla. These signals may aid in directing this pathogen to an appropriate host and invasion site for completing its life cycle.

  3. Nerve root degeneration and regeneration by intrathecal phenol in rats: a morphologic approach.

    PubMed

    Romero-Figueroa, Socorro; Aldrete, J Antonio; Martínez-Cruz, Angelina; Orozco, Sandra; Castillo, Sebastian; Castillo-Henkel, Carlos; Guízar-Sahagún, Gabriel

    2006-12-01

    Intrathecal injection of phenol (ITP) has been used to control intractable pain and spasticity. Direct caustic nerve damage has been postulated as the mechanism of analgesia. Sensation is commonly recovered, suggesting that a spontaneous regeneration process takes place. There is, however, a lack of mechanistic information on ITP therapy. To define morphologically the neurolysis and regeneration phenomena produced by ITP, anesthetized rats were subjected to laminectomy at L5; 5 microl of 22% phenol in saline solution or vehicle (control) was injected. Light and electron microscopy studies of nerve roots were performed at 2, 14, and 60 days after injection. Rats given ITP showed at the early stage a variable amount of roots with signs of infarction characterized by loss of axon-myelin units and thrombosis of intra-root vessels. At 14 days, abundance of macrophages removing debris, open vessels, and nerve sprouts was identified in damaged roots. At this time, non-myelinating glial fibrillary acidic protein-positive Schwann cells were observed in both damaged and apparently undamaged roots. At 60 days, abundance of 2',3'-cyclic nucleotide 3'-phosphodiesterase-positive Schwann cells myelinating newly formed axons was observed in damaged roots. Control rats did not show signs of neural or vascular pathology. Attempting to prevent thrombosis, another group of rats received heparin before ITP; these anti-coagulated rats developed radicular thrombosis, neurolysis, and hemorrhage. In conclusion, neurolysis produced by ITP is associated with acute ischemia (not prevented by heparin) and is followed by vascular, nerve, and myelin regeneration. Our results help understand the lack of efficacy of and some complications by ITP clinical therapy.

  4. Microstructural changes in compressed nerve roots treated by percutaneous transforaminal endoscopic discectomy in patients with lumbar disc herniation

    PubMed Central

    Wu, Weifei; Liang, Jie; Chen, Ying; Chen, Aihua; Wu, Bin; Yang, Zong

    2016-01-01

    Abstract To investigate the microstructural changes in compressed nerves using diffusion tensor imaging (DTI) of herniated disc treated with percutaneous transforaminal endoscopic discectomy. Diffusion tensor imaging has been widely used to visualize peripheral nerves, and the microstructure of compressed nerve roots can be assessed using DTI. However, the microstructural changes after surgery are not well-understood in patients with lumbar disc herniation. Thirty-four consecutive patients with foraminal disc herniation affecting unilateral sacral 1 (S1) nerve roots were enrolled in this study. DTI with tractography was performed on S1 nerve roots before and after surgery. The mean fractional anisotropy (FA) and apparent diffusion coefficient values were calculated from tractography images. In compressed nerve roots, the FA value before surgery was significantly lower than that after surgery (P = 0.000). A significant difference in FA values was found between the compressed and normal sides before surgery (P = 0.000). However, no significant difference was found between the compressed and normal sides after surgery (P = 0.057). A significant difference in apparent diffusion coefficient values was found before and after surgery at the compressed side (P = 0.023). However, no significant difference was found between the compressed and normal sides after surgery (P = 0.203). We show that the diffusion parameters of compressed nerve roots were not significantly different before and after percutaneous transforaminal endoscopic discectomy, indicating that the microstructure of the nerve root recovered after surgery. PMID:27749591

  5. Gene profiling of the red light signalling pathways in roots.

    PubMed

    Molas, Maria Lia; Kiss, John Z; Correll, Melanie J

    2006-01-01

    Red light, acting through the phytochromes, controls numerous aspects of plant development. Many of the signal transduction elements downstream of the phytochromes have been identified in the aerial portions of the plant; however, very few elements in red-light signalling have been identified specifically for roots. Gene profiling studies using microarrays and quantitative Real-Time PCR were performed to characterize gene expression changes in roots of Arabidopsis seedlings exposed to 1 h of red light. Several factors acting downstream of phytochromes in red-light signalling in roots were identified. Some of the genes found to be differentially expressed in this study have already been characterized in the red-light-signalling pathway for whole plants. For example, PHYTOCHROME KINASE 1 (PKS1), LONG HYPOCOTYL 5 (HY5), EARLY FLOWERING 4 (ELF4), and GIGANTEA (GI) were all significantly up-regulated in roots of seedlings exposed to 1 h of red light. The up-regulation of SUPPRESSOR OF PHYTOCHROME A RESPONSES 1 (SPA1) and CONSTITUTIVE PHOTOMORPHOGENIC 1-like (COP1-like) genes suggests that the PHYA-mediated pathway was attenuated by red light. In addition, genes involved in lateral root and root hair formation, root plastid development, phenylpropanoid metabolism, and hormone signalling were also regulated by exposure to red light. Interestingly, members of the RPT2/NPH3 (ROOT PHOTOTROPIC 2/NON PHOTOTROPIC HYPOCOTYL 3) family, which have been shown to mediate blue-light-induced phototropism, were also differentially regulated in roots in red light. Therefore, these results suggest that red and blue light pathways interact in roots of seedlings and that many elements involved in red-light-signalling found in the aerial portions of the plant are differentially expressed in roots within 1 h of red light exposure.

  6. Intracerebroventricular administration of nerve growth factor induces gliogenesis in sensory ganglia, dorsal root, and within the dorsal root entry zone.

    PubMed

    Schlachetzki, Johannes C M; Pizzo, Donald P; Morrissette, Debbi A; Winkler, Jürgen

    2014-01-01

    Previous studies indicated that intracerebroventricular administration of nerve growth factor (NGF) leads to massive Schwann cell hyperplasia surrounding the medulla oblongata and spinal cord. This study was designed to characterize the proliferation of peripheral glial cells, that is, Schwann and satellite cells, in the trigeminal ganglia and dorsal root ganglia (DRG) of adult rats during two weeks of NGF infusion using bromodeoxyuridine (BrdU) to label dividing cells. The trigeminal ganglia as well as the cervical and lumbar DRG were analyzed. Along the entire neuraxis a small number of dividing cells were observed within these regions under physiological condition. NGF infusion has dramatically increased the generation of new cells in the neuronal soma and axonal compartments of sensory ganglia and along the dorsal root and the dorsal root entry zone. Quantification of BrdU positive cells within sensory ganglia revealed a 2.3- to 3-fold increase in glial cells compared to controls with a similar response to NGF for the different peripheral ganglia examined. Immunofluorescent labeling with S100β revealed that Schwann and satellite cells underwent mitosis after NGF administration. These data indicate that intracerebroventricular NGF infusion significantly induces gliogenesis in trigeminal ganglia and the spinal sensory ganglia and along the dorsal root entry zone as well as the dorsal root.

  7. Anatomical evidence for the absence of a morphologically distinct cranial root of the accessory nerve in man.

    PubMed

    Lachman, Nirusha; Acland, Robert D; Rosse, Cornelius

    2002-01-01

    The accessory nerve is conventionally described as having a cranial and spinal root. According to standard descriptions the cranial root (or part) is formed by rootlets that emerge from the medulla between the olive and the inferior cerebellar peduncle. These rootlets are considered to join the spinal root, travel with it briefly, then separate within the jugular foramen to become part of the vagus nerve. In 15 fresh specimens we exposed the posterior cranial fossa with a coronal cut through the foramen magnum and explored the course of each posterior medullary rootlet (PMR) arising from within the retro-olivary groove. We chose the caudal end of the olive as the landmark for the caudal end of the medulla. In all specimens every PMR that did not contribute to the glossopharyngeal nerve joined the vagus nerve at the jugular foramen. The distance between the caudal limit of the olive and the origin of the most caudal PMR that contributed to the vagus nerve ranged from 1-21 mm (mean = 8.8 mm). All rootlets that joined the accessory nerve arose caudal to the olive. The distance from the caudal limit of the olive and the most rostral accessory rootlet ranged from 1-15 mm (mean = 5.4 mm). We were unable to demonstrate any connection between the accessory and vagus nerves within the jugular foramen. Our findings indicate that the accessory nerve has no cranial root; it consists only of the structure hitherto referred to as its spinal root.

  8. A Whitacre-type spinal needle does not prevent intravascular injection during cervical nerve root injections.

    PubMed

    Candido, Kenneth D; Ghaly, Ramsis F; Mackerley, Sara; Knezevic, Nebojsa Nick

    2010-07-01

    We present a case of intravascular injection in a 41-year-old female during cervical selective nerve root injection using a 22-gauge 3.5-inch Whitacre-type pencil-point subarachnoid needle with a curve placed at the distal tip positioned using continual live fluoroscopic guidance. After negative aspiration for blood and cerebrospinal fluid and no elicited paresthesias during the procedure, 1 mL of contrast was injected. Initial imaging at C6 captured the outline of the nerve root along with a significant amount of transient vascular runoff. This case report demonstrates that Whitacre-type spinal needles do not prevent vascular injection, and that aspiration of the needle is not a reliable sign of intravascular injection.

  9. CNS-derived glia ensheath peripheral nerves and mediate motor root development.

    PubMed

    Kucenas, Sarah; Takada, Norio; Park, Hae-Chul; Woodruff, Elvin; Broadie, Kendal; Appel, Bruce

    2008-02-01

    Motor function requires that motor axons extend from the spinal cord at regular intervals and that they are myelinated by Schwann cells. Little attention has been given to another cellular structure, the perineurium, which ensheaths the motor nerve, forming a flexible, protective barrier. Consequently, the origin of perineurial cells and their roles in motor nerve formation are poorly understood. Using time-lapse imaging in zebrafish, we show that perineurial cells are born in the CNS, arising as ventral spinal-cord glia before migrating into the periphery. In embryos lacking perineurial glia, motor neurons inappropriately migrated outside of the spinal cord and had aberrant axonal projections, indicating that perineurial glia carry out barrier and guidance functions at motor axon exit points. Additionally, reciprocal signaling between perineurial glia and Schwann cells was necessary for motor nerve ensheathment by both cell types. These insights reveal a new class of CNS-born glia that critically contributes to motor nerve development.

  10. Calcium-Mediated Abiotic Stress Signaling in Roots

    PubMed Central

    Wilkins, Katie A.; Matthus, Elsa; Swarbreck, Stéphanie M.; Davies, Julia M.

    2016-01-01

    Roots are subjected to a range of abiotic stresses as they forage for water and nutrients. Cytosolic free calcium is a common second messenger in the signaling of abiotic stress. In addition, roots take up calcium both as a nutrient and to stimulate exocytosis in growth. For calcium to fulfill its multiple roles must require strict spatio-temporal regulation of its uptake and efflux across the plasma membrane, its buffering in the cytosol and its sequestration or release from internal stores. This prompts the question of how specificity of signaling output can be achieved against the background of calcium’s other uses. Threats to agriculture such as salinity, water availability and hypoxia are signaled through calcium. Nutrient deficiency is also emerging as a stress that is signaled through cytosolic free calcium, with progress in potassium, nitrate and boron deficiency signaling now being made. Heavy metals have the capacity to trigger or modulate root calcium signaling depending on their dose and their capacity to catalyze production of hydroxyl radicals. Mechanical stress and cold stress can both trigger an increase in root cytosolic free calcium, with the possibility of membrane deformation playing a part in initiating the calcium signal. This review addresses progress in identifying the calcium transporting proteins (particularly channels such as annexins and cyclic nucleotide-gated channels) that effect stress-induced calcium increases in roots and explores links to reactive oxygen species, lipid signaling, and the unfolded protein response. PMID:27621742

  11. Accuracy of cone-beam computed tomography in defining spatial relationships between third molar roots and inferior alveolar nerve

    PubMed Central

    Pippi, Roberto; Santoro, Marcello; D’Ambrosio, Ferdinando

    2016-01-01

    Objective: Cone-beam computed tomography (CBCT) has been proposed in surgical planning of lower third molar extraction. The aim of the present study was to assess the reliability of CBCT in defining third molar root morphology and its spatial relationships with the inferior alveolar nerve (IAN). Materials and Methods: Intraoperative and radiographic variables of 74 lower third molars were retrospectively analyzed. Intraoperative variables included IAN exposure, number of roots, root morphology of extracted third molars, and presence/absence of IAN impression on the root surface. Radiographic variables included presence/absence of the cortex separating IAN from the third molar roots on CBCT examination, number of roots and root morphology on both orthopantomography (OPG) and CBCT. The statistical association between variables was evaluated using the Fisher's exact test. Results: In all cases of intraoperative IAN exposure, the cortex appeared discontinuous on CBCT images. All cases, in which the cortical bone was continuous on CBCT images, showed no association with nerve exposure. In all cases in which nerve impression was identified on the root surface, the IAN cortex showed interruptions on CBCT images. No nerve impression was identified in any of the cases, in which the cortex appeared continuous on CBCT images. CBCT also highlighted accessory roots and apical anomalies/curvatures, not visible on the OPG. Conclusions: CBCT seems to provide reliable and accurate information about the third molar root morphology and its relationship with the IAN. PMID:28042257

  12. Comparison with Magnetic Resonance Three-Dimensional Sequence for Lumbar Nerve Root with Intervertebral Foramen

    PubMed Central

    Takashima, Hiroyuki; Shishido, Hiroki; Yoshimoto, Mitsunori; Imamura, Rui; Akatsuka, Yoshihiro; Terashima, Yoshinori; Fujiwara, Hiroyoshi; Nagae, Masateru; Kubo, Toshikazu; Yamashita, Toshihiko

    2016-01-01

    Study Design Prospective study based on magnetic resonance (MR) imaging of the lumbar spinal root of the intervertebral foramen. Purpose This study was to compare MR three-dimensional (3D) sequences for the evaluation of the lumbar spinal root of the intervertebral foramen. Overview of Literature The diagnosis of spinal disorders by MR imaging is commonly performed using two-dimensional T1- and T2-weighted images, whereas 3D MR images can be used for acquiring further detailed data using thin slices with multi-planar reconstruction. Methods On twenty healthy volunteers, we investigated the contrast-to-noise ratio (CNR) of the lumbar spinal root of the intervertebral foramen with a 3D balanced sequence. The sequences used were the fast imaging employing steady state acquisition and the coherent oscillatory state acquisition for the manipulation of image contrast (COSMIC). COSMIC can be used with or without fat suppression (FS). We compared these sequence to determine the optimized visualization sequence for the lumbar spinal root of the intervertebral foramen. Results For the CNR between the nerve root and the peripheral tissue, these were no significant differences between the sequences at the entry of foramen. There was a significant difference and the highest CNR was seen with COSMIC-FS for the intra- and extra-foramen. Conclusions In this study, the findings suggest that the COSMIC-FS sequences should be used for the internal or external foramen for spinal root disorders. PMID:26949459

  13. Peripheral nerve injury modulates neurotrophin signaling in the peripheral and central nervous system.

    PubMed

    Richner, Mette; Ulrichsen, Maj; Elmegaard, Siri Lander; Dieu, Ruthe; Pallesen, Lone Tjener; Vaegter, Christian Bjerggaard

    2014-12-01

    Peripheral nerve injury disrupts the normal functions of sensory and motor neurons by damaging the integrity of axons and Schwann cells. In contrast to the central nervous system, the peripheral nervous system possesses a considerable capacity for regrowth, but regeneration is far from complete and functional recovery rarely returns to pre-injury levels. During development, the peripheral nervous system strongly depends upon trophic stimulation for neuronal differentiation, growth and maturation. The perhaps most important group of trophic substances in this context is the neurotrophins (NGF, BDNF, NT-3 and NT-4/5), which signal in a complex spatial and timely manner via the two structurally unrelated p75(NTR) and tropomyosin receptor kinase (TrkA, Trk-B and Trk-C) receptors. Damage to the adult peripheral nerves induces cellular mechanisms resembling those active during development, resulting in a rapid and robust increase in the synthesis of neurotrophins in neurons and Schwann cells, guiding and supporting regeneration. Furthermore, the injury induces neurotrophin-mediated changes in the dorsal root ganglia and in the spinal cord, which affect the modulation of afferent sensory signaling and eventually may contribute to the development of neuropathic pain. The focus of this review is on the expression patterns of neurotrophins and their receptors in neurons and glial cells of the peripheral nervous system and the spinal cord. Furthermore, injury-induced changes of expression patterns and the functional consequences in relation to axonal growth and remyelination as well as to neuropathic pain development will be reviewed.

  14. Volatile signalling by sesquiterpenes from ectomycorrhizal fungi reprogrammes root architecture

    PubMed Central

    Ditengou, Franck A.; Müller, Anna; Rosenkranz, Maaria; Felten, Judith; Lasok, Hanna; van Doorn, Maja Miloradovic; Legué, Valerie; Palme, Klaus; Schnitzler, Jörg-Peter; Polle, Andrea

    2015-01-01

    The mutualistic association of roots with ectomycorrhizal fungi promotes plant health and is a hallmark of boreal and temperate forests worldwide. In the pre-colonization phase, before direct contact, lateral root (LR) production is massively stimulated, yet little is known about the signals exchanged during this step. Here, we identify sesquiterpenes (SQTs) as biologically active agents emitted by Laccaria bicolor while interacting with Populus or Arabidopsis. We show that inhibition of fungal SQT production by lovastatin strongly reduces LR proliferation and that (–)-thujopsene, a low-abundance SQT, is sufficient to stimulate LR formation in the absence of the fungus. Further, we show that the ectomycorrhizal ascomycote, Cenococcum geophilum, which cannot synthesize SQTs, does not promote LRs. We propose that the LR-promoting SQT signal creates a win-win situation by enhancing the root surface area for plant nutrient uptake and by improving fungal access to plant-derived carbon via root exudates. PMID:25703994

  15. Experimental studies on the effect of chymopapain on nerve root compression caused by intervertebral disk material.

    PubMed

    Krempen, J F; Minnig, D I; Smith, B S

    1975-01-01

    Chymopapain degrades the nucleus pulposus portion of the intervertebral disk of rabbits. The degradation is not grossly visible until 15 days post-injection. Depolymerization of the chondromucoprotein and decreases in the ability of a disk to imbibe fluid, is, in effect, a "chemical decompression" of the nucleur pulposus. The enzyme must come into direct contact with the chondromucoprotein complex of the disk material, and to a significant extent also must reach the area of disk material adjacent to the herniated annulus. Rapid depolymerization of the chondromucoprotein complex on a biomechanical level, and "decompression" of disk material on a biomechanical level can be correlated with relief of pain in all types of disk herniation in human beings. A primary biochemical change in the disk material would lead to a secondary decrease in inflammation if the change led to a "decompression" of the chondromucoprotein. Since the primary effect of chymopapain is on the chondromucoprotein of the disk, beneficial results would not be expected if nerve root compression is due to bony impingement or scar tissue following previous surgery. Chymopapain did not seem to possess any anti-inflammatory properties when bone was used as an irritant under a nerve root. However, this was technically difficult to evaluate and the possibility that chymopapain may also interfere with a chemical mediator of pain or interfere directly with an inflammatory reaction secondary to root compression can not be excluded.

  16. Microvascular decompression of trigeminal nerve root for treatment of a patient with hemimasticatory spasm.

    PubMed

    Dou, Ning-Ning; Zhong, Jun; Zhou, Qiu-Meng; Zhu, Jin; Wang, Yong-Nan; Li, Shi-Ting

    2014-05-01

    Hemimasticatory spasm is a rare disease; with little knowledge of the pathogenesis, it has still been intractable today. We presented a 56-year-old woman with involuntary painful spasm in her left masseter muscle for 11 years. The patient was successfully treated with microvascular decompression surgery. An offending superior cerebellar artery was found to contact with the motor branch of the trigeminal nerve root, which was then removed away and pieces of soft wadding were interposed between the nerve and the vessel to assure the separation. Postoperatively, the symptom totally disappeared and no recurrence was observed during the 7 months' follow-up. The treatment as well as the pathogenesis of the disease was reviewed, and we put forward a new hypothesis.

  17. Sector computed tomographic spine scanning in the diagnosis of lumbar nerve root entrapment

    SciTech Connect

    Risius, B.; Modic, M.T.; Hardy, R.W. Jr.; Duchesneau, P.M.; Weinstein, M.A.

    1982-04-01

    The diagnosis of lumbar nerve root entrapment was made by sector computed tomography (CT) scanning in 25 patients whose myelograms were normal at the site of the CT scan abnormalities. Sector CT scanning demonstrates preoperatively which neural foramina are narrow. This information, correlated with the patient's history and physical examination, indicates which foramina should be operated on and prevents unnecessary exploration of normal neutral foramina. CT findings were confirmed surgically in 14 patients. Eleven of these 14 patients had excellent postoperative results and remain pain free.

  18. Dorsal root ganglion myeloid zinc finger protein 1 contributes to neuropathic pain after peripheral nerve trauma.

    PubMed

    Li, Zhisong; Gu, Xiyao; Sun, Linlin; Wu, Shaogen; Liang, Lingli; Cao, Jing; Lutz, Brianna Marie; Bekker, Alex; Zhang, Wei; Tao, Yuan-Xiang

    2015-04-01

    Peripheral nerve injury-induced changes in gene transcription and translation in primary sensory neurons of the dorsal root ganglion (DRG) are considered to contribute to neuropathic pain genesis. Transcription factors control gene expression. Peripheral nerve injury increases the expression of myeloid zinc finger protein 1 (MZF1), a transcription factor, and promotes its binding to the voltage-gated potassium 1.2 (Kv1.2) antisense (AS) RNA gene in the injured DRG. However, whether DRG MZF1 participates in neuropathic pain is still unknown. Here, we report that blocking the nerve injury-induced increase of DRG MZF1 through microinjection of MZF1 siRNA into the injured DRG attenuated the initiation and maintenance of mechanical, cold, and thermal pain hypersensitivities in rats with chronic constriction injury (CCI) of the sciatic nerve, without affecting locomotor functions and basal responses to acute mechanical, heat, and cold stimuli. Mimicking the nerve injury-induced increase of DRG MZF1 through microinjection of recombinant adeno-associated virus 5 expressing full-length MZF1 into the DRG produced significant mechanical, cold, and thermal pain hypersensitivities in naive rats. Mechanistically, MZF1 participated in CCI-induced reductions in Kv1.2 mRNA and protein and total Kv current and the CCI-induced increase in neuronal excitability through MZF1-triggered Kv1.2 AS RNA expression in the injured DRG neurons. MZF1 is likely an endogenous trigger of neuropathic pain and might serve as a potential target for preventing and treating this disorder.

  19. Cranial Nerve Development Requires Co-Ordinated Shh and Canonical Wnt Signaling

    PubMed Central

    Kurosaka, Hiroshi; Trainor, Paul A.; Leroux-Berger, Margot; Iulianella, Angelo

    2015-01-01

    Cranial nerves govern sensory and motor information exchange between the brain and tissues of the head and neck. The cranial nerves are derived from two specialized populations of cells, cranial neural crest cells and ectodermal placode cells. Defects in either cell type can result in cranial nerve developmental defects. Although several signaling pathways are known to regulate cranial nerve formation our understanding of how intercellular signaling between neural crest cells and placode cells is coordinated during cranial ganglia morphogenesis is poorly understood. Sonic Hedgehog (Shh) signaling is one key pathway that regulates multiple aspects of craniofacial development, but whether it co-ordinates cranial neural crest cell and placodal cell interactions during cranial ganglia formation remains unclear. In this study we examined a new Patched1 (Ptch1) loss-of-function mouse mutant and characterized the role of Ptch1 in regulating Shh signaling during cranial ganglia development. Ptch1Wig/ Wig mutants exhibit elevated Shh signaling in concert with disorganization of the trigeminal and facial nerves. Importantly, we discovered that enhanced Shh signaling suppressed canonical Wnt signaling in the cranial nerve region. This critically affected the survival and migration of cranial neural crest cells and the development of placodal cells as well as the integration between neural crest and placodes. Collectively, our findings highlight a novel and critical role for Shh signaling in cranial nerve development via the cross regulation of canonical Wnt signaling. PMID:25799573

  20. TNFa/TNFR2 signaling is required for glial ensheathment at the dorsal root entry zone.

    PubMed

    Smith, Cody J; Wheeler, Michael A; Marjoram, Lindsay; Bagnat, Michel; Deppmann, Christopher D; Kucenas, Sarah

    2017-04-05

    Somatosensory information from the periphery is routed to the spinal cord through centrally-projecting sensory axons that cross into the central nervous system (CNS) via the dorsal root entry zone (DREZ). The glial cells that ensheath these axons ensure rapid propagation of this information. Despite the importance of this glial-axon arrangement, how this afferent nerve is assembled during development is unknown. Using in vivo, time-lapse imaging we show that as centrally-projecting pioneer axons from dorsal root ganglia (DRG) enter the spinal cord, they initiate expression of the cytokine TNFalpha. This induction coincides with ensheathment of these axons by associated glia via a TNF receptor 2 (TNFR2)-mediated process. This work identifies a signaling cascade that mediates peripheral glial-axon interactions and it functions to ensure that DRG afferent projections are ensheathed after pioneer axons complete their navigation, which promotes efficient somatosensory neural function.

  1. Activating transcription factor 3, a useful marker for regenerative response after nerve root injury.

    PubMed

    Lindå, Hans; Sköld, Mattias K; Ochsmann, Thomas

    2011-01-01

    Activating transcription factor 3 (ATF3) is induced in various tissues in response to stress. In this experiment, ATF3 expression was studied in adult rats subjected either to a dorsal or ventral root avulsion (VRA; L4-6), or sciatic nerve transection (SNT). Post-operative survival times varied between 1.5 h and 3 weeks. In additional experiments an avulsed ventral root was directly replanted to the spinal cord. Dorsal root ganglias (DRGs) from humans exposed to traumatic dorsal root avulsions were also examined. After SNT ATF3 immunoreactivity (ATF3 IR) was detected in a few DRG neurons already 6 h after the lesion. After 24 h the number had clearly increased and still at 3 weeks DRG neurons remained labeled. In the ventral horn, ATF3 IR in motoneurons (MN) was first detected 24 h after the SNT, and still 3 weeks post-operatively lesioned MN showed ATF3 labeling. After a VRA many spinal MN showed ATF3 IR already after 3 h, and after 6 h all MN were labeled. At 3 weeks a majority of the lesioned MN had died, but all the remaining ones were labeled. When an avulsed ventral root was directly replanted, MN survived and were still labeled at 5 weeks. In DRG, a few neurons were labeled already at 1.5 h after a dorsal root avulsion. At 24 h the number had increased but still only a minority of the neurons were labeled. At 3 days the number of labeled neurons was reduced, and a further reduction was at hand at 7 days and 3 weeks. In parallel, in humans, 3 days after a traumatic dorsal root avulsion, only a few DRG neurons showed ATF3 IR. At 6 weeks no labeled neurons could be detected. These facts imply that ATF3 response to axotomy involves a distance-dependent mechanism. ATF3 also appears to be a useful and reliable neuronal marker of nerve lesions even in humans. In addition, ATF3 up-regulation in both motor and sensory neurons seems to be linked to regenerative competence.

  2. MicroRNA Signatures of Drought Signaling in Rice Root

    PubMed Central

    Nikpay, Nava; Ebrahimi, Mohammad Ali; Bihamta, Mohammad Reza; Mardi, Mohsen; Salekdeh, Ghasem Hosseini

    2016-01-01

    Background Drought stress is one of the most important abiotic stresses and the main constraint to rice agriculture. MicroRNA-mediated post-transcriptional gene regulation is one of the ways to establish drought stress tolerance in plants. MiRNAs are 20–24-nt regulatory RNAs that play an important role in regulating plant gene expression upon exposure to biotic and abiotic stresses. Methodology/Principal Findings In this study, we applied a partial root drying system as well as a complete root drying system to identify miRNAs involved in conditions of drought stress, drought signaling and wet signaling using high-throughput sequencing. To this end, we produced four small RNA libraries: (1) fully-watered (WW), (2) fully-droughted (WD), and split-root systems where (3) one-half was well watered (SpWW) and (4) the other half was water-deprived (SpWD). Our analysis revealed 10,671 and 783 unique known and novel miRNA reads in all libraries, respectively. We identified, 65 (52 known + 13 novel), 72 (61 known + 11 novel) and 51 (38 known + 13 novel) miRNAs that showed differential expression under conditions of drought stress, drought signaling and wet signaling, respectively. The results of quantitative real-time PCR showed expression patterns similar to the high-throughput sequencing results. Furthermore, our target prediction led to the identification of 244, 341 and 239 unique target genes for drought-stress-, drought-signaling- and wet-signaling-responsive miRNAs, respectively. Conclusions/Significance Our results suggest that miRNAs that are responsive under different conditions could play different roles in the regulation of abscisic acid signaling, calcium signaling, detoxification and lateral root formation. PMID:27276090

  3. Nerve growth factor signaling in prostate health and disease.

    PubMed

    Arrighi, Nicola; Bodei, Serena; Zani, Danilo; Simeone, Claudio; Cunico, Sergio Cosciani; Missale, Cristina; Spano, Pierfranco; Sigala, Sandra

    2010-06-01

    The prostate is one of the most abundant sources of nerve growth factor (NGF) in different species, including humans. NGF and its receptors are implicated in the control of prostate cell proliferation and apoptosis and it can either support or suppress cell growth. The co-expression of both NGF receptors, p75(NGFR) and tropomyosin-related kinase A (trkA), represents a crucial condition for the antiproliferative effect of NGF; indeed, p75(NGFR) is progressively lost during prostate tumorigenesis and its disappearance represents a malignancy marker of prostate adenocarcinoma (PCa). Interestingly, a dysregulation of NGF signal transduction was found in a number of human tumors. This review summarizes the current knowledge on the role of NGF and its receptors in prostate and in PCa. Conclusions bring to the hypothesis that the NGF network could be a candidate for future pharmacological manipulation in the PCa therapy: in particular the re-expression of p75(NTR) and/or the negative modulation of trkA could represent a target to induce apoptosis and to reduce proliferation and invasiveness of PCa.

  4. Hindlimb spasticity after unilateral motor cortex lesion in rats is reduced by contralateral nerve root transfer

    PubMed Central

    Zong, Haiyang; Ma, Fenfen; Zhang, Laiyin; Lu, Huiping; Gong, Jingru; Cai, Min; Lin, Haodong; Zhu, Yizhun; Hou, Chunlin

    2016-01-01

    Lower extremity spasticity is a common sequela among patients with acquired brain injury. The optimum treatment remains controversial. The aim of our study was to test the feasibility and effectiveness of contralateral nerve root transfer in reducing post stroke spasticity of the affected hindlimb muscles in rats. In our study, we for the first time created a novel animal hindlimb spastic hemiplegia model in rats with photothrombotic lesion of unilateral motor cortex and we established a novel surgical procedure in reducing motor cortex lesion-induced hindlimb spastic hemiplegia in rats. Thirty six rats were randomized into three groups. In group A, rats received sham operation. In group B, rats underwent unilateral hindlimb motor cortex lesion. In group C, rats underwent unilateral hindlimb cortex lesion followed by contralateral L4 ventral root transfer to L5 ventral root of the affected side. Footprint analysis, Hoffmann reflex (H-reflex), cholera toxin subunit B (CTB) retrograde tracing of gastrocnemius muscle (GM) motoneurons and immunofluorescent staining of vesicle glutamate transporter 1 (VGLUT1) on CTB-labelled motoneurons were used to assess spasticity of the affected hindlimb. Sixteen weeks postoperatively, toe spread and stride length recovered significantly in group C compared with group B (P<0.001). Hmax (H-wave maximum amplitude)/Mmax (M-wave maximum amplitude) ratio of gastrocnemius and plantaris muscles (PMs) significantly reduced in group C (P<0.01). Average VGLUT1 positive boutons per CTB-labelled motoneurons significantly reduced in group C (P<0.001). We demonstrated for the first time that contralateral L4 ventral root transfer to L5 ventral root of the affected side was effective in relieving unilateral motor cortex lesion-induced hindlimb spasticity in rats. Our data indicated that this could be an alternative treatment for unilateral lower extremity spasticity after brain injury. Therefore, contralateral neurotization may exert a potential

  5. C5 Nerve root palsies following cervical spine surgery: A review

    PubMed Central

    Epstein, Nancy E.; Hollingsworth, Renee

    2015-01-01

    Background: Cervical C5 nerve root palsies may occur in between 0% and 30% of routine anterior or posterior cervical spine operations. They are largely attributed to traction injuries/increased cord migration following anterior/posterior decompressions. Of interest, almost all studies cite spontaneous resolution of these deficits without surgery with 3–24 postoperative months. Methods: Different studies cite various frequencies for C5 root palsies following anterior or posterior cervical spine surgery. In their combined anterior/posterior series involving C4-C5 level decompressions, Libelski et al. cited up to a 12% incidence of C5 palsies. In Gu et al. series, C5 root palsies occurred in 3.1% of double-door laminoplasty, 4.5% of open-door laminoplasty, and 11.3% of laminectomy. Miller et al. observed an intermediate 6.9% frequency of C5 palsies followed by posterior cervical decompressions and fusions (PCDF). Results: Gu et al. also identified multiple risk factors for developing C5 palsies following posterior surgery; male gender, ossification of the posterior longitudinal ligament (OPLL), narrower foramina, laminectomy, and marked dorsal spinal cord drift. Miller et al. also identified an average $1918 increased cost for physical/occupational therapy for patients with C5 palsies. Conclusions: The incidence of C5 root deficits for anterior/posterior cervical surgery at C4-C5 was 12% in one series, and ranged up to 11.3% for laminectomies, while others cited 0–30%. Although identification of preoperative risk factors for C5 root deficits may help educate patients regarding these risks, there is no clear method for their avoidance at this time. PMID:26005577

  6. Preservation and Tissue Handling Technique on Iatrogenic Dural Tear with Herniated Nerve Root at Cauda Equina Level

    PubMed Central

    Djaja, Yoshi Pratama; Saleh, Ifran; Safri, Ahmad Yanuar

    2016-01-01

    Iatrogenic or incidental dural tear is a relatively common complication in lumbar decompression surgery. Although mostly there are no changes that occurred in long-term result following an incidental durotomy, the sequelae are not always benign especially when the herniated nerve root is involved. Preservation and tissue handling is paramount in order to prevent further injury. Two cases of dural tear with herniated nerve root complicating the lumbar decompression surgery are presented. Direct watertight repair was performed using the preservation and tissue handling concept. Assessing the relative size between the dural tear and the root mass is the key in determining whether enlargement of tear is needed. Whenever feasible, the tear will not be enlarged. Opening the vent by using a suture anchor and manually repositioning the nerve root with a fine instrument is the key for an atraumatic handling of the herniated nerve root. Clinical and neurophysiology examination was performed postoperatively and no further neurologic deficit occurred despite the iatrogenic injury. Although some debate on a few intraoperative and postoperative details still persists, tissue handling and preservation concept should be applied in all cases. PMID:28127488

  7. Macrophages related to leptomeninges and ventral nerve roots. An ultrastructural study.

    PubMed Central

    Fraher, J P; McDougall, R D

    1975-01-01

    In immature rats active macrophages were frequently seen projecting into the subarachnoid space from the surface of the leptomeninges. They also occurred between the layers of the pia and within the nerve roots. They were most frequent during the first two weeks after birth, which is a period of rapid neural growth and myelination in ventral roots. In contrast, they were much fewer at later stages. The ultrastructural characteristics of these cells are described. It is suggested that these cells take part in tissue growth and remodelling by the removal of material which degenerates or becomes redundant during development. For example, they may ingest effete leptomeningeal cells or fragments of them. Those within the ventral roots may phagocytose abnormal Schwann cells, or the myelin of sheaths which have failed to develop normally. It is also suggested that macrophages may be involved in the excavation of the subarachnoid space. Another possible function in which they may be involved is the ingestion of material, possibly of a protein nature, from the cerebrospinal fluid. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:1213953

  8. Antral bony wall erosion, trigeminal nerve injury, and enophthalmos after root canal surgery

    PubMed Central

    Ferreira, Eduardo; Antunes, Luís; Dinis, Paulo Borges

    2016-01-01

    Introduction: The frequently used irrigant in dental surgery, sodium hypochlorite, is occasionally the cause of minor, usually circumscribed, adverse effects. Severe, extensive complications, with lasting sequelae, however, also can occur, as in the case we report herein. Case Report: A 55-year-old woman underwent an endodontic procedure on a maxillary molar, whose roots, unknown to the surgeon, were protruding into the maxillary sinus. After sodium hypochlorite root canal irrigation, the patient immediately developed intense facial pain, facial edema, and periorbital cellulitis. An emergency department evaluation diagnosed an intense inflammatory disease of the maxillary sinus, with significant destruction of its bony walls, accompanied by midface paraesthesia due to infraorbital nerve injury. In the following weeks, the patient slowly developed enophthalmos due to bone erosion of the orbit floor. Treatment, besides prolonged oral steroids, required the endoscopic endonasal opening of the maxillary sinus for profuse irrigation. Two years later, the patient maintained a complete loss of function of the maxillary sinus, anesthesia-paraesthesia of the midface, and inferior dystonia of the eye with an enophthalmos. Conclusion: Dentists, maxillofacial surgeons, and otorhinolaryngologists should all be aware of the whole spectrum of complications of even the simplest dental work. Sodium hypochlorite irrigations should be used cautiously in root canal surgery, with the full awareness of its potential for causing soft-tissue damage. PMID:27465790

  9. Generation of New Neurons in Dorsal Root Ganglia in Adult Rats after Peripheral Nerve Crush Injury

    PubMed Central

    2015-01-01

    The evidence of neurons generated ex novo in sensory ganglia of adult animals is still debated. In the present study, we investigated, using high resolution light microscopy and stereological analysis, the changes in the number of neurons in dorsal root ganglia after 30 days from a crush lesion of the rat brachial plexus terminal branches. Results showed, as expected, a relevant hypertrophy of dorsal root ganglion neurons. In addition, we reported, for the first time in the literature, that neuronal hypertrophy was accompanied by massive neuronal hyperplasia leading to a 42% increase of the number of primary sensory neurons. Moreover, ultrastructural analyses on sensory neurons showed that there was not a relevant neuronal loss as a consequence of the nerve injury. The evidence of BrdU-immunopositive neurons and neural progenitors labeled with Ki67, nanog, nestin, and sox-2 confirmed the stereological evidence of posttraumatic neurogenesis in dorsal root ganglia. Analysis of morphological changes following axonal damage in addition to immunofluorescence characterization of cell phenotype suggested that the neuronal precursors which give rise to the newly generated neurons could be represented by satellite glial cells that actively proliferate after the lesion and are able to differentiate toward the neuronal lineage. PMID:25722894

  10. Nerve growth factor (NGF) and diabetic neuropathy in the rat: morphological investigations of the sural nerve, dorsal root ganglion, and spinal cord.

    PubMed

    Unger, J W; Klitzsch, T; Pera, S; Reiter, R

    1998-09-01

    A number of functions for nerve growth factor (NGF) have been described over the past years, including its role for neuronal function and regeneration during toxic or metabolic neuropathies. In order to further assess the effects of NGF on the somatosensory system in diabetic neuropathy, the sural nerve, dorsal root ganglia (DRG), and dorsal horn of the spinal cord were investigated by morphological and quantitative methods in rats after 12 weeks of uncontrolled streptozotocin-induced diabetes mellitus. The results from our study suggest a twofold effect of NGF: (1) In sural nerve treatment with NGF (0.1 or 0.5 mg/kg) for 12 weeks was able to reverse distinct diabetes-related alterations in myelinated nerve fiber morphology, such as myelin thickness. These changes occurred in the entire myelinated population of sensory nerves and were not restricted to nociceptive nerve fibers. (2) The NGF effect on neurotransmitters of the sensory, nociceptive system was reflected by increased CGRP and substance P content in the DRG and in the dorsal horn of the spinal cord. No change of trkA receptor immunostaining was seen in DRGs of diabetic rats; however, a reduction of trkA immunoreactivity of DRG neurons was noted after long-term NGF treatment of healthy controls. The data demonstrate that NGF regulates a number of neuronal parameters along peripheral and central parts of the somatosensory pathway in the adult. This neurotrophic support may be essential for inducing functionally significant regenerative mechanisms in diabetic neuropathy.

  11. Cyclic AMP Signaling: A Molecular Determinant of Peripheral Nerve Regeneration

    PubMed Central

    Knott, Eric P.; Assi, Mazen; Pearse, Damien D.

    2014-01-01

    Disruption of axonal integrity during injury to the peripheral nerve system (PNS) sets into motion a cascade of responses that includes inflammation, Schwann cell mobilization, and the degeneration of the nerve fibers distal to the injury site. Yet, the injured PNS differentiates itself from the injured central nervous system (CNS) in its remarkable capacity for self-recovery, which, depending upon the length and type of nerve injury, involves a series of molecular events in both the injured neuron and associated Schwann cells that leads to axon regeneration, remyelination repair, and functional restitution. Herein we discuss the essential function of the second messenger, cyclic adenosine monophosphate (cyclic AMP), in the PNS repair process, highlighting the important role the conditioning lesion paradigm has played in understanding the mechanism(s) by which cyclic AMP exerts its proregenerative action. Furthermore, we review the studies that have therapeutically targeted cyclic AMP to enhance endogenous nerve repair. PMID:25177696

  12. Ultrasonographic nerve enlargement of the median and ulnar nerves and the cervical nerve roots in patients with demyelinating Charcot-Marie-Tooth disease: distinction from patients with chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Sugimoto, Takamichi; Ochi, Kazuhide; Hosomi, Naohisa; Takahashi, Tetsuya; Ueno, Hiroki; Nakamura, Takeshi; Nagano, Yoshito; Maruyama, Hirofumi; Kohriyama, Tatsuo; Matsumoto, Masayasu

    2013-10-01

    Demyelinating Charcot-Marie-Tooth disease (CMT) and chronic inflammatory demyelinating polyneuropathy (CIDP) are both demyelinating polyneuropathies. The differences in nerve enlargement degree and pattern at multiple evaluation sites/levels are not well known. We investigated the differences in nerve enlargement degree and the distribution pattern of nerve enlargement in patients with demyelinating CMT and CIDP, and verified the appropriate combination of sites/levels to differentiate between these diseases. Ten patients (aged 23-84 years, three females) with demyelinating CMT and 16 patients (aged 30-85 years, five females) with CIDP were evaluated in this study. The nerve sizes were measured at 24 predetermined sites/levels from the median and ulnar nerves and the cervical nerve roots (CNR) using ultrasonography. The evaluation sites/levels were classified into three regions: distal, intermediate and cervical. The number of sites/levels that exhibited nerve enlargement (enlargement site number, ESN) in each region was determined from the 24 sites/levels and from the selected eight screening sites/levels, respectively. The cross-sectional areas of the peripheral nerves were markedly larger at all evaluation sites in patients with demyelinating CMT than in patients with CIDP (p < 0.01). However, the nerve sizes of CNR were not significantly different between patients with either disease. When we evaluated ESN of four selected sites for screening from the intermediate region, the sensitivity and specificity to distinguish between demyelinating CMT and CIDP were 0.90 and 0.94, respectively, with the cut-off value set at four. Nerve ultrasonography is useful to detect nerve enlargement and can clarify morphological differences in nerves between patients with demyelinating CMT and CIDP.

  13. Confocal imaging reveals three-dimensional fine structure difference between ventral and dorsal nerve roots.

    PubMed

    Wu, Yuxiang; Sui, Tao; Cao, Xiaojian; Lv, Xiaohua; Zeng, Shaoqun; Sun, Peng

    2011-05-01

    Peripheral nerve injury repair is one of the most challenging problems in neurosurgery, partially due to lack of knowledge of three-dimensional (3-D) fine structure and organization of peripheral nerves. In this paper, we explored the structures of nerve fibers in ventral and dorsal nerves with a laser scanning confocal microscopy. Thick tissue staining results suggested that nerve fibers have a different 3-D structure in ventral and dorsal nerves, and reconstruction from serial sectioning images showed that in ventral nerves the nerve fibers travel in a winding form, while in dorsal nerves, the nerve fibers form in a parallel cable pattern. These structural differences could help surgeons to differentiate ventral and dorsal nerves in peripheral nerve injury repair, and also facilitate scientists to get a deeper understanding about nerve fiber organization.

  14. Confocal imaging reveals three-dimensional fine structure difference between ventral and dorsal nerve roots

    NASA Astrophysics Data System (ADS)

    Wu, Yuxiang; Sui, Tao; Cao, Xiaojian; Lv, Xiaohua; Zeng, Shaoqun; Sun, Peng

    2011-05-01

    Peripheral nerve injury repair is one of the most challenging problems in neurosurgery, partially due to lack of knowledge of three-dimensional (3-D) fine structure and organization of peripheral nerves. In this paper, we explored the structures of nerve fibers in ventral and dorsal nerves with a laser scanning confocal microscopy. Thick tissue staining results suggested that nerve fibers have a different 3-D structure in ventral and dorsal nerves, and reconstruction from serial sectioning images showed that in ventral nerves the nerve fibers travel in a winding form, while in dorsal nerves, the nerve fibers form in a parallel cable pattern. These structural differences could help surgeons to differentiate ventral and dorsal nerves in peripheral nerve injury repair, and also facilitate scientists to get a deeper understanding about nerve fiber organization.

  15. More nerve root injuries occur with minimally invasive lumbar surgery, especially extreme lateral interbody fusion: A review

    PubMed Central

    Epstein, Nancy E.

    2016-01-01

    Background: In the lumbar spine, do more nerve root injuries occur utilizing minimally invasive surgery (MIS) techniques versus open lumbar procedures? To answer this question, we compared the frequency of nerve root injuries for multiple open versus MIS operations including diskectomy, laminectomy with/without fusion addressing degenerative disc disease, stenosis, and/or degenerative spondylolisthesis. Methods: Several of Desai et al. large Spine Patient Outcomes Research Trial studies showed the frequency for nerve root injury following an open diskectomy ranged from 0.13% to 0.25%, for open laminectomy/stenosis with/without fusion it was 0%, and for open laminectomy/stenosis/degenerative spondylolisthesis with/without fusion it was 2%. Results: Alternatively, one study compared the incidence of root injuries utilizing MIS transforaminal lumbar interbody fusion (TLIF) versus posterior lumbar interbody fusion (PLIF) techniques; 7.8% of PLIF versus 2% of TLIF patients sustained root injuries. Furthermore, even higher frequencies of radiculitis and nerve root injuries occurred during anterior lumbar interbody fusions (ALIFs) versus extreme lateral interbody fusions (XLIFs). These high frequencies were far from acceptable; 15.8% following ALIF experienced postoperative radiculitis, while 23.8% undergoing XLIF sustained root/plexus deficits. Conclusions: This review indicates that MIS (TLIF/PLIF/ALIF/XLIF) lumbar surgery resulted in a higher incidence of root injuries, radiculitis, or plexopathy versus open lumbar surgical techniques. Furthermore, even a cursory look at the XLIF data demonstrated the greater danger posed to neural tissue by this newest addition to the MIS lumbar surgical armamentariu. The latter should prompt us as spine surgeons to question why the XLIF procedure is still being offered to our patients? PMID:26904372

  16. Increased response to glutamate in small diameter dorsal root ganglion neurons after sciatic nerve injury.

    PubMed

    Gong, Kerui; Kung, Ling-Hsuan; Magni, Giulia; Bhargava, Aditi; Jasmin, Luc

    2014-01-01

    Glutamate in the peripheral nervous system is involved in neuropathic pain, yet we know little how nerve injury alters responses to this neurotransmitter in primary sensory neurons. We recorded neuronal responses from the ex-vivo preparations of the dorsal root ganglia (DRG) one week following a chronic constriction injury (CCI) of the sciatic nerve in adult rats. We found that small diameter DRG neurons (<30 µm) exhibited increased excitability that was associated with decreased membrane threshold and rheobase, whereas responses in large diameter neurons (>30 µm) were unaffected. Puff application of either glutamate, or the selective ionotropic glutamate receptor agonists alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainic acid (KA), or the group I metabotropic receptor (mGluR) agonist (S)-3,5-dihydroxyphenylglycine (DHPG), induced larger inward currents in CCI DRGs compared to those from uninjured rats. N-methyl-D-aspartate (NMDA)-induced currents were unchanged. In addition to larger inward currents following CCI, a greater number of neurons responded to glutamate, AMPA, NMDA, and DHPG, but not to KA. Western blot analysis of the DRGs revealed that CCI resulted in a 35% increase in GluA1 and a 60% decrease in GluA2, the AMPA receptor subunits, compared to uninjured controls. mGluR1 receptor expression increased by 60% in the membrane fraction, whereas mGluR5 receptor subunit expression remained unchanged after CCI. These results show that following nerve injury, small diameter DRG neurons, many of which are nociceptive, have increased excitability and an increased response to glutamate that is associated with changes in receptor expression at the neuronal membrane. Our findings provide further evidence that glutamatergic transmission in the periphery plays a role in nociception.

  17. Meralgia paresthetica-like syndrome may be caused by transient lumbar nerve root injury without definite compression: a case report.

    PubMed

    Dharmasaroja, Pornpatr; Dharmasaroja, Permphan

    2010-12-01

    Meralgia paresthetica is a well-known sensory syndrome describing paresthesia and/or anesthesia in the anterolateral aspect of the thigh that is supplied by the lateral femoral cutaneous nerve. Compression of the nerve usually occurs at the point where it passes between the anterior superior iliac spine and the inguinal ligament. Proximal lesions such as lumbar radiculopathy, lumbar disc herniation, and spinal stenosis have been reported to cause meralgia paresthetica-like syndrome. These proximal lesions directly injure L2 and L3 spinal nerve roots and cause a constant compression of the nerve roots. The presented paper introduces a hypothesis that this syndrome can be caused by transient injury to the L2 and L3 nerve roots by the upper adjacent disc bulge without definite compression. This hypothesis is supported by lumbar spine magnetic resonance imaging of a patient presenting with a meralgia paresthetica-like symptom during bending forward and twisting of the body, showing no L2/L3 herniated disc but mildly posterior bulging of T12/L1 disc. This hypothesis emphasizes an importance of appropriate postures in patients with meralgia paresthetica-like symptoms in order to prevent long-term morbidity.

  18. Microstructural changes are coincident with the improvement of clinical symptoms in surgically treated compressed nerve roots

    PubMed Central

    Wu, Weifei; Liang, Jie; Chen, Ying; Chen, Aihua; Wu, Yongde; Yang, Zong

    2017-01-01

    Diffusion tensor imaging (DTI) has been widely used to visualize peripheral nerves, but the microstructure of compressed nerve roots can be assessed using DTI. However, there are no data regarding the association among microstructural changes evaluated using DTI, the symptoms assessed using the Oswestry Disability Index (ODI) and the duration of symptoms after surgery in patients with lumbar disc herniation (LDH). Thirty patients with unilateral radiculopathy were investigated using DTI. The changes in the mean fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) values as well as the correlation between these changes and the severity and duration of the clinical symptoms were investigated before and at least one month after surgery. The FA values were significantly increased after surgical treatment (p < 0.0001). Both the ADC and ODI values were noticeably decreased (p < 0.0001). A strong positive correlation between the preoperative and postoperative DTI parameters (p < 0.0001) as well as between the preoperative ODI and postoperative ODI/ODI changes (p < 0.0001) were found. In addition, there was a significant positive correlation between the changes in the DTI parameters and changes in the ODI (p < 0.0001). This preliminary study suggests it may be possible to use DTI to diagnose, quantitatively evaluate and follow-up patients with LDH. PMID:28294192

  19. Near-infrared signals associated with electrical stimulation of peripheral nerves

    PubMed Central

    Fantini, Sergio; Chen, Debbie K.; Martin, Jeffrey M.; Sassaroli, Angelo; Bergethon, Peter R.

    2011-01-01

    We report our studies on the optical signals measured non-invasively on electrically stimulated peripheral nerves. The stimulation consists of the delivery of 0.1 ms current pulses, below the threshold for triggering any visible motion, to a peripheral nerve in human subjects (we have studied the sural nerve and the median nerve). In response to electrical stimulation, we observe an optical signal that peaks at about 100 ms post-stimulus, on a much longer time scale than the few milliseconds duration of the electrical response, or sensory nerve action potential (SNAP). While the 100 ms optical signal we measured is not a direct optical signature of neural activation, it is nevertheless indicative of a mediated response to neural activation. We argue that this may provide information useful for understanding the origin of the fast optical signal (also on a 100 ms time scale) that has been measured non-invasively in the brain in response to cerebral activation. Furthermore, the optical response to peripheral nerve activation may be developed into a diagnostic tool for peripheral neuropathies, as suggested by the delayed optical signals (average peak time: 230 ms) measured in patients with diabetic neuropathy with respect to normal subjects (average peak time: 160 ms). PMID:22399834

  20. Near-infrared signals associated with electrical stimulation of peripheral nerves

    NASA Astrophysics Data System (ADS)

    Fantini, Sergio; Chen, Debbie K.; Martin, Jeffrey M.; Sassaroli, Angelo; Bergethon, Peter R.

    2009-02-01

    We report our studies on the optical signals measured non-invasively on electrically stimulated peripheral nerves. The stimulation consists of the delivery of 0.1 ms current pulses, below the threshold for triggering any visible motion, to a peripheral nerve in human subjects (we have studied the sural nerve and the median nerve). In response to electrical stimulation, we observe an optical signal that peaks at about 100 ms post-stimulus, on a much longer time scale than the few milliseconds duration of the electrical response, or sensory nerve action potential (SNAP). While the 100 ms optical signal we measured is not a direct optical signature of neural activation, it is nevertheless indicative of a mediated response to neural activation. We argue that this may provide information useful for understanding the origin of the fast optical signal (also on a 100 ms time scale) that has been measured non-invasively in the brain in response to cerebral activation. Furthermore, the optical response to peripheral nerve activation may be developed into a diagnostic tool for peripheral neuropathies, as suggested by the delayed optical signals (average peak time: 230 ms) measured in patients with diabetic neuropathy with respect to normal subjects (average peak time: 160 ms).

  1. Enhanced adenoviral gene delivery to motor and dorsal root ganglion neurons following injection into demyelinated peripheral nerves.

    PubMed

    Zhang, Yongjie; Zheng, Yiyan; Zhang, Yi Ping; Shields, Lisa B E; Hu, Xiaoling; Yu, Panpan; Burke, Darlene A; Wang, Heming; Jun, Cai; Byers, Jonathan; Whittemore, Scott R; Shields, Christopher B

    2010-08-15

    Injection of viral vectors into peripheral nerves may transfer specific genes into their dorsal root ganglion (DRG) neurons and motoneurons. However, myelin sheaths of peripheral axons block the entry of viral particles into nerves. We studied whether mild, transient peripheral nerve demyelination prior to intraneural viral vector injection would enhance gene transfer to target DRG neurons and motoneurons. The right sciatic nerve of C57BL/6 mice was focally demyelinated with 1% lysolecithin, and the left sciatic nerve was similarly injected with saline (control). Five days after demyelination, 0.5 microl of Ad5-GFP was injected into both sciatic nerves at the site of previous injection. The effectiveness of gene transfer was evaluated by counting GFP(+) neurons in the DRGs and ventral horns. After peripheral nerve demyelination, there was a fivefold increase in the number of infected DRG neurons and almost a 15-fold increase in the number of infected motoneurons compared with the control, nondemyelinated side. Focal demyelination reduced the myelin sheath barrier, allowing greater virus-axon contact. Increased CXADR expression on the demyelinated axons facilitated axoplasmic viral entry. No animals sustained any prolonged neurological deficits. Increased gene delivery into DRG neurons and motoneurons may provide effective treatment for amyotrophic lateral sclerosis, pain, and spinal cord injury.

  2. Genetic Analysis of Gravity Signal Transduction in Arabidopsis Roots

    NASA Astrophysics Data System (ADS)

    Masson, Patrick; Strohm, Allison; Barker, Richard; Su, Shih-Heng

    Like most other plant organs, roots use gravity as a directional guide for growth. Specialized cells within the columella region of the root cap (the statocytes) sense the direction of gravity through the sedimentation of starch-filled plastids (amyloplasts). Amyloplast movement and/or pressure on sensitive membranes triggers a gravity signal transduction pathway within these cells, which leads to a fast transcytotic relocalization of plasma-membrane associated auxin-efflux carrier proteins of the PIN family (PIN3 and PIN7) toward the bottom membrane. This leads to a polar transport of auxin toward the bottom flank of the cap. The resulting lateral auxin gradient is then transmitted toward the elongation zones where it triggers a curvature that ultimately leads to a restoration of vertical downward growth. Our laboratory is using strategies derived from genetics and systems biology to elucidate the molecular mechanisms that modulate gravity sensing and signal transduction in the columella cells of the root cap. Our previous research uncovered two J-domain-containing proteins, ARG1 and ARL2, as contributing to this process. Mutations in the corresponding paralogous genes led to alterations of root and hypocotyl gravitropism accompanied by an inability for the statocytes to develop a cytoplasmic alkalinization, relocalize PIN3, and transport auxin laterally, in response to gravistimulation. Both proteins are associated peripherally to membranes belonging to various compartments of the vesicular trafficking pathway, potentially modulating the trafficking of defined proteins between plasma membrane and endosomes. MAR1 and MAR2, on the other end, are distinct proteins of the plastidic outer envelope protein import TOC complex (the transmembrane channel TOC75 and the receptor TOC132, respectively). Mutations in the corresponding genes enhance the gravitropic defects of arg1. Using transformation-rescue experiments with truncated versions of TOC132 (MAR2), we have shown

  3. Movements elicited by electrical stimulation of muscles, nerves, intermediate spinal cord, and spinal roots in anesthetized and decerebrate cats.

    PubMed

    Aoyagi, Yoichiro; Mushahwar, Vivian K; Stein, Richard B; Prochazka, Arthur

    2004-03-01

    Electrical stimulation offers the possibility of restoring motor function of paralyzed limbs after spinal-cord injury or stroke, but few data are available to compare possible sites of stimulation, such as muscle, nerve, spinal roots, or spinal cord. The aim of this study was to establish some characteristics of stimulation at these sites in the anesthetized and midcollicular decerebrate cat. The hind limb was constrained to move in the sagittal plane against a spring load. Ventral-root stimulation only produced movements down and back; the direction moved systematically backward the more caudal the stimulated roots. In contrast, dorsal-root stimulation only produced movements up and forward. Thus, neither method alone could produce the full range of normal movements. Muscle, nerve, and intraspinal stimulation within the intermediate regions of the gray matter generated discrete, selective movements in a wide range of directions. Muscle stimulation required an order of magnitude more current. Single microwire electrodes located in the spinal gray matter could activate a synergistic group of muscles, and generally had graded recruitment curves, but the direction of movement occasionally changed abruptly as stimulus strength increased. Nerve stimulation produced the largest movements against the spring load (>80% of the passive range of motion) and was the most reproducible from animal to animal. However, recruitment curves with nerve stimulation were quite steep, so fine control of movement might be difficult. The muscle, nerve, and spinal cord all seem to be feasible sites to restore motor function. The pros and cons from this study may be helpful in deciding the best site for a particular application, but further tests are needed in the chronically transected spinal cord to assess the applicability of these results to human patients.

  4. Effects of lower limb neurodynamic mobilization on intraneural fluid dispersion of the fourth lumbar nerve root: an unembalmed cadaveric investigation

    PubMed Central

    Gilbert, Kerry K.; Smith, Michael P.; Sobczak, Stéphane; James, C. Roger; Sizer, Phillip S.; Brismée, Jean-Michel

    2015-01-01

    Objectives Manual and physical therapists incorporate neurodynamic mobilisation (NDM) to improve function and decrease pain. Little is known about the mechanisms by which these interventions affect neural tissue. The objective of this research was to assess the effects of repetitive straight leg raise (SLR) NDM on the fluid dynamics within the fourth lumbar nerve root in unembalmed cadavers. Methods A biomimetic solution (Toluidine Blue Stock 1% and Plasma) was injected intraneurally, deep to the epineurium, into the L4 nerve roots of seven unembalmed cadavers. The initial dye spread was allowed to stabilise and measured with a digital calliper. Once the initial longitudinal dye spread stabilised, an intervention strategy (repetitive SLR) was applied incorporating NDMs (stretch/relax cycles) at a rate of 30 repetitions per minute for 5 minutes. Post-intervention calliper measurements of the longitudinal dye spread were measured. Results The mean experimental posttest longitudinal dye spread measurement (1.1 ± 0.9 mm) was significantly greater (P = 0.02) than the initial stabilised pretest longitudinal dye spread measurement. Increases ranged from 0.0 to 2.6 mm and represented an average of 7.9% and up to an 18.1% increase in longitudinal dye spread. Discussion Passive NDM in the form of repetitive SLR induced a significant increase in longitudinal fluid dispersion in the L4 nerve root of human cadaveric specimen. Lower limb NDM may be beneficial in promoting nerve function by limiting or altering intraneural fluid accumulation within the nerve root, thus preventing the adverse effects of intraneural oedema. PMID:26955255

  5. Genetic analysis of gravity signal transduction in roots

    NASA Astrophysics Data System (ADS)

    Masson, Patrick; Strohm, Allison; Baldwin, Katherine

    To grow downward into the soil, roots use gravity as a guide. Specialized cells, named stato-cytes, enable this directional growth response by perceiving gravity. Located in the columella region of the cap, these cells sense a reorientation of the root within the gravity field through the sedimentation of, and/or tension/pressure exerted by, dense amyloplasts. This process trig-gers a gravity signal transduction pathway that leads to a fast alkalinization of the cytoplasm and a change in the distribution of the plasma membrane-associated auxin-efflux carrier PIN3. The latter protein is uniformly distributed within the plasma membrane on all sides of the cell in vertically oriented roots. However, it quickly accumulates at the bottom side upon gravis-timulation. This process correlates with a preferential transport of auxin to the bottom side of the root cap, resulting in a lateral gradient across the tip. This gradient is then transported to the elongation zone where it promotes differential cellular elongation, resulting in downward curvature. We isolated mutations that affect gravity signal transduction at a step that pre-cedes cytoplasmic alkalinization and/or PIN3 relocalization and lateral auxin transport across the cap. arg1 and arl2 mutations identify a common genetic pathway that is needed for all three gravity-induced processes in the cap statocytes, indicating these genes function early in the pathway. On the other hand, adk1 affects gravity-induced PIN3 relocalization and lateral auxin transport, but it does not interfere with cytoplasmic alkalinization. ARG1 and ARL2 encode J-domain proteins that are associated with membranes of the vesicular trafficking path-way whereas ADK1 encodes adenosine kinase, an enzyme that converts adenosine derived from nucleic acid metabolism and the AdoMet cycle into AMP, thereby alleviating feedback inhibi-tion of this important methyl-donor cycle. Because mutations in ARG1 (and ARL2) do not completely eliminate

  6. Yiqi Huayu recipe relieves nerve root constriction induced radicular neuralgia by down-regulating TRPV4 expression in dorsal root ganglion

    PubMed Central

    Tang, Zhanying; Cui, Xuejun; Hu, Zhijun; Xiao, Jing; Li, Weiwei; Yang, Qiangling; Liu, Dan; Lin, Jie; Wang, Yongjun; Shi, Qi

    2015-01-01

    The aim of this study was to observe the effects of Yiqi Huayu recipe on TRPV4 expression in radicular neuralgia model induced by chronic constriction to the rat lumber nerve root. Healthy male SD rats were divided into 3 groups for radicular neuralgia (RN) model construction: the sham operation group, model groups (day 3, 7, 14 and 28), and medication groups (day 3, 7, 14 and 28). Von-Frey hairs test was performed to detect the 50% with drawal threshold (50% TPW) for rats of each group. The expression of TRPV4 in dorsal root ganglion was detected at both mRNA and protein level. Rats from all model groups displayed hyperalgesia with significantly reduced 50% TPW values compared with sham-operation group (P<0.01); Yiqi Huayu recipe medication groups showed higher 50% TPW than model group since 7 days post medication (P<0.01); the medication groups showed decreased TRPV4 expression than that of model groups (P<0.01). In conclusion, Yiqi Huayu recipe alleviates nerve root constriction induced radicular neuralgia by repressing TRPV4 expression in dorsal root ganglion. PMID:26770465

  7. Apical control, gravitropic signaling, and the growth of lateral roots in Arabidopsis

    NASA Astrophysics Data System (ADS)

    Mullen, Jack L.; Wolverton, Chris; Hangarter, Roger P.

    Most research on gravity responses in plants has focused on primary roots and shoots, which typically grow in a vertical orientation. However, the patterns of lateral organ growth, which generally have large effects on overall plant architecture, are such that the organs are typically not vertical. In lateral roots of Arabidopsis, growth is initially in a nearly horizontal orientation but changes to a near-vertical orientation as the lateral root develops. Although the non-vertical lateral roots are gravitropically competent, following gravitropic reorientation of seedlings, the lateral roots on the upper flank of the primary root have different growth patterns from those on the lower side of the primary root. The differences are in part dependent on reorientation of the primary root, suggesting that gravitropic signaling from the primary root also contributes to the control of lateral root growth. The hormone auxin appears to play a role in this signaling between the primary and lateral roots, as auxin transport inhibitors applied to the primary root affect lateral root growth. Also, lateral roots of pin3 mutants, which are impaired in polar auxin transport, have altered lateral root orientations. However, other signals from the primary root tip also play an important role in regulating lateral root growth.

  8. Nerves Control Redox Levels in Mature Tissues Through Schwann Cells and Hedgehog Signaling

    PubMed Central

    Meda, Francesca; Gauron, Carole; Rampon, Christine; Teillon, Jérémie; Volovitch, Michel

    2016-01-01

    Abstract Aims: Recent advances in redox biology have emphasized the role of hydrogen peroxide (H2O2) in the modulation of signaling pathways and revealed that H2O2 plays a role in cellular remodeling in adults. Thus, an understanding of the mechanisms that control H2O2 levels in mature tissue would be of great interest. Results: We used a denervation strategy to demonstrate that sensory neurons are responsible for controlling H2O2 levels under normal conditions and after being lesioned. Moreover, we demonstrate that severed nerves respond to appendage amputation via the induction of Hedgehog signaling and that this signaling is responsible for H2O2 production in the wounded epidermis. Finally, we show that H2O2 and nerve growth are regulated via reciprocal action in adults. Innovation and Conclusion: These data support a new paradigm for the regulation of tissue homeostasis: H2O2 attracts nerves and nerves control H2O2 levels in a positive feedback loop. This finding suggests that the peripheral nerve redox environment could be a target for manipulating cell plasticity in adults. Antioxid. Redox Signal. 24, 299–311. PMID:26442784

  9. Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia.

    PubMed

    Ernsberger, Uwe

    2009-06-01

    Manipulation of neurotrophin (NT) signalling by administration or depletion of NTs, by transgenic overexpression or by deletion of genes coding for NTs and their receptors has demonstrated the importance of NT signalling for the survival and differentiation of neurons in sympathetic and dorsal root ganglia (DRG). Combination with mutation of the proapoptotic Bax gene allows the separation of survival and differentiation effects. These studies together with cell culture analysis suggest that NT signalling directly regulates the differentiation of neuron subpopulations and their integration into neural networks. The high-affinity NT receptors trkA, trkB and trkC are restricted to subpopulations of mature neurons, whereas their expression at early developmental stages largely overlaps. trkC is expressed throughout sympathetic ganglia and DRG early after ganglion formation but becomes restricted to small neuron subpopulations during embryogenesis when trkA is turned on. The temporal relationship between trkA and trkC expression is conserved between sympathetic ganglia and DRG. In DRG, NGF signalling is required not only for survival, but also for the differentiation of nociceptors. Expression of neuropeptides calcitonin gene-related peptide and substance P, which specify peptidergic nociceptors, depends on nerve growth factor (NGF) signalling. ret expression indicative of non-peptidergic nociceptors is also promoted by the NGF-signalling pathway. Regulation of TRP channels by NGF signalling might specify the temperature sensitivity of afferent neurons embryonically. The manipulation of NGF levels "tunes" heat sensitivity in nociceptors at postnatal and adult stages. Brain-derived neurotrophic factor signalling is required for subpopulations of DRG neurons that are not fully characterized; it affects mechanical sensitivity in slowly adapting, low-threshold mechanoreceptors and might involve the regulation of DEG/ENaC ion channels. NT3 signalling is required for the

  10. Neurosurgical procedures, spinal nerve roots - one stage removal of thoracic dumb-bell tumor: role of spinal evoked potential.

    PubMed

    Srivastava, Dharmendra Kumar; Singh, Deepak; Tiwari, Bhuwan Chandra; Awasthi, Namarata; Hussain, Nuzhat

    2014-02-01

    We report a rare case of benign thoracic dumb-bell tumor in the upper posterior mediastinum, which was successfully removed by posterolateral thoracotomy and foraminotomy, using intraoperative monitoring of spinal motor-evoked potentials. This technique has many advantages including minimal morbidity and mortality, a single incision, one-step complete resection with adequate exposure, spinal stabilization, avoidance of laminectomy, nerve root identification, and good predicted postoperative function.

  11. [Teflon granuloma after microvascular decompression of the trigeminal nerve root in a patient with recurrent trigeminal neuralgia].

    PubMed

    Rzaev, D A; Kulikova, E V; Moysak, G I; Voronina, E I; Ageeva, T A

    2016-01-01

    The use of a Teflon implant for Jannetta surgery in patients with trigeminal neuralgia is complicated in rare cases by the development of a Teflon granuloma and can cause recurrent facial pain. The article presents a clinical case of a Teflon granuloma developed after microvascular decompression of the trigeminal nerve root, describes the surgical findings and histological picture, and analyzes the literature, causes of granuloma development, and recommendations for treatment of these patients.

  12. Cyclic programmed cell death stimulates hormone signaling and root development in Arabidopsis.

    PubMed

    Xuan, Wei; Band, Leah R; Kumpf, Robert P; Van Damme, Daniël; Parizot, Boris; De Rop, Gieljan; Opdenacker, Davy; Möller, Barbara K; Skorzinski, Noemi; Njo, Maria F; De Rybel, Bert; Audenaert, Dominique; Nowack, Moritz K; Vanneste, Steffen; Beeckman, Tom

    2016-01-22

    The plant root cap, surrounding the very tip of the growing root, perceives and transmits environmental signals to the inner root tissues. In Arabidopsis thaliana, auxin released by the root cap contributes to the regular spacing of lateral organs along the primary root axis. Here, we show that the periodicity of lateral organ induction is driven by recurrent programmed cell death at the most distal edge of the root cap. We suggest that synchronous bursts of cell death in lateral root cap cells release pulses of auxin to surrounding root tissues, establishing the pattern for lateral root formation. The dynamics of root cap turnover may therefore coordinate primary root growth with root branching in order to optimize the uptake of water and nutrients from the soil.

  13. Chromate induces adventitious root formation via auxin signalling and SOLITARY-ROOT/IAA14 gene function in Arabidopsis thaliana.

    PubMed

    López-Bucio, José; Ortiz-Castro, Randy; Ruíz-Herrera, León Francisco; Juárez, Consuelo Vargas; Hernández-Madrigal, Fátima; Carreón-Abud, Yazmín; Martínez-Trujillo, Miguel

    2015-04-01

    Morphological root plasticity optimizes nutrient and water uptake by plants and is a promising target to improve tolerance to metal toxicity. Exposure to sublethal chromate [Cr(VI)] concentrations inhibits root growth, decreases photosynthesis and compromises plant development and productivity. Despite the increasing environmental problem that Cr(VI) represents, to date, the Cr tolerance mechanisms of plants are not well understood, and it remains to be investigated whether root architecture remodelling is important for plant adaptation to Cr(VI) stress. In this report, we analysed the growth response of Arabidopsis thaliana seedlings to concentrations of Cr(VI) that strongly repress primary and lateral root growth. Interestingly, adventitious roots started developing, branched and allowed seedlings to grow under highly growth-repressing Cr(VI) concentrations. Cr(VI) negatively regulates auxin transport and response gene expression in the primary root tip, as evidenced by decreased expression of auxin-related reporters DR5::GFP, DR5::uidA and PIN1::PIN1::GFP, and then, another auxin maximum is established at the site of adventitious root initiation that drives adventitious root organogenesis. Both primary root growth inhibition and adventitious root formation induced by high Cr(VI) levels are blocked by a gain-of-function mutation in the SOLITARY-ROOT/IAA14 gene of Arabidopsis. These data provide evidence that suggests a critical role for auxin transport and signalling via IAA14/SLR1 in the developmental program linking Cr(VI) to root architecture remodelling.

  14. A purely extradural lumbar nerve root cavernoma mimicking acute myeloid leukemia recurrence: Case report and literature review

    PubMed Central

    Oliveira, Edson; Lavrador, José Pedro; Teixeira, Joaquim; Pignatelli, Alexandra; Livraghi, Sérgio

    2016-01-01

    Background: Myeloid sarcoma (MS) is a malignant tumor that usually occurs concomitantly with or following acute myeloid leukemia (AML). Cavernomas are benign congenital malformations that are unusual in the spine and exceedingly rare in pure extradural locations. Case Description: We report a 73-year-old female with a previous medical history of AML in remission for 3 years who presented with symptoms of low back pain and right lower extremity radiculopathy. A magnetic resonance scan showed an extradural, foraminal lesion centered at the L2 level involving the right L2 nerve root. In view of the history of AML, this lesion was potentially considered MS, a form of AML relapse. Surgery consisting of a right L1 and L2 hemilaminectomy facilitated gross total resection of the purely extradural lesion the proved histologically to be a cavernoma. Conclusion: In patients with a history of leukemia, MS must be considered in the differential diagnosis for any epidural or nerve root lesion that appears following treatment. Although rare, cavernomas must be considered among the differential diagnoses for epidural nerve root lesions in the setting of AML. PMID:28028446

  15. Surgical treatment for total root avulsion type brachial plexus injuries by neurotization: A prospective comparison study between total and hemicontralateral C7 nerve root transfer

    PubMed Central

    Tu, Yuan-Kun; Tsai, Yi-Jung; Chang, Chih-Han; Su, Fong-Chin; Hsiao, Chih-Kun; Tan, Jacqueline Siau-Woon

    2014-01-01

    Purpose: We conducted a clinical study to evaluate the effects of neurotization, especially comparing the total contralateral C7 (CC7) root transfer to hemi-CC7 transfer, on total root avulsion brachial plexus injuries (BPI). Methods: Forty patients who received neurotization for BPI were enrolled in this prospective study. Group 1 (n = 20) received hemi-CC7 transfer for hand function, while group 2 (n = 20) received total-CC7 transfer. Additional neurotization included spinal accessory, phrenic, and intercostal nerve transfer for shoulder and elbow function. The results were evaluated with an average of 6 years follow-up. Results: Group 1 had fewer donor site complications (15%) than group 2 (45%); group 2 had significantly better hand M3 and M4 motor function (65%) than group 1 (30%; P = 0.02). There was no difference in sensory recovery. Significantly, better shoulder function was obtained by simultaneous neurotization on both suprascapular and axillary nerves. Conclusions: Total-CC7 transfer had better hand recovery but more donor complications than hemi-CC7. Neurotization on both supra-scapular and axillary nerves improved shoulder recovery. © 2013 The Authors. Microsurgery published by Wiley Periodicals, Inc. Microsurgery 34:91–101, 2014. PMID:23913440

  16. Coding of signals in noise by amphibian auditory nerve fibers.

    PubMed

    Narins, P M

    1987-01-01

    Rate-level (R-L) functions derived for pure-tones and pure-tones in broadband noise were obtained for auditory nerve fibers in the treefrog, Eleutherodactylus coqui. Normalized R-L functions for low-frequency, low-threshold fibers exhibit a horizontal rightward shift in the presence of broadband background noise. The magnitude of this shift is directly proportional to the noise spectrum level, and inversely proportional to the fiber's threshold. R-L functions for mid- and high-frequency fibers also show a horizontal shift, but to a lesser degree, consistent with their elevated thresholds relative to the low-frequency fibers. The implications of these findings for the processing of biologically significant sounds in the high levels of background noise in the animal's natural habitat are considered.

  17. Sympathetic nerve stimulation induces local endothelial Ca2+ signals to oppose vasoconstriction of mouse mesenteric arteries.

    PubMed

    Nausch, Lydia W M; Bonev, Adrian D; Heppner, Thomas J; Tallini, Yvonne; Kotlikoff, Michael I; Nelson, Mark T

    2012-02-01

    It is generally accepted that the endothelium regulates vascular tone independent of the activity of the sympathetic nervous system. Here, we tested the hypothesis that the activation of sympathetic nerves engages the endothelium to oppose vasoconstriction. Local inositol 1,4,5-trisphosphate (IP(3))-mediated Ca(2+) signals ("pulsars") in or near endothelial projections to vascular smooth muscle (VSM) were measured in an en face mouse mesenteric artery preparation. Electrical field stimulation of sympathetic nerves induced an increase in endothelial cell (EC) Ca(2+) pulsars, recruiting new pulsar sites without affecting activity at existing sites. This increase in Ca(2+) pulsars was blocked by bath application of the α-adrenergic receptor antagonist prazosin or by TTX but was unaffected by directly picospritzing the α-adrenergic receptor agonist phenylephrine onto the vascular endothelium, indicating that nerve-derived norepinephrine acted through α-adrenergic receptors on smooth muscle cells. Moreover, EC Ca(2+) signaling was not blocked by inhibitors of purinergic receptors, ryanodine receptors, or voltage-dependent Ca(2+) channels, suggesting a role for IP(3), rather than Ca(2+), in VSM-to-endothelium communication. Block of intermediate-conductance Ca(2+)-sensitive K(+) channels, which have been shown to colocalize with IP(3) receptors in endothelial projections to VSM, enhanced nerve-evoked constriction. Collectively, our results support the concept of a transcellular negative feedback module whereby sympathetic nerve stimulation elevates EC Ca(2+) signals to oppose vasoconstriction.

  18. Sympathetic nerve stimulation induces local endothelial Ca2+ signals to oppose vasoconstriction of mouse mesenteric arteries

    PubMed Central

    Nausch, Lydia W. M.; Bonev, Adrian D.; Heppner, Thomas J.; Tallini, Yvonne; Kotlikoff, Michael I.

    2012-01-01

    It is generally accepted that the endothelium regulates vascular tone independent of the activity of the sympathetic nervous system. Here, we tested the hypothesis that the activation of sympathetic nerves engages the endothelium to oppose vasoconstriction. Local inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ signals (“pulsars”) in or near endothelial projections to vascular smooth muscle (VSM) were measured in an en face mouse mesenteric artery preparation. Electrical field stimulation of sympathetic nerves induced an increase in endothelial cell (EC) Ca2+ pulsars, recruiting new pulsar sites without affecting activity at existing sites. This increase in Ca2+ pulsars was blocked by bath application of the α-adrenergic receptor antagonist prazosin or by TTX but was unaffected by directly picospritzing the α-adrenergic receptor agonist phenylephrine onto the vascular endothelium, indicating that nerve-derived norepinephrine acted through α-adrenergic receptors on smooth muscle cells. Moreover, EC Ca2+ signaling was not blocked by inhibitors of purinergic receptors, ryanodine receptors, or voltage-dependent Ca2+ channels, suggesting a role for IP3, rather than Ca2+, in VSM-to-endothelium communication. Block of intermediate-conductance Ca2+-sensitive K+ channels, which have been shown to colocalize with IP3 receptors in endothelial projections to VSM, enhanced nerve-evoked constriction. Collectively, our results support the concept of a transcellular negative feedback module whereby sympathetic nerve stimulation elevates EC Ca2+ signals to oppose vasoconstriction. PMID:22140050

  19. Microelectronic neural bridge for signal regeneration and function rebuilding over two separate nerves

    NASA Astrophysics Data System (ADS)

    Xiaoyan, Shen; Zhigong, Wang; Xiaoying, Lü; Shushan, Xie; Zonghao, Huang

    2011-06-01

    According to the feature of neural signals, a micro-electronic neural bridge (MENB) has been designed. It consists of two electrode arrays for neural signal detection and functional electrical stimulation (FES), and a microelectronic circuit for signal amplifying, processing, and FES driving. The core of the system is realized in 0.5-μm CMOS technology and used in animal experiments. A special experimental strategy has been designed to demonstrate the feasibility of the system. With the help of the MENB, the withdrawal reflex function of the left/right leg of one spinal toad has been rebuilt in the corresponding leg of another spinal toad. According to the coherence analysis between the source and regenerated neural signals, the controlled spinal toad's sciatic nerve signal is delayed by 0.72 ms in relation to the sciatic nerve signal of the source spinal toad and the cross-correlation function reaches a value of 0.73. This shows that the regenerated signal is correlated with the source sciatic signal significantly and the neural activities involved in reflex function have been regenerated. The experiment demonstrates that the MENB is useful in rebuilding the neural function between nerves of different bodies.

  20. Neuromuscular nicotinic receptors mediate bladder contractions following bladder reinnervation with somatic to autonomic nerve transfer after decentralization by spinal root transection

    PubMed Central

    Gomez-Amaya, Sandra M.; Barbe, Mary F.; Lamarre, Neil S.; Brown, Justin M.; Braverman, Alan S.; Ruggieri, Michael R.

    2015-01-01

    This study investigates whether the reinnervated neuronal pathway mediates contraction via the same neurotransmitter and receptor mechanisms as the original pathway. Following bladder decentralization by transection of sacral roots, peripheral nerve transfer was performed with bilateral genitofemoral to pelvic nerve transfer (GFNT) and unilateral (left) femoral nerve to bilateral pelvic nerve transfer (FNT). Reinnervation was assessed 7.5 months post operatively by monitoring bladder pressure during electrical stimulation of the transferred nerves, spinal ventral roots, and spinal cord. Of the 17 animals with GFNT, 14 (82%) demonstrated functional bladder reinnervation as evidenced by increased bladder pressure during stimulation of the transferred GFN or the L3 or L4 spinal ventral roots. Lumbar spinal cord stimulation caused increased bladder pressure in 9 of 10 (90%) animals with FNT. Succinylcholine (SCh) virtually eliminated bladder pressure increases induced by electrical stimulation of the transferred somatic nerves or the lumbar spinal segments that contribute axons to these donor nerves. In control animals (either un-operated or sham-operated) SCh had no effect on nerve evoked bladder pressure increases but substantially reduced urethra and anal sphincter pressure induced by stimulation of either the lumbosacral spinal cord or the S2-3 spinal ventral roots. The reinnervated detrusor muscles of GFNT and FNT animals also contained increased alpha1 nicotinic receptor subunit immunoreactivity in punctate dots on detrusor muscle fascicles and in neuronal cell bodies, staining not observed in control animals. PMID:25444958

  1. Effect of FGF-2 and sciatic nerve grafting on ChAT expression in dorsal root ganglia neurons of spinal cord transected rats.

    PubMed

    Guzen, Fausto Pierdoná; de Araújo, Dayane Pessoa; Lucena, Eudes Euler de Souza; de Morais, Hécio Henrique Araújo; Cavalcanti, José Rodolfo Lopes de Paiva; do Nascimento, Expedito Silva; Costa, Miriam Stela Maris de Oliveira; Cavalcante, Jeferson Sousa

    2016-03-11

    Neurotrophic factors and peripheral nerves are known to be good substrates for bridging CNS trauma. The involvement of fibroblast growth factor-2 (FGF-2) activation in the dorsal root ganglion (DRG) was examined following spinal cord injury in the rat. We evaluated whether FGF-2 increases the ability of a sciatic nerve graft to enhance neuronal plasticity, in a gap promoted by complete transection of the spinal cord. The rats were subjected to a 4mm-long gap at low thoracic level and were repaired with saline (Saline or control group, n=10), or fragment of the sciatic nerve (Nerve group, n=10), or fragment of the sciatic nerve to which FGF-2 (Nerve+FGF-2 group, n=10) had been added immediately after lesion. The effects of the FGF-2 and fragment of the sciatic nerve grafts on neuronal plasticity were investigated using choline acetyl transferase (ChAT)-immunoreactivity of neurons in the dorsal root ganglion after 8 weeks. Preservation of the area and diameter of neuronal cell bodies in dorsal root ganglion (DRG) was seen in animals treated with the sciatic nerve, an effect enhanced by the addition of FGF-2. Thus, the addition of exogenous FGF-2 to a sciatic nerve fragment grafted in a gap of the rat spinal cord submitted to complete transection was able to improve neuroprotection in the DRG. The results emphasized that the manipulation of the microenvironment in the wound might amplify the regenerative capacity of peripheral neurons.

  2. Assessment of Anteroposterior Subpedicular Approach and Oblique Scotty Dog Subpedicular Approach for Selective Nerve Root Block

    PubMed Central

    Yeh, Yu-Cheng; Luo, Chi-An; Joey-Tan, Kit-Yang

    2017-01-01

    Background The technique used to administer a selective nerve root block (SNRB) varies depending on individual expertise. Both the anteroposterior (AP) subpedicular approach and oblique Scotty dog subpedicular approach are widely practiced. However, the literature does not provide a clear consensus regarding which approach is more suitable. Hence, we decided to analyse the procedural parameters and clinical outcomes following SNRBs using these two approaches. Methods Patients diagnosed with a single lumbar herniated intervertebral disc (HIVD) refractory to conservative management but not willing for immediate surgery were selected for a prospective nonrandomized comparative study. An SNRB was administered as a therapeutic alternative using the AP subpedicular approach in one group (n = 25; mean age, 45 ± 5.4 years) and the oblique Scotty dog subpedicular approach in the other group (n = 22; mean age, 43.8 ± 4.7 years). Results were compared in terms of the duration of the procedure, the number of C-arm exposures, accuracy, pain relief, functional outcome and the duration of relief. Results Our results suggest that the oblique Scotty dog subpedicular approach took a significantly longer duration (p = 0.02) and a greater number of C-arm exposures (p = 0.001). But, its accuracy of needle placement was 95.5% compared to only 72% using the AP subpedicular approach (p = 0.03). There was no significant difference in terms of clinical outcomes between these approaches. Conclusions The AP subpedicular approach was simple and facile, but the oblique Scotty dog subpedicular approach was more accurate. However, a brief window period of pain relief was achieved irrespective of the approaching technique used. PMID:28261430

  3. The role of vascular damage and fibrosis in the pathogenesis of nerve root damage.

    PubMed

    Jayson, M I

    1992-06-01

    Vascular damage and fibrosis are common within the vertebral canal and intervertebral foramen. The grossest examples occur in patients who have previously undergone oil-based myelography or spinal surgery. The mechanisms of fibrosis in the latter instance may be related to persisting cotton debris from sponges used during the operation. This debris may act as a fibrogenic stimulus. However, in cadaveric studies of nonoperated spines, the author and his colleagues have found clear evidence of vascular damage and fibrosis within the spines, and this vascular damage is significantly related to the severity of degenerative disk disease. Degenerative disk disease with osteophytic proliferation and disk protrusion may lead to compression of epidural veins with dilation of noncompressed veins. There is a significant statistical relationship between the extent of the disk degeneration and prolapse and the evidence of venous compression and dilatation. The dilatated veins may contain antemortem thromboses. In turn, there is a significant statistical relationship between the evidence for venous obstruction and perineural fibrosis. Such a relationship also exists between perineural fibrosis and neuronal atrophy. If therefore appears likely that venous obstruction with resultant hypoxia is an important mechanism leading to nerve root damage. In the peripheral blood, significant defects in the fibrinolytic system correlate with the severity of the symptoms. However, it was not possible to correlate these changes with individual clinical or imaging features. These fibrinolytic changes are recognized as markers of vascular damage and may reflect the pathologic processes that the author and his colleagues have demonstrated. It is uncertain whether they play any secondary pathogenic role in the chronicity of these back problems.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Bayesian spatial filters for the extraction of source signals, a study in the peripheral nerve

    PubMed Central

    Tang, Yuang; Durand, Dominique M.

    2015-01-01

    The ability to extract physiological source signals to control various prosthetics offer tremendous therapeutic potential to improve the quality of life for patients suffering from motor disabilities. Regardless of the modality, recordings of physiological source signals are contaminated with noise and interference along with crosstalk between the sources. These impediments render the task of isolating potential physiological source signals for control difficult. In this paper, a novel Bayesian Source Filter for signal Extraction (BSFE) algorithm for extracting physiological source signals for control is presented. The BSFE algorithm is based on the source localization method Champagne and constructs spatial filters using Bayesian methods that simultaneously maximize the signal to noise ratio of the recovered source signal of interest while minimizing crosstalk interference between sources. When evaluated over peripheral nerve recordings obtained in-vivo, the algorithm achieved the highest signal to noise interference ratio (>7.00±3.45dB) amongst the group of methodologies compared with average correlation between the extracted source signal and the original source signal > 0.93. The results support the efficacy of the BSFE algorithm for extracting source signals from the peripheral nerve or as a pre-filtering stage for BCI methods. PMID:24608686

  5. Blood-nerve barrier: distribution of anionic sites on the endothelial plasma membrane and basal lamina of dorsal root ganglia.

    PubMed

    Bush, M S; Reid, A R; Allt, G

    1991-09-01

    Previous investigations of the blood-nerve barrier have correlated the greater permeability of ganglionic endoneurial vessels, compared to those of nerve trunks, with the presence of fenestrations and open intercellular junctions. Recent studies have demonstrated reduced endothelial cell surface charge in blood vessels showing greater permeability. To determine the distribution of anionic sites on the plasma membranes and basal laminae of endothelial cells in dorsal root ganglia, cationic colloidal gold and cationic ferritin were used. Electron microscopy revealed the existence of endothelial microdomains with differing labelling densities. Labelling indicated that caveolar and fenestral diaphragms and basal laminae are highly anionic at physiological pH, luminal plasma membranes and endothelial processes are moderately charged and abluminal plasma membranes are weakly anionic. Tracers did not occur in caveolae or cytoplasmic vesicles. In vitro tracer experiments at pH values of 7.3, 5.0, 3.5 and 2.0 indicated that the anionic charge on the various endothelial domains was contributed by chemical groups with differing pKa values. In summary, the labelling of ganglionic and sciatic nerve vessels was similar except for the heavy labelling of diaphragms in a minority of endoneurial vessels in ganglia. This difference is likely to account in part for the greater permeability of ganglionic endoneurial vessels. The results are discussed with regard to the blood-nerve and -brain barriers and vascular permeability in other tissues and a comparison made between the ultrastructure and anionic microdomains of epi-, peri- and endoneurial vessels of dorsal root ganglia and sciatic nerves.

  6. Nerve growth factor signal transduction in mature pig oligodendrocytes.

    PubMed

    Althaus, H H; Hempel, R; Klöppner, S; Engel, J; Schmidt-Schultz, T; Kruska, L; Heumann, R

    1997-12-01

    It has previously been shown that nerve growth factor (NGF) is of functional significance for mature pig oligodendrocytes (OLs) in culture. The present data give evidence for the expression of TrkA, the so-called high-affinity NGF receptor, and of p75NTR, the so-called low-affinity NGF receptor. TrkA is upregulated during culturing, in contrast to the p75 receptor. Exposure of OLs to NGF induces an autophosphorylation of TrkA via its intrinsic tyrosine kinase. K-252a inhibits the TrkA autophosphorylation, which reduces the OL process formation to control levels. To the tyrosine-phosphorylated sites of TrkA several proteins, such as phospholipase C-gamma1, the adaptor protein SHC, the phosphotyrosine phosphatase SH-PTP2 (SYP) associate via their SH2 phosphotase SH-PTP2 domain. The association of SHC to TrkA is shown by co-immunoprecipitation. Indirect evidence for a possible activation of PLC-gamma1 is given by an NGF-induced increase of oligodendroglial [Ca2+]i. Downstream from TrkA, a mitogen-activated protein kinase cascade, which includes Erk1 and Erk2, is operating. An in-gel myelin basic protein kinase assay revealed that NGF activates predominantly Erk1. Finally, it is shown that NGF stimulates expression of c-fos.

  7. S3 Dorsal Root Ganglion/Nerve Root Stimulation for Refractory Postsurgical Perineal Pain: Technical Aspects of Anchorless Sacral Transforaminal Lead Placement

    PubMed Central

    Zuidema, X.; Breel, J.; Wille, F.

    2016-01-01

    Chronic perineal pain limits patients in physical and sexual activities, leading to social and psychological distress. In most cases, this pain develops after surgery in the urogenital area or as a consequence of trauma. Neuromodulation is one of the options in chronic postsurgical perineal pain treatment. We present a case of refractory perineal pain after right sided surgical resection of a Bartholin's cyst which was treated with third sacral nerve root/dorsal root ganglion stimulation using the transforaminal approach. We describe a new anchorless lead placement technique using a unique curved lead delivery sheath. We postulate that this new posterior foraminal technique of lead placement is simple, safe, and reversible and may lower the occurrence of lead related complications. PMID:27123351

  8. The role of Gd-enhanced three-dimensional MRI fast low-angle shot (FLASH) in the evaluation of symptomatic lumbosacral nerve roots.

    PubMed

    Kikkawa, I; Sugimoto, H; Saita, K; Ookami, H; Nakama, S; Hoshino, Y

    2001-01-01

    In the field of lumbar spine disorders, three-dimensional (3-D) magnetic resonance imaging (MRI) can clearly depict a lumbar nerve root from the distal region to the dorsal root ganglion. In this study, we used a gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) enhanced-three-dimensional (3-D) fast low-angle shot (FLASH) sequence when examining lumbosacral disorders. The subjects were 33 patients (14 men and 19 women) in whom lumbosacral neural compression had been diagnosed clinically. Twenty-one patients had lumbar disc herniation, 11 had lumbar spinal stenosis, and 1 had lumbar radiculopathy caused by rheumatoid arthritis. Five subjects with low back pain were also studied as a control group. In all patients and in all 5 of the controls, the dorsal root ganglion of every root was enhanced clearly. There was no root enhancement in the 5 controls. Enhancement of the symptomatic nerve roots, caused by compression, was found in 11 of the 33 patients. All 11 patients had radiculopathy, and muscle weakness was more frequent in patients with enhanced nerve roots than in those without enhancement. There was no enhancement of the cauda equina, even in the patients with cauda syndrome. The enhancement effect may reflect some pathological condition of the compressed nerve root and needs to be studied further.

  9. Effective gene expression in the rat dorsal root ganglia with a non-viral vector delivered via spinal nerve injection

    PubMed Central

    Chang, Ming-Fong; Hsieh, Jung-Hsien; Chiang, Hao; Kan, Hung-Wei; Huang, Cho-Min; Chellis, Luke; Lin, Bo-Shiou; Miaw, Shi-Chuen; Pan, Chun-Liang; Chao, Chi-Chao; Hsieh, Sung-Tsang

    2016-01-01

    Delivering gene constructs into the dorsal root ganglia (DRG) is a powerful but challenging therapeutic strategy for sensory disorders affecting the DRG and their peripheral processes. The current delivery methods of direct intra-DRG injection and intrathecal injection have several disadvantages, including potential injury to DRG neurons and low transfection efficiency, respectively. This study aimed to develop a spinal nerve injection strategy to deliver polyethylenimine mixed with plasmid (PEI/DNA polyplexes) containing green fluorescent protein (GFP). Using this spinal nerve injection approach, PEI/DNA polyplexes were delivered to DRG neurons without nerve injury. Within one week of the delivery, GFP expression was detected in 82.8% ± 1.70% of DRG neurons, comparable to the levels obtained by intra-DRG injection (81.3% ± 5.1%, p = 0.82) but much higher than those obtained by intrathecal injection. The degree of GFP expression by neurofilament(+) and peripherin(+) DRG neurons was similar. The safety of this approach was documented by the absence of injury marker expression, including activation transcription factor 3 and ionized calcium binding adaptor molecule 1 for neurons and glia, respectively, as well as the absence of behavioral changes. These results demonstrated the efficacy and safety of delivering PEI/DNA polyplexes to DRG neurons via spinal nerve injection. PMID:27748450

  10. Heterogeneous responses of dorsal root ganglion neurons in neuropathies induced by peripheral nerve trauma and the antiretroviral drug stavudine

    PubMed Central

    Boateng, EK; Novejarque, A; Pheby, T; Rice, ASC; Huang, W

    2015-01-01

    Background Heterogeneity is increasingly recognized in clinical presentation of neuropathic pain (NP), but less often recognized in animal models. Neurochemical dysregulation in rodent dorsal root ganglia (DRG) is associated with peripheral nerve trauma, but poorly studied in non-traumatic NP conditions. Methods This study aimed to investigate the temporal expressions of activating transcription factor-3 (ATF-3), growth-associated protein-43 (GAP-43), neuropeptide Y (NPY) and galanin in traumatic and non-traumatic rat models of neuropathies associated with NP. Expressions of these markers were examined in the DRG at different time points following tibial nerve transection (TNT) injury and antiretroviral drug stavudine (d4T) administration using immunohistochemistry. The development of sensory gain following these insults was assessed by measuring limb withdrawal to a punctate mechanical stimulus. Results Both TNT-injured and d4T-treated rats developed hindpaw mechanical hypersensitivity. Robust expressions of ATF-3, GAP-43, NPY and galanin in both small- and large-sized L5 DRG neurons were observed in the DRG from TNT-injured rats. In contrast, d4T-treated rats did not exhibit any significant neurochemical changes in the DRG. Conclusions Taken together, the results suggest that ATF-3, GAP-43, NPY and galanin are likely indicators of nerve trauma-associated processes and not generic markers for NP. These experiments also demonstrate distinct expression patterns of neurochemical markers in the DRG and emphasize the mechanistic difference between nerve trauma and antiretroviral drug-associated NP. PMID:25070481

  11. Upregulation of EMMPRIN (OX47) in Rat Dorsal Root Ganglion Contributes to the Development of Mechanical Allodynia after Nerve Injury.

    PubMed

    Wang, Qun; Sun, Yanyuan; Ren, Yingna; Gao, Yandong; Tian, Li; Liu, Yang; Pu, Yanan; Gou, Xingchun; Chen, Yanke; Lu, Yan

    2015-01-01

    Matrix metalloproteinases (MMPs) are widely implicated in inflammation and tissue remodeling associated with various neurodegenerative diseases and play an important role in nociception and allodynia. Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) plays a key regulatory role for MMP activities. However, the role of EMMPRIN in the development of neuropathic pain is not clear. Western blotting, real-time quantitative RT-PCR (qRT-PCR), and immunofluorescence were performed to determine the changes of messenger RNA and protein of EMMPRIN/OX47 and their cellular localization in the rat dorsal root ganglion (DRG) after nerve injury. Paw withdrawal threshold test was examined to evaluate the pain behavior in spinal nerve ligation (SNL) model. The lentivirus containing OX47 shRNA was injected into the DRG one day before SNL. The expression level of both mRNA and protein of OX47 was markedly upregulated in ipsilateral DRG after SNL. OX47 was mainly expressed in the extracellular matrix of DRG. Administration of shRNA targeted against OX47 in vivo remarkably attenuated mechanical allodynia induced by SNL. In conclusion, peripheral nerve injury induced upregulation of OX47 in the extracellular matrix of DRG. RNA interference against OX47 significantly suppressed the expression of OX47 mRNA and the development of mechanical allodynia. The altered expression of OX47 may contribute to the development of neuropathic pain after nerve injury.

  12. Novel Immunohistochemical Techniques Using Discrete Signal Amplification Systems for Human Cutaneous Peripheral Nerve Fiber Imaging

    PubMed Central

    Wang, Ningshan; Gibbons, Christopher H.; Freeman, Roy

    2011-01-01

    Confocal imaging uses immunohistochemical binding of specific antibodies to visualize tissues, but technical obstacles limit more widespread use of this technique in the imaging of peripheral nerve tissue. These obstacles include same-species antibody cross-reactivity and weak fluorescent signals of individual and co-localized antigens. The aims of this study were to develop new immunohistochemical techniques for imaging of peripheral nerve fibers. Three-millimeter punch skin biopsies of healthy individuals were fixed, frozen, and cut into 50-µm sections. Tissues were stained with a variety of antibody combinations with two signal amplification systems, streptavidin-biotin-fluorochrome (sABC) and tyramide-horseradish peroxidase-fluorochrome (TSA), used simultaneously to augment immunohistochemical signals. The combination of the TSA and sABC amplification systems provided the first successful co-localization of sympathetic adrenergic and sympathetic cholinergic nerve fibers in cutaneous human sweat glands and vasomotor and pilomotor systems. Primary antibodies from the same species were amplified individually without cross-reactivity or elevated background interference. The confocal fluorescent signal-to-noise ratio increased, and image clarity improved. These modifications to signal amplification systems have the potential for widespread use in the study of human neural tissues. PMID:21411809

  13. Thyroid hormone reduces the loss of axotomized sensory neurons in dorsal root ganglia after sciatic nerve transection in adult rat.

    PubMed

    Schenker, Michel; Kraftsik, Rudolf; Glauser, Liliane; Kuntzer, Thierry; Bogousslavsky, Julien; Barakat-Walter, Ibtissam

    2003-11-01

    We have shown that a local administration of thyroid hormones (T3) at the level of transected rat sciatic nerve induced a significant increase in the number of regenerated axons. To address the question of whether local administration of T3 rescues the axotomized sensory neurons from death, in the present study we estimated the total number of surviving neurons per dorsal root ganglion (DRG) in three experimental group animals. Forty-five days following rat sciatic nerve transection, the lumbar (L4 and L5) DRG were removed from PBS-control, T3-treated as well as from unoperated rats, and serial sections (1 microm) were cut. The physical dissector method was used to estimate the total number of sensory neurons in the DRGs. Our results revealed that in PBS-control rats transection of sciatic nerve leads to a significant (P < 0.001) decrease in the mean number of sensory neurons (8743.8 +/- 748.6) compared with the number of neurons in nontransected ganglion (mean 13,293.7 +/- 1368.4). However, administration of T3 immediately after sciatic nerve transection rescues a great number of axotomized neurons so that their mean neuron number (12,045.8 +/- 929.8) is not significantly different from the mean number of neurons in the nontransected ganglion. In addition, the volume of ganglia showed a similar tendency. These results suggest that T3 rescues a high number of axotomized sensory neurons from death and allows these cells to grow new axons. We believe that the relative preservation of neurons is important in considering future therapeutic approaches of human peripheral nerve lesion and sensory neuropathy.

  14. Roles of proteome dynamics and cytokinin signaling in root to hypocotyl ratio changes induced by shading roots of Arabidopsis seedlings.

    PubMed

    Novák, Jan; Černý, Martin; Pavlů, Jaroslav; Zemánková, Jana; Skalák, Jan; Plačková, Lenka; Brzobohatý, Břetislav

    2015-05-01

    In nature, root systems of most terrestrial plants are protected from light exposure by growing in a dark soil environment. Hence, in vitro cultivation in transparent Petri dishes leads to physiological perturbations, but the mechanisms underlying root-mediated light perception and responses have not been fully elucidated. Thus, we compared Arabidopsis thaliana seedling development in transparent and darkened Petri dishes at low light intensity (20 µmol m(-2) s(-1)), allowing us to follow (inter alia) hypocotyl elongation, which is an excellent process for studying interactions of signals involved in the regulation of growth and developmental responses. To obtain insights into molecular events underlying differences in seedling growth under these two conditions, we employed liquid chromatography-mass spectrometry (LC-MS) shotgun proteomics (available via the PRIDE deposit PXD001612). In total, we quantified the relative abundances of peptides representing 1,209 proteins detected in all sample replicates of LC-MS analyses. Comparison of MS spectra after manual validation revealed 48 differentially expressed proteins. Functional classification, analysis of available gene expression data and literature searches revealed alterations associated with root illumination (inter alia) in autotrophic CO2 fixation, C compound and carbohydrate metabolism, and nitrogen metabolism. The results also indicate a previously unreported role for cytokinin plant hormones in the escape-tropism response to root illumination. We complemented these results with reverse transcription followed by quantitative PCR (RT-qPCR), chlorophyll fluorescence and detailed cytokinin signaling analyses, detecting in the latter a significant increase in the activity of the cytokinin two-component signaling cascade in roots and implicating the cytokinin receptor AHK3 as the major mediator of root to hypocotyl signaling in responses to root illumination.

  15. De novo expression of Nav1.7 in injured putative proprioceptive afferents: Multiple tetrodotoxin-sensitive sodium channels are retained in the rat dorsal root after spinal nerve ligation.

    PubMed

    Fukuoka, T; Miyoshi, K; Noguchi, K

    2015-01-22

    Tetrodotoxin-sensitive (TTX-s) spontaneous activity is recorded from the dorsal roots after peripheral nerve injury. Primary sensory neurons in the dorsal root ganglion (DRG) express multiple TTX-s voltage-gated sodium channel α-subunits (Navs). Since Nav1.3 increases, whereas all other Navs decrease, in the DRG neurons after peripheral nerve lesion, Nav1.3 is proposed to be critical for the generation of these spontaneous discharges and the contributions of other Navs have been ignored. Here, we re-evaluate the changes in expression of three other TTX-s Navs, Nav1.1, Nav1.6 and Nav1.7, in the injured 5th lumbar (L5) primary afferent components following L5 spinal nerve ligation (SNL) using in situ hybridization histochemistry and immunohistochemistry. While the overall signal intensities for these Nav mRNAs decreased, many injured DRG neurons still expressed these transcripts at clearly detectable levels. All these Nav proteins accumulated at the proximal stump of the ligated L5 spinal nerve. The immunostaining patterns of Nav1.6 and Nav1.7 associated with the nodes of Ranvier were maintained in the ipsilateral L5 dorsal root. Interestingly, putative proprioceptive neurons characterized by α3 Na+/K+ ATPase-immunostaining specifically lacked Nav1.7 mRNA in naïve DRG but displayed de novo expression of this transcript following SNL. Nav1.7-immunoreactive fibers were significantly increased in the ipsilateral gracile nucleus where central axonal branches of the injured A-fiber afferents terminated. These data indicate that multiple TTX-s channel subunits could contribute to the generation and propagation of the spontaneous discharges in the injured primary afferents. Specifically, Nav1.7 may cause some functional changes in sensory processing in the gracile nucleus after peripheral nerve injury.

  16. Role of dorsal root ganglion K2P1.1 in peripheral nerve injury-induced neuropathic pain

    PubMed Central

    Mao, Qingxiang; Yuan, Jingjing; Xiong, Ming; Wu, Shaogen; Chen, Liyong; Bekker, Alex; Yang, Tiande

    2017-01-01

    Peripheral nerve injury-caused hyperexcitability and abnormal ectopic discharges in the primary sensory neurons of dorsal root ganglion (DRG) play a key role in neuropathic pain development and maintenance. The two-pore domain background potassium (K2P) channels have been identified as key determinants of the resting membrane potential and neuronal excitability. However, whether K2P channels contribute to neuropathic pain is still elusive. We reported here that K2P1.1, the first identified mammalian K2P channel, was highly expressed in mouse DRG and distributed in small-, medium-, and large-sized DRG neurons. Unilateral lumbar (L) 4 spinal nerve ligation led to a significant and time-dependent reduction of K2P1.1 mRNA and protein in the ipsilateral L4 DRG, but not in the contralateral L4 or ipsilateral L3 DRG. Rescuing this reduction through microinjection of adeno-associated virus-DJ expressing full-length K2P1.1 mRNA into the ipsilateral L4 DRG blocked spinal nerve ligation-induced mechanical, thermal, and cold pain hypersensitivities during the development and maintenance periods. This DRG viral microinjection did not affect acute pain and locomotor function. Our findings suggest that K2P1.1 participates in neuropathic pain development and maintenance and may be a potential target in the management of this disorder. PMID:28326939

  17. Downregulation of ClC-3 in dorsal root ganglia neurons contributes to mechanical hypersensitivity following peripheral nerve injury.

    PubMed

    Pang, Rui-Ping; Xie, Man-Xiu; Yang, Jie; Shen, Kai-Feng; Chen, Xi; Su, Ying-Xue; Yang, Chao; Tao, Jing; Liang, Si-Jia; Zhou, Jia-Guo; Zhu, He-Quan; Wei, Xu-Hong; Li, Yong-Yong; Qin, Zhi-Hai; Liu, Xian-Guo

    2016-11-01

    ClC-3 chloride channel/antiporter has been demonstrated to play an important role in synaptic transmission in central nervous system. However, its expression and function in sensory neurons is poorly understood. In present work, we found that ClC-3 is expressed at high levels in dorsal root ganglia (DRG). Co-immunofluorescent data showed that ClC-3 is mainly distributed in A- and C-type nociceptive neurons. ClC-3 expression in DRG is decreased in the spared nerve injury (SNI) model of neuropathic pain. Knockdown of local ClC-3 in DRG neurons with siRNA increased mechanical sensitivity in naïve rats, while overexpression of ClC-3 reversed the hypersensitivity to mechanical stimuli after peripheral nerve injury. In addition, genetic deletion of ClC-3 enhances mouse mechanical sensitivity but did not affect thermal and cold threshold. Restoration of ClC-3 expression in ClC-3 deficient mice reversed the mechanical sensitivity. Mechanistically, loss of ClC-3 enhanced mechanical sensitivity through increasing the excitability of DRG neurons. These data indicate that ClC-3 is an endogenous inhibitor of neuropathic pain development. Downregulation of ClC-3 by peripheral nerve injury is critical for mechanical hypersensitivity. Our findings suggest that ClC-3 is a novel therapeutic target for treating neuropathic pain.

  18. Monitoring of immune cell response to B cell depletion therapy and nerve root injury using SPIO enhanced MRI

    NASA Astrophysics Data System (ADS)

    Thorek, Daniel L.

    2009-12-01

    Magnetic resonance (MR) is a robust platform for non-invasive, high-resolution anatomical imaging. However, MR imaging lacks the requisite sensitivity and contrast for imaging at the cellular level. This represents a clinical impediment to greater diagnostic accuracy. Recent advances have allowed for the in vivo visualization of populations and even of individual cells using superparamagnetic iron oxide (SPIO) MR contrast agents. These nanoparticles, commonly manifested as a core of a single iron oxide crystal or cluster of crystals coated in a biocompatible shell, function to shorten proton relaxation times. In MR imaging these constructs locally dephase protons, resulting in a decrease in signal (hypointensity) localized to the region of accumulation of SPIO. In the context of immune cell imaging, SPIO can provide insight into the cellular migration patterns, trafficking, temporal dynamics and progression of diseases and their related pathological states. Furthermore, by visualizing the presence and activity of immune cells, SPIO-enabled cellular imaging can help evaluate the efficacy of therapy in immune disorders. This thesis examines the production, modification and application of SPIO in a range of in vitro and in vivo immune-response-relevant cellular systems. The role of different nanoparticle characteristics including diameter, surface charge and concentration are investigated in the labeling of T cells in culture. Following optimization of SPIO loading conditions for lymphocytes, the effect these particles have on the activation of primary B cells are elucidated. B cells are tracked using a variety of modalities, with and without the application of B cell depleting therapy. This is to evaluate the efficacy of SPIO as in vivo marker for B cell distribution. Unmodified SPIO were applied to monitor macrophage infiltration in a transient nerve root compression model, with implications for neck pain diagnosis and treatment. Nanoparticle accumulation and MR

  19. Fluoroscopically guided extraforaminal cervical nerve root blocks: analysis of epidural flow of the injectate with respect to needle tip position.

    PubMed

    Shipley, Kyle; Riew, K Daniel; Gilula, Louis A

    2014-02-01

    Study Design Retrospective evaluation of consecutively performed fluoroscopically guided cervical nerve root blocks. Objective To describe the incidence of injectate central epidural flow with respect to needle tip position during fluoroscopically guided extraforaminal cervical nerve root blocks (ECNRBs). Methods Between February 19, 2003 and June 11, 2003, 132 consecutive fluoroscopically guided ECNRBs performed with contrast media in the final injected material (injectate) were reviewed on 95 patients with average of 1.3 injections per patient. Fluoroscopic spot images documenting the procedure were obtained as part of standard quality assurance. An independent observer not directly involved in the procedures retrospectively reviewed the images, and the data were placed into a database. Image review was performed to determine optimal needle tip positioning for injectate epidural flow. Results Central epidural injectate flow was obtained in only 28.9% of injections with the needle tip lateral to midline of the lateral mass (zone 2). 83.8% of injectate went into epidural space when the needle tip was medial to midline of the lateral mass (zone 3). 100% of injectate flowed epidurally when the needle tip was medial to or at the medial cortex of the lateral mass (zone 4). There was no statistically significant difference with regards to central epidural flow and the needle tip position on lateral view. Conclusion To ensure central epidural flow with ECNRBs one must be prepared to pass the needle tip medial to midplane of the lateral mass or to medial cortex of the lateral mass. Approximately 16% of ECNRBs with needle tip medial to midline of the lateral mass did not flow into epidural space. One cannot claim a nerve block is an epidural block unless epidural flow of injectate is observed.

  20. Root gravitropism in response to a signal originating outside of the cap

    NASA Technical Reports Server (NTRS)

    Wolverton, Chris; Mullen, Jack L.; Ishikawa, Hideo; Evans, Michael L.

    2002-01-01

    We have developed image analysis software linked to a rotating stage, allowing constraint of any user-selected region of a root at a prescribed angle during root gravitropism. This device allows the cap of a graviresponding root to reach vertical while maintaining a selected region within the elongation zone at a gravistimulated angle. Under these conditions gravitropic curvature of roots of Zea mays L. continues long after the root cap reaches vertical, indicating that a signal from outside of the cap can contribute to the curvature response.

  1. The Role of 5-HT3 Receptors in Signaling from Taste Buds to Nerves

    PubMed Central

    Vandenbeuch, Aurelie; Voigt, Anja; Meyerhof, Wolfgang; Kinnamon, Sue C.; Finger, Thomas E.

    2015-01-01

    5-HT3 receptors that play a significant role in the neurotransmission of taste information from taste buds to nerves. In addition, we show that the anesthetic pentobarbital, widely used in taste nerve recordings, blocks 5-HT3 signaling. Therefore, many conclusions drawn from those data need to be reexamined in light of this anesthetic effect. PMID:26631478

  2. Autoregulation of root nodule formation: signals of both symbiotic partners studied in a split-root system of Vicia sativa subsp. nigra.

    PubMed

    van Brussel, Anton A N; Tak, Teun; Boot, Kees J M; Kijne, Jan W

    2002-04-01

    Inhibition of root nodule formation on leguminous plants by already induced or existing root nodules is called autoregulation of root nodule formation (AUT). Optimal conditions for AUT were determined using a split-root technique newly developed for Vicia sativa subsp. nigra. Infection of a root A with nodulating Rhizobium leguminosarum bv. viciae bacteria systemically inhibited nodulation of a spatially separated root B inoculated 2 days later with the same bacteria. This treatment gives complete AUT (total absence of nodules on root B). Only partial AUT of root B was obtained by incubation of root A with mitogenic nodulation (Nod) factors or with a noninfective strain producing normal mitogenic Nod factors. Nonmitogenic Nod factors did not evoke AUT. We identified two systemic plant signals induced by Rhizobium bacteria. Signal 1 (at weak buffering) was correlated with sink formation in root A and induced acidification of B-root medium. This signal is induced by treatment of root A with (i) nodulating rhizobia, (ii) mitogenic Nod factors, (iii) nonmitogenic Nod factors, or (iv) the cytokinin zeatin. Signal 2 (at strong buffering) could only be evoked by treatment with nodulating rhizobia or with mitogenic Nod factors. Most probably, this signal represents the specific AUT signal. Induction of complete AUT appears to require actively dividing nodule cells in nodule primordia, nodule meristems, or both of root A.

  3. Emerging roots alter epidermal cell fate through mechanical and reactive oxygen species signaling.

    PubMed

    Steffens, Bianka; Kovalev, Alexander; Gorb, Stanislav N; Sauter, Margret

    2012-08-01

    A central question in biology is how spatial information is conveyed to locally establish a developmental program. Rice (Oryza sativa) can survive flash floods by the emergence of adventitious roots from the stem. Epidermal cells that overlie adventitious root primordia undergo cell death to facilitate root emergence. Root growth and epidermal cell death are both controlled by ethylene. This study aimed to identify the signal responsible for the spatial control of cell death. Epidermal cell death correlated with the proximity to root primordia in wild-type and ADVENTITIOUS ROOTLESS1 plants, indicating that the root emits a spatial signal. Ethylene-induced root growth generated a mechanical force of ~18 millinewtons within 1 h. Force application to epidermal cells above root primordia caused cell death in a dose-dependent manner and was inhibited by 1-methylcyclopropene or diphenylene iodonium, an inhibitor of NADPH oxidase. Exposure of epidermal cells not overlying a root to either force and ethylene or force and the catalase inhibitor aminotriazole induced ectopic cell death. Genetic downregulation of the reactive oxygen species (ROS) scavenger METALLOTHIONEIN2b likewise promoted force-induced ectopic cell death. Hence, reprogramming of epidermal cell fate by the volatile plant hormone ethylene requires two signals: mechanosensing for spatial resolution and ROS for cell death signaling.

  4. A literature review reveals that trials evaluating treatment of non-specific low back pain use inconsistent criteria to identify serious pathologies and nerve root involvement

    PubMed Central

    Williams, Ciaran; Hancock, Mark J; Ferreira, Manuela; Ferreira, Paulo; Maher, Chris G

    2012-01-01

    Objectives The broad aim of this study was to assess the homogeneity of patients included in trials of non-specific low back pain (NSLBP). To do this, we investigated the consistency and clarity of criteria used to identify and exclude participants with serious pathologies and nerve root compromise in randomized controlled trials, investigating interventions for NSLBP. Methods We searched Medline database for randomized controlled trials of low back pain (LBP). published between 2000 and 2009. We then randomly selected and screened trials for inclusion until we had 50 eligible trials. Data were extracted on the criteria used to identify cases of serious conditions (e.g. cancer, fracture) and nerve root involvement. Results The majority of papers (35/50) explicitly excluded patients with serious pathology. However, the terminology used and examples given were highly variable. Nerve root involvement was an exclusion criterion in the majority but not all studies. The criteria used for excluding patients with nerve root involvement varied greatly between studies. The most common criteria were ‘motor, sensory or reflex changes’ (nine studies), followed by ‘pain radiating below the knee’ (five studies) and ‘reduced straight leg raise which reproduces leg pain’ (five studies). In half of the included studies, the criteria used, while alluding to nerve root involvement, were not explained adequately for us to determine the types of patients included or excluded. Discussion The inconsistent and unclear criteria used to identify cases of serious pathology and nerve root compromise means that published trials of LBP likely include heterogeneous patient populations. This trait limits our ability to make comparisons across trials or pool studies. Standardization and consensus is important for future research. PMID:23633884

  5. Painful Nerve Injury Upregulates Thrombospondin-4 Expression in Dorsal Root Ganglia

    PubMed Central

    Pan, Bin; Yu, Hongwei; Park, John; Yu, Yanhui Peter; Luo, Z. David; Hogan, Quinn H.

    2014-01-01

    Thrombospondin-4 (TSP4) belongs to a family of large oligomeric, extracellular matrix glycoproteins that mediate interactions between cells and interactions of cells with underlying matrix components. Recent evidence shows that TSP4 may contribute to the generation of neuropathic pain. However, there is no systematic examination of TSP4 expression in the DRGs after injury. We therefore investigated whether TSP4 protein level is changed in DRGs after injury following spinal nerve ligation (SNL) and spared nerve injury (SNI) in rats using western blot, immunohistochemistry, and immunocytochemistry. After nerve ligation, TSP4 protein level is up-regulated in the axotomized somata of the L5 DRG. There is substantial additional TSP4 in the non-neuronal compartment of the L5 DRG that does not co-stain for markers of satellite glia, microglia, or Schwann cells and appears to be in the interstitial space. Evidence of intracellular overexpression of TSP4 persists in neurons dissociated from the L5 DRG after SNL. These findings indicate that following peripheral nerve injury, TSP4 protein expression is elevated in the cytoplasm of axotomized sensory neurons and in the surrounding interstitial space. PMID:25327416

  6. Implementation of linear sensory signaling via multiple coordinated mechanisms at central vestibular nerve synapses.

    PubMed

    McElvain, Lauren E; Faulstich, Michael; Jeanne, James M; Moore, Jeffrey D; du Lac, Sascha

    2015-03-04

    Signal transfer in neural circuits is dynamically modified by the recent history of neuronal activity. Short-term plasticity endows synapses with nonlinear transmission properties, yet synapses in sensory and motor circuits are capable of signaling linearly over a wide range of presynaptic firing rates. How do such synapses achieve rate-invariant transmission despite history-dependent nonlinearities? Here, ultrastructural, biophysical, and computational analyses demonstrate that concerted molecular, anatomical, and physiological refinements are required for central vestibular nerve synapses to linearly transmit rate-coded sensory signals. Vestibular synapses operate in a physiological regime of steady-state depression imposed by tonic firing. Rate-invariant transmission relies on brief presynaptic action potentials that delimit calcium influx, large pools of rapidly mobilized vesicles, multiple low-probability release sites, robust postsynaptic receptor sensitivity, and efficient transmitter clearance. Broadband linear synaptic filtering of head motion signals is thus achieved by coordinately tuned synaptic machinery that maintains physiological operation within inherent cell biological limitations.

  7. Perineurial glia require Notch signaling during motor nerve development but not regeneration

    PubMed Central

    Binari, Laura A.; Lewis, Gwendolyn M.; Kucenas, Sarah

    2013-01-01

    Motor nerves play the critical role of shunting information out of the CNS to targets in the periphery. Their formation requires the coordinated development of distinct cellular components, including motor axons and the Schwann cells and perineurial glia that ensheath them. During nervous system assembly, these glial cells must migrate long distances and terminally differentiate, ensuring the efficient propagation of action potentials. Although we know quite a bit about the mechanisms that control Schwann cell development during this process, nothing is known about the mechanisms that mediate the migration and differentiation of perineurial glia. Using in vivo imaging in zebrafish, we demonstrate that Notch signaling is required for both perineurial migration and differentiation during nerve formation, but not regeneration. Interestingly, loss of Notch signaling in perineurial cells also causes a failure of Schwann cell differentiation, demonstrating that Schwann cells require perineurial glia for aspects of their own development. These studies describe a novel mechanism that mediates multiple aspects of perineurial development and reveal the critical importance of perineurial glia for Schwann cell maturation and nerve formation. PMID:23467342

  8. Pincher, a pinocytic chaperone for nerve growth factor/TrkA signaling endosomes

    PubMed Central

    Shao, Yufang; Akmentin, Wendy; Toledo-Aral, Juan Jose; Rosenbaum, Julie; Valdez, Gregorio; Cabot, John B.; Hilbush, Brian S.; Halegoua, Simon

    2002-01-01

    Acentral tenet of nerve growth factor (NGF) action that is poorly understood is its ability to mediate cytoplasmic signaling, through its receptor TrkA, that is initiated at the nerve terminal and conveyed to the soma. We identified an NGF-induced protein that we termed Pincher (pinocytic chaperone) that mediates endocytosis and trafficking of NGF and its receptor TrkA. In PC12 cells, overexpression of Pincher dramatically stimulated NGF-induced endocytosis of TrkA, unexpectedly at sites of clathrin-independent macropinocytosis within cell surface ruffles. Subsequently, a system of Pincher-containing tubules mediated the delivery of NGF/TrkA-containing vesicles to cytoplasmic accumulations. These vesicles selectively and persistently mediated TrkA-erk5 mitogen-activated protein kinase signaling. A dominant inhibitory mutant form of Pincher inhibited the NGF-induced endocytosis of TrkA, and selectively blocked TrkA-mediated cytoplasmic signaling of erk5, but not erk1/2, kinases. Our results indicate that Pincher mediates pinocytic endocytosis of functionally specialized NGF/TrkA endosomes with persistent signaling potential. PMID:12011113

  9. Parathyroid hormone receptor signalling in osterix-expressing mesenchymal progenitors is essential for tooth root formation.

    PubMed

    Ono, Wanida; Sakagami, Naoko; Nishimori, Shigeki; Ono, Noriaki; Kronenberg, Henry M

    2016-04-12

    Dental root formation is a dynamic process in which mesenchymal cells migrate toward the site of the future root, differentiate and secrete dentin and cementum. However, the identities of dental mesenchymal progenitors are largely unknown. Here we show that cells expressing osterix are mesenchymal progenitors contributing to all relevant cell types during morphogenesis. The majority of cells expressing parathyroid hormone-related peptide (PTHrP) are in the dental follicle and on the root surface, and deletion of its receptor (PPR) in these progenitors leads to failure of eruption and significantly truncated roots lacking periodontal ligaments. The PPR-deficient progenitors exhibit accelerated cementoblast differentiation with upregulation of nuclear factor I/C (Nfic). Deletion of histone deacetylase-4 (HDAC4) partially recapitulates the PPR deletion root phenotype. These findings indicate that PPR signalling in dental mesenchymal progenitors is essential for tooth root formation, underscoring importance of the PTHrP-PPR system during root morphogenesis and tooth eruption.

  10. Parathyroid hormone receptor signalling in osterix-expressing mesenchymal progenitors is essential for tooth root formation

    PubMed Central

    Ono, Wanida; Sakagami, Naoko; Nishimori, Shigeki; Ono, Noriaki; Kronenberg, Henry M.

    2016-01-01

    Dental root formation is a dynamic process in which mesenchymal cells migrate toward the site of the future root, differentiate and secrete dentin and cementum. However, the identities of dental mesenchymal progenitors are largely unknown. Here we show that cells expressing osterix are mesenchymal progenitors contributing to all relevant cell types during morphogenesis. The majority of cells expressing parathyroid hormone-related peptide (PTHrP) are in the dental follicle and on the root surface, and deletion of its receptor (PPR) in these progenitors leads to failure of eruption and significantly truncated roots lacking periodontal ligaments. The PPR-deficient progenitors exhibit accelerated cementoblast differentiation with upregulation of nuclear factor I/C (Nfic). Deletion of histone deacetylase-4 (HDAC4) partially recapitulates the PPR deletion root phenotype. These findings indicate that PPR signalling in dental mesenchymal progenitors is essential for tooth root formation, underscoring importance of the PTHrP–PPR system during root morphogenesis and tooth eruption. PMID:27068606

  11. Cytokinin interplay with ethylene, auxin, and glucose signaling controls Arabidopsis seedling root directional growth.

    PubMed

    Kushwah, Sunita; Jones, Alan M; Laxmi, Ashverya

    2011-08-01

    Optimal root architecture is established by multiple intrinsic (e.g. hormones) and extrinsic (e.g. gravity and touch) signals and is established, in part, by directed root growth. We show that asymmetrical exposure of cytokinin (CK) at the root tip in Arabidopsis (Arabidopsis thaliana) promotes cell elongation that is potentiated by glucose in a hexokinase-influenced, G protein-independent manner. This mode of CK signaling requires the CK receptor, ARABIDOPSIS HISTIDINE KINASE4 and, at a minimum, its cognate type B ARABIDOPSIS RESPONSE REGULATORS ARR1, ARR10, and ARR11 for full responsiveness, while type A response regulators act redundantly to attenuate this CK response. Ethylene signaling through the ethylene receptor ETHYLENE RESISTANT1 and its downstream signaling element ETHYLENE INSENSITIVE2 are required for CK-induced root cell elongation. Negative and positive feedback loops are reinforced by CK regulation of the expression of the genes encoding these elements in both the CK and ethylene signaling pathways. Auxin transport facilitated by PIN-FORMED2 as well as auxin signaling through control of the steady-state level of transcriptional repressors INDOLE-3-ACETIC ACID7 (IAA7), IAA14, and IAA17 via TRANSPORT INHIBITOR RESPONSE1/AUXIN SIGNALING F-BOX PROTEIN are involved in CK-induced root cell elongation. This action lies downstream of ethylene and CK induction. Intrinsic signaling in this response operates independently of the extrinsic signal touch, although actin filament organization, which is important in the touch response, may be important for this response, since latrunculin B can induce similar growth. This root growth response may have adaptive significance, since CK responsiveness is inversely related to root coiling and waving, two root behaviors known to be important for fitness.

  12. Time-Dependent Nerve Growth Factor Signaling Changes in the Rat Retina During Optic Nerve Crush-Induced Degeneration of Retinal Ganglion Cells

    PubMed Central

    Mesentier-Louro, Louise A.; De Nicolò, Sara; Rosso, Pamela; De Vitis, Luigi A.; Castoldi, Valerio; Leocani, Letizia; Mendez-Otero, Rosalia; Santiago, Marcelo F.; Tirassa, Paola; Rama, Paolo; Lambiase, Alessandro

    2017-01-01

    Nerve growth factor (NGF) is suggested to be neuroprotective after nerve injury; however, retinal ganglion cells (RGC) degenerate following optic-nerve crush (ONC), even in the presence of increased levels of endogenous NGF. To further investigate this apparently paradoxical condition, a time-course study was performed to evaluate the effects of unilateral ONC on NGF expression and signaling in the adult retina. Visually evoked potential and immunofluorescence staining were used to assess axonal damage and RGC loss. The levels of NGF, proNGF, p75NTR, TrkA and GFAP and the activation of several intracellular pathways were analyzed at 1, 3, 7 and 14 days after crush (dac) by ELISA/Western Blot and PathScan intracellular signaling array. The progressive RGC loss and nerve impairment featured an early and sustained activation of apoptotic pathways; and GFAP and p75NTR enhancement. In contrast, ONC-induced reduction of TrkA, and increased proNGF were observed only at 7 and 14 dac. We propose that proNGF and p75NTR contribute to exacerbate retinal degeneration by further stimulating apoptosis during the second week after injury, and thus hamper the neuroprotective effect of the endogenous NGF. These findings might aid in identifying effective treatment windows for NGF-based strategies to counteract retinal and/or optic-nerve degeneration. PMID:28067793

  13. Time-Dependent Nerve Growth Factor Signaling Changes in the Rat Retina During Optic Nerve Crush-Induced Degeneration of Retinal Ganglion Cells.

    PubMed

    Mesentier-Louro, Louise A; De Nicolò, Sara; Rosso, Pamela; De Vitis, Luigi A; Castoldi, Valerio; Leocani, Letizia; Mendez-Otero, Rosalia; Santiago, Marcelo F; Tirassa, Paola; Rama, Paolo; Lambiase, Alessandro

    2017-01-05

    Nerve growth factor (NGF) is suggested to be neuroprotective after nerve injury; however, retinal ganglion cells (RGC) degenerate following optic-nerve crush (ONC), even in the presence of increased levels of endogenous NGF. To further investigate this apparently paradoxical condition, a time-course study was performed to evaluate the effects of unilateral ONC on NGF expression and signaling in the adult retina. Visually evoked potential and immunofluorescence staining were used to assess axonal damage and RGC loss. The levels of NGF, proNGF, p75(NTR), TrkA and GFAP and the activation of several intracellular pathways were analyzed at 1, 3, 7 and 14 days after crush (dac) by ELISA/Western Blot and PathScan intracellular signaling array. The progressive RGC loss and nerve impairment featured an early and sustained activation of apoptotic pathways; and GFAP and p75(NTR) enhancement. In contrast, ONC-induced reduction of TrkA, and increased proNGF were observed only at 7 and 14 dac. We propose that proNGF and p75(NTR) contribute to exacerbate retinal degeneration by further stimulating apoptosis during the second week after injury, and thus hamper the neuroprotective effect of the endogenous NGF. These findings might aid in identifying effective treatment windows for NGF-based strategies to counteract retinal and/or optic-nerve degeneration.

  14. It's time to make changes: modulation of root system architecture by nutrient signals.

    PubMed

    Giehl, Ricardo F H; Gruber, Benjamin D; von Wirén, Nicolaus

    2014-03-01

    Root growth and development are of outstanding importance for the plant's ability to acquire water and nutrients from different soil horizons. To cope with fluctuating nutrient availabilities, plants integrate systemic signals pertaining to their nutritional status into developmental pathways that regulate the spatial arrangement of roots. Changes in the plant nutritional status and external nutrient supply modulate root system architecture (RSA) over time and determine the degree of root plasticity which is based on variations in the number, extension, placement, and growth direction of individual components of the root system. Roots also sense the local availability of some nutrients, thereby leading to nutrient-specific modifications in RSA, that result from the integration of systemic and local signals into the root developmental programme at specific steps. An in silico analysis of nutrient-responsive genes involved in root development showed that the majority of these specifically responded to the deficiency of individual nutrients while a minority responded to more than one nutrient deficiency. Such an analysis provides an interesting starting point for the identification of the molecular players underlying the sensing and transduction of the nutrient signals that mediate changes in the development and architecture of root systems.

  15. Development of the Poplar-Laccaria bicolor Ectomycorrhiza Modifies Root Auxin Metabolism, Signaling, and Response1

    PubMed Central

    Vayssières, Alice; Pěnčík, Ales; Felten, Judith; Kohler, Annegret; Ljung, Karin; Martin, Francis; Legué, Valérie

    2015-01-01

    Root systems of host trees are known to establish ectomycorrhizae (ECM) interactions with rhizospheric fungi. This mutualistic association leads to dramatic developmental modifications in root architecture, with the formation of numerous short and swollen lateral roots ensheathed by a fungal mantle. Knowing that auxin plays a crucial role in root development, we investigated how auxin metabolism, signaling, and response are affected in poplar (Populus spp.)-Laccaria bicolor ECM roots. The plant-fungus interaction leads to the arrest of lateral root growth with simultaneous attenuation of the synthetic auxin response element DR5. Measurement of auxin-related metabolites in the free-living partners revealed that the mycelium of L. bicolor produces high concentrations of the auxin indole-3-acetic acid (IAA). Metabolic profiling showed an accumulation of IAA and changes in the indol-3-pyruvic acid-dependent IAA biosynthesis and IAA conjugation and degradation pathways during ECM formation. The global analysis of auxin response gene expression and the regulation of AUXIN SIGNALING F-BOX PROTEIN5, AUXIN/IAA, and AUXIN RESPONSE FACTOR expression in ECM roots suggested that symbiosis-dependent auxin signaling is activated during the colonization by L. bicolor. Taking all this evidence into account, we propose a model in which auxin signaling plays a crucial role in the modification of root growth during ECM formation. PMID:26084921

  16. Development of the Poplar-Laccaria bicolor Ectomycorrhiza Modifies Root Auxin Metabolism, Signaling, and Response.

    PubMed

    Vayssières, Alice; Pěnčík, Ales; Felten, Judith; Kohler, Annegret; Ljung, Karin; Martin, Francis; Legué, Valérie

    2015-09-01

    Root systems of host trees are known to establish ectomycorrhizae (ECM) interactions with rhizospheric fungi. This mutualistic association leads to dramatic developmental modifications in root architecture, with the formation of numerous short and swollen lateral roots ensheathed by a fungal mantle. Knowing that auxin plays a crucial role in root development, we investigated how auxin metabolism, signaling, and response are affected in poplar (Populus spp.)-Laccaria bicolor ECM roots. The plant-fungus interaction leads to the arrest of lateral root growth with simultaneous attenuation of the synthetic auxin response element DR5. Measurement of auxin-related metabolites in the free-living partners revealed that the mycelium of L. bicolor produces high concentrations of the auxin indole-3-acetic acid (IAA). Metabolic profiling showed an accumulation of IAA and changes in the indol-3-pyruvic acid-dependent IAA biosynthesis and IAA conjugation and degradation pathways during ECM formation. The global analysis of auxin response gene expression and the regulation of AUXIN SIGNALING F-BOX PROTEIN5, AUXIN/IAA, and AUXIN RESPONSE FACTOR expression in ECM roots suggested that symbiosis-dependent auxin signaling is activated during the colonization by L. bicolor. Taking all this evidence into account, we propose a model in which auxin signaling plays a crucial role in the modification of root growth during ECM formation.

  17. The Emerging Role of Reactive Oxygen Species Signaling during Lateral Root Development1[C][W

    PubMed Central

    Manzano, Concepción; Pallero-Baena, Mercedes; Casimiro, Ilda; De Rybel, Bert; Orman-Ligeza, Beata; Van Isterdael, Gert; Beeckman, Tom; Draye, Xavier; Casero, Pedro; del Pozo, Juan C.

    2014-01-01

    Overall root architecture is the combined result of primary and lateral root growth and is influenced by both intrinsic genetic programs and external signals. One of the main questions for root biologists is how plants control the number of lateral root primordia and their emergence through the main root. We recently identified S-phase kinase-associated protein2 (SKP2B) as a new early marker for lateral root development. Here, we took advantage of its specific expression pattern in Arabidopsis (Arabidopsis thaliana) in a cell-sorting and transcriptomic approach to generate a lateral root-specific cell sorting SKP2B data set that represents the endogenous genetic developmental program. We first validated this data set by showing that many of the identified genes have a function during root growth or lateral root development. Importantly, genes encoding peroxidases were highly represented in our data set. Thus, we next focused on this class of enzymes and showed, using genetic and chemical inhibitor studies, that peroxidase activity and reactive oxygen species signaling are specifically required during lateral root emergence but, intriguingly, not for primordium specification itself. PMID:24879433

  18. The Emerging Role of Reactive Oxygen Species Signaling during Lateral Root Development.

    PubMed

    Manzano, Concepción; Pallero-Baena, Mercedes; Casimiro, Ilda; De Rybel, Bert; Orman-Ligeza, Beata; Van Isterdael, Gert; Beeckman, Tom; Draye, Xavier; Casero, Pedro; Del Pozo, Juan C

    2014-07-01

    Overall root architecture is the combined result of primary and lateral root growth and is influenced by both intrinsic genetic programs and external signals. One of the main questions for root biologists is how plants control the number of lateral root primordia and their emergence through the main root. We recently identified S-phase kinase-associated protein2 (SKP2B) as a new early marker for lateral root development. Here, we took advantage of its specific expression pattern in Arabidopsis (Arabidopsis thaliana) in a cell-sorting and transcriptomic approach to generate a lateral root-specific cell sorting SKP2B data set that represents the endogenous genetic developmental program. We first validated this data set by showing that many of the identified genes have a function during root growth or lateral root development. Importantly, genes encoding peroxidases were highly represented in our data set. Thus, we next focused on this class of enzymes and showed, using genetic and chemical inhibitor studies, that peroxidase activity and reactive oxygen species signaling are specifically required during lateral root emergence but, intriguingly, not for primordium specification itself.

  19. STZ causes depletion of immune cells in sciatic nerve and dorsal root ganglion in experimental diabetes.

    PubMed

    Hidmark, Asa S; Nawroth, Peter P; Fleming, Thomas

    2017-05-15

    Streptozotocin (STZ) treatment, a common model for inducing diabetes in rodent models, induces thermal hyperalgesia and neuronal toxicity independently of hyperglycemia by oxidizing and activating TRPA1 and TRPV1. Following treatment with STZ, CD45(+) immune cells were found to be depleted in sciatic nerve (SN) and DRG in mice, prior to hyperglycemia. Macrophages were also lost in DRG and NFκB-p65-activation was increased in SN macrophages. Immune cells were significantly reduced in both SN and DRG up to three weeks, post-treatment. Loss of PNS-resident macrophages in response to STZ-mediated toxicity may affect the regenerative capacity of the nerve in response to further injury caused by diabetes.

  20. Wnt-Ror signaling to SIA and SIB neurons directs anterior axon guidance and nerve ring placement in C. elegans

    PubMed Central

    Kennerdell, Jason R.; Fetter, Richard D.; Bargmann, Cornelia I.

    2009-01-01

    Summary Wnt signaling through Frizzled proteins guides posterior cells and axons in C. elegans into different spatial domains. Here we demonstrate an essential role for Wnt signaling through Ror tyrosine kinase homologs in the most prominent anterior neuropil, the nerve ring. A genetic screen uncovered cwn-2, the C. elegans homolog of Wnt5, as a regulator of nerve ring placement. In cwn-2 mutants, all neuronal structures in and around the nerve ring are shifted to an abnormal anterior position. cwn-2 is required at the time of nerve ring formation; it is expressed by cells posterior of the nerve ring, but its precise site of expression is not critical for its function. In nerve ring development, cwn-2 acts primarily through the Wnt receptor CAM-1 (Ror), together with the Frizzled protein MIG-1, with parallel roles for the Frizzled protein CFZ-2. The identification of CAM-1 as a CWN-2 receptor contrasts with CAM-1 action as a non-receptor in other C. elegans Wnt pathways. Cell-specific rescue of cam-1 and cell ablation experiments reveal a crucial role for the SIA and SIB neurons in positioning the nerve ring, linking Wnt signaling to specific cells that organize the anterior nervous system. PMID:19855022

  1. Mechanisms of nerve growth factor signaling in bone nociceptors and in an animal model of inflammatory bone pain.

    PubMed

    Nencini, Sara; Ringuet, Mitchell; Kim, Dong-Hyun; Chen, Yu-Jen; Greenhill, Claire; Ivanusic, Jason J

    2017-01-01

    Sequestration of nerve growth factor has been used successfully in the management of pain in animal models of bone disease and in human osteoarthritis. However, the mechanisms of nerve growth factor-induced bone pain and its role in modulating inflammatory bone pain remain to be determined. In this study, we show that nerve growth factor receptors (TrkA and p75) and some other nerve growth factor-signaling molecules (TRPV1 and Nav1.8, but not Nav1.9) are expressed in substantial proportions of rat bone nociceptors. We demonstrate that nerve growth factor injected directly into rat tibia rapidly activates and sensitizes bone nociceptors and produces acute behavioral responses with a similar time course. The nerve growth factor-induced changes in the activity and sensitivity of bone nociceptors we report are dependent on signaling through the TrkA receptor, but are not affected by mast cell stabilization. We failed to show evidence for longer term changes in expression of TrkA, TRPV1, Nav1.8 or Nav1.9 in the soma of bone nociceptors in a rat model of inflammatory bone pain. Thus, retrograde transport of NGF/TrkA and increased expression of some of the common nerve growth factor signaling molecules do not appear to be important for the maintenance of inflammatory bone pain. The findings are relevant to understand the basis of nerve growth factor sequestration and other therapies directed at nerve growth factor signaling, in managing pain in bone disease.

  2. Long-distance signals positively regulate the expression of iron uptake genes in tobacco roots.

    PubMed

    Enomoto, Yusuke; Hodoshima, Hirotaka; Shimada, Hiroaki; Shoji, Kazuhiro; Yoshihara, Toshihiro; Goto, Fumiyuki

    2007-12-01

    Long-distance signals generated in shoots are thought to be associated with the regulation of iron uptake from roots; however, the signaling mechanism is still unknown. To elucidate whether the signal regulates iron uptake genes in roots positively or negatively, we analyzed the expressions of two representative iron uptake genes: NtIRT1 and NtFRO1 in tobacco (Nicotiana tabacum L.) roots, after shoots were manipulated in vitro. When iron-deficient leaves were treated with Fe(II)-EDTA, the expressions of both genes were significantly reduced; nevertheless iron concentration in the roots maintained a similar level to that in roots grown under iron-deficient conditions. Next, all leaves from tobacco plants grown under the iron-deficient condition were excised. The expression of two genes were quickly reduced below half within 2 h after the leaf excision and gradually disappeared by the end of a 24-h period. The NtIRT1 expression was compared among the plants whose leaves were cut off in various patterns. The expression increased in proportion to the dry weight of iron-deficient leaves, although no relation was observed between the gene expression and the position of excised leaves. Interestingly, the NtIRT1 expression in hairy roots increased under the iron-deficient condition, suggesting that roots also have the signaling mechanism of iron status as well as shoots. Taken together, these results indicate that the long-distance signal generated in iron-deficient tissues including roots is a major factor in positive regulation of the expression of NtIRT1 and NtFRO1 in roots, and that the strength of the signal depends on the size of plants.

  3. Sciatic nerve injury induces apoptosis of dorsal root ganglion satellite glial cells and selectively modifies neurosteroidogenesis in sensory neurons.

    PubMed

    Schaeffer, Véronique; Meyer, Laurence; Patte-Mensah, Christine; Eckert, Anne; Mensah-Nyagan, Ayikoe G

    2010-01-15

    Neurosteroids are synthesized either by glial cells, by neurons, or within the context of neuron-glia cross-talk. Various studies suggested neurosteroid involvement in the control of neurodegeneration but there is no evidence showing that the natural protection of nerve cells against apoptosis directly depends on their own capacity to produce neuroprotective neurosteroids. Here, we investigated the interactions between neurosteroidogenesis and apoptosis occurring in sensory structures of rats subjected to neuropathic pain generated by sciatic nerve chronic constriction injury (CCI). Using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), we observed no apoptotic cells in the spinal cord up to 30 days after CCI although pain symptoms such as mechano-allodynia, thermal and mechanical hyperalgesia were evidenced with the Hargreaves's behavioral and von Frey filament tests. In contrast, double-labeling experiments combining TUNEL and immunostaining with antibodies against glutamine synthetase or neuronal nuclei protein revealed apoptosis occurrence in satellite glial cells (SGC) (not in neurons) of CCI rat ipsilateral dorsal root ganglia (DRG) at day 30 after injury. Pulse-chase experiments coupled with high performance liquid chromatography and flow scintillation detection showed that, among numerous biosynthetic pathways converting [(3)H]pregnenolone into various [(3)H]neurosteroids, only [(3)H]estradiol formation was selectively modified and upregulated in DRG of CCI rats. Consistently, immunohistochemical investigations localized aromatase (estradiol-synthesizing enzyme) in DRG neurons but not in SGC. Pharmacological inhibition of aromatase caused apoptosis of CCI rat DRG neurons. Altogether, our results suggest that endogenously produced neurosteroids such as estradiol may be pivotal for the protection of DRG sensory neurons against sciatic nerve CCI-induced apoptosis.

  4. Induced jasmonate signaling leads to contrasting effects on root damage and herbivore performance.

    PubMed

    Lu, Jing; Robert, Christelle Aurélie Maud; Riemann, Michael; Cosme, Marco; Mène-Saffrané, Laurent; Massana, Josep; Stout, Michael Joseph; Lou, Yonggen; Gershenzon, Jonathan; Erb, Matthias

    2015-03-01

    Induced defenses play a key role in plant resistance against leaf feeders. However, very little is known about the signals that are involved in defending plants against root feeders and how they are influenced by abiotic factors. We investigated these aspects for the interaction between rice (Oryza sativa) and two root-feeding insects: the generalist cucumber beetle (Diabrotica balteata) and the more specialized rice water weevil (Lissorhoptrus oryzophilus). Rice plants responded to root attack by increasing the production of jasmonic acid (JA) and abscisic acid, whereas in contrast to in herbivore-attacked leaves, salicylic acid and ethylene levels remained unchanged. The JA response was decoupled from flooding and remained constant over different soil moisture levels. Exogenous application of methyl JA to the roots markedly decreased the performance of both root herbivores, whereas abscisic acid and the ethylene precursor 1-aminocyclopropane-1-carboxylic acid did not have any effect. JA-deficient antisense 13-lipoxygenase (asLOX) and mutant allene oxide cyclase hebiba plants lost more root biomass under attack from both root herbivores. Surprisingly, herbivore weight gain was decreased markedly in asLOX but not hebiba mutant plants, despite the higher root biomass removal. This effect was correlated with a herbivore-induced reduction of sucrose pools in asLOX roots. Taken together, our experiments show that jasmonates are induced signals that protect rice roots from herbivores under varying abiotic conditions and that boosting jasmonate responses can strongly enhance rice resistance against root pests. Furthermore, we show that a rice 13-lipoxygenase regulates root primary metabolites and specifically improves root herbivore growth.

  5. Induced Jasmonate Signaling Leads to Contrasting Effects on Root Damage and Herbivore Performance1

    PubMed Central

    Lu, Jing; Robert, Christelle Aurélie Maud; Riemann, Michael; Cosme, Marco; Mène-Saffrané, Laurent; Massana, Josep; Stout, Michael Joseph; Lou, Yonggen; Gershenzon, Jonathan; Erb, Matthias

    2015-01-01

    Induced defenses play a key role in plant resistance against leaf feeders. However, very little is known about the signals that are involved in defending plants against root feeders and how they are influenced by abiotic factors. We investigated these aspects for the interaction between rice (Oryza sativa) and two root-feeding insects: the generalist cucumber beetle (Diabrotica balteata) and the more specialized rice water weevil (Lissorhoptrus oryzophilus). Rice plants responded to root attack by increasing the production of jasmonic acid (JA) and abscisic acid, whereas in contrast to in herbivore-attacked leaves, salicylic acid and ethylene levels remained unchanged. The JA response was decoupled from flooding and remained constant over different soil moisture levels. Exogenous application of methyl JA to the roots markedly decreased the performance of both root herbivores, whereas abscisic acid and the ethylene precursor 1-aminocyclopropane-1-carboxylic acid did not have any effect. JA-deficient antisense 13-lipoxygenase (asLOX) and mutant allene oxide cyclase hebiba plants lost more root biomass under attack from both root herbivores. Surprisingly, herbivore weight gain was decreased markedly in asLOX but not hebiba mutant plants, despite the higher root biomass removal. This effect was correlated with a herbivore-induced reduction of sucrose pools in asLOX roots. Taken together, our experiments show that jasmonates are induced signals that protect rice roots from herbivores under varying abiotic conditions and that boosting jasmonate responses can strongly enhance rice resistance against root pests. Furthermore, we show that a rice 13-lipoxygenase regulates root primary metabolites and specifically improves root herbivore growth. PMID:25627217

  6. Microsurgical procedures in the peripheral nerves and the dorsal root entry zone for the treatment of spasticity.

    PubMed

    Sindou, M; Keravel, Y

    1988-01-01

    When spasticity becomes severe and harmful, in spite of physical and medical therapy, neurosurgery can give functional improvement. This paper deals with the long term results of Selective Peripheral Neurotomies of the Tibial Nerve and Selective Posterior Rhizotomies in the Dorsal Root Entry Zone, in 123 patients with spastic disorders localized to the limbs. The micro-techniques and intra-operative electro-stimulation for identification of the nervous structures responsible for the spastic components, can give a substantial reduction of the harmful spasticity, without suppressing the useful muscle tone and impairing the residual motor and sensory functions. The results were effective, with a 1 to 13 year follow-up (5 on average), in 89% of 47 Selective Peripheral Neurotomies of the tibial nerve for spastic foot, in 92% of 53 Selective Posterior Rhizotomies for paraplegia and in 87% of 23 Selective Posterior Rhizotomies for hemiplegia. In the most severe situations ("comfort" indications), correction of the abnormal postures and relief of pain facilitated nursing and physiotherapy. Sometimes there was reappearance of some useful voluntary movements. In the less affected patients ("functional" indications), the suppression of the harmful spastic components made the persistant capacities more effective.

  7. A fungal endophyte helps plants to tolerate root herbivory through changes in gibberellin and jasmonate signaling.

    PubMed

    Cosme, Marco; Lu, Jing; Erb, Matthias; Stout, Michael Joseph; Franken, Philipp; Wurst, Susanne

    2016-08-01

    Plant-microbe mutualisms can improve plant defense, but the impact of root endophytes on below-ground herbivore interactions remains unknown. We investigated the effects of the root endophyte Piriformospora indica on interactions between rice (Oryza sativa) plants and its root herbivore rice water weevil (RWW; Lissorhoptrus oryzophilus), and how plant jasmonic acid (JA) and GA regulate this tripartite interaction. Glasshouse experiments with wild-type rice and coi1-18 and Eui1-OX mutants combined with nutrient, jasmonate and gene expression analyses were used to test: whether RWW adult herbivory above ground influences subsequent damage caused by larval herbivory below ground; whether P. indica protects plants against RWW; and whether GA and JA signaling mediate these interactions. The endophyte induced plant tolerance to root herbivory. RWW adults and larvae acted synergistically via JA signaling to reduce root growth, while endophyte-elicited GA biosynthesis suppressed the herbivore-induced JA in roots and recovered plant growth. Our study shows for the first time the impact of a root endophyte on plant defense against below-ground herbivores, adds to growing evidence that induced tolerance may be an important root defense, and implicates GA as a signal component of inducible plant tolerance against biotic stress.

  8. MADS-box transcription factor AGL21 regulates lateral root development and responds to multiple external and physiological signals.

    PubMed

    Yu, Lin-Hui; Miao, Zi-Qing; Qi, Guo-Feng; Wu, Jie; Cai, Xiao-Teng; Mao, Jie-Li; Xiang, Cheng-Bin

    2014-11-01

    Plant root system morphology is dramatically influenced by various environmental cues. The adaptation of root system architecture to environmental constraints, which mostly depends on the formation and growth of lateral roots, is an important agronomic trait. Lateral root development is regulated by the external signals coordinating closely with intrinsic signaling pathways. MADS-box transcription factors are known key regulators of the transition to flowering and flower development. However, their functions in root development are still poorly understood. Here we report that AGL21, an AGL17-clade MADS-box gene, plays a crucial role in lateral root development. AGL21 was highly expressed in root, particularly in the root central cylinder and lateral root primordia. AGL21 overexpression plants produced more and longer lateral roots while agl21 mutants showed impaired lateral root development, especially under nitrogen-deficient conditions. AGL21 was induced by many plant hormones and environmental stresses, suggesting a function of this gene in root system plasticity in response to various signals. Furthermore, AGL21 was found positively regulating auxin accumulation in lateral root primordia and lateral roots by enhancing local auxin biosynthesis, thus stimulating lateral root initiation and growth. We propose that AGL21 may be involved in various environmental and physiological signals-mediated lateral root development and growth.

  9. Antagonism of Nerve Growth Factor-TrkA Signaling and the Relief of Pain

    PubMed Central

    Mantyh, Patrick W.; Koltzenburg, Martin; Mendell, Lorne M.; Tive, Leslie; Shelton, David L.

    2011-01-01

    Nerve growth factor (NGF) was originally discovered as a neurotrophic factor essential for the survival of sensory and sympathetic neurons during development. However in the adult, NGF has been found to play an important role in nociceptor sensitization following tissue injury. Here we outline mechanisms by which NGF activation of its cognate receptor, tropomyosin-related kinase A receptor, regulates a host of ion channels, receptors, and signaling molecules to enhance acute and chronic pain. Further, we document that peripherally restricted antagonism of NGF-tropomyosin-related kinase A receptor signaling is effective for controlling human pain while appearing to maintain normal nociceptor function. Understanding whether there are any unexpected adverse events as well as how humans may change their behavior and use of the injured/degenerating tissue following significant pain relief without sedation will be required to fully appreciate the patient populations that may benefit from these therapies targeting NGF. PMID:21602663

  10. Electrical signaling, stomatal conductance, ABA and ethylene content in avocado trees in response to root hypoxia.

    PubMed

    Gil, Pilar M; Gurovich, Luis; Schaffer, Bruce; García, Nicolás; Iturriaga, Rodrigo

    2009-02-01

    Avocado (Persea americana Mill.) trees are among the most sensitive of fruit tree species to root hypoxia as a result of flooded or poorly drained soil. Similar to drought stress, an early physiological response to root hypoxia in avocado is a reduction of stomatal conductance. It has been previously determined in avocado trees that an extracellular electrical signal between the base of stem and leaves is produced and related to reductions in stomatal conductance in response to drought stress. The current study was designed to determine if changes in the extracellular electrical potential between the base of the stem and leaves in avocado trees could also be detected in response to short-term (min) or long-term (days) root hypoxia, and if these signals could be related to stomatal conductance (gs), root and leaf ABA and ACC concentrations, ethylene emission from leaves and leaf abscission. In contrast to previous observations for drought-stressed trees, short-term or long-term root hypoxia did not stimulate an electrical potential difference between the base of the stem and leaves. Short-term hypoxia did not result in a significant decrease in gs compared with plants in the control treatment, and no differences in ABA concentration were found between plants subjected to hypoxia and control plants. Long-term hypoxia in the root zone resulted in a significant decrease in gs, increased leaf ethylene and increased leaf abscission. The results indicate that for avocado trees exposed to root hypoxia, electrical signals do not appear to be the primary root-to-shoot communication mechanism involved in signaling for stomatal closure as a result of hypoxia in the root zone.

  11. Electrical signaling, stomatal conductance, ABA and Ethylene content in avocado trees in response to root hypoxia

    PubMed Central

    Gurovich, Luis; Schaffer, Bruce; García, Nicolás; Iturriaga, Rodrigo

    2009-01-01

    Avocado (Persea americana Mill.) trees are among the most sensitive of fruit tree species to root hypoxia as a result of flooded or poorly drained soil. Similar to drought stress, an early physiological response to root hypoxia in avocado is a reduction of stomatal conductance. It has been previously determined in avocado trees that an extracellular electrical signal between the base of stem and leaves is produced and related to reductions in stomatal conductance in response to drought stress. The current study was designed to determine if changes in the extracellular electrical potential between the base of the stem and leaves in avocado trees could also be detected in response to short-term (min) or long-term (days) root hypoxia, and if these signals could be related to stomatal conductance (gs), root and leaf ABA and ACC concentrations, ethylene emission from leaves and leaf abscission. In contrast to previous observations for drought-stressed trees, short-term or long-term root hypoxia did not stimulate an electrical potential difference between the base of the stem and leaves. Short-term hypoxia did not result in a significant decrease in gs compared with plants in the control treatment, and no differences in ABA concentration were found between plants subjected to hypoxia and control plants. Long-term hypoxia in the root zone resulted in a significant decrease in gs, increased leaf ethylene and increased leaf abscission. The results indicate that for avocado trees exposed to root hypoxia, electrical signals do not appear to be the primary root-to-shoot communication mechanism involved in signaling for stomatal closure as a result of hypoxia in the root zone. PMID:19649181

  12. Translaminar Microendoscopic Herniotomy for Cranially Migrated Lumbar Disc Herniations Encroaching on the Exiting Nerve Root in the Preforaminal and Foraminal Zones

    PubMed Central

    Tono, Osamu; Senba, Hideyuki; Kitamura, Takahiro; Komiya, Norihiro; Oga, Masayoshi; Shidahara, Satoshi

    2013-01-01

    Study Design Case series. Purpose The aim of this study was to describe translaminar microendoscopic herniotomy (TL-MEH) for cranially migrated lumbar disc herniations encroaching on the exiting nerve root in the preforaminal and foraminal zones and to report preliminary results of the procedure. Overview of Literature Conventional interlaminar approaches for preforaminal and foraminal lumbar disc herniations result in extensive removal of the lamina and facet joint to remove disc fragments safely. More destructive approaches increase the risk of postoperative segmental instability. Methods TL-MEH is a minimally invasive procedure for herniotomy via the translaminar approach using a microendoscopic technique. TL-MEH was performed in seven patients with a cranially migrated lumbar disc herniation encroaching on the exiting nerve root. The disc fragments were located in the preforaminal zone in four patients, and in the preforaminal and foraminal zones in three. Results All patients experienced immediate relief from symptoms after surgery and satisfactory results at the final follow-up. Surgical complications, such as a dural tear, nerve injury, and surgical site infection, were not investigated. Conclusions TL-MEH seemed to be an effective and safe alternative minimally invasive surgical option for patients with a cranially migrated lumbar disc herniation encroaching the exiting nerve root in the preforaminal and foraminal zones. PMID:24066214

  13. A molecular mechanism of optic nerve regeneration in fish: the retinoid signaling pathway.

    PubMed

    Kato, Satoru; Matsukawa, Toru; Koriyama, Yoshiki; Sugitani, Kayo; Ogai, Kazuhiro

    2013-11-01

    The fish optic nerve regeneration process takes more than 100 days after axotomy and comprises four stages: neurite sprouting (1-4 days), axonal elongation (5-30 days), synaptic refinement (35-80 days) and functional recovery (100-120 days). We screened genes specifically upregulated in each stage from axotomized fish retina. The mRNAs for heat shock protein 70 and insulin-like growth factor-1 rapidly increased in the retinal ganglion cells soon after axotomy and function as cell-survival factors. Purpurin mRNA rapidly and transiently increased in the photoreceptors and purpurin protein diffusely increased in all nuclear layers at 1-4 days after injury. The purpurin gene has an active retinol-binding site and a signal peptide. Purpurin with retinol functions as a sprouting factor for thin neurites. This neurite-sprouting effect was closely mimicked by retinoic acid and blocked by its inhibitor. We propose that purpurin works as a retinol transporter to supply retinoic acid to damaged RGCs which in turn activates target genes. We also searched for genes involved in the second stage of regeneration. The mRNA of retinoid-signaling molecules increased in retinal ganglion cells at 7-14 days after injury and tissue transglutaminase and neuronal nitric oxide synthase mRNAs, RA-target genes, increased in retinal ganglion cells at 10-30 days after injury. They function as factors for the outgrowth of thick, long neurites. Here we present a retinoid-signaling hypothesis to explain molecular events during the early stages of optic nerve regeneration in fish.

  14. Nitric Oxide Signaling and Neural Stem Cell Differentiation in Peripheral Nerve Regeneration

    PubMed Central

    Tao Li, Jessica; Somasundaram, Chandra; Bian, Ka; Xiong, Weijun; Mahmooduddin, Faiz; Nath, Rahul K.; Murad, Ferid

    2010-01-01

    Objective: The objective was to examine whether nitric oxide signaling plays a role in human embryonic stem cell differentiation into neural cells. This article reviews current literature on nitric oxide signaling and neural stem cell differentiation for potential therapeutic application to peripheral nerve regeneration. Methods: Human embryonic H9-stem cells were grown, maintained on mitomycin C–treated mouse embryonic fibroblast feeder layer, cultured on Matrigel to be feeder-free, and used for all the experiments. Fluorescent dual-immunolabeling and confocal image analysis were used to detect the presence of the neural precursor cell markers nestin and nitric oxide synthase-1. Fluorescence-activated cell sorting analysis was used to determine the percentage of expression. Results: We have shown the confocal image of stage 1 human embryonic stem cells coexpressing nestin and nitric oxide synthase-1. Fluorescence-activated cell sorting analysis indicated 24.3% positive labeling of nitric oxide synthase-1. Adding retinoic acid (10−6 M) to the culture medium increased the percent of nitric oxide synthase-1 positive cells to 33.9%. Combining retinoic acid (10−6 M) with 8-brom cyclic guanosine monophosphate (10−5 M), the fluorescence-activated cell sorting analysis demonstrated a further increase of nitric oxide synthase-1 positive cells to 45.4%. Our current results demonstrate a prodifferentiation potency of nitric oxide synthase-1, stimulated by retinoic acid with and without cyclic guanosine monophosphate. Conclusion: We demonstrated for the first time how nitric oxide/cyclic guanosine monophosphate signaling contributes to the development of neural precursors derived from human embryonic stem cells and enhances the differentiation of precursors toward functional neurons for peripheral nerve regeneration. PMID:20563304

  15. Calcium and protein phosphorylation in the transduction of gravity signal in corn roots

    NASA Technical Reports Server (NTRS)

    Friedmann, M.; Poovaiah, B. W.

    1991-01-01

    The involvement of calcium and protein phosphorylation in the transduction of gravity signal was studied using corn roots of a light-insensitive variety (Zea mays L., cv. Patriot). The gravitropic response was calcium-dependent. Horizontal placement of roots preloaded with 32P for three minutes resulted in changes in protein phosphorylation of polypeptides of 32 and 35 kD. Calcium depletion resulted in decreased phosphorylation of these phosphoproteins and replenishment of calcium restored the phosphorylation.

  16. Nerve root distribution of deltoid and biceps brachii muscle in cervical spondylotic myelopathy: a potential risk factor for postoperative shoulder muscle weakness after posterior decompression.

    PubMed

    Yonemura, Hiroshi; Kaneko, Kazuo; Taguchi, Toshihiko; Fujimoto, Hideaki; Toyoda, Kouichiro; Kawai, Shinya

    2004-01-01

    To investigate the nerve root distribution of deltoid and biceps brachii muscle, compound muscle action potentials (CMAPs) were recorded intraoperatively following nerve root stimulation in cervical spondylotic myelopathy. A total of 19 upper limbs in 12 patients aged 55-72 years (mean, 65.5 years) with cervical spondylotic myelopathy were examined. CMAPs were recorded from deltoid and biceps brachii muscle following C5 and C6 root stimulation. Although both C5 and C6 roots were innervated for deltoid and biceps brachii muscle in all subjects, the amplitude ratio of CMAPs (C5/C6) differed individually depending on the symptomatic intervertebral levels of the spinal cord. The C5 root predominantly innervated both deltoid and biceps brachii in patients with symptomatic cord lesions at the C4-C5 intervertebral level compared to patients with symptomatic cord lesions at the C5-C6 intervertebral level. Although no patients sustained postoperative radiculopathy in our study, severe weakness and unfavorable recovery are expected when the C5 root in patients with C4-C5 myelopathy is damaged. From the electrophysiological aspect, C4-C5 cord lesions are likely to be a potential risk factor for postoperative shoulder muscle weakness in patients with compressive cervical myelopathy.

  17. Implementation of linear sensory signaling via multiple coordinated mechanisms at central vestibular nerve synapses

    PubMed Central

    McElvain, Lauren E.; Faulstich, Michael; Jeanne, James M.; Moore, Jeffrey D.; du Lac, Sascha

    2015-01-01

    Summary Signal transfer in neural circuits is dynamically modified by the recent history of neuronal activity. Short-term plasticity endows synapses with nonlinear transmission properties, yet synapses in sensory and motor circuits are capable of signaling linearly over a wide range of presynaptic firing rates. How do such synapses achieve rate-invariant transmission despite history-dependent nonlinearities? Here, ultrastructural, biophysical, and computational analyses demonstrate that concerted molecular, anatomical, and physiological refinements are required for central vestibular nerve synapses to linearly transmit rate-coded sensory signals. Vestibular synapses operate in a physiological regime of steady-state depression imposed by tonic firing. Rate-invariant transmission relies on brief presynaptic action potentials that delimit calcium influx, large pools of rapidly mobilized vesicles, multiple low-probability release sites, robust postsynaptic receptor sensitivity, and efficient transmitter clearance. Broadband linear synaptic filtering of head motion signals is thus achieved by coordinately tuned synaptic machinery that maintains physiological operation within inherent cell biological limitations. PMID:25704949

  18. Malignant peripheral nerve sheath tumour (MPNST): the clinical implications of cellular signalling pathways.

    PubMed

    Katz, Daniela; Lazar, Alexander; Lev, Dina

    2009-10-19

    Malignant peripheral nerve sheath tumour (MPNST) is a rare malignancy accounting for 3-10% of all soft tissue sarcomas. Most MPNSTs arise in association with peripheral nerves or deep neurofibromas and may originate from neural crest cells, although the specific cell of origin is uncertain. Approximately half of MPNSTs occur in the setting of neurofibromatosis type 1 (NF1), an autosomal dominant disorder with an incidence of approximately one in 3500 persons; the remainder of MPNSTs develop sporadically. In addition to a variety of clinical manifestations, approximately 8-13% of NF1 patients develop MPNSTs, which are the leading cause of NF1-related mortality. Surgical resection is the mainstay of MPNST clinical management. However, because of invasive growth, propensity to metastasise, and limited sensitivity to chemotherapy and radiation, MPNST has a guarded to poor prognosis. Five-year survival rates of only 20-50% indicate an urgent need for improved therapeutic approaches. Recent work in this field has identified several altered intracellular signal transduction cascades and deregulated tyrosine kinase receptors, posing the possibility of personalised, targeted therapeutics. However, expanded knowledge of MPNST molecular pathobiology will be needed to meaningfully apply such approaches for the benefit of afflicted patients.

  19. Root-Shoot Signaling crosstalk involved in the shoot growth promoting action of rhizospheric humic acids

    PubMed Central

    Olaetxea, Maite; Mora, Verónica; García, Andrés Calderin; Santos, Leandro Azevedo; Baigorri, Roberto; Fuentes, Marta; Garnica, María; Berbara, Ricardo Luis Louro; Zamarreño, Angel Maria; Garcia-Mina, Jose M.

    2016-01-01

    ABSTRACT Numerous studies have shown the ability of humic substances to improve plant development. This action is normally reflected in an enhancement of crop yields and quality. However, the mechanisms responsible for this action of humic substances remain rather unknown. Our studies have shown that the shoot promoting action of sedimentary humic acids is dependent of its ability to increase root hydraulic conductivity through signaling pathways related to ABA, which in turn is affected in roots by humic acids in an IAA-NO dependent way. Furthermore, these studies also indicate that the primary action of humic acids in roots might also be physical, resulting from a transient mild stress caused by humic acids associated with a fouling-cleaning cycle of wall cell pores. Finally the role of alternative signal molecules, such as ROS, and corresponding signaling pathways are also discussed and modeled in the context of the above-mentioned framework. PMID:26966789

  20. Median nerve stimulation modulates extracellular signals in the primary motor area of a macaque monkey.

    PubMed

    Papazachariadis, Odysseas; Dante, Vittorio; Ferraina, Stefano

    2013-08-29

    Aiming to better define the functional influence of somatosensory stimuli on the primary motor cortex (M1) of primates, we investigated changes in extracellular neural activity induced by repetitive median nerve stimulation (MNS). We described neural adaptation and signal integration in both the multiunit activity (MUA) and the local field potential (LFP). To identify integration of initial M1 activity in the MNS response, we tested the correlation between peak amplitude responses and band energy preceding the peaks. Most of the sites studied in the M1 resulted responsive to MNS. MUA response peak amplitude decreased significantly in time in all sites during repetitive MNS, LFP response peak amplitude instead resulted more variable. Similarly, correlation analysis with the initial activity revealed a significant influence when tested using MUA peak amplitude modulation and a less significant correlation when tested using LFP peak amplitude. Our findings improve current knowledge on mechanisms underlying early M1 changes consequent to afferent somatosensory stimuli.

  1. Selective inhibition of extracellular signal-regulated kinases 1/2 blocks nerve growth factor to brain-derived neurotrophic factor signaling and suppresses the development of and reverses already established pain behavior in rats.

    PubMed

    Matsuoka, Y; Yang, J

    2012-03-29

    Brain-derived neurotrophic factor (BDNF) plays a key role in the development of pathological pain. Although it is known that nerve growth factor (NGF) induces BDNF mRNA through extracellular signal-regulated kinases (ERK), whether ERK1/2 or ERK5, two closely related members of the ERK family, mediate this signal is still unclear because classical MEK inhibitors block both pathways. We studied the involvement of ERK-signaling in NGF induction of BDNF in PC12 cells, cultured dorsal root ganglia neurons, and in rats subjected to neuropathic pain models using ERK1/2- and ERK5-specific tools. Selective activation of ERK1/2 upregulated BDNF mRNA in PC12 cells, whereas selective ERK5 activation did not. AZD6244, a potent selective inhibitor of ERK1/2 activation, blocked NGF induction of BDNF mRNA in vitro suggesting that NGF induction of BDNF is mediated by ERK1/2. siRNA experiments indicated that both ERK1 or ERK2 can signal suggesting that both pathways must be blocked to prevent NGF-induced increase in BDNF mRNA. I.p. injection of AZD6244 prevented the development of pain in rats subjected to the chronic constriction injury and reversed already established pain in the spared nerve injury model. Immunohistochemical studies showed decreased phospho-ERK1/2-immunoreactivity in dorsal root ganglia and BDNF immunoreactivity in ipsilateral spinal dorsal horn in the drug-treated rats. Our results suggest the possible use of AZD6244, already in human clinical trials as an anticancer agent, for the treatment of pathological pain.

  2. Clinical validation study to measure the performance of the Nerve Root Sedimentation Sign for the diagnosis of lumbar spinal stenosis.

    PubMed

    Staub, Lukas P; Barz, Thomas; Melloh, Markus; Lord, Sarah J; Chatfield, Mark; Bossuyt, Patrick M

    2011-05-01

    Lumbar spinal stenosis is a common degenerative disorder of the spine in elderly patients that can be effectively treated with decompression surgery in some patients. Radiological findings in the diagnostic work-up of the patients do not always correlate well with clinical symptoms, and guidance about when to proceed to surgery is inconsistent. The recently described Nerve Root Sedimentation Sign in magnetic resonance scans has been shown to discriminate well between selected patients with and without lumbar spinal stenosis, but the performance of this new test, when used in a broad patient population, is not yet known. We describe the design of a single-centre retrospective chart review to assess the clinical validity of the Sedimentation Sign by evaluating its association with health outcomes in patients with suspected lumbar spinal stenosis. The Sedimentation Sign will be cross-classified with decisions for surgery based on existing tests and patient outcomes in follow-up examinations at 24months. The results will be used to estimate: i) how well the Sedimentation Sign can distinguish between patients that do or do not benefit from surgery, and ii) the concordance between the Sedimentation Sign and existing tests to explore its possible value as a triage test. This study design will provide data to estimate the potential benefits and harms of using the Sedimentation Sign to guide surgical decisions. The observed proportion of discordant test results will help inform the design of future randomised controlled trials of the Sedimentation Sign.

  3. Monocyte Traffic, Dorsal Root Ganglion Histopathology, and Loss of Intraepidermal Nerve Fiber Density in SIV Peripheral Neuropathy

    PubMed Central

    Lakritz, Jessica R.; Bodair, Ayman; Shah, Neal; O'Donnell, Ryan; Polydefkis, Michael J.; Miller, Andrew D.; Burdo, Tricia H.

    2016-01-01

    HIV-associated sensory neuropathy remains the most common neurological complication of HIV infection and is characterized by dorsal root ganglion (DRG) inflammation and intraepidermal nerve fiber density (IENFD) loss. Chronic peripheral immune cell activation and accumulation may cause damage to the DRG, but has not been fully investigated yet. By using an SIV-infected, CD8-lymphocyte–depleted rhesus macaque model, we defined immune cells surrounding DRG neurons and their role in DRG pathology, measured cell traffic from the bone marrow to the DRGs using 5-bromo-2-deoxyuridine (BrdU) pulse, and serially measured IENFD. We found an increase in CD68+ and CD163+ macrophages in DRGs of SIV-infected animals. MAC387+ recently recruited monocytes/macrophages were increased, along with BrdU+ cells, in the DRGs of SIV-infected macaques. We demonstrated that 78.1% of all BrdU+ cells in DRGs were also MAC387+. The number of BrdU+ monocytes correlated with severe DRG histopathology, which included neuronophagia, neuronal loss, and Nageotte nodules. These data demonstrate that newly recruited MAC387+BrdU+ macrophages may play a significant role in DRG pathogenesis. IENFD decreased early (day 21), consistent with the development of sensory neuropathy in SIV-infected macaques. Decreased IENFD was associated with elevated BrdU+ cells in the DRG. These data suggest that increased recruitment of macrophages to DRG is associated with severe DRG histopathology and IENFD loss. PMID:25956030

  4. Multi-scale simulations predict responses to non-invasive nerve root stimulation

    NASA Astrophysics Data System (ADS)

    Laakso, Ilkka; Matsumoto, Hideyuki; Hirata, Akimasa; Terao, Yasuo; Hanajima, Ritsuko; Ugawa, Yoshikazu

    2014-10-01

    Objective. Established biophysical neurone models have achieved limited success in reproducing electrophysiological responses to non-invasive stimulation of the human nervous system. This is related to our insufficient knowledge of the induced electric currents inside the human body. Despite the numerous research and clinical applications of non-invasive stimulation, it is still unclear which internal sites are actually affected by it. Approach. We performed multi-scale computer simulations that, by making use of advances in computing power and numerical algorithms, combine a microscopic model of electrical excitation of neurones with a macroscopic electromagnetic model of the realistic whole-body anatomy. Main results. The simulations yield responses consistent with those experimentally recorded following magnetic and electrical motor root stimulation in human subjects, and reproduce the observed amplitudes and latencies for a wide variety of stimulation parameters. Significance. Our findings demonstrate that modern computational techniques can produce detailed predictions about which and where neurones are activated, leading to improved understanding of the physics and basic mechanisms of non-invasive stimulation and enabling potential new applications that make use of improved targeting of stimulation.

  5. Characterization of Thoracic Motor and Sensory Neurons and Spinal Nerve Roots in Canine Degenerative Myelopathy, a Potential Disease Model of Amyotrophic Lateral Sclerosis

    PubMed Central

    Morgan, Brandie R.; Coates, Joan R.; Johnson, Gayle C.; Shelton, G. Diane; Katz, Martin L.

    2014-01-01

    Canine Degenerative Myelopathy (DM) is a progressive adult-onset multisystem degenerative disease with many features in common with amyotrophic lateral sclerosis (ALS). As with some forms of ALS, DM is associated with mutations in superoxide dismutase 1 (SOD1). Clinical signs include general proprioceptive ataxia and spastic upper motor neuron paresis in pelvic limbs, which progress to flaccid tetraplegia and dysphagia. The purpose of this study was to characterize DM as a potential disease model for ALS. We previously reported that intercostal muscle atrophy develops in dogs with advanced stage DM. To determine if other components of the thoracic motor unit (MU) also demonstrated morphological changes consistent with dysfunction, histopathologic and morphometric analyses were conducted on thoracic spinal motor neurons (MN) and dorsal root ganglia (DRG), and in motor and sensory nerve root axons from DM-affected Boxers and Pembroke Welsh Corgis (PWCs). No alterations in MNs, or motor root axons were observed in either breed. However, advanced stage PWCs exhibited significant losses of sensory root axons, and numerous DRG sensory neurons displayed evidence of degeneration. These results indicate that intercostal muscle atrophy in DM is not preceded by physical loss of the motor neurons innervating these muscles, or of their axons. Axonal loss in thoracic sensory roots and sensory nerve death suggest sensory involvement may play an important role in DM disease progression. Further analysis of the mechanisms responsible for these morphological findings would aid in the development of therapeutic intervention for DM and some forms of ALS. PMID:24375814

  6. Effects of mechanostimulation on gravitropism and signal persistence in flax roots.

    PubMed

    John, Susan P; Hasenstein, Karl H

    2011-09-01

    Gravitropism describes curvature of plants in response to gravity or differential acceleration and clinorotation is commonly used to compensate unilateral effect of gravity. We report on experiments that examine the persistence of the gravity signal and separate mechanostimulation from gravistimulation. Flax roots were reoriented (placed horizontally for 5, 10 or 15 min) and clinorotated at a rate of 0.5 to 5 rpm either vertically (parallel to the gravity vector and root axis) or horizontally (perpendicular to the gravity vector and parallel to the root axis). Image sequences showed that horizontal clinorotation did not affect root growth rate (0.81 ± 0.03 mm h-1) but vertical clinorotation reduced root growth by about 7%. The angular velocity (speed of clinorotation) did not affect growth for either direction. However, maximal curvature for vertical clinorotation decreased with increasing rate of rotation and produced straight roots at 5 rpm. In contrast, horizontal clinorotation increased curvature with increasing angular velocity. The point of maximal curvature was used to determine the longevity (memory) of the gravity signal, which lasted about 120 min. The data indicate that mechanostimulation modifies the magnitude of the graviresponse but does not affect memory persistence.

  7. Chronic recording of hand prosthesis control signals via a regenerative peripheral nerve interface in a rhesus macaque

    NASA Astrophysics Data System (ADS)

    Irwin, Z. T.; Schroeder, K. E.; Vu, P. P.; Tat, D. M.; Bullard, A. J.; Woo, S. L.; Sando, I. C.; Urbanchek, M. G.; Cederna, P. S.; Chestek, C. A.

    2016-08-01

    Objective. Loss of even part of the upper limb is a devastating injury. In order to fully restore natural function when lacking sufficient residual musculature, it is necessary to record directly from peripheral nerves. However, current approaches must make trade-offs between signal quality and longevity which limit their clinical potential. To address this issue, we have developed the regenerative peripheral nerve interface (RPNI) and tested its use in non-human primates. Approach. The RPNI consists of a small, autologous partial muscle graft reinnervated by a transected peripheral nerve branch. After reinnervation, the graft acts as a bioamplifier for descending motor commands in the nerve, enabling long-term recording of high signal-to-noise ratio (SNR), functionally-specific electromyographic (EMG) signals. We implanted nine RPNIs on separate branches of the median and radial nerves in two rhesus macaques who were trained to perform cued finger movements. Main results. No adverse events were noted in either monkey, and we recorded normal EMG with high SNR (>8) from the RPNIs for up to 20 months post-implantation. Using RPNI signals recorded during the behavioral task, we were able to classify each monkey’s finger movements as flexion, extension, or rest with >96% accuracy. RPNI signals also enabled functional prosthetic control, allowing the monkeys to perform the same behavioral task equally well with either physical finger movements or RPNI-based movement classifications. Significance. The RPNI signal strength, stability, and longevity demonstrated here represents a promising method for controlling advanced prosthetic limbs and fully restoring natural movement.

  8. Relative effectiveness of electrically- vs mechanically-elicited EMGs in detecting pedicle wall perforation and surgically-induced nerve root damage.

    PubMed

    Kobara, N; Owen, J H; Kostuik, J; Huckell, C; Tooke, S M

    2000-02-01

    Electrical stimulation of a pedicle hole and screw with recording EMGs from the lower extremities has been used as an indicator in detecting perforations of the pedicle. Mechanically-elicited EMGs are reported to be sensitive to mechanical irritation of nerve roots. This study analyzed the sensitivity of the data elicited by two EMG monitoring methods in the presence of a neurologic deficit caused by a malpositioned screw to determine the relative effectiveness of electrically- vs mechanically-elicited EMGs in detecting pedicle wall perforations and nerve root damage in patients undergoing spinal surgery utilizing transpedicular instrumentation. One hundred and four surgeries were monitored using the two EMG methods. Six hundred and fifty-four pedicle holes were prepared and 650 placed pedicle screws were electrically tested. Mechanically-elicited EMGs were monitored from a total of 618 muscles. Electrically-elicited EMGs showed a 62% true-positive rate and a 0.2% false-negative rate in detecting pedicle wall perforations. None of the patients who initially demonstrated abnormal electrically-elicited EMGs demonstrated any post-operative neurologic problems due to an incorrect screw placement. Only one patient who had abnormal mechanically-elicited EMGs during the procedures related to instrumentation developed new L4 radiculopathy immediately post-operatively which was consistent with the level of mechanically-elicited EMGs. Mechanically-elicited EMGs showed a 100% true-positive rate for nerve root irritation and a 3.5% false-negative rate in detecting pedicle wall perforations by malpositioned screw. In conclusion, although mechanically-elicited EMGs were an insensitive technique in detecting a perforation of the pedicle, mechanically-elicited EMGs were more beneficial than electrically-elicited EMGs in detecting the risk of nerve root irritation.

  9. ARL2, ARG1 and PIN3 define a gravity signal transduction pathway in root statocytes.

    PubMed

    Harrison, Benjamin R; Masson, Patrick H

    2008-01-01

    ALTERED RESPONSE TO GRAVITY1 (ARG1) and its paralog ARG1-LIKE2 (ARL2) are J-domain proteins that are required for normal root and hypocotyl gravitropism. In this paper, we show that both ARL2 and ARG1 function in a gravity signal transduction pathway with PIN3, an auxin efflux facilitator that is expressed in the statocytes. In gravi-stimulated roots, PIN3 relocalizes to the lower side of statocytes, a process that is thought to, in part, drive the asymmetrical redistribution of auxin toward the lower flank of the root. We show that ARL2 and ARG1 are required for PIN3 relocalization and asymmetrical distribution of auxin upon gravi-stimulation. ARL2 is expressed specifically in the root statocytes, where it localizes to the plasma membrane. Upon ectopic expression, ARL2 is also found at the cell plate of dividing cells during cytokinesis, an area of intense membrane dynamics. Mutations in ARL2 and ARG1 also result in auxin-related expansion of the root cap columella, consistent with a role for ARL2 and ARG1 in regulating auxin flux through the root tip. Together these data suggest that ARL2 and ARG1 functionally link gravity sensation in the statocytes to auxin redistribution through the root cap.

  10. Ultrasonographic reference values for peripheral nerves and nerve roots in the normal population of children and adolescents: study protocol for an observational-prospective trial

    PubMed Central

    Décard, Bernhard F; Schädelin, Sabine; Grimm, Alexander; Fischer, Dirk; Hafner, Patricia

    2016-01-01

    Background High-resolution ultrasonography is a new and promising technique to evaluate peripheral and spinal nerves. Its validity as a diagnostic tool in neurological diseases has been demonstrated in adults. Up to now no reference values have been published in children and adolescents although this technique would be ideal in this population as it is fast and non-invasive. Methods/design Our aim is to generate ultrasonographic reference values for several peripheral nerves (median, ulnar, radial, tibial, sural, peroneal and tibial nerve) as well as for the spinal nerves C5 and C6 and the vagus nerve in children and adolescents. In an observational prospective study, we will recruit 205 children and adolescents aged between ≥2 and ≤18 years without neuromuscular symptoms/signs and without a history of neuromuscular disease. After the collection of demographic and anthropometric data (height, weight, body mass index, age, gender and handedness) and a neurologic examination, a high-resolution ultrasonography of peripheral and spinal nerves at several anatomic landmarks will be performed. These data will be used to estimate age-dependent percentile curves and to evaluate inter-rater, intrarater and interequipment reliability of the measurements. Ethics and dissemination This study was approved by the local ethics committee (EKNZ 2015-210). The findings from this study will be disseminated through peer-reviewed publications and conference presentations. Trial registration number NCT02570802, pre-results publication. PMID:27940636

  11. Signal Strength Is an Important Determinant of Accuracy of Nerve Fiber Layer Thickness Measurement by Optical Coherence Tomography

    PubMed Central

    Wu, Ziqiang; Huang, Jingjing; Dustin, Laurie; Sadda, Srinivas

    2009-01-01

    Purpose To investigate the effect of signal strength on the measurement of the retinal nerve fiber layer (RNFL) using optical coherence tomography (OCT). Methods Eyes with known or suspected glaucoma or non-glaucomatous optic atrophy were scanned twice within the same visit using Stratus OCT's Fast Nerve Fiber Layer Thickness (FNFLT) protocol. Only those eyes with two high quality scans (signal strengths of at least 5 and different from each other, no error messages, and no obvious segmentation errors) were included in the study. The RNFL thickness measurements from the initial and the repeat scans were compared and then correlated with the differences in signal strength. Subgroup analyses were performed similarly among patients with average RNFL thickness less than 90 microns and those with at least 90 microns. Results Scans with higher signal strengths are associated with greater RNFL thickness measurements if the signal strength is less than 7. Scans with signal strength of at least 7 have higher reproducibility. This is true among all patients as well as subgroups divided on the basis of average RNFL thickness. Additionally, we found that the greater the variability between the initial and repeat scans, the greater the variability in the RNFL thickness measurements. Scans with higher signal strengths have less variability, especially when the optic nerve is relatively healthy. Conclusions When measuring the RNFL thickness with the Stratus OCT, it is important to aim for a signal strength of at least 7. Visual field testing may be more reliable in some patients, especially when the optic nerve is significantly compromised. PMID:19295375

  12. Brassinosteroid signaling directs formative cell divisions and protophloem differentiation in Arabidopsis root meristems.

    PubMed

    Kang, Yeon Hee; Breda, Alice; Hardtke, Christian S

    2017-01-15

    Brassinosteroids (BRs) trigger an intracellular signaling cascade through its receptors BR INSENSITIVE 1 (BRI1), BRI1-LIKE 1 (BRL1) and BRL3. Recent studies suggest that BR-independent inputs related to vascular differentiation, for instance root protophloem development, modulate downstream BR signaling components. Here, we report that protophloem sieve element differentiation is indeed impaired in bri1 brl1 brl3 mutants, although this effect might not be mediated by canonical downstream BR signaling components. We also found that their small meristem size is entirely explained by reduced cell elongation, which is, however, accompanied by supernumerary formative cell divisions in the radial dimension. Thus, reduced cell expansion in conjunction with growth retardation, because of the need to accommodate supernumerary formative divisions, can account for the overall short root phenotype of BR signaling mutants. Tissue-specific re-addition of BRI1 activity partially rescued subsets of these defects through partly cell-autonomous, partly non-cell-autonomous effects. However, protophloem-specific BRI1 expression essentially rescued all major bri1 brl1 brl3 root meristem phenotypes. Our data suggest that BR perception in the protophloem is sufficient to systemically convey BR action in the root meristem context.

  13. Up-regulation of brain-derived neurotrophic factor is regulated by extracellular signal-regulated protein kinase 5 and by nerve growth factor retrograde signaling in colonic afferent neurons in colitis

    PubMed Central

    Yu, Sharon J; Grider, John R; Gulick, Melisa A; Xia, Chun-mei; Shen, Shanwei; Qiao, Li-Ya

    2012-01-01

    Brain-derived neurotrophic factor (BDNF) plays an essential role in sensory neuronal activation in response to visceral inflammation. Here we report that BDNF up-regulation in the primary afferent neurons in the dorsal root ganglia (DRG) in a rat model of colitis is mediated by the activation of endogenous extracellular signal-regulated protein kinases (ERK) 5 and by nerve growth factor (NGF) retrograde signaling. At 7 days of colitis, the expression level of BDNF is increased in conventional neuronal tracing dye Fast Blue labeled primary afferent neurons project to the distal colon. In these neurons, the phosphorylation (activation) level of ERK5 is also increased. In contrast, the level of phospho-ERK1/2 is not changed in the DRG during colitis. Prevention of the ERK5 activation in vivo with an intrathecal application of the MEK inhibitor PD98059 significantly attenuates the colitis-induced increases in BDNF expression in the DRG. Further studies show that BDNF up-regulation in the DRG is triggered by NGF retrograde signaling which also involves activation of the MEK/ERK pathways. Application of exogenous NGF exclusively to the compartment containing DRG nerve terminals in an ex vivo ganglia-nerve preparation has markedly increased the BDNF expression level in the DRG neuronal cell body that is placed in a different compartment; this BDNF elevation is attenuated by U0126, PD98059 and a specific ERK5 inhibitor BIX02188. These results demonstrate the mechanisms and pathways by which BDNF expression is elevated in primary sensory neurons following visceral inflammation that is mediated by increased activity of ERK5 and is likely to be triggered by the elevated NGF level in the inflamed viscera. PMID:22921460

  14. Selective decrease of small sensory neurons in lumbar dorsal root ganglia labeled with horseradish peroxidase after ND:YAG laser irradiation of the tibial nerve in the rat

    SciTech Connect

    Wesselmann, U.; Lin, S.F.; Rymer, W.Z. )

    1991-02-01

    Recent electrophysiological evidence indicates that Q-switched Nd:YAG laser irradiation might have selective effects on neural impulse transmission in small slow conducting sensory nerve fibers as compared to large diameter afferents. In an attempt to clarify the ultimate fate of sensory neurons after laser application to their peripheral axons, we have used horseradish peroxidase (HRP) as a cell marker to retrogradely label sensory neurons innervating the distal hindlimb in the rat. Pulsed Nd:YAG laser light was applied to the tibial nerve at pulse energies of 70 or 80 mJ/pulse for 5 min in experimental rats. Seven days later HRP was applied to the left (laser-treated) and to the contralateral (untreated) tibial nerve proximal to the site of laser irradiation. In control animals the numbers of HRP-labeled dorsal root ganglion cells were not significantly different between the right and the left side. In contrast, after previous laser irradiation labeling was always less on the laser-treated side (2183 +/- 513 cells, mean +/- SEM) as compared to the untreated side (3937 +/- 225). Analysis of the dimensions of labeled cells suggested that the reduction of labeled cells on the laser-treated side was mainly due to a deficit in small sensory neurons. Since the conduction velocity of nerve fibers is related to the size of their somata, our histological data imply that laser light selectively affects retrograde transport mechanisms for HRP in slow conducting sensory nerve fibers.

  15. Multilayered Organization of Jasmonate Signalling in the Regulation of Root Growth

    PubMed Central

    Gasperini, Debora; Chételat, Aurore; Acosta, Ivan F.; Goossens, Jonas; Pauwels, Laurens; Goossens, Alain; Dreos, René; Alfonso, Esteban; Farmer, Edward E.

    2015-01-01

    Physical damage can strongly affect plant growth, reducing the biomass of developing organs situated at a distance from wounds. These effects, previously studied in leaves, require the activation of jasmonate (JA) signalling. Using a novel assay involving repetitive cotyledon wounding in Arabidopsis seedlings, we uncovered a function of JA in suppressing cell division and elongation in roots. Regulatory JA signalling components were then manipulated to delineate their relative impacts on root growth. The new transcription factor mutant myc2-322B was isolated. In vitro transcription assays and whole-plant approaches revealed that myc2-322B is a dosage-dependent gain-of-function mutant that can amplify JA growth responses. Moreover, myc2-322B displayed extreme hypersensitivity to JA that totally suppressed root elongation. The mutation weakly reduced root growth in undamaged plants but, when the upstream negative regulator NINJA was genetically removed, myc2-322B powerfully repressed root growth through its effects on cell division and cell elongation. Furthermore, in a JA-deficient mutant background, ninja1 myc2-322B still repressed root elongation, indicating that it is possible to generate JA-responses in the absence of JA. We show that NINJA forms a broadly expressed regulatory layer that is required to inhibit JA signalling in the apex of roots grown under basal conditions. By contrast, MYC2, MYC3 and MYC4 displayed cell layer-specific localisations and MYC3 and MYC4 were expressed in mutually exclusive regions. In nature, growing roots are likely subjected to constant mechanical stress during soil penetration that could lead to JA production and subsequent detrimental effects on growth. Our data reveal how distinct negative regulatory layers, including both NINJA-dependent and -independent mechanisms, restrain JA responses to allow normal root growth. Mechanistic insights from this work underline the importance of mapping JA signalling components to specific

  16. Different functional reorganization of motor cortex after transfer of the contralateral C7 to different recipient nerves in young rats with total brachial plexus root avulsion.

    PubMed

    Pan, Feng; Wei, Hai-feng; Chen, Liang; Gu, Yu-dong

    2012-12-07

    Clinically, contralateral C7 transfer is used for nerve reconstruction in brachial plexus injuries. Postoperatively, synchronous motions at the donor limb are noteworthy. This study studied if different recipient nerves influenced transhemispheric functional reorganization of motor cortex after this procedure. 90 young rats with total root avulsion of the brachial plexus were divided into groups 1-3 of contralateral C7 transfer to anterior division of the upper trunk, to both the musculocutaneous and median nerves, and to the median nerve, respectively. After reinnervation of target muscles, number of sites for forelimb representations in bilateral motor cortices was determined by intracortical microstimulation at 1.5, 3, 6, 9, and 12 months postoperatively. At nine months, transhemispheric reorganization of nerves neurotized by contralateral C7 was fulfilled in four of six rats in group 1, one of six in group 2 and none in group 3, respectively; at 12 months, that was fulfilled in five of six in group 1, four of six in groups 2 and 3, respectively. Logistic regression analysis showed that rate of fulfilled transhemispheric reorganization in group 1 was 12.19 times that in group 3 (95% CI 0.006-0.651, p=0.032). At 12 months, number of sites for hindlimb representations which had encroached upon original forelimb representations on the uninjured side was statistically more in group 3 than in group 2 (t=9.5, p<0.0001). It is concluded that contralateral C7 transfer to upper trunk or to both the musculocutaneous and median nerves induces faster transhemispheric functional reorganization of motor cortex than that to median nerve alone in rats.

  17. Leptin signaling in the nucleus tractus solitarii increases sympathetic nerve activity to the kidney.

    PubMed

    Mark, Allyn L; Agassandian, Khristofor; Morgan, Donald A; Liu, Xuebo; Cassell, Martin D; Rahmouni, Kamal

    2009-02-01

    The hypothalamic arcuate nucleus was initially regarded as the principal site of leptin action, but there is increasing evidence for functional leptin receptors in extrahypothalamic sites, including the nucleus tractus solitarii (NTS). We demonstrated previously that arcuate injection of leptin increases sympathetic nerve activity (SNA) to brown adipose tissue and kidney. In this study, we tested the hypothesis that leptin signaling in the NTS affects sympathetic neural outflow. Using a stereotaxic device in anesthetized rats, we microinjected leptin (0.25 to 1.00 microg) or saline into the NTS while recording SNA to kidney and brown adipose tissue. Microinjection of leptin into the commissural and medial subnuclei of the caudal NTS at the level of the area postrema in Sprague-Dawley rats produced a dose-related increase in renal SNA (+112+/-15% with leptin 1 microg; n=7; P<0.001) but did not increase SNA to brown adipose tissue (-15+/-12%; P value not significant). This effect depended on intact functional leptin receptors, because it was not observed in Zucker obese rats that have a missense mutation in the leptin receptor. Rostral NTS injection of leptin failed to increase SNA, indicating that leptin signaling in the NTS is probably confined to the caudal NTS at the level of the area postrema. In summary, this study demonstrates that leptin signaling in the caudal NTS increases SNA to the kidney but not to the brown adipose tissue. The study strengthens the concept of a distributed brain network of leptin action and demonstrates that these distributed brain sites can mediate contrasting sympathetic responses to leptin.

  18. The impact of spinal cord nerve roots and denticulate ligaments on cerebrospinal fluid dynamics in the cervical spine.

    PubMed

    Heidari Pahlavian, Soroush; Yiallourou, Theresia; Tubbs, R Shane; Bunck, Alexander C; Loth, Francis; Goodin, Mark; Raisee, Mehrdad; Martin, Bryn A

    2014-01-01

    Cerebrospinal fluid (CSF) dynamics in the spinal subarachnoid space (SSS) have been thought to play an important pathophysiological role in syringomyelia, Chiari I malformation (CM), and a role in intrathecal drug delivery. Yet, the impact that fine anatomical structures, including nerve roots and denticulate ligaments (NRDL), have on SSS CSF dynamics is not clear. In the present study we assessed the impact of NRDL on CSF dynamics in the cervical SSS. The 3D geometry of the cervical SSS was reconstructed based on manual segmentation of MRI images of a healthy volunteer and a patient with CM. Idealized NRDL were designed and added to each of the geometries based on in vivo measurments in the literature and confirmation by a neuroanatomist. CFD simulations were performed for the healthy and patient case with and without NRDL included. Our results showed that the NRDL had an important impact on CSF dynamics in terms of velocity field and flow patterns. However, pressure distribution was not altered greatly although the NRDL cases required a larger pressure gradient to maintain the same flow. Also, the NRDL did not alter CSF dynamics to a great degree in the SSS from the foramen magnum to the C1 level for the healthy subject and CM patient with mild tonsillar herniation (∼ 6 mm). Overall, the NRDL increased fluid mixing phenomena and resulted in a more complex flow field. Comparison of the streamlines of CSF flow revealed that the presence of NRDL lead to the formation of vortical structures and remarkably increased the local mixing of the CSF throughout the SSS.

  19. The Impact of Spinal Cord Nerve Roots and Denticulate Ligaments on Cerebrospinal Fluid Dynamics in the Cervical Spine

    PubMed Central

    Heidari Pahlavian, Soroush; Yiallourou, Theresia; Tubbs, R. Shane; Bunck, Alexander C.; Loth, Francis; Goodin, Mark; Raisee, Mehrdad; Martin, Bryn A.

    2014-01-01

    Cerebrospinal fluid (CSF) dynamics in the spinal subarachnoid space (SSS) have been thought to play an important pathophysiological role in syringomyelia, Chiari I malformation (CM), and a role in intrathecal drug delivery. Yet, the impact that fine anatomical structures, including nerve roots and denticulate ligaments (NRDL), have on SSS CSF dynamics is not clear. In the present study we assessed the impact of NRDL on CSF dynamics in the cervical SSS. The 3D geometry of the cervical SSS was reconstructed based on manual segmentation of MRI images of a healthy volunteer and a patient with CM. Idealized NRDL were designed and added to each of the geometries based on in vivo measurments in the literature and confirmation by a neuroanatomist. CFD simulations were performed for the healthy and patient case with and without NRDL included. Our results showed that the NRDL had an important impact on CSF dynamics in terms of velocity field and flow patterns. However, pressure distribution was not altered greatly although the NRDL cases required a larger pressure gradient to maintain the same flow. Also, the NRDL did not alter CSF dynamics to a great degree in the SSS from the foramen magnum to the C1 level for the healthy subject and CM patient with mild tonsillar herniation (∼6 mm). Overall, the NRDL increased fluid mixing phenomena and resulted in a more complex flow field. Comparison of the streamlines of CSF flow revealed that the presence of NRDL lead to the formation of vortical structures and remarkably increased the local mixing of the CSF throughout the SSS. PMID:24710111

  20. [Exploration Research of Treatment Effect Improvement of Transcutaneous Electrical Nerve Stimulation Using Parameter-changing Chaotic Signal].

    PubMed

    Zheng, Jincun; Zhang, Hui; Qin, Binyi; Wang, Hai; Nie, Guochao; Chen, Tiejun

    2015-10-01

    This article presents a transcutaneous electric stimulator that is based on chaotic signal. Firstly, we in the study used the MATLAB platform in the PC to generate chaotic signal through the chaos equation, and then we transferred the signal out by data acquisition equipment of USB-6251 manufactured by NI Company. In order to obtain high-power signal for transcutaneous electric stimulator, we used the chip of LM3886 to amplify the signal. Finally, we used the power-amplified chaotic signal to stimulate the internal nerve of human through the electrodes fixed on the skin. We obtained different stimulation effects of transcutaneous electric stimulator by changing the parameters of chaotic model. The preliminary test showed that the randomness of chaotic signals improved the applicability of electrical stimulation and the rules of chaos ensured that the stimulation was comfort. The method reported in this paper provides a new way for the design of transcutaneous electric stimulator.

  1. Cyclic GMP is involved in auxin signalling during Arabidopsis root growth and development.

    PubMed

    Nan, Wenbin; Wang, Xiaomin; Yang, Lei; Hu, Yanfeng; Wei, Yuantao; Liang, Xiaolei; Mao, Lina; Bi, Yurong

    2014-04-01

    The second messenger cyclic guanosine 3',5'-monophosphate (cGMP) plays an important role in plant development and responses to stress. Recent studies indicated that cGMP is a secondary signal generated in response to auxin stimulation. cGMP also mediates auxin-induced adventitious root formation in mung bean and gravitropic bending in soybean. Nonetheless, the mechanism of the participation of cGMP in auxin signalling to affect these growth and developmental processes is largely unknown. In this report we provide evidence that indole-3-acetic acid (IAA) induces cGMP accumulation in Arabidopsis roots through modulation of the guanylate cyclase activity. Application of 8-bromo-cGMP (a cell-permeable cGMP derivative) increases auxin-dependent lateral root formation, root hair development, primary root growth, and gene expression. In contrast, inhibitors of endogenous cGMP synthesis block these processes induced by auxin. Data also showed that 8-bromo-cGMP enhances auxin-induced degradation of Aux/IAA protein modulated by the SCF(TIR1) ubiquitin-proteasome pathway. Furthermore, it was found that 8-bromo-cGMP is unable to directly influence the auxin-dependent TIR1-Aux/IAA interaction as evidenced by pull-down and yeast two-hybrid assays. In addition, we provide evidence for cGMP-mediated modulation of auxin signalling through cGMP-dependent protein kinase (PKG). Our results suggest that cGMP acts as a mediator to participate in auxin signalling and may govern this process by PKG activity via its influence on auxin-regulated gene expression and auxin/IAA degradation.

  2. Polarity reversal of the optical rotation signals with change in direction of impulse conduction along the lobster nerve.

    PubMed Central

    Watanabe, A

    1993-01-01

    1. The optical rotation signal of nerve associated with excitation was recorded from peripheral nerve taken from a walking leg of a spiny lobster and its properties were analysed. 2. The polarity of the optical rotation signal was reversed when the site of stimulation was changed with reference to the site of optical recording, so that the direction of impulse conduction was reversed, in most of the preparations. 3. Apart from the main response, which is associated with the conducted impulse, a pre-response was found to exist, which manifested itself on anodic stimulation, in a tetrodotoxin-treated nerve, or during the refractory period of the nerve, when the site of stimulation was close to the site of optical recording. The polarity of the pre-response was also reversed when the site of stimulation was changed with reference to the site of optical recording. 4. When the nerve was inclined from the horizontal level, so that the angle of incidence of light to the nerve was changed, the main response changed its amplitude and sometimes its polarity, whereas the pre-response remained practically unchanged. Thus the dependence on the angle of incidence was different between the pre-response and the main response. 5. It is suggested that the dependence of amplitude and polarity of the main response on the angle of incidence of light cannot be explained by the change in molecular axes of the membrane macromolecules, but can only be explained by their conformational change; and therefore the main response can be used as a monitor for the molecular conformation. PMID:8410706

  3. Effects of Myoga on Memory and Synaptic Plasticity by Regulating Nerve Growth Factor-Mediated Signaling.

    PubMed

    Kim, Hyo Geun; Lim, Soonmin; Hong, Jongki; Kim, Ae-Jung; Oh, Myung Sook

    2016-02-01

    The flower bud of Zingiber mioga Roscoe, known as 'myoga' or Japanese ginger, has a pungent aroma and is commonly consumed as a spice, with pickles, or as a health supplement in Eastern Asia. Here, we evaluated the activity of myoga in the brain, focusing especially on nerve growth factor (NGF), which is believed to mediate synaptic plasticity, supporting learning and memory. In a rat primary hippocampal astrocyte culture system, treatment with myoga extract for 24 h significantly stimulated the production of NGF. In mice administered myoga extract for 14 days, 200 and 400 mg/kg/day treatment resulted in increased NGF levels in the hippocampus. Myoga extract treatment also regulated the phosphorylation of extracellular signal-regulated kinases and cAMP response element-binding protein in the mouse hippocampus, leading to increased synaptic plasticity. In addition, it significantly increased novel object recognition time and spontaneous alternation, indicating improvement in learning and memory. These results suggest that myoga helps regulate NGF and synaptic plasticity, increasing memory ability.

  4. Nerve signaling regulates basal keratinocyte proliferation in the blastema apical epithelial cap in the axolotl (Ambystoma mexicanum).

    PubMed

    Satoh, Akira; Bryant, Susan V; Gardiner, David M

    2012-06-15

    The ability of adult vertebrates to repair tissue damage is widespread and impressive; however, the ability to regenerate structurally complex organs such as the limb is limited largely to the salamanders. The fact that most of the tissues of the limb can regenerate has led investigators to question and identify the barriers to organ regeneration. From studies in the salamander, it is known that one of the earliest steps required for successful regeneration involves signaling between nerves and the wound epithelium/apical epithelial cap (AEC). In this study we confirm an earlier report that the keratinocytes of the AEC acquire their function coincident with exiting the cell cycle. We have discovered that this unique, coordinated behavior is regulated by nerve signaling and is associated with the presence of gap junctions between the basal keratinocytes of the AEC. Disruption of nerve signaling results in a loss of gap junction protein, the reentry of the cells into the cell cycle, and regenerative failure. Finally, coordinated exit from the cell cycle appears to be a conserved behavior of populations of cells that function as signaling centers during both development and regeneration.

  5. Selenite-induced hormonal and signalling mechanisms during root growth of Arabidopsis thaliana L.

    PubMed

    Lehotai, Nóra; Kolbert, Zsuzsanna; Peto, Andrea; Feigl, Gábor; Ördög, Attila; Kumar, Devanand; Tari, Irma; Erdei, László

    2012-09-01

    Selenium excess can cause toxicity symptoms, e.g. root growth inhibition in non-hyperaccumulator plants such as Arabidopsis. Selenite-induced hormonal and signalling mechanisms in the course of development are poorly understood; therefore this study set out to investigate the possible hormonal and signalling processes using transgenic and mutant Arabidopsis plants. Significant alterations were observed in the root architecture of the selenite-treated plants, due to the loss of cell viability in the root apex. During mild selenite excess, the plants showed symptoms of the morphogenic response: primary root (PR) shortening and increased initiation of laterals, ensuring better nutrient and water uptake and stress acclimation. As well as lower meristem cell activity, the second reason for the Se-induced growth hindrance is the hormonal imbalance, since the in situ expression of the auxin-responsive DR5::GUS, and consequently the auxin levels, significantly decreased, while that of the cytokinin-inducible ARR5::GUS and the ethylene biosynthetic ACS8::GUS increased. It is assumed that auxin and ethylene might positively regulate selenium tolerance, since reduced levels of them resulted in sensitivity. Moreover, high cytokinin levels caused notable selenite tolerance. During early seedling development, nitric oxide (NO) contents decreased but hydrogen peroxide levels increased reflecting the antagonism between the two signal molecules during Se excess. High levels of NO in gsnor1-3, lead to selenite tolerance, while low NO production in nia1nia2 resulted in selenite sensitivity. Consequently, NO derived from the root nitrate reductase activity is responsible for the large-scale selenite tolerance in Arabidopsis.

  6. A temporal variation in nonneuronal protein synthesis in dorsal root ganglia and nerve and its significance to studies of axonal transport

    SciTech Connect

    Snyder, R.E.; O'Brien, D.W.; Nihei, T.

    1984-03-01

    Protein synthesis and fast axonal transport were studied in vitro using dorsal root ganglia (DRG)-sciatic nerve preparations from the amphibian Xenopus laevis. It was observed that the rate of incorporation of (/sup 3/H)leucine into protein in DRG and isolated segments of nerve began to increase 9 to 11 h after killing the animal, attaining at 13 to 17 h a maximum of 5- to 10-times preincrease (less than 9 h) values. At the same time as an increase in the rate of incorporation began, synthesis commenced in DRG and nerve exposed to cycloheximide (125 micrograms/ml). Whereas cycloheximide reduced fast axonal transport to 1 to 3% of control values in preparations maintained 20 to 24 h in vitro, cycloheximide reduced incorporation in DRG to only 80% of control values. N-terminal labeling studies showed that both the increased incorporation and cycloheximide-insensitive incorporation resulted from protein synthesis. Autoradiographic and incorporation studies indicated that nonneuronal cells situated in the ganglion capsule and perineural sheath of the nerve were responsible for both the increased incorporation and cycloheximide-insensitive synthesis. The findings have implications for the study of axonal transport.

  7. Root signalling and modulation of stomatal closure in flooded citrus seedlings.

    PubMed

    Rodríguez-Gamir, Juan; Ancillo, Gema; González-Mas, M Carmen; Primo-Millo, Eduardo; Iglesias, Domingo J; Forner-Giner, M Angeles

    2011-06-01

    In this work, we studied the sequence of responses induced by flooding in citrus plants, with the aim of identifying the signals that lead to stomatal closure. One-year-old seedlings of Carrizo citrange, grown in sand under greenhouse conditions, were waterlogged for 35 d and compared with normally watered well-drained plants. Significant decreases in stomatal conductance and transpiration were detected between flooded and control seedlings from a week after the beginning of the experiment. However ABA concentration in leaves only started to increase after three weeks of flooding, suggesting that stomata closed in the absence of a rise in foliar ABA. Therefore, stomatal closure in waterlogged seedlings does not appear to be induced by ABA, at least during the early stages of flood-stress. The low levels of ABA detected in roots and xylem sap from flooded seedlings indicated that it is very unlikely that the ABA increase in the leaves of these plants is due to ABA translocation from roots to shoots. We propose that ABA is produced in old leaves and transported to younger leaves. Flooding had no effect on water potential or the relative water content of leaves. Soil flooding reduced root hydraulic conductance in citrus seedlings. This effect was already evident after a week of waterlogging, and at the end of the experiment, flood-stressed seedlings reached values of root hydraulic conductance below 12% of that of control plants. This reduction was related to down-regulation of the expression of PIP aquaporins. In addition, whole plant transpiration was reduced by 56% after 35 d under flooding conditions. Flood-stress also decreased the pH of sap extracted from citrus roots. Evidence is presented suggesting that acidosis induced by anoxic stress in roots causes gating of aquaporins, thereby decreasing hydraulic conductance. Additionally, stomatal closure finely balances-out low pH-mediated losses of root hydraulic conductance therefore maintaining stable leaf

  8. AtrbohD and AtrbohF positively regulate abscisic acid-inhibited primary root growth by affecting Ca2+ signalling and auxin response of roots in Arabidopsis.

    PubMed

    Jiao, Yiheng; Sun, Lirong; Song, Yalin; Wang, Limin; Liu, Liping; Zhang, Liyue; Liu, Bo; Li, Ning; Miao, Chen; Hao, Fushun

    2013-11-01

    Reactive oxygen species (ROS) originating from the NADPH oxidases AtrbohD and AtrbohF play an important role in abscisic acid (ABA)-inhibited primary root growth in Arabidopsis. However, the mechanisms underlying this process remain elusive. In this study, the double mutant atrbohD1/F1 and atrbohD2/F2, in which both AtrbohD and AtrbohF were disrupted, were less sensitive to ABA suppression of root cell elongation than wild-type (WT) plants. Furthermore, the double mutants showed impaired ABA responses in roots, including ROS generation, cytosolic Ca(2+) increases, and activation of plasma membrane Ca(2+)-permeable channels compared with WT. Exogenous H2O2 can activate the Ca(2+) currents in roots of atrbohD1/F1. In addition, exogenous application of the auxin transport inhibitor naphthylphthalamic acid effectively promoted ABA inhibition of root growth of the mutants relative to that of WT. The ABA-induced decreases in auxin sensitivity of the root tips were more pronounced in WT than in atrbohD1/F1. These findings suggest that both AtrbohD and AtrbohF are essential for ABA-promoted ROS production in roots. ROS activate Ca(2+) signalling and reduce auxin sensitivity of roots, thus positively regulating ABA-inhibited primary root growth in Arabidopsis.

  9. Tomato susceptibility to root-knot nematodes requires an intact jasmonic acid signaling pathway.

    PubMed

    Bhattarai, Kishor K; Xie, Qi-Guang; Mantelin, Sophie; Bishnoi, Usha; Girke, Thomas; Navarre, Duroy A; Kaloshian, Isgouhi

    2008-09-01

    Responses of resistant (Mi-1/Mi-1) and susceptible (mi-1/ mi-1) tomato (Solanum lycopersicum) to root-knot nematodes (RKNs; Meloidogyne spp.) infection were monitored using cDNA microarrays, and the roles of salicylic acid (SA) and jasmonic acid (JA) defense signaling were evaluated in these interactions. Array analysis was used to compare transcript profiles in incompatible and compatible interactions of tomato roots 24 h after RKN infestation. The jai1 and def1 tomato mutant, altered in JA signaling, and tomato transgenic line NahG, altered in SA signaling, in the presence or absence of the RKN resistance gene Mi-1, were evaluated. The array analysis identified 1,497 and 750 genes differentially regulated in the incompatible and compatible interactions, respectively. Of the differentially regulated genes, 37% were specific to the incompatible interactions. NahG affected neither Mi-1 resistance nor basal defenses to RKNs. However, jai1 reduced tomato susceptibility to RKNs while not affecting Mi-1 resistance. In contrast, the def1 mutant did not affect RKN susceptibility. These results indicate that JA-dependent signaling does not play a role in Mi-1-mediated defense; however, an intact JA signaling pathway is required for tomato susceptibility to RKNs. In addition, low levels of SA might be sufficient for basal and Mi-1 resistance to RKNs.

  10. Characterization of thoracic motor and sensory neurons and spinal nerve roots in canine degenerative myelopathy, a potential disease model of amyotrophic lateral sclerosis.

    PubMed

    Morgan, Brandie R; Coates, Joan R; Johnson, Gayle C; Shelton, G Diane; Katz, Martin L

    2014-04-01

    Canine degenerative myelopathy (DM) is a progressive, adult-onset, multisystem degenerative disease with many features in common with amyotrophic lateral sclerosis (ALS). As with some forms of ALS, DM is associated with mutations in superoxide dismutase 1 (SOD1). Clinical signs include general proprioceptive ataxia and spastic upper motor neuron paresis in pelvic limbs, which progress to flaccid tetraplegia and dysphagia. The purpose of this study was to characterize DM as a potential disease model for ALS. We previously reported that intercostal muscle atrophy develops in dogs with advanced-stage DM. To determine whether other components of the thoracic motor unit (MU) also demonstrated morphological changes consistent with dysfunction, histopathologic and morphometric analyses were conducted on thoracic spinal motor neurons (MNs) and dorsal root ganglia (DRG) and in motor and sensory nerve root axons from DM-affected boxers and Pembroke Welsh corgis (PWCs). No alterations in MNs or motor root axons were observed in either breed. However, advanced-stage PWCs exhibited significant losses of sensory root axons, and numerous DRG sensory neurons displayed evidence of degeneration. These results indicate that intercostal muscle atrophy in DM is not preceded by physical loss of the motor neurons innervating these muscles, nor of their axons. Axonal loss in thoracic sensory roots and sensory neuron death suggest that sensory involvement may play an important role in DM disease progression. Further analysis of the mechanisms responsible for these morphological findings would aid in the development of therapeutic intervention for DM and some forms of ALS.

  11. Flavonoids and strigolactones in root exudates as signals in symbiotic and pathogenic plant-fungus interactions.

    PubMed

    Steinkellner, Siegrid; Lendzemo, Venasius; Langer, Ingrid; Schweiger, Peter; Khaosaad, Thanasan; Toussaint, Jean-Patrick; Vierheilig, Horst

    2007-07-05

    Secondary plant compounds are important signals in several symbiotic and pathogenic plant-microbe interactions. The present review is limited to two groups of secondary plant compounds, flavonoids and strigolactones, which have been reported in root exudates. Data on flavonoids as signaling compounds are available from several symbiotic and pathogenic plant-microbe interactions, whereas only recently initial data on the role of strigolactones as plant signals in the arbuscular mycorrhizal symbiosis have been reported. Data from other plant-microbe interactions and strigolactones are not available yet. In the present article we are focusing on flavonoids in plant-fungal interactions such as the arbuscular mycorrhizal (AM) association and the signaling between different Fusarium species and plants. Moreover the role of strigolactones in the AM association is discussed and new data on the effect of strigolactones on fungi, apart from arbuscular mycorrhizal fungi (AMF), are provided.

  12. AtNIGT1/HRS1 integrates nitrate and phosphate signals at the Arabidopsis root tip

    PubMed Central

    Medici, Anna; Marshall-Colon, Amy; Ronzier, Elsa; Szponarski, Wojciech; Wang, Rongchen; Gojon, Alain; Crawford, Nigel M; Ruffel, Sandrine; Coruzzi, Gloria M; Krouk, Gabriel

    2015-01-01

    Nitrogen and phosphorus are among the most widely used fertilizers worldwide. Nitrate (NO3−) and phosphate (PO43−) are also signaling molecules whose respective transduction pathways are being intensively studied. However, plants are continuously challenged with combined nutritional deficiencies, yet very little is known about how these signaling pathways are integrated. Here we report the identification of a highly NO3−-inducible NRT1.1-controlled GARP transcription factor, HRS1, document its genome-wide transcriptional targets, and validate its cis-regulatory-elements. We demonstrate that this transcription factor and a close homolog repress primary root growth in response to P deficiency conditions, but only when NO3− is present. This system defines a molecular logic gate integrating P and N signals. We propose that NO3− and P signaling converge via double transcriptional and post-transcriptional control of the same protein, HRS1 PMID:25723764

  13. Strigolactones: Chemical Signals for Fungal Symbionts and Parasitic Weeds in Plant Roots

    PubMed Central

    AKIYAMA, KOHKI; HAYASHI, HIDEO

    2006-01-01

    • Aims Arbuscular mycorrhizae are formed between >80 % of land plants and arbuscular mycorrhizal (AM) fungi. This Botanical Briefing highlights the chemical identification of strigolactones as a host-recognition signal for AM fungi, and their role in the establishment of arbuscular mycorrhizae as well as in the seed germination of parasitic weeds. • Scope Hyphal branching has long been described as the first morphological event in host recognition by AM fungi during the pre-infection stages. Host roots release signalling molecules called ‘branching factors’ that induce extensive hyphal branching in AM fungi. Strigolactones exuded from host roots have recently been identified as an inducer of hyphal branching in AM fungi. Strigolactones are a group of sesquiterpenes, previously isolated as seed germination stimulants for the parasitic weeds Striga and Orobanche. Parasitic weeds might find their potential hosts by detecting strigolactones, which are released from plant roots upon phosphate deficiency in communication with AM fungi. In addition to acting as a signalling molecule, strigolactones might stimulate the production of fungal symbiotic signals called ‘Myc factors’ in AM fungi. • Conclusions Isolation and identification of plant symbiotic signals open up new ways for studying the molecular basis of plant–AM-fungus interactions. This discovery provides a clear answer to a long-standing question in parasitic plant biology: what is the natural role for germination stimulants? It could also provide a new strategy for the management and control of beneficial fungal symbionts and of devastating parasitic weeds in agriculture and natural ecosystems. PMID:16574693

  14. Action potential broadening and frequency-dependent facilitation of calcium signals in pituitary nerve terminals.

    PubMed

    Jackson, M B; Konnerth, A; Augustine, G J

    1991-01-15

    Hormone release from nerve terminals in the neurohypophysis is a sensitive function of action potential frequency. We have investigated the cellular mechanisms responsible for this frequency-dependent facilitation by combining patch clamp and fluorimetric Ca2+ measurements in single neurosecretory terminals in thin slices of the rat posterior pituitary. In these terminals both action potential-induced changes in the intracellular Ca2+ concentration ([Ca2+]i) and action potential duration were enhanced by high-frequency stimuli, all with a frequency dependence similar to that of hormone release. Furthermore, brief voltage clamp pulses inactivated a K+ current with a very similar frequency dependence. These results support a model for frequency-dependent facilitation in which the inactivation of a K+ current broadens action potentials, leading to an enhancement of [Ca2+]i signals. Further experiments tested for a causal relationship between action potential broadening and facilitation of [Ca2+]i changes. First, increasing the duration of depolarization, either by broadening action potentials with the K(+)-channel blocker tetraethylammonium or by applying longer depolarizing voltage clamp steps, increased [Ca2+]i changes. Second, eliminating frequency-dependent changes in duration, by voltage clamping the terminal with constant duration pulses, substantially reduced the frequency-dependent enhancement of [Ca2+]i changes. These results indicate that action potential broadening contributes to frequency-dependent facilitation of [Ca2+]i changes. However, the small residual frequency dependence of [Ca2+]i changes seen with constant duration stimulation suggests that a second process, distinct from action potential broadening, also contributes to facilitation. These two frequency-dependent mechanisms may also contribute to activity-dependent plasticity in synaptic terminals.

  15. Jasmonate signaling is activated in the very early stages of iron deficiency responses in rice roots.

    PubMed

    Kobayashi, Takanori; Itai, Reiko Nakanishi; Senoura, Takeshi; Oikawa, Takaya; Ishimaru, Yasuhiro; Ueda, Minoru; Nakanishi, Hiromi; Nishizawa, Naoko K

    2016-07-01

    Under low iron availability, plants induce the expression of various genes involved in iron uptake and translocation at the transcriptional level. This iron deficiency response is affected by various plant hormones, but the roles of jasmonates in this response are not well-known. We investigated the involvement of jasmonates in rice iron deficiency responses. High rates of jasmonate-inducible genes were induced during the very early stages of iron deficiency treatment in rice roots. Many jasmonate-inducible genes were also negatively regulated by the ubiquitin ligases OsHRZ1 and OsHRZ2 and positively regulated by the transcription factor IDEF1. Ten out of 35 genes involved in jasmonate biosynthesis and signaling were rapidly induced at 3 h of iron deficiency treatment, and this induction preceded that of known iron deficiency-inducible genes involved in iron uptake and translocation. Twelve genes involved in jasmonate biosynthesis and signaling were also upregulated in HRZ-knockdown roots. Endogenous concentrations of jasmonic acid and jasmonoyl isoleucine tended to be rapidly increased in roots in response to iron deficiency treatment, whereas these concentrations were higher in HRZ-knockdown roots under iron-sufficient conditions. Analysis of the jasmonate-deficient cpm2 mutant revealed that jasmonates repress the expression of many iron deficiency-inducible genes involved in iron uptake and translocation under iron sufficiency, but this repression is partly canceled under an early stage of iron deficiency. These results indicate that jasmonate signaling is activated during the very early stages of iron deficiency, which is partly regulated by IDEF1 and OsHRZs.

  16. The kinetics of root gravitropism in PIN mutants suggest redundancy in the signal transduction pathway

    NASA Astrophysics Data System (ADS)

    Wolverton, Chris

    plays a role in efflux to the columella. Pin4 mutants showed no deficiencies in gravitropism, in fact responding at a greater rate than wild-type roots over the first hour (22 deg h-1 ). PIN7 has been localized to the vascular tissue of the elongation zone and to the central columella. Like pin4 mutants, pin7 mutants did not show a significantly reduced gravitropic response relative to wild-type roots. Interestingly, roots of pin3pin7 double mutants showed curvature and growth rates similar to pin7 single mutants and wild-type roots, suggesting a genetic interaction between PIN3 and PIN7 in this pathway. These results suggest a significant degree of redundancy in the regulation of directional auxin transport and perhaps in the gravity signaling pathway in roots in general.

  17. Rhizobium Lipo-chitooligosaccharide Signaling Triggers Accumulation of Cytokinins in Medicago truncatula Roots.

    PubMed

    van Zeijl, Arjan; Op den Camp, Rik H M; Deinum, Eva E; Charnikhova, Tatsiana; Franssen, Henk; Op den Camp, Huub J M; Bouwmeester, Harro; Kohlen, Wouter; Bisseling, Ton; Geurts, René

    2015-08-01

    Legume rhizobium symbiosis is initiated upon perception of bacterial secreted lipo-chitooligosaccharides (LCOs). Perception of these signals by the plant initiates a signaling cascade that leads to nodule formation. Several studies have implicated a function for cytokinin in this process. However, whether cytokinin accumulation and subsequent signaling are an integral part of rhizobium LCO signaling remains elusive. Here, we show that cytokinin signaling is required for the majority of transcriptional changes induced by rhizobium LCOs. In addition, we demonstrate that several cytokinins accumulate in the root susceptible zone 3 h after rhizobium LCO application, including the biologically most active cytokinins, trans-zeatin and isopentenyl adenine. These responses are dependent on calcium- and calmodulin-dependent protein kinase (CCaMK), a key protein in rhizobial LCO-induced signaling. Analysis of the ethylene-insensitive Mtein2/Mtsickle mutant showed that LCO-induced cytokinin accumulation is negatively regulated by ethylene. Together with transcriptional induction of ethylene biosynthesis genes, it suggests a feedback loop negatively regulating LCO signaling and subsequent cytokinin accumulation. We argue that cytokinin accumulation is a key step in the pathway leading to nodule organogenesis and that this is tightly controlled by feedback loops.

  18. Impacts of Rho kinase inhibitor Fasudil on Rho/ROCK signaling pathway in rabbits with optic nerve injury

    PubMed Central

    Yu, Jianglong; Lin, Lin; Luan, Xinping; Jing, Xiepan; Maierab

    2015-01-01

    Objective: The aim of this study was to study the impacts of Rho kinase inhibitor Fasudil on expressions of Rho/ROCK signaling pathway associated genes in rabbits with optic nerve injury (ONI), and to explore the therapeutic mechanisms towards ONI. Methods: The rabbit ONI model was established, then the rabbits were divided into model group (treated with saline), control group (treated with dexamethasone, Dex), and intervention group (treated with Fasudil, Fas). The eyeball and optic nerve were sampled at 3, 7, 14 and 21 days after injury. The morphological changes of retina and optic nerve were observed. The expressions of RhoA, Caspase-3, Rock 2 and Nogo-A gene were determined by immunohistochemistry and real-time polymerase chain reaction (RT-PCR) methods. Results: At different time after injury, there were significant differences of RhoA, Caspase-3, Rock 2 and Nogo-A gene expression among three groups (P < 0.05). Conclusions: After ONI, Fas can decrease the expression of Caspase-3 gene, and down-regulate the expressions of Nogo-A and Rock 2 gene. Therefore, it can treat ONI through affecting the Rho/ROCK signaling pathway. PMID:26823796

  19. Strigolactones spatially influence lateral root development through the cytokinin signaling network.

    PubMed

    Jiang, Lingxiang; Matthys, Cedrick; Marquez-Garcia, Belen; De Cuyper, Carolien; Smet, Lien; De Keyser, Annick; Boyer, François-Didier; Beeckman, Tom; Depuydt, Stephen; Goormachtig, Sofie

    2016-01-01

    Strigolactones are important rhizosphere signals that act as phytohormones and have multiple functions, including modulation of lateral root (LR) development. Here, we show that treatment with the strigolactone analog GR24 did not affect LR initiation, but negatively influenced LR priming and emergence, the latter especially near the root-shoot junction. The cytokinin module ARABIDOPSIS HISTIDINE KINASE3 (AHK3)/ARABIDOPSIS RESPONSE REGULATOR1 (ARR1)/ARR12 was found to interact with the GR24-dependent reduction in LR development, because mutants in this pathway rendered LR development insensitive to GR24. Additionally, pharmacological analyses, mutant analyses, and gene expression analyses indicated that the affected polar auxin transport stream in mutants of the AHK3/ARR1/ARR12 module could be the underlying cause. Altogether, the data reveal that the GR24 effect on LR development depends on the hormonal landscape that results from the intimate connection with auxins and cytokinins, two main players in LR development.

  20. Ethylene's role in phosphate starvation signaling: more than just a root growth regulator.

    PubMed

    Nagarajan, Vinay K; Smith, Aaron P

    2012-02-01

    Phosphate (Pi) is a common limiter of plant growth due to its low availability in most soils. Plants have evolved elaborate mechanisms for sensing Pi deficiency and for initiating adaptive responses to low Pi conditions. Pi signaling pathways are modulated by both local and long-distance, or systemic, sensing mechanisms. Local sensing of low Pi initiates major root developmental changes aimed at enhancing Pi acquisition, whereas systemic sensing governs pathways that modulate expression of numerous genes encoding factors involved in Pi transport and distribution. The gaseous phytohormone ethylene has been shown to play an integral role in regulating local, root developmental responses to Pi deficiency. Comparatively, a role for ethylene in systemic Pi signaling has been more circumstantial. However, recent studies have revealed that ethylene acts to modulate a number of systemically controlled Pi starvation responses. Herein we highlight the findings from these studies and offer a model for how ethylene biosynthesis and responsiveness are integrated into both local and systemic Pi signaling pathways.

  1. Catechol, a major component of smoke, influences primary root growth and root hair elongation through reactive oxygen species-mediated redox signaling.

    PubMed

    Wang, Ming; Schoettner, Matthias; Xu, Shuqing; Paetz, Christian; Wilde, Julia; Baldwin, Ian T; Groten, Karin

    2017-03-01

    Nicotiana attenuata germinates from long-lived seedbanks in native soils after fires. Although smoke signals have been known to break seed dormancy, whether they also affect seedling establishment and root development remains unclear. In order to test this, seedlings were treated with smoke solutions. Seedlings responded in a dose-dependent manner with significantly increased primary root lengths, due mainly to longitudinal cell elongation, increased numbers of lateral roots and impaired root hair development. Bioassay-driven fractionations and NMR were used to identify catechol as the main active compound for the smoke-induced root phenotype. The transcriptome analysis revealed that mainly genes related to auxin biosynthesis and redox homeostasis were altered after catechol treatment. However, histochemical analyses of reactive oxygen species (ROS) and the inability of auxin applications to rescue the phenotype clearly indicated that highly localized changes in the root's redox-status, rather than in levels of auxin, are the primary effector. Moreover, H2 O2 application rescued the phenotype in a dose-dependent manner. Chemical cues in smoke not only initiate seed germination, but also influence seedling root growth; understanding how these cues work provides new insights into the molecular mechanisms by which plants adapt to post-fire environments.

  2. Root-to-shoot signalling when soil moisture is heterogeneous: increasing the proportion of root biomass in drying soil inhibits leaf growth and increases leaf abscisic acid concentration.

    PubMed

    Martin-Vertedor, Ana Isabel; Dodd, Ian C

    2011-07-01

    To determine whether root-to-shoot signalling of soil moisture heterogeneity depended on root distribution, wild-type (WT) and abscisic acid (ABA)-deficient (Az34) barley (Hordeum vulgare) plants were grown in split pots into which different numbers of seminal roots were inserted. After establishment, all plants received the same irrigation volumes, with one pot watered (w) and the other allowed to dry the soil (d), imposing three treatments (1 d: 3 w, 2 d: 2 w, 3 d: 1 w) that differed in the number of seminal roots exposed to drying soil. Root distribution did not affect leaf water relations and had no sustained effect on plant evapotranspiration (ET). In both genotypes, leaf elongation was less and leaf ABA concentrations were higher in plants with more roots in drying soil, with leaf ABA concentrations and water potentials 30% and 0.2 MPa higher, respectively, in WT plants. Whole-pot soil drying increased xylem ABA concentrations, but maximum values obtained when leaf growth had virtually ceased (100 nm in Az34, 330 nm in WT) had minimal effects (<40% leaf growth inhibition) when xylem supplied to detached shoots. Although ABA may not regulate leaf growth in vivo, genetic variation in foliar ABA concentration in the field may indicate different root distributions between upper (drier) and lower (wetter) soil layers.

  3. The Role of 5-HT3 Receptors in Signaling from Taste Buds to Nerves.

    PubMed

    Larson, Eric D; Vandenbeuch, Aurelie; Voigt, Anja; Meyerhof, Wolfgang; Kinnamon, Sue C; Finger, Thomas E

    2015-12-02

    Activation of taste buds triggers the release of several neurotransmitters, including ATP and serotonin (5-hydroxytryptamine; 5-HT). Type III taste cells release 5-HT directly in response to acidic (sour) stimuli and indirectly in response to bitter and sweet tasting stimuli. Although ATP is necessary for activation of nerve fibers for all taste stimuli, the role of 5-HT is unclear. We investigated whether gustatory afferents express functional 5-HT3 receptors and, if so, whether these receptors play a role in transmission of taste information from taste buds to nerves. In mice expressing GFP under the control of the 5-HT(3A) promoter, a subset of cells in the geniculate ganglion and nerve fibers in taste buds are GFP-positive. RT-PCR and in situ hybridization confirmed the presence of 5-HT(3A) mRNA in the geniculate ganglion. Functional studies show that only those geniculate ganglion cells expressing 5-HT3A-driven GFP respond to 10 μM 5-HT and this response is blocked by 1 μM ondansetron, a 5-HT3 antagonist, and mimicked by application of 10 μM m-chlorophenylbiguanide, a 5-HT3 agonist. Pharmacological blockade of 5-HT3 receptors in vivo or genetic deletion of the 5-HT3 receptors reduces taste nerve responses to acids and other taste stimuli compared with controls, but only when urethane was used as the anesthetic. We find that anesthetic levels of pentobarbital reduce taste nerve responses apparently by blocking the 5-HT3 receptors. Our results suggest that 5-HT released from type III cells activates gustatory nerve fibers via 5-HT3 receptors, accounting for a significant proportion of the neural taste response.

  4. Plant Hormone Homeostasis, Signaling, and Function during Adventitious Root Formation in Cuttings

    PubMed Central

    Druege, Uwe; Franken, Philipp; Hajirezaei, Mohammad R.

    2016-01-01

    Adventitious root (AR) formation in cuttings is a multiphase developmental process, resulting from wounding at the cutting site and isolation from the resource and signal network of the whole plant. Though, promotive effects of auxins are widely used for clonal plant propagation, the regulation and function of plant hormones and their intricate signaling networks during AR formation in cuttings are poorly understood. In this focused review, we discuss our recent publications on the involvement of polar auxin transport (PAT) and transcriptional regulation of auxin and ethylene action during AR formation in petunia cuttings in a broad context. Integrating new findings on cuttings of other plant species and general models on plant hormone networks, a model on the regulation and function of auxin, ethylene, and jasmonate in AR formation of cuttings is presented. PAT and cutting off from the basipetal auxin drain are considered as initial principles generating early accumulation of IAA in the rooting zone. This is expected to trigger a self-regulatory process of auxin canalization and maximization to responding target cells, there inducing the program of AR formation. Regulation of auxin homeostasis via auxin influx and efflux carriers, GH3 proteins and peroxidases, of flavonoid metabolism, and of auxin signaling via AUX/IAA proteins, TOPLESS, ARFs, and SAUR-like proteins are postulated as key processes determining the different phases of AR formation. NO and H2O2 mediate auxin signaling via the cGMP and MAPK cascades. Transcription factors of the GRAS-, AP2/ERF-, and WOX-families link auxin signaling to cell fate specification. Cyclin-mediated governing of the cell cycle, modifications of sugar metabolism and microtubule and cell wall remodeling are considered as important implementation processes of auxin function. Induced by the initial wounding and other abiotic stress factors, up-regulation of ethylene biosynthesis, and signaling via ERFs and early accumulation of

  5. Nerve repulsion by the lens and cornea during cornea innervation is dependent on Robo-Slit signaling and diminishes with neuron age.

    PubMed

    Schwend, Tyler; Lwigale, Peter Y; Conrad, Gary W

    2012-03-01

    The cornea, the most densely innervated tissue on the surface of the body, becomes innervated in a series of highly coordinated developmental events. During cornea development, chick trigeminal nerve growth cones reach the cornea margin at embryonic day (E)5, where they are initially repelled for days from E5 to E8, instead encircling the corneal periphery in a nerve ring prior to entering on E9. The molecular events coordinating growth cone guidance during cornea development are poorly understood. Here we evaluated a potential role for the Robo-Slit nerve guidance family. We found that Slits 1, 2 and 3 expression in the cornea and lens persisted during all stages of cornea innervation examined. Robo1 expression was developmentally regulated in trigeminal cell bodies, expressed robustly during nerve ring formation (E5-8), then later declining concurrent with projection of growth cones into the cornea. In this study we provide in vivo and in vitro evidence that Robo-Slit signaling guides trigeminal nerves during cornea innervation. Transient, localized inhibition of Robo-Slit signaling, by means of beads loaded with inhibitory Robo-Fc protein implanted into the developing eyefield in vivo, led to disorganized nerve ring formation and premature cornea innervation. Additionally, when trigeminal explants (source of neurons) were oriented adjacent to lens vesicles or corneas (source of repellant molecules) in organotypic tissue culture both lens and cornea tissues strongly repelled E7 trigeminal neurites, except in the presence of inhibitory Robo-Fc protein. In contrast, E10 trigeminal neurites were not as strongly repelled by cornea, and presence of Robo-Slit inhibitory protein had no effect. In full, these findings suggest that nerve repulsion from the lens and cornea during nerve ring formation is mediated by Robo-Slit signaling. Later, a shift in nerve guidance behavior occurs, in part due to molecular changes in trigeminal neurons, including Robo1 downregulation

  6. New insights into the signaling pathways controlling defense gene expression in rice roots during the arbuscular mycorrhizal symbiosis.

    PubMed

    Campos-Soriano, Lidia; Segundo, Blanca San

    2011-04-01

    Mycorrhizal fungi form a mutualistic relationship with the roots of most plant species. This association provides the arbuscular mycorrhizal (AM) fungus with sugars while the fungus improves the uptake of water and mineral nutrients in the host plant. Moreover, the induction of defence gene expression in mycorrhizal roots has been described. While salicylic acid (SA)-regulated Pathogenesis-Related (PR) proteins accumulate in rice roots colonized by the AM fungus G. intraradices, the SA content is not significantly altered in the mycorrhizal roots. Sugars, in addition to being a source of carbon for the fungus, might act as signals for the control of defence gene expression. We hypothesize that increased demands for sugars by the fungus might be responsible for the activation of the host defence responses which will then contribute to the stabilization of root colonization by the AM fungus. An excessive root colonization might change a mutualistic association into a parasitic association.

  7. Strigolactones, host recognition signals for root parasitic plants and arbuscular mycorrhizal fungi, from Fabaceae plants.

    PubMed

    Yoneyama, Kaori; Xie, Xiaonan; Sekimoto, Hitoshi; Takeuchi, Yasutomo; Ogasawara, Shin; Akiyama, Kohki; Hayashi, Hideo; Yoneyama, Koichi

    2008-07-01

    Both root parasitic plants and arbuscular mycorrhizal (AM) fungi take advantage of strigolactones, released from plant roots as signal molecules in the initial communication with host plants, in order to commence parasitism and mutualism, respectively. In this study, strigolactones in root exudates from 12 Fabaceae plants, including hydroponically grown white lupin (Lupinus albus), a nonhost of AM fungi, were characterized by comparing retention times of germination stimulants on reverse-phase high-performance liquid chromatography (HPLC) with those of standards and by using tandem mass spectrometry (LC/MS/MS). All the plant species examined were found to exude known strigolactones, such as orobanchol, orobanchyl acetate, and 5-deoxystrigol, suggesting that these strigolactones are widely distributed in the Fabaceae. It should be noted that even the nonmycotrophic L. albus exuded orobanchol, orobanchyl acetate, 5-deoxystrigol, and novel germination stimulants. By contrast to the mycotrophic Fabaceae plant Trifolium pratense, in which phosphorus deficiency promoted strigolactone exudation, neither phosphorus nor nitrogen deficiency increased exudation of these strigolactones in L. albus. Therefore, the regulation of strigolactone production and/or exudation seems to be closely related to the nutrient acquisition strategy of the plants.

  8. A CLE-WOX signalling module regulates root meristem maintenance and vascular tissue development in rice.

    PubMed

    Chu, Huangwei; Liang, Wanqi; Li, Juan; Hong, Fan; Wu, Yunfei; Wang, Likai; Wang, Juan; Wu, Ping; Liu, Chunming; Zhang, Qifa; Xu, Jian; Zhang, Dabing

    2013-12-01

    CLAVATA3 (CLV3)/ENDOSPERM SURROUNDING REGION (ESR)-related (CLE) proteins belong to a small peptide family conserved in plants. Recent studies in Arabidopsis and rice have revealed a key role for CLEs in mediating cell-cell communication and stem cell maintenance during plant development, but how CLE signalling controls root development in the rice remains largely unknown. Here it is shown that exogenous application of a synthetic dodeca-amino acid peptide corresponding to the CLE motif of the rice FON2-LIKE CLE PROTEIN2 (FCP2p) protein or overexpression of FCP2 terminates root apical meristem (RAM) activity and impairs late metaxylem formation. FCP2p treatment suppresses the expression of the rice QUIESCENT-CENTER-SPECIFIC HOMEOBOX (QHB) gene, a putative orthologue of Arabidopsis WUSCHEL (WUS)-RELATED HOMEOBOX 5 (WOX5) gene, in both quiescent centre and late metaxylem cells; whereas inducible overexpression of QHB reduces the sensitivity of rice to FCP2p treatment. These results together suggest that in rice RAM maintenance and late metaxylem development are probably controlled by the mutual regulation between FCP2 and QHB. Moreover, a cross-species peptide treatment experiment in Arabidopsis implies that FCP2 has both evolutionarily conserved and species-specific roles in root development.

  9. GENETIC MODIFICATION OF GIBBERELLIC ACID SIGNALING TO PROMOTE CARBON SEQUESTRATION IN TREE ROOTS AND STEMS

    SciTech Connect

    Busov, Victor

    2013-03-05

    Semidwarfism has been used extensively in row crops and horticulture to promote yield, reduce lodging, and improve harvest index, and it might have similar benefits for trees for short-rotation forestry or energy plantations, reclamation, phytoremediation, or other applications. We studied the effects of the dominant semidwarfism transgenes GA Insensitive (GAI) and Repressor of GAI-Like, which affect gibberellin (GA) action, and the GA catabolic gene, GA 2-oxidase, in nursery beds and in 2-year-old high-density stands of hybrid poplar (Populus tremula - Populus alba). Twenty-nine traits were analyzed, including measures of growth, morphology, and physiology. Endogenous GA levels were modified in most transgenic events; GA(20) and GA(8), in particular, had strong inverse associations with tree height. Nearly all measured traits varied significantly among genotypes, and several traits interacted with planting density, including aboveground biomass, root-shoot ratio, root fraction, branch angle, and crown depth. Semidwarfism promoted biomass allocation to roots over shoots and substantially increased rooting efficiency with most genes tested. The increased root proportion and increased leaf chlorophyll levels were associated with changes in leaf carbon isotope discrimination, indicating altered water use efficiency. Semidwarf trees had dramatically reduced growth when in direct competition with wild-type trees, supporting the hypothesis that semidwarfism genes could be effective tools to mitigate the spread of exotic, hybrid, and transgenic plants in wild and feral populations. We modified gibberellin (GA) metabolism and signaling in transgenic poplars using dominant transgenes and studied their effects for 3 years under field conditions. The transgenes that we employed either reduced the bioactive GAs, or attenuated their signaling. The majority of transgenic trees had significant and in many cases dramatic changes in height, crown architecture, foliage morphology

  10. The promoting effects of alginate oligosaccharides on root development in Oryza sativa L. mediated by auxin signaling.

    PubMed

    Zhang, Yunhong; Yin, Heng; Zhao, Xiaoming; Wang, Wenxia; Du, Yuguang; He, Ailing; Sun, Kegang

    2014-11-26

    Alginate oligosaccharides (AOS), which are marine oligosaccharides, are involved in regulating plant root growth, but the promotion mechanism for AOS remains unclear. Here, AOS (10-80 mg/L) induced the expression of auxin-related gene (OsYUCCA1, OsYUCCA5, OsIAA11 and OsPIN1) in rice (Oryza sativa L.) tissues to accelerate auxin biosynthesis and transport, and reduced indole-3-acetic acid (IAA) oxidase activity in rice roots. These changes resulted in the increase of 37.8% in IAA concentration in rice roots, thereby inducing the expression of root development-related genes, promoting root growth in a dose-dependent manner, which were inhibited by auxin transport inhibitor 2,3,5-triiodo benzoic acid (TIBA) and calcium-chelating agent ethylene glycol bis (2-aminoethyl) tetraacetic acid (EGTA). AOS also induced calcium signaling generation in rice roots. Those results indicated that auxin mediated AOS regulation of root development, and calcium signaling may act mainly in the upstream of auxin in the regulation of AOS on rice root development.

  11. Serotonin modulates Arabidopsis root growth via changes in reactive oxygen species and jasmonic acid-ethylene signaling.

    PubMed

    Pelagio-Flores, Ramón; Ruiz-Herrera, León Francisco; López-Bucio, José

    2016-09-01

    Serotonin (5-hydroxytryptamine) is a bioactive indoleamine with neurotransmitter function in vertebrates, which represents an emerging signaling molecule in plants, playing key roles in the development and defense. In this study, the role of reactive oxygen species (ROS) and jasmonic acid (JA)-ethylene (Et) signaling in root developmental alterations induced by serotonin was investigated. An Arabidopsis thaliana mutant defective at the RADICAL-INDUCED CELL DEATH1 (RCD1) locus was resistant to paraquat-induced ROS accumulation in primary roots and showed decreased inhibition or root growth in response to serotonin. A suite of JA- and Et-related mutants including coronatine insensitive1, jasmonic acid resistant1 (jar1), etr1, ein2 and ein3 showed tolerance to serotonin in the inhibition of primary root growth and ROS redistribution within the root tip when compared with wild-type (WT) seedlings. Competence assays between serotonin and AgNO3 , a well-known blocker of Et action, showed that primary root growth in medium supplemented with serotonin was normalized by AgNO3 , whereas roots of eto3, an Et overproducer mutant, were oversensitive to serotonin. Comparison of ROS levels in WT, etr1, jar1 and rcd1 primary root tips using the ROS-specific probe 2',7'-dichlorofluorescein diacetate and confocal imaging showed that serotonin inhibition of primary root growth likely occurs independently of its conversion into melatonin. Our results provide compelling evidence that serotonin affects ROS distribution in roots, involving RCD1 and components of the JA-Et signaling pathways.

  12. Uranium perturbs signaling and iron uptake response in Arabidopsis thaliana roots.

    PubMed

    Doustaly, Fany; Combes, Florence; Fiévet, Julie B; Berthet, Serge; Hugouvieux, Véronique; Bastien, Olivier; Aranjuelo, Iker; Leonhardt, Nathalie; Rivasseau, Corinne; Carrière, Marie; Vavasseur, Alain; Renou, Jean-Pierre; Vandenbrouck, Yves; Bourguignon, Jacques

    2014-04-01

    Uranium is a natural element which is mainly redistributed in the environment due to human activity, including accidents and spillages. Plants may be useful in cleaning up after incidents, although little is yet known about the relationship between metal speciation and plant response. Here, J-Chess modeling was used to predict U speciation and exposure conditions affecting U bioavailability for plants. The model was confirmed by exposing Arabidopsis thaliana plants to U under hydroponic conditions. The early root response was characterized using complete Arabidopsis transcriptome microarrays (CATMA). Expression of 111 genes was modified at the three timepoints studied. The associated biological processes were further examined by real-time quantitative RT-PCR. Annotation revealed that oxidative stress, cell wall and hormone biosynthesis, and signaling pathways (including phosphate signaling) were affected by U exposure. The main actors in iron uptake and signaling (IRT1, FRO2, AHA2, AHA7 and FIT1) were strongly down-regulated upon exposure to uranyl. A network calculated using IRT1, FRO2 and FIT1 as bait revealed a set of genes whose expression levels change under U stress. Hypotheses are presented to explain how U perturbs the iron uptake and signaling response. These results give preliminary insights into the pathways affected by uranyl uptake, which will be of interest for engineering plants to help clean areas contaminated with U.

  13. Nerve injury-induced changes in Homer/glutamate receptor signaling contribute to the development and maintenance of neuropathic pain.

    PubMed

    Obara, Ilona; Goulding, Scott P; Hu, Jia-Hua; Klugmann, Matthias; Worley, Paul F; Szumlinski, Karen K

    2013-10-01

    While group 1 metabotropic glutamate receptors (mGluRs) and ionotropic N-methyl-d-aspartate (NMDA) receptors regulate nociception, the precise molecular mechanism(s) contributing to glutamate signaling in chronic pain remain unclear. Here we not only confirmed the key involvement of Homer proteins in neuropathic pain, but also distinguished between the functional roles for different Homer family members and isoforms. Chronic constriction injury (CCI) of the sciatic nerve induced long-lasting, time-dependent increases in the postsynaptic density expression of the constitutively expressed (CC) isoforms Homer1b/c and/or Homer2a/b in the spinal dorsal horn and supraspinal structures involved in nociception (prefrontal cortex, thalamus), that co-occurred with increases in their associated mGluRs, NR2 subunits of the NMDA receptor, and the activation of downstream kinases. Virus-mediated overexpression of Homer1c and Homer2b after spinal (intrathecal) virus injection exacerbated CCI-induced mechanical and cold hypersensitivity, however, Homer1 and Homer2 gene knockout (KO) mice displayed no changes in their neuropathic phenotype. In contrast, overexpression of the immediate early gene (IEG) Homer1a isoform reduced, while KO of Homer1a gene potentiated neuropathic pain hypersensitivity. Thus, nerve injury-induced increases in CC-Homers expression promote pain in pathological states, but IEG-Homer induction protects against both the development and maintenance of neuropathy. Additionally, exacerbated pain hypersensitivity in transgenic mice with reduced Homer binding to mGluR5 supports also an inhibitory role for Homer interactions with mGluR5 in mediating neuropathy. Such data indicate that nerve injury-induced changes in glutamate receptor/Homer signaling contribute in dynamic but distinct ways to neuropathic pain processing, which has relevance for the etiology of chronic pain symptoms and its treatment.

  14. Spinal nerve ligation decreases γ-aminobutyric acidB receptors on specific populations of immunohistochemically identified neurons in L5 dorsal root ganglion of the rat.

    PubMed

    Engle, Mitchell P; Merrill, Michelle A; Marquez De Prado, Blanca; Hammond, Donna L

    2012-06-01

    This study examined the distribution of γ-aminobutyric acid (GABA)(B) receptors on immunohistochemically identified neurons, and levels of GABA(B(1)) and GABA(B(2)) mRNA, in the L4 and L5 dorsal root ganglia (DRG) of the rat in the absence of injury and 2 weeks after L5 spinal nerve ligation. In uninjured DRG, GABA(B(1)) immunoreactivity colocalized exclusively with the neuronal marker (NeuN) and did not colocalize with the satellite cell marker S-100. The GABA(B(1)) subunit colocalized to >97% of DRG neurons immunoreactive (IR) for neurofilament 200 (N52) or calcitonin gene-related peptide (CGRP), or labeled by isolectin B4 (IB4). Immunoreactivity for GABA(B(2)) was not detectable. L5 spinal nerve ligation did not alter the number of GABA(B(1)) -IR neurons or its colocalization pattern in the L4 DRG. However, ligation reduced the number of GABA(B(1)) -IR neurons in the L5 DRG by ≈38% compared with sham-operated and naïve rats. Specifically, ligation decreased the number of CGRP-IR neurons in the L5 DRG by 75%, but did not decrease the percent colocalization of GABA(B(1)) in those that remained. In the few IB4-positive neurons that remained in the L5 DRG, colocalization of GABA(B(1)) -IR decreased to 75%. Ligation also decreased levels of GABA(B(1)) and GABA(B(2)) mRNA in the L5, but not the L4 DRG compared with sham-operated or naïve rats. These findings indicate that the GABA(B) receptor is positioned to presynaptically modulate afferent transmission by myelinated, unmyelinated, and peptidergic afferents in the dorsal horn. Loss of GABA(B) receptors on primary afferent neurons may contribute to the development of mechanical allodynia after L5 spinal nerve ligation.

  15. Analysis of the spinal nerve roots in relation to the adjacent vertebral bodies with respect to a posterolateral vertebral body replacement procedure

    PubMed Central

    Awwad, Waleed; Bourget-Murray, Jonathan; Zeiadin, Nadil; Mejia, Juan P; Steffen, Thomas; Algarni, Abdulrahman D; Alsaleh, Khalid; Ouellet, Jean; Weber, Michael; Jarzem, Peter F

    2017-01-01

    Objective: This study aims to improve the understanding of the anatomic variations along the thoracic and lumbar spine encountered during an all-posterior vertebrectomy, and reconstruction procedure. This information will help improve our understanding of human spine anatomy and will allow better planning for a vertebral body replacement (VBR) through either a transpedicular or costotransversectomy approach. Summary of Background Data: The major challenge to a total posterior approach vertebrectomy and VBR in the thoracolumbar spine lies in the preservation of important neural structures. Methods: This was a retrospective analysis. Hundred normal magnetic resonance imaging (MRI) spinal studies (T1–L5) on sagittal T2-weighted MRI images were studied to quantify: (1) mid-sagittal vertebral body (VB) dimensions (anterior, midline, and posterior VB height), (2) midline VB and associated intervertebral discs height, (3) mean distance between adjacent spinal nerve roots (DNN) and mean distance between the inferior endplate of the superior vertebrae to its respective spinal nerve root (DNE), and (4) posterior approach expansion ratio (PAER). Results: (1) The mean anterior VB height gradually increased craniocaudally from T1 to L5. The mean midline and posterior VB height showed a similar pattern up to L2. Mean posterior VB height was larger than the mean anterior VB height from T1 to L2, consistent with anterior wedging, and then measured less than the mean anterior VB height, indicating posterior wedging. (2) Midline VB and intervertebral disc height gradually increased from T1 to L4. (3) DNN and DNE were similar, whereby they gradually increased from T1 to L3. (5) Mean PAER varied between 1.69 (T12) and 2.27 (L5) depending on anatomic level. Conclusions: The dimensions of the thoracic and lumbar vertebrae and discs vary greatly. Thus, any attempt at carrying out a VBR from a posterior approach should take into account the specifications at each spinal level. PMID

  16. The neuronal architecture of the anteroventral cochlear nucleus of the cat in the region of the cochlear nerve root: Golgi and Nissl methods.

    PubMed

    Tolbert, L P; Morest, D K

    1982-01-01

    This report characterizes the cells and fibers in one part of the cochlear nucleus, the posterior division of the anteroventral cochlear nucleus. This includes the region where the cochlear nerve root enters the brain and begins to form endings. Nissl stains reveal the somata of globular cells with dispersed Nissl substance and those of multipolar cells with coarse, clumped Nissl bodies. Both parts of the posterior division contain cells with each Nissl pattern, but in different relative numbers and locations. Golgi impregnations demonstrate two types of neurons: bushy cells, with short bush-like dendrites, and stellate and elongate cells, with long tapered dendrites. Several varieties of bushy cells, differing in the morphology of the cell body and in the size and extent of the dendritic field, can be distinguished. Comparison of the distributions of these cell types, as well as cellular morphology, suggest that the globular cells recognized in Nissl stains correspond to bushy neurons, while the multipolar cells correspond to stellate and elongate neurons. Golgi impregnations reveal large end-bulbs and smaller boutons from cochlear nerve fibers, as well as boutons from other, unidentified sources, ending in this region. The particular arrangements of the dendritic fields of the different cell types and the axonal endings associated with them indicate that these neurons must have different physiological properties, since they define different domains with respect to the cochlear and non-cochlear inputs.

  17. Cdc42 Promotes Schwann Cell Proliferation and Migration Through Wnt/β-Catenin and p38 MAPK Signaling Pathway After Sciatic Nerve Injury.

    PubMed

    Han, Bin; Zhao, Jun-Ying; Wang, Wu-Tao; Li, Zheng-Wei; He, Ai-Ping; Song, Xiao-Yang

    2017-01-17

    Schwann cells (SCs) are unique glial cells in the peripheral nerve and may secrete multiple neurotrophic factors, adhesion molecules, extracellular matrix molecules to form the microenvironment of peripheral nerve regeneration, guiding and supporting nerve proliferation and migration. Cdc42 plays an important regulatory role in dynamic changes of the cytoskeleton. However, there is a little study referred to regulation and mechanism of Cdc42 on glial cells after peripheral nerve injury. The present study investigated the role of Cdc42 in the proliferation and migration of SCs after sciatic nerve injury. Cdc42 expression was tested, showing that the mRNA and protein expression levels of Cdc42 were significantly up-regulated after sciatic nerve injury. Then, we isolated and purified SCs from injuried sciatic nerve at day 7. The purified SCs were transfected with Cdc42 siRNA and pcDNA3.1-Cdc42, and the cell proliferation, cell cycle and migration were assessed. The results implied that Cdc42 siRNA remarkably inhibited Schwann cell proliferation and migration, and resulted in S phase arrest. While pcDNA3.1-Cdc42 showed a contrary effect. Besides, we also observed that Cdc42 siRNA down-regulated the protein expression of β-catenin, Cyclin D1, c-myc and p-p38, which were up-regulated by pcDNA3.1-Cdc42. Meanwhile, the inhibitor of Wnt/β-catenin and p38 MAPK signaling pathway IWP-2 and SB203580 significantly inhibited the effect of pcDNA3.1-Cdc42 on cell proliferation and migration. Overall, our data indicate that Cdc42 regulates Schwann cell proliferation and migration through Wnt/β-catenin and p38 MAPK signaling pathway after sciatic nerve injury, which provides further insights into the therapy of the sciatic nerve injury.

  18. Cytosolic Ca(2+) Signals Enhance the Vacuolar Ion Conductivity of Bulging Arabidopsis Root Hair Cells.

    PubMed

    Wang, Yi; Dindas, Julian; Rienmüller, Florian; Krebs, Melanie; Waadt, Rainer; Schumacher, Karin; Wu, Wei-Hua; Hedrich, Rainer; Roelfsema, M Rob G

    2015-11-02

    Plant cell expansion depends on the uptake of solutes across the plasma membrane and their storage within the vacuole. In contrast to the well-studied plasma membrane, little is known about the regulation of ion transport at the vacuolar membrane. We therefore established an experimental approach to study vacuolar ion transport in intact Arabidopsis root cells, with multi-barreled microelectrodes. The subcellular position of electrodes was detected by imaging current-injected fluorescent dyes. Comparison of measurements with electrodes in the cytosol and vacuole revealed an average vacuolar membrane potential of -31 mV. Voltage clamp recordings of single vacuoles resolved the activity of voltage-independent and slowly deactivating channels. In bulging root hairs that express the Ca(2+) sensor R-GECO1, rapid elevation of the cytosolic Ca(2+) concentration was observed, after impalement with microelectrodes, or injection of the Ca(2+) chelator BAPTA. Elevation of the cytosolic Ca(2+) level stimulated the activity of voltage-independent channels in the vacuolar membrane. Likewise, the vacuolar ion conductance was enhanced during a sudden increase of the cytosolic Ca(2+) level in cells injected with fluorescent Ca(2+) indicator FURA-2. These data thus show that cytosolic Ca(2+) signals can rapidly activate vacuolar ion channels, which may prevent rupture of the vacuolar membrane, when facing mechanical forces.

  19. Increased expression of HCN2 channel protein in L4 dorsal root ganglion neurons following axotomy of L5- and inflammation of L4-spinal nerves in rats.

    PubMed

    Smith, T; Al Otaibi, M; Sathish, J; Djouhri, L

    2015-06-04

    A hallmark of peripheral neuropathic pain (PNP) is chronic spontaneous pain and/or hypersensitivity to normally painful stimuli (hyperalgesia) or normally nonpainful stimuli (allodynia).This pain results partly from abnormal hyperexcitability of dorsal root ganglion (DRG) neurons. We have previously shown, using a modified version of the lumbar 5 (L5)-spinal nerve ligation model of PNP (mSNA model involving L5-spinal nerve axotomy plus loose ligation of the lumbar 4 (L4)-spinal nerve with neuroinflammation-inducing chromic-gut), that L4 DRG neurons exhibit increased spontaneous activity, the key characteristic of neuronal hyperexcitability. The underlying ionic and molecular mechanisms of the hyperexcitability of L4 DRG neurons are incompletely understood, but could result from changes in expression and/or function of ion channels including hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which are active near the neuron's resting membrane potential, and which produce an excitatory inward current that depolarizes the membrane potential toward the threshold of action potential generation. Therefore, in the present study we used the mSNA model to investigate whether: (a) expression of HCN1-HCN3 channels is altered in L4 DRG neurons which, in the mSNA model, are essential for transmission of the evoked pain, and which contribute to chronic spontaneous pain, and (b) local (intraplantar) blockade of these HCN channels, with a specific blocker, ZD7288, attenuates chronic spontaneous pain and/or evoked pain in mSNA rats. We found 7days after mSNA: (1) a significant increase in HCN2-immunoreactivity in small (<30μm) DRG neurons (predominantly IB4-negative neurons), and in the proportion of small neurons expressing HCN2 (putative nociceptors); (2) no significant change in HCN1- or HCN3-immunoreactivity in all cell types; and (3) attenuation, with ZD7288 (100μM intraplantar), of chronic spontaneous pain behavior (spontaneous foot lifting) and mechanical

  20. Dual regulation of the Arabidopsis high-affinity root iron uptake system by local and long-distance signals.

    PubMed

    Vert, Grégory A; Briat, Jean-François; Curie, Catherine

    2003-06-01

    Regulation of the root high-affinity iron uptake system by whole-plant signals was investigated at the molecular level in Arabidopsis, through monitoring FRO2 and IRT1 gene expression. These two genes encode the root ferric-chelate reductase and the high-affinity iron transporter, respectively, involved in the iron deficiency-induced uptake system. Recovery from iron-deficient conditions and modulation of apoplastic iron pools indicate that iron itself plays a major role in the regulation of root iron deficiency responses at the mRNA and protein levels. Split-root experiments show that the expression of IRT1 and FRO2 is controlled both by a local induction from the root iron pool and through a systemic pathway involving a shoot-borne signal, both signals being integrated to tightly control production of the root iron uptake proteins. We also show that IRT1 and FRO2 are expressed during the day and down-regulated at night and that this additional control is overruled by iron starvation, indicating that the nutritional status prevails on the diurnal regulation. Our work suggests, for the first time to our knowledge, that like in grasses, the root iron acquisition in strategy I plants may also be under diurnal regulation. On the basis of the new molecular insights provided in this study and given the strict coregulation of IRT1 and FRO2 observed, we present a model of local and long-distance regulation of the root iron uptake system in Arabidopsis.

  1. Ageing-induced changes in the redox status of peripheral motor nerves imply an effect on redox signalling rather than oxidative damage

    PubMed Central

    McDonagh, Brian; Scullion, Siobhan M.; Vasilaki, Aphrodite; Pollock, Natalie; McArdle, Anne; Jackson, Malcolm J.

    2016-01-01

    Ageing is associated with loss of skeletal muscle fibres, atrophy of the remaining fibres and weakness. These changes in muscle are accompanied by disruption of motor neurons and neuromuscular junctions although the direct relationship between the nerve and muscle degeneration is not understood. Oxidative changes have been implicated in the mechanisms leading to age-related loss of muscle mass and in degeneration of the central nervous system, but little is known about age-related changes in oxidation in specific peripheral nerves that supply muscles that are affected by ageing. We have therefore examined the sciatic nerve of old mice at an age when loss of tibialis anterior muscle mass and function is apparent. Sciatic nerve from old mice did not show a gross increase in oxidative damage, but electron paramagnetic resonance (EPR) studies indicated an increase in the activity of superoxide and/or peroxynitrite in the nerves of old mice at rest that was further exacerbated by electrical stimulation of the nerve to activate muscle contractions. Proteomic analyses indicated that specific redox-sensitive proteins are increased in content in the nerves of old mice that may reflect an adaptation to regulate the increased superoxide/peroxynitrite and maintain redox homoeostasis. Analysis of redox active cysteines showed some increase in reversible oxidation in specific proteins in nerves of old mice, but this was not universally seen across all redox-active cysteines. Detailed analysis of the redox-active cysteine in one protein in the nerve of old mice that is key to redox signalling (Peroxiredoxin 6, Cys 47) showed a minor increase in reversible oxidation that would be compatible with a change in its redox signalling function. In conclusion, the data presented indicate that sciatic nerve from old mice does not show a gross increase in oxidative damage similar to that seen in the TA and other muscles that it innervates. Our results indicate an adaptation to increased

  2. Ageing-induced changes in the redox status of peripheral motor nerves imply an effect on redox signalling rather than oxidative damage.

    PubMed

    McDonagh, Brian; Scullion, Siobhan M; Vasilaki, Aphrodite; Pollock, Natalie; McArdle, Anne; Jackson, Malcolm J

    2016-05-01

    Ageing is associated with loss of skeletal muscle fibres, atrophy of the remaining fibres and weakness. These changes in muscle are accompanied by disruption of motor neurons and neuromuscular junctions although the direct relationship between the nerve and muscle degeneration is not understood. Oxidative changes have been implicated in the mechanisms leading to age-related loss of muscle mass and in degeneration of the central nervous system, but little is known about age-related changes in oxidation in specific peripheral nerves that supply muscles that are affected by ageing. We have therefore examined the sciatic nerve of old mice at an age when loss of tibialis anterior muscle mass and function is apparent. Sciatic nerve from old mice did not show a gross increase in oxidative damage, but electron paramagnetic resonance (EPR) studies indicated an increase in the activity of superoxide and/or peroxynitrite in the nerves of old mice at rest that was further exacerbated by electrical stimulation of the nerve to activate muscle contractions. Proteomic analyses indicated that specific redox-sensitive proteins are increased in content in the nerves of old mice that may reflect an adaptation to regulate the increased superoxide/peroxynitrite and maintain redox homoeostasis. Analysis of redox active cysteines showed some increase in reversible oxidation in specific proteins in nerves of old mice, but this was not universally seen across all redox-active cysteines. Detailed analysis of the redox-active cysteine in one protein in the nerve of old mice that is key to redox signalling (Peroxiredoxin 6, Cys 47) showed a minor increase in reversible oxidation that would be compatible with a change in its redox signalling function. In conclusion, the data presented indicate that sciatic nerve from old mice does not show a gross increase in oxidative damage similar to that seen in the TA and other muscles that it innervates. Our results indicate an adaptation to increased

  3. A diagnosis challenge-L4 nerve root compression as the initial presentation of chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Cojocaru, Inimioara Mihaela; Alexianu, Marilena; Bastian, Alexandra; Sapira, Violeta; Herţea, Cristina; Cojocaru, M

    2012-01-01

    The authors present the case of a 65-year-old woman who was admitted for paraparesis and paresthesias in the inferior limbs. The neurological examination revealed the difficulty in extension of the right foot and of the right toe, accompanied by paresthesias located in the anterolateral area of the right leg, dorsum and plantar area of the foot, the reduction of the right knee jerk, and of the ankle tendon jerk both sides. The vertebro-spinal MRI showed lumbar canal stenosis with L4 intraforaminal compression on the right, and L2-L3 on the left. CSF examination revealed mild increase in protein concentration. The morphological picture of the sural nerve biopsy was compatible with a chronic inflammatory neuropathy and severe muscular lesions of neurogenic origin were observed on right gastrocnemius muscle biopsy. The diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) was established. Solu-medrol (0.5 g/d)-5 days, then medrol (prednisolone) was done, followed by improving of the symptomatology. For the relapse of the disease intravenous immunoglobulins (IVIG)-0.4 g/kg/d-5 days was the elective treatment. Six months later she presented a new relapse. IVIG were administered with the remission of the sensitive symptoms. A chronic treatment with medrol was recommended. The diagnosis of L4 disc herniation was obvious in the studied case, but the electroneurographic examination brought extra data for the associated diagnosis of CIDP whose onset was asymmetrical and initially paucisymptomatic. Neither the electroneurographic examination nor the CSF examination were total relevant for CIDP, imposing the sural nerve biopsy. The diagnosis of CIDP involves a team-work composed of neurologist, electroneurophysiologist and neuropathologist.

  4. Geometric analysis of Arabidopsis root apex reveals a new aspect of the ethylene signal transduction pathway in development.

    PubMed

    Cervantes, Emilio; Tocino, Angel

    2005-09-01

    Structurally, ethylene is the simplest phytohormone and regulates multiple aspects of plant growth and development. Its effects are mediated by a signal transduction cascade involving receptors, MAP kinases and transcription factors. Many morphological effects of ethylene in plant development, including root size, have been previously described. In this article a combined geometric and algebraic approach has been used to analyse the shape and the curvature in the root apex of Arabidopsis seedlings. The process requires the fitting of Bézier curves that reproduce the root apex shape, and the calculation of the corresponding curvatures. The application of the method has allowed us to identify significant differences in the root curvatures of ethylene insensitive mutants (ein2-1 and etr1-1) with respect to the wild-type Columbia.

  5. Geometric analysis of Arabidopsis root apex reveals a new aspect of the ethylene signal transduction pathway in development

    NASA Technical Reports Server (NTRS)

    Cervantes, Emilio; Tocino, Angel

    2005-01-01

    Structurally, ethylene is the simplest phytohormone and regulates multiple aspects of plant growth and development. Its effects are mediated by a signal transduction cascade involving receptors, MAP kinases and transcription factors. Many morphological effects of ethylene in plant development, including root size, have been previously described. In this article a combined geometric and algebraic approach has been used to analyse the shape and the curvature in the root apex of Arabidopsis seedlings. The process requires the fitting of Bezier curves that reproduce the root apex shape, and the calculation of the corresponding curvatures. The application of the method has allowed us to identify significant differences in the root curvatures of ethylene insensitive mutants (ein2-1 and etr1-1) with respect to the wild-type Columbia.

  6. Exogenous Modulation of Retinoic Acid Signaling Affects Adult RGC Survival in the Frog Visual System after Optic Nerve Injury

    PubMed Central

    Duprey-Díaz, Mildred V.; Blagburn, Jonathan M.; Blanco, Rosa E.

    2016-01-01

    After lesions to the mammalian optic nerve, the great majority of retinal ganglion cells (RGCs) die before their axons have even had a chance to regenerate. Frog RGCs, on the other hand, suffer only an approximately 50% cell loss, and we have previously investigated the mechanisms by which the application of growth factors can increase their survival rate. Retinoic acid (RA) is a vitamin A-derived lipophilic molecule that plays major roles during development of the nervous system. The RA signaling pathway is also present in parts of the adult nervous system, and components of it are upregulated after injury in peripheral nerves but not in the CNS. Here we investigate whether RA signaling affects long-term RGC survival at 6 weeks after axotomy. Intraocular injection of all-trans retinoic acid (ATRA), the retinoic acid receptor (RAR) type-α agonist AM80, the RARβ agonist CD2314, or the RARγ agonist CD1530, returned axotomized RGC numbers to almost normal levels. On the other hand, inhibition of RA synthesis with disulfiram, or of RAR receptors with the pan-RAR antagonist Ro-41-5253, or the RARβ antagonist LE135E, greatly reduced the survival of the axotomized neurons. Axotomy elicited a strong activation of the MAPK, STAT3 and AKT pathways; this activation was prevented by disulfiram or by RAR antagonists. Finally, addition of exogenous ATRA stimulated the activation of the first two of these pathways. Future experiments will investigate whether these strong survival-promoting effects of RA are mediated via the upregulation of neurotrophins. PMID:27611191

  7. Root gravitropism: an experimental tool to investigate basic cellular and molecular processes underlying mechanosensing and signal transmission in plants

    NASA Technical Reports Server (NTRS)

    Boonsirichai, K.; Guan, C.; Chen, R.; Masson, P. H.

    2002-01-01

    The ability of plant organs to use gravity as a guide for growth, named gravitropism, has been recognized for over two centuries. This growth response to the environment contributes significantly to the upward growth of shoots and the downward growth of roots commonly observed throughout the plant kingdom. Root gravitropism has received a great deal of attention because there is a physical separation between the primary site for gravity sensing, located in the root cap, and the site of differential growth response, located in the elongation zones (EZs). Hence, this system allows identification and characterization of different phases of gravitropism, including gravity perception, signal transduction, signal transmission, and curvature response. Recent studies support some aspects of an old model for gravity sensing, which postulates that root-cap columellar amyloplasts constitute the susceptors for gravity perception. Such studies have also allowed the identification of several molecules that appear to function as second messengers in gravity signal transduction and of potential signal transducers. Auxin has been implicated as a probable component of the signal that carries the gravitropic information between the gravity-sensing cap and the gravity-responding EZs. This has allowed the identification and characterization of important molecular processes underlying auxin transport and response in plants. New molecular models can be elaborated to explain how the gravity signal transduction pathway might regulate the polarity of auxin transport in roots. Further studies are required to test these models, as well as to study the molecular mechanisms underlying a poorly characterized phase of gravitropism that is independent of an auxin gradient.

  8. Involvement of PACAP/ADNP signaling in the resistance to cell death in malignant peripheral nerve sheath tumor (MPNST) cells.

    PubMed

    Castorina, Alessandro; Giunta, Salvatore; Scuderi, Soraya; D'Agata, Velia

    2012-11-01

    Malignant peripheral nerve sheath tumors (MPNSTs) are sarcomas able to grow under conditions of metabolic stress caused by insufficient nutrients or oxygen. Both pituitary adenylate cyclase-activating polypeptide (PACAP) and activity-dependent neuroprotective protein (ADNP) have glioprotective potential. However, whether PACAP/ADNP signaling is involved in the resistance to cell death in MPNST cells remains to be clarified. Here, we investigated the involvement of this signaling system in the survival response of MPNST cells against hydrogen peroxide (H(2)O(2))-evoked death both in the presence of normal serum (NS) and in serum-starved (SS) cells. Results showed that ADNP levels increased time-dependently (6-48 h) in SS cells. Treatment with PACAP38 (10(-9) to 10(-5) M) dose-dependently increased ADNP levels in NS but not in SS cells. PAC(1)/VPAC receptor antagonists completely suppressed PACAP-stimulated ADNP increase and partially reduced ADNP expression in SS cells. NS-cultured cells exposed to H(2)O(2) showed significantly reduced cell viability (~50 %), increased p53 and caspase-3, and DNA fragmentation, without affecting ADNP expression. Serum starvation significantly reduced H(2)O(2)-induced detrimental effects in MPNST cells, which were not further ameliorated by PACAP38. Altogether, these finding provide evidence for the involvement of an endogenous PACAP-mediated ADNP signaling system that increases MPNST cell resistance to H(2)O(2)-induced death upon serum starvation.

  9. Root water potential integrates discrete soil physical properties to influence ABA signalling during partial rootzone drying.

    PubMed

    Dodd, Ian C; Egea, Gregorio; Watts, Chris W; Whalley, W Richard

    2010-08-01

    To investigate the influence of different growing substrates (two mineral, two organic) on root xylem ABA concentration ([ABA](root)) and the contribution of the drying root system to total sap flow during partial rootzone drying (PRD), sunflower (Helianthus annuus L.) shoots were grafted onto the root systems of two plants grown in separate pots. Sap flow through each hypocotyl was measured below the graft union when one pot ('wet') was watered and other ('dry') was not. Each substrate gave unique relationships between dry pot matric potential (Psi(soil)), volumetric water content ((v)) or penetrometer resistance (Q) and either the fraction of photoperiod sap flow from roots in drying soil or [ABA](root). However, decreased relative sap flow, and increased [ABA](root), from roots in drying soil varied with root water potential (Psi(root)) more similarly across a range of substrates. The gradient between Psi(soil) and Psi(root) was greater in substrates with high sand or peat proportions, which may have contributed to a more sensitive response of [ABA](root) to Psi(soil) in these substrates. Whole plant transpiration was most closely correlated with the mean Psi(soil) of both pots, and then with detached leaf xylem ABA concentration. Although Psi(root) best predicted decreased relative sap flow, and increased [ABA](root), from roots in drying soil across a range of substrates, the inaccessibility of this variable in field studies requires a better understanding of how measurable soil variables (Psi(soil), (v), Q) affect Psi(root).

  10. Impacts of anti-nerve growth factor antibody on pain-related behaviors and expressions of opioid receptor in spinal dorsal horn and dorsal root ganglia of rats with cancer-induced bone pain

    PubMed Central

    Ding, Yuanyuan; Wang, Zhibin; Ma, Jiaming; Hong, Tao; Zhu, Yongqiang; Li, Hongxi; Pan, Shinong

    2016-01-01

    Objective To investigate the impacts of anti-nerve growth factor antibody on pain-related behaviors and expressions of μ-opioid receptor in spinal dorsal horn and dorsal root ganglia of rats with cancer-induced bone pain. Methods The rats were randomly grouped and then injected with 10 μl of phosphate buffer saline or Walker256 tumor cells into the upper segment of left tibia. Thirteen days after the injection, the intrathecal catheterization was performed, followed by the injection of saline, anti-nerve growth factor, nerve growth factor, and naloxone twice a day. The pain ethological changes were measured at the set time points; the expression changes of μ-opioid receptor protein and mRNA in spinal dorsal horn and dorsal root ganglia were detected on the 18th day. Results After the tumor cells were injected into the tibia, hyperalgesia appeared and the expression of μ-opioid receptor protein and mRNA in spinal dorsal horn and dorsal root ganglia was increased, compared with the sham group; after intrathecally injected anti-nerve growth factor, the significant antinociceptive effects appeared, and the μ-opioid receptor expression was increased, compared with the cancer pain group; the μ-opioid receptor expressions in the other groups showed no statistical significance. The naloxone pretreatment could mostly inverse the antinociception effects of anti-nerve growth factor. Conclusions Anti-nerve growth factor could reduce hyperalgesia in the cancer-induced bone pain rats, and the antinociceptive effects were related with the upregulation of μ-opioid receptor. PMID:27118770

  11. Extracellular Nm23H1 stimulates neurite outgrowth from dorsal root ganglia neurons in vitro independently of nerve growth factor supplementation or its nucleoside diphosphate kinase activity

    SciTech Connect

    Wright, K.T.; Seabright, R.; Logan, A.; Lilly, A.J.; Khanim, F.; Bunce, C.M.; Johnson, W.E.B.

    2010-07-16

    Research highlights: {yields} Extracellular Nm23H1 stimulates nerve growth. {yields} Extracellular Nm23H1 provides pathfinding cues to growth cones. {yields} The neurotrophic activity of Nm23H1 is independent of NDP kinase activity. {yields} The neurotrophic activity of Nm23H1 is independent of NGF. -- Abstract: The nucleoside diphosphate (NDP) kinase, Nm23H1, is a highly expressed during neuronal development, whilst induced over-expression in neuronal cells results in increased neurite outgrowth. Extracellular Nm23H1 affects the survival, proliferation and differentiation of non-neuronal cells. Therefore, this study has examined whether extracellular Nm23H1 regulates nerve growth. We have immobilised recombinant Nm23H1 proteins to defined locations of culture plates, which were then seeded with explants of embryonic chick dorsal root ganglia (DRG) or dissociated adult rat DRG neurons. The substratum-bound extracellular Nm23H1 was stimulatory for neurite outgrowth from chick DRG explants in a concentration-dependent manner. On high concentrations of Nm23H1, chick DRG neurite outgrowth was extensive and effectively limited to the location of the Nm23H1, i.e. neuronal growth cones turned away from adjacent collagen-coated substrata. Nm23H1-coated substrata also significantly enhanced rat DRG neuronal cell adhesion and neurite outgrowth in comparison to collagen-coated substrata. These effects were independent of NGF supplementation. Recombinant Nm23H1 (H118F), which does not possess NDP kinase activity, exhibited the same activity as the wild-type protein. Hence, a novel neuro-stimulatory activity for extracellular Nm23H1 has been identified in vitro, which may function in developing neuronal systems.

  12. Effects of combined electrical stimulation of the dorsal column and dorsal roots on wide-dynamic range neuronal activity in nerve-injured rats

    PubMed Central

    Yang, Fei; Zhang, Tong; Tiwari, Vinod; Shu, Bin; Zhang, Chen; Wang, Yun; Vera-Portocarrero, Louis P.; Raja, Srinivasa N.; Guan, Yun

    2015-01-01

    Objectives Electrical stimulation at the dorsal column (DC) and dorsal root (DR) may inhibit spinal wide-dynamic-range (WDR) neuronal activity in nerve-injured rats. The objective of this study was to determine if applying electrical conditioning stimulation (CS) at both sites provides additive or synergistic benefits. Materials and Methods By conducting in vivo extracellular recordings of WDR neurons in rats that had undergone L5 spinal nerve ligation, we tested whether combining 50 Hz CS at the two sites in either a concurrent (2.5 minutes) or alternate (5 minutes) pattern inhibits WDR neuronal activity better than CS at DC alone (5 minutes). The intensities of CS were determined by recording antidromic compound action potentials to graded stimulation at the DC and DR. We measured the current thresholds that resulted in the first detectable Aα/β waveform (Ab0) and the peak Aα/β waveform (Ab1) to select CS intensity at each site. The same number of electrical pulses and amount of current were delivered in different patterns to allow comparison. Results At a moderate intensity of 50%(Ab0+Ab1), different patterns of CS all attenuated the C-component of WDR neurons in response to graded intracutaneous electrical stimuli (0.1-10 mA, 2 ms), and inhibited windup in response to repetitive noxious stimuli (0.5 Hz). However, the inhibitory effects did not differ significantly between different patterns. At the lower intensity (Ab0), no CS inhibited WDR neurons. Conclusions These findings suggest that combined stimulation of DC and DR may not be superior to DC stimulation alone for inhibition of WDR neurons. PMID:26307526

  13. [The role of panoramic radiography in assessing the risk of injury to the inferior alveolar nerve before the extraction of mandibular wisdom teeth. The effect of the extent of root curvature and inferior alveolar canal-root tip overlap on the risk assessment].

    PubMed

    Szalma, József; Lempel, Edina; Csuta, Tamás; Bártfai, Dóra; Jeges, Sára; Olasz, Lajos

    2010-06-01

    The aim of the present study was to determine on panoramic radiographic images the effect of the distance between the root curvatures and inferior alveolar canal (IAC) root tip overlap on the surgeon's risk assessment predicting inferior alveolar nerve (IAN) paresthesia after lower third molar removal. In this case-control study 41 cases with postoperative IAN paresthesia and 359 controls without any postoperative complications were involved. Demographic data, root curvatures and the extent of IAC-root tip overlap were registered. The cases of major curvature--larger than 90 degrees (P=0.015; odds ratio [OR]=2.65), the "deepest" superimposition (P<0.001; OR=1.96), female gender (P=0.020) and increased age (P=0.008) were significantly associated with IAN paresthesia. Assessing root curvatures and the extent of IAC-root tip overlap for predicting IAN paresthesia after mandibular third molar removal should help to improve risk assessment.

  14. Sulphate as a xylem-borne chemical signal precedes the expression of ABA biosynthetic genes in maize roots.

    PubMed

    Ernst, Laura; Goodger, Jason Q D; Alvarez, Sophie; Marsh, Ellen L; Berla, Bert; Lockhart, Eric; Jung, Jiyul; Li, Pinghua; Bohnert, Hans J; Schachtman, Daniel P

    2010-07-01

    Recent reports suggest that early sensing of soil water stress by plant roots and the concomitant reduction in stomatal conductance may not be mediated by root-sourced abscisic acid (ABA), but that other xylem-borne chemicals may be the primary stress signal(s). To gain more insight into the role of root-sourced ABA, the timing and location of the expression of genes for key enzymes involved in ABA biosynthesis in Zea mays roots was measured and a comprehensive analysis of root xylem sap constituents from the early to the later stages of water stress was conducted. Xylem sap and roots were sampled from plants at an early stage of water stress when only a reduction in leaf conductance was measured, as well as at later stages when leaf xylem pressure potential decreased. It was found that the majority of ABA biosynthetic genes examined were only significantly expressed in the elongation region of roots at a later stage of water stress. Apart from ABA, sulphate was the only xylem-borne chemical that consistently showed significantly higher concentrations from the early to the later stages of stress. Moreover, there was an interactive effect of ABA and sulphate in decreasing maize transpiration rate and Vicia faba stomatal aperture, as compared to ABA alone. The expression of a sulphate transporter gene was also analysed and it was found that it had increased in the elongation region of roots from the early to the later stages of water stress. Our results support the suggestion that in the early stage of water stress, increased levels of ABA in xylem sap may not be due to root biosynthesis, ABA glucose ester catabolism or pH-mediated redistribution, but may be due to shoot biosynthesis and translocation to the roots. The analysis of xylem sap mineral content and bioassays indicate that the anti-transpirant effect of the ABA reaching the stomata at the early stages of water stress may be enhanced by the increased concentrations of sulphate in the xylem which is also

  15. Instrumentation to evaluate neural signal recording properties of micromachined microelectrodes inserted in invertebrate nerve.

    PubMed

    Banks, D J; Balachandran, W; Richards, P R; Ewins, D

    2002-05-01

    The design and characterization of instrumentation for application in evaluating the neural signal recording properties of probe-type microelectrodes, micromachined from silicon, are reported. Key aspects include the close matching of gain and frequency response between channels (better than 1%), flexibility in signal conditioning options, the ability to operate with a wide range of (microelectrode) recording site dimensions (4 microm x 4 micrm to 50 microm x 50 microm), and hence impedances, and the facility to monitor and store instrumentation settings on computer along with the recorded signals. Noise levels ranged from 3.7 microV rms for a 50 microm site, to 11.7 microV rms for a microm site, measured in saline. Close matching between channels was required to enable comparisons between different sites and different probes to be made with confidence; however, the instrumentation could be readily applied to less demanding applications.

  16. Disruption of Wnt/β-catenin Signaling in Odontoblasts and Cementoblasts Arrests Tooth Root Development in Postnatal Mouse Teeth

    PubMed Central

    Zhang, Ran; Yang, Guan; Wu, Ximei; Xie, Jing; Yang, Xiao; Li, Tiejun

    2013-01-01

    Tooth development undergoes a series of complex reciprocal interactions between dental epithelium and the underlying mesenchymal cells. Compared with the study in tooth crown formation, little is known about the molecular mechanism underlying the development of tooth roots. In the present study, we conditionally knock out β-catenin gene (Ctnnb1) within developing odontoblasts and cementoblasts during the development of tooth roots, and observed rootless molars as well as incomplete incisors. Histological analyses revealed intact structure of molar crown and labial side of incisor, however, as for the molar roots and the lingual portion of incisor, the formation of dentin and periodontal tissues were greatly hampered. In situ hybridization experiments using probes of odontoblastic marker genes collagen type I, alpha 1 (Col1a1), osteocalcin (OC) and dentin sialophosphoprotein (Dspp) manifested striking undifferentiation of root odontoblasts in which Ctnnb1 was eliminated. Bromodeoxyuridine (BrdU) labeling and proliferating cell nuclear antigen (PCNA) immunohistochemical experiments also showed retarded proliferation of pre-odontoblasts in mutant mice. However, cell apoptosis was not affected. Additionally, a disrupted formation of cementoblasts, suggested by the absence of transcripts of bone sialoprotein (Bsp) in follicle mesenchyme, was also evident in mutant mice. Our study provides strong in vivo evidence to confirm that Wnt/β-catenin signaling is functionally significant to root odontogenesis and cementogenesis during the tooth root development. PMID:23494738

  17. NO signaling is a key component of the root growth response to nitrate in Zea mays L.

    PubMed

    Trevisan, Sara; Manoli, Alessandro; Quaggiotti, Silvia

    2014-01-01

    Roots are considered to be a vital organ system of plants due to their involvement in water and nutrient uptake, anchorage, propagation, storage functions, secondary metabolite (including hormones) biosynthesis, and accumulation. Crops are strongly dependent on the availability of nitrogen in soil and on the efficiency of nitrogen utilization for biomass production and yield. However, knowledge about molecular responses to nitrogen fluctuations mainly derives from the study of model species. Nitric oxide (NO) has been proposed to be implicated in plant adaptation to environment, but its exact role in the response of plants to nutritional stress is still under evaluation. Recently a novel role for NO production and scavenging, thanks to the coordinate spatio-temporal expression of nitrate reductase and non-symbiotic hemoglobins, in the maize root response to nitrate has been postulated. This control of NO homeostasis is preferentially accomplished by the cells of the root transition zone (TZ) which seem to represent the most nitrate responsive portion of maize root. The TZ is already known to function as a sensory center able to gather information from the external environment and to re-elaborate them in an adequate response. These results indicate that it could play a central role also for nitrate sensing by roots. A lot of work is still needed to identify and characterize other upstream and downstream signals involved in the "nitrate-NO" pathway, leading to root architecture adjustments and finally to stress adaptation.

  18. Disruption of Wnt/β-catenin signaling in odontoblasts and cementoblasts arrests tooth root development in postnatal mouse teeth.

    PubMed

    Zhang, Ran; Yang, Guan; Wu, Ximei; Xie, Jing; Yang, Xiao; Li, Tiejun

    2013-01-01

    Tooth development undergoes a series of complex reciprocal interactions between dental epithelium and the underlying mesenchymal cells. Compared with the study in tooth crown formation, little is known about the molecular mechanism underlying the development of tooth roots. In the present study, we conditionally knock out β-catenin gene (Ctnnb1) within developing odontoblasts and cementoblasts during the development of tooth roots, and observed rootless molars as well as incomplete incisors. Histological analyses revealed intact structure of molar crown and labial side of incisor, however, as for the molar roots and the lingual portion of incisor, the formation of dentin and periodontal tissues were greatly hampered. In situ hybridization experiments using probes of odontoblastic marker genes collagen type I, alpha 1 (Col1a1), osteocalcin (OC) and dentin sialophosphoprotein (Dspp) manifested striking undifferentiation of root odontoblasts in which Ctnnb1 was eliminated. Bromodeoxyuridine (BrdU) labeling and proliferating cell nuclear antigen (PCNA) immunohistochemical experiments also showed retarded proliferation of pre-odontoblasts in mutant mice. However, cell apoptosis was not affected. Additionally, a disrupted formation of cementoblasts, suggested by the absence of transcripts of bone sialoprotein (Bsp) in follicle mesenchyme, was also evident in mutant mice. Our study provides strong in vivo evidence to confirm that Wnt/β-catenin signaling is functionally significant to root odontogenesis and cementogenesis during the tooth root development.

  19. Deficits in foot skin sensation are related to alterations in balance control in chronic low back patients experiencing clinical signs of lumbar nerve root impingement.

    PubMed

    Frost, Lydia R; Bijman, Marc; Strzalkowski, Nicholas D J; Bent, Leah R; Brown, Stephen H M

    2015-05-01

    Chronic low back pain (LBP) patients with radiculopathy, or sciatica, experience pain, tingling or numbness radiating down their leg due to compression of the lumbar nerve root. The resulting reduction in somatosensory information from the foot sole may contribute to deficits in standing balance control. This work was designed to investigate the relationship between foot skin sensitivity and standing balance control in chronic LBP patients with associated radiculopathy. Patients (n=9) and matched healthy controls (n=9) were recruited to the study, and were tested for balance control in both quiet standing as well as during rapid arm raise perturbation trials on a force plate. Foot skin sensitivity was tested bilaterally for vibratory threshold (3, 40 and 250 Hz) and touch (monofilament) threshold. Results demonstrate that patients had reduced sensitivity to 250 Hz vibration in their affected compared to unaffected foot (at the great toe and heel), as well as compared to controls (at the great toe), but there were no differences with lower frequency vibratory testing or with monofilament testing. While there were no significant between-group differences in balance measures, moderate statistically significant correlations between 250 Hz sensitivity and quiet standing balance parameters were uncovered. Thus, patients demonstrate reduced high-frequency vibratory sensitivity at the foot sole, and correlations with quiet standing balance measures indicate a connection between these foot skin sensitivity deficits and alterations in balance control. Clinically, this identifies high frequency vibration testing as an important measure of skin sensitivity in patients with radiculopathy.

  20. In Vivo Characterization of Intracellular Signaling Pathways Activated by the Nerve Agent Sarin

    DTIC Science & Technology

    2004-03-01

    Ca+2/calmodulin-dependent protein phosphatase signaling cascade, which dephosphorylates T34- DARPP-32 (Nishi et al., 1999). Activation of the D 1...phosphorylation state of DARPP-32 at Ser-102 (S102) and Ser-137 (S137) (see Figure 1). For example, S 102 on DARPP-32 is phosphorylated by casein kinase...cGMP-dependent protein kinase (PKG) (Girault et al., 1989). DARPP-32 is also phosphorylated on amino acid S137 by casein kinase I (CK1). Increases in

  1. Changes in cytosolic pH within Arabidopsis root columella cells play a key role in the early signaling pathway for root gravitropism

    NASA Technical Reports Server (NTRS)

    Scott, A. C.; Allen, N. S.; Davies, E. (Principal Investigator)

    1999-01-01

    Ratiometric wide-field fluorescence microscopy with 1',7'- bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF)-dextran demonstrated that gravistimulation leads to rapid changes in cytoplasmic pH (pHc) in columella cells of Arabidopsis roots. The pHc of unstimulated columella cells in tiers 2 and 3, known sites of graviperception (E.B. Blancaflor, J.B. Fasano, S. Gilroy [1998] Plant Physiol 116: 213-222), was 7.22 +/- 0.02 pH units. Following gravistimulation, the magnitude and direction of pHc changes in these cells depended on their location in the columella. Cells in the lower side of tier 2 became more alkaline by 0.4 unit within 55 s of gravistimulation, whereas alkalinization of the cells on the upper side was slower (100 s). In contrast, all cells in tier 3 acidified by 0.4 pH unit within 480 s after gravistimulation. Disrupting these pHc changes in the columella cells using pHc modifiers at concentrations that do not affect root growth altered the gravitropic response. Acidifying agents, including bafilomycin A1, enhanced curvature, whereas alkalinizing agents disrupted gravitropic bending. These results imply that pHc changes in the gravisensing cells and the resultant pH gradients across the root cap are important at an early stage in the signal cascade leading to the gravitropic response.

  2. Diagnosis of Nerve Root Compromise of the Lumbar Spine: Evaluation of the Performance of Three-dimensional Isotropic T2-weighted Turbo Spin-Echo SPACE Sequence at 3T

    PubMed Central

    Sung, Jinkyeong; Jung, Joon-Yong; Jang, Jinhee; Kim, Jin-Sung; Kim, Young-Hoon; Ha, Kee-Yong

    2017-01-01

    Objective To explore the performance of three-dimensional (3D) isotropic T2-weighted turbo spin-echo (TSE) sampling perfection with application optimized contrasts using different flip angle evolution (SPACE) sequence on a 3T system, for the evaluation of nerve root compromise by disc herniation or stenosis from central to extraforaminal location of the lumbar spine, when used alone or in combination with conventional two-dimensional (2D) TSE sequence. Materials and Methods Thirty-seven patients who had undergone 3T spine MRI including 2D and 3D sequences, and had subsequent spine surgery for nerve root compromise at a total of 39 nerve levels, were analyzed. A total of 78 nerve roots (48 symptomatic and 30 asymptomatic sites) were graded (0 to 3) using different MRI sets of 2D, 3D (axial plus sagittal), 3D (all planes), and combination of 2D and 3D sequences, with respect to the nerve root compromise caused by posterior disc herniations, lateral recess stenoses, neural foraminal stenoses, or extraforaminal disc herniations; grading was done independently by two readers. Diagnostic performance was compared between different imaging sets using the receiver operating characteristics (ROC) curve analysis. Results There were no statistically significant differences (p = 0.203 to > 0.999) in the ROC curve area between the imaging sets for both readers 1 and 2, except for combined 2D and 3D (0.843) vs. 2D (0.802) for reader 1 (p = 0.035), and combined 2D and 3D (0.820) vs. 3D including all planes (0.765) for reader 2 (p = 0.049). Conclusion The performance of 3D isotropic T2-weighted TSE sequence of the lumbar spine, whether axial plus sagittal images, or all planes of images, was not significantly different from that of 2D TSE sequences, for the evaluation of nerve root compromise of the lumbar spine. Combining 2D and 3D might possibly improve the diagnostic accuracy compared with either one. PMID:28096733

  3. Electromechanical Nerve Stimulator

    NASA Technical Reports Server (NTRS)

    Tcheng, Ping; Supplee, Frank H., Jr.; Prass, Richard L.

    1993-01-01

    Nerve stimulator applies and/or measures precisely controlled force and/or displacement to nerve so response of nerve measured. Consists of three major components connected in tandem: miniature probe with spherical tip; transducer; and actuator. Probe applies force to nerve, transducer measures force and sends feedback signal to control circuitry, and actuator positions force transducer and probe. Separate box houses control circuits and panel. Operator uses panel to select operating mode and parameters. Stimulator used in research to characterize behavior of nerve under various conditions of temperature, anesthesia, ventilation, and prior damage to nerve. Also used clinically to assess damage to nerve from disease or accident and to monitor response of nerve during surgery.

  4. The effect of single-pulse transcranial magnetic stimulation and peripheral nerve stimulation on complexity of EMG signal: fractal analysis.

    PubMed

    Cukic, M; Oommen, J; Mutavdzic, D; Jorgovanovic, N; Ljubisavljevic, M

    2013-07-01

    The aim of this study was to examine whether single-pulse transcranial magnetic stimulation (spTMS) affects the pattern of corticospinal activity once voluntary drive has been restored after spTMS-induced EMG silence. We used fractal dimension (FD) to explore the 'complexity' of the electromyography (EMG) signal, and median frequency of the spectra (MDF) to examine changes in EMG spectral characteristics. FD and MDF of the raw EMG epochs immediately before were compared with those obtained from epochs after the EMG silence. Changes in FD and MDF after spTMS were examined with three levels of muscle contraction corresponding to weak (20-40%), moderate (40-60%) and strong (60-80% of maximal voluntary contraction) and three intensities of stimulation set at 10, 20 and 30% above the resting motor threshold. FD was calculated using the Higuchi fractal dimension algorithm. Finally, to discern the origin of FD changes between the CNS and muscle, we compared the effects of spTMS with the effects of peripheral nerve stimulation (PNS) on FD and MDF. The results show that spTMS induced significant decrease in both FD and MDF of EMG signal after stimulation. PNS did not have any significant effects on FD nor MDF. Changes in TMS intensity did not have any significant effect on FD or MDF after stimulation nor had the strength of muscle contraction. However, increase in contraction strength decreased FD before stimulation but only between weak and moderate contraction. The results suggest that the effects of spTMS on corticospinal activity, underlying voluntary motor output, outlast the TMS stimulus. It appears that the complexity of the EMG signal is reduced after spTMS, suggesting that TMS alters the dynamics of the ongoing corticospinal activity most likely temporarily synchronizing the neural network activity. Further studies are needed to confirm whether observed changes after TMS occur at the cortical level.

  5. Influence of ATP-binding cassette transporters in root exudation of phytoalexins, signals, and disease resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The roots of plants secrete compounds as a way to exchange information with organ-isms living in the soil. Here, we report the involvement of seven root-expressed ATP-binding cassette (ABC) transporters corresponding to both full and half-size molecules (Atabcg36, Atabcg37, Atabcc5, Atabcf1, Atabcf3...

  6. The Interaction between Rice ERF3 and WOX11 Promotes Crown Root Development by Regulating Gene Expression Involved in Cytokinin Signaling[OPEN

    PubMed Central

    Song, Yaling; Huang, Yulan

    2015-01-01

    Crown roots are the main components of the fibrous root system in rice (Oryza sativa). WOX11, a WUSCHEL-related homeobox gene specifically expressed in the emerging crown root meristem, is a key regulator in crown root development. However, the nature of WOX11 function in crown root development has remained elusive. Here, we identified a rice AP2/ERF protein, ERF3, which interacts with WOX11 and was expressed in crown root initials and during crown root growth. Functional analysis revealed that ERF3 was essential for crown root development and acts in auxin- and cytokinin-responsive gene expression. Downregulation of ERF3 in wox11 mutants produced a more severe root phenotype. Also, increased expression of ERF3 could partially complement wox11, indicating that the two genes functioned cooperatively to regulate crown root development. ERF3 and WOX11 shared a common target, the cytokinin-responsive gene RR2. The expression of ERF3 and WOX11 only partially overlapped, underlining a spatio-temporal control of RR2 expression and crown root development. Furthermore, ERF3-regulated RR2 expression was involved in crown root initiation, while the ERF3/WOX11 interaction likely repressed RR2 during crown root elongation. These results define a mechanism regulating gene expression involved in cytokinin signaling during different stages of crown root development in rice. PMID:26307379

  7. Solitary fibrous tumour of the vagus nerve.

    PubMed

    Scholsem, Martin; Scholtes, Felix

    2012-04-01

    We describe the complete removal of a foramen magnum solitary fibrous tumour in a 36-year-old woman. It originated on a caudal vagus nerve rootlet, classically described as the 'cranial' accessory nerve root. This ninth case of immunohistologically confirmed cranial or spinal nerve SFT is the first of the vagus nerve.

  8. Transcriptional and Functional Classification of the GOLVEN/ROOT GROWTH FACTOR/CLE-Like Signaling Peptides Reveals Their Role in Lateral Root and Hair Formation1[W][OA

    PubMed Central

    Fernandez, Ana; Drozdzecki, Andrzej; Hoogewijs, Kurt; Nguyen, Anh; Beeckman, Tom; Madder, Annemieke; Hilson, Pierre

    2013-01-01

    The GOLVEN (GLV)/ROOT GROWTH FACTORS/CLE-Like small signaling peptide family is encoded by 11 genes in Arabidopsis (Arabidopsis thaliana). Some of them have already been shown to control root meristem maintenance, auxin fluxes, and gravitropic responses. As a basis for the detailed analysis of their function, we determined the expression domains for each of the 11 GLV genes with promoter-reporter lines. Although they are collectively active in all examined plant parts, GLV genes have highly specific transcription patterns, generally restricted to very few cells or cell types in the root and shoot and in vegetative and reproductive tissues. GLV functions were further investigated with the comparative analysis of root phenotypes induced by gain- and loss-of-function mutants or in treatments with GLV-derived synthetic peptides. We identified functional classes that relate to the gene expression domains in the primary root and suggest that different GLV signals trigger distinct downstream pathways. Interestingly, GLV genes transcribed at the early stages of lateral root development strongly inhibited root branching when overexpressed. Furthermore, transcription patterns together with mutant phenotypes pointed to the involvement of GLV4 and GLV8 in root hair formation. Overall, our data suggest that nine GLV genes form three subgroups according to their expression and function within the root and offer a comprehensive framework to study the role of the GLV signaling peptides in plant development. PMID:23370719

  9. The effect of botulinum neurotoxin A on sciatic nerve injury-induced neuroimmunological changes in rat dorsal root ganglia and spinal cord.

    PubMed

    Mika, J; Rojewska, E; Makuch, W; Korostynski, M; Luvisetto, S; Marinelli, S; Pavone, F; Przewlocka, B

    2011-02-23

    Botulinum neurotoxin serotype A (BoNT/A) acts by cleaving synaptosome-associated-protein-25 (SNAP-25) in nerve terminals to inhibit neuronal release and shows long-lasting antinociceptive action in neuropathic pain. However, its precise mechanism of action remains unclear. Our study aimed to characterize BoNT/A-induced neuroimmunological changes after chronic constriction injury (CCI) of the sciatic nerve. In the ipsilateral lumbar spinal cords of CCI-exposed rats, the mRNA of microglial marker (complement component 1q, C1q), astroglial marker (glial fibrillary acidic protein, GFAP), and prodynorphin were upregulated, as measured by reverse transcription-polymerase chain reaction (RT-PCR). No changes appeared in mRNA for proenkephalin, pronociceptin, or neuronal and inducible nitric oxide synthase (NOS1 and NOS2, respectively). In the dorsal root ganglia (DRG), an ipsilateral upregulation of prodynorphin, pronociceptin, C1q, GFAP, NOS1 and NOS2 mRNA and a downregulation of proenkephalin mRNA were observed. A single intraplantar BoNT/A (75 pg/paw) injection induced long-lasting antinociception in this model. BoNT/A diminished the injury-induced ipsilateral spinal upregulation of C1q mRNA. In the ipsilateral DRG a significant decrease of C1q-positive cell activation and of the upregulation of prodynorphin, pronociceptin and NOS1 mRNA was also observed following BoNT/A admistration. BoNT/A also diminished the injury-induced upregulation of SNAP-25 expression in both structures. We provide evidence that BoNT/A impedes injury-activated neuronal function in structures distant from the injection site, which is demonstrated by its influence on NOS1, prodynorphin and pronociceptin mRNA levels in the DRG. Moreover, the silence of microglia/macrophages after BoNT/A administration could be secondary to the inhibition of neuronal activity, but this decrease in neuroimmune interactions could be the key to the long-lasting BoNT/A effect on neuropathic pain.

  10. Erythropoietin promotes axonal regeneration after optic nerve crush in vivo by inhibition of RhoA/ROCK signaling pathway.

    PubMed

    Tan, Haibo; Zhong, Yisheng; Shen, Xi; Cheng, Yu; Jiao, Qin; Deng, Lianfu

    2012-11-01

    We investigated whether the RhoA/ROCK pathway was involved in the effect of erythropoietin (EPO) to promote retinal ganglion cells (RGCs) axonal regeneration in a rat optic nerve crush (ONC) model. We demonstrated that both EPO and ROCK inhibitor Y-27632 significantly enhanced RGCs survival and axon regeneration in vivo, and the effects of these agents were additive. Expression of active-RhoA was decreased after EPO or Y-27632 per pull down assay and affinity precipitation. Administration of EPO and Y-27632 cocktail resulted in even more RhoA inactivation, decreased expression of ROCK-1 and ROCK-2, and increased expression of growth associated protein-43 (GAP-43) protein per immunohistochemistry and western blot analysis. Down-regulation of active-RhoA, ROCK-1, and ROCK-2 expression by EPO coincided with the appearance of larger numbers of regenerating axons. In conclusion, the RhoA/ROCK signaling pathway was involved in the EPO effect to promote RGCs axon regeneration after ONC.

  11. Schwann cell proliferation and differentiation that is induced by ferulic acid through MEK1/ERK1/2 signalling promotes peripheral nerve remyelination following crush injury in rats

    PubMed Central

    Zhu, Xiaoyan; Li, Kun; Guo, Xin; Wang, Jian; Xiang, Yang

    2016-01-01

    Schwann cell proliferation and differentiation is critical for the remyelination of injured peripheral nerves. Ferulic acid (FA) is a widely used antioxidant agent with neuroprotective properties. However, the potentially beneficial effects of FA on Schwann cells are unknown. Therefore, the present study was designed to examine the effects of FA on Schwann cell proliferation and differentiation. By using the cultured primary Schwann cells and proliferation assay, the results identified that FA was capable of increasing Schwann cell proliferation and expression of myelin-associated glycoprotein (MAG) and myelin basic protein (MBP) in vitro. It was also observed that the beneficial effect of FA treatment on Schwann cells was mainly dependent on the activation of MEK1/ERK1/2 signalling. Furthermore, FA was intraperitoneally administered to rats with sciatic nerve crush injury, and the results revealed an increase in Schwann cell proliferation and differentiation, while the MAG and MBP expression levels in sciatic nerves were markedly upregulated following FA administration. In conclusion, the current results demonstrate that Schwann cell proliferation and differentiation is induced by FA through MEK1/ERK1/2 signalling and that FA may accelerate injured peripheral nerve remyelination. PMID:27588110

  12. Local root abscisic acid (ABA) accumulation depends on the spatial distribution of soil moisture in potato: implications for ABA signalling under heterogeneous soil drying

    PubMed Central

    Puértolas, Jaime; Conesa, María R.; Ballester, Carlos; Dodd, Ian C.

    2015-01-01

    Patterns of root abscisic acid (ABA) accumulation ([ABA]root), root water potential (Ψroot), and root water uptake (RWU), and their impact on xylem sap ABA concentration ([X-ABA]) were measured under vertical partial root-zone drying (VPRD, upper compartment dry, lower compartment wet) and horizontal partial root-zone drying (HPRD, two lateral compartments: one dry, the other wet) of potato (Solanum tuberosum L.). When water was withheld from the dry compartment for 0–10 d, RWU and Ψroot were similarly lower in the dry compartment when soil volumetric water content dropped below 0.22cm3 cm–3 for both spatial distributions of soil moisture. However, [ABA]root increased in response to decreasing Ψroot in the dry compartment only for HPRD, resulting in much higher ABA accumulation than in VPRD. The position of the sampled roots (~4cm closer to the surface in the dry compartment of VPRD than in HPRD) might account for this difference, since older (upper) roots may accumulate less ABA in response to decreased Ψroot than younger (deeper) roots. This would explain differences in root ABA accumulation patterns under vertical and horizontal soil moisture gradients reported in the literature. In our experiment, these differences in root ABA accumulation did not influence [X-ABA], since the RWU fraction (and thus ABA export to shoots) from the dry compartment dramatically decreased simultaneously with any increase in [ABA]root. Thus, HPRD might better trigger a long-distance ABA signal than VPRD under conditions allowing simultaneous high [ABA]root and relatively high RWU fraction. PMID:25547916

  13. Local root abscisic acid (ABA) accumulation depends on the spatial distribution of soil moisture in potato: implications for ABA signalling under heterogeneous soil drying.

    PubMed

    Puértolas, Jaime; Conesa, María R; Ballester, Carlos; Dodd, Ian C

    2015-04-01

    Patterns of root abscisic acid (ABA) accumulation ([ABA]root), root water potential (Ψroot), and root water uptake (RWU), and their impact on xylem sap ABA concentration ([X-ABA]) were measured under vertical partial root-zone drying (VPRD, upper compartment dry, lower compartment wet) and horizontal partial root-zone drying (HPRD, two lateral compartments: one dry, the other wet) of potato (Solanum tuberosum L.). When water was withheld from the dry compartment for 0-10 d, RWU and Ψroot were similarly lower in the dry compartment when soil volumetric water content dropped below 0.22cm(3) cm(-3) for both spatial distributions of soil moisture. However, [ABA]root increased in response to decreasing Ψroot in the dry compartment only for HPRD, resulting in much higher ABA accumulation than in VPRD. The position of the sampled roots (~4cm closer to the surface in the dry compartment of VPRD than in HPRD) might account for this difference, since older (upper) roots may accumulate less ABA in response to decreased Ψroot than younger (deeper) roots. This would explain differences in root ABA accumulation patterns under vertical and horizontal soil moisture gradients reported in the literature. In our experiment, these differences in root ABA accumulation did not influence [X-ABA], since the RWU fraction (and thus ABA export to shoots) from the dry compartment dramatically decreased simultaneously with any increase in [ABA]root. Thus, HPRD might better trigger a long-distance ABA signal than VPRD under conditions allowing simultaneous high [ABA]root and relatively high RWU fraction.

  14. Integration of hormonal signaling networks and mobile microRNAs is required for vascular patterning in Arabidopsis roots

    PubMed Central

    Muraro, Daniele; Mellor, Nathan; Pound, Michael P.; Help, Hanna; Lucas, Mikaël; Chopard, Jérôme; Byrne, Helen M.; Godin, Christophe; Hodgman, T. Charlie; King, John R.; Pridmore, Tony P.; Helariutta, Ykä; Bennett, Malcolm J.; Bishopp, Anthony

    2014-01-01

    As multicellular organisms grow, positional information is continually needed to regulate the pattern in which cells are arranged. In the Arabidopsis root, most cell types are organized in a radially symmetric pattern; however, a symmetry-breaking event generates bisymmetric auxin and cytokinin signaling domains in the stele. Bidirectional cross-talk between the stele and the surrounding tissues involving a mobile transcription factor, SHORT ROOT (SHR), and mobile microRNA species also determines vascular pattern, but it is currently unclear how these signals integrate. We use a multicellular model to determine a minimal set of components necessary for maintaining a stable vascular pattern. Simulations perturbing the signaling network show that, in addition to the mutually inhibitory interaction between auxin and cytokinin, signaling through SHR, microRNA165/6, and PHABULOSA is required to maintain a stable bisymmetric pattern. We have verified this prediction by observing loss of bisymmetry in shr mutants. The model reveals the importance of several features of the network, namely the mutual degradation of microRNA165/6 and PHABULOSA and the existence of an additional negative regulator of cytokinin signaling. These components form a plausible mechanism capable of patterning vascular tissues in the absence of positional inputs provided by the transport of hormones from the shoot. PMID:24381155

  15. The role of Ca 2+-related signaling in photodynamic injury of nerve and glial cells

    NASA Astrophysics Data System (ADS)

    Lobanov, A. V.; Petin, Y. O.; Uzdensky, A. B.

    2007-05-01

    Photodynamic therapy (PDT) inhibited and irreversibly abolished firing, caused necrosis of neurons, necrosis, apoptosis and proliferation of glial cells in the isolated crayfish stretch receptor. The role in these processes of the central components of Ca 2+-mediated signaling pathway: phospholipase C, calmodulin, calmodulin-dependent kinase II, and protein kinase C was studied using their inhibitors: ET-18, fluphenazine, KN-93, or staurosporine, respectively. ET-18 reduced functional inactivation of neurons, necrosis and apoptosis of glial cells. Fluphenazine and KN-93 reduced PDT-induced necrosis of neurons and glial cells. Staurosporine enhanced PDT-induced glial apoptosis. PDTinduced gliosis was prevented by KN-93 and staurosporine. Therefore, phospholipase C participated in neuron inactivation and glial necrosis and apoptosis. Calmodulin and calmodulin-dependent kinase II were involved in PDT-induced necrosis of neurons and glial cells but not in glial apoptosis. Protein kinase C protected glia from apoptosis and participated in PDT-induced gliosis and loss of neuronal activity. These data may be used for modulation of PDT of brain tumors.

  16. ARG1 and ARL2 contribute to gravity signal transduction in the statocytes of Arabidopsis thaliana roots and hypocotyls

    NASA Astrophysics Data System (ADS)

    Masson, Patrick; Harrison, Benjamin; Stanga, John; Otegui, Marisa; Sedbrook, John

    Gravity is an important cue that plant organs use to guide their growth. Each organ is characterized by a defined gravity set point angle that dictates its optimal orientation within the gravity field. Specialized cells, named statocytes, enable this directional growth response by perceiving gravity via the sedimentation of, and/or tension/pressure exerted by, starch-filled plastids within their cytoplasm. Located in the columella region of the cap in roots and in the endodermis of hypocotyls and stems, these cells modulate the lateral transport of auxin across the corresponding organ in a gravistimulus-dependent manner. Upon plant reorientation within the gravity field, a gravity signal transduction pathway is activated within those cells, which in roots leads to a relocalization of the PIN3 auxin efflux carrier toward the lower membrane and an alkalinization of the cytoplasm. In turn, these events appear to promote a lateral transport of auxin toward the bottom side of the stimulated organ, which promotes a curvature. We previously uncovered ARG1 and ARL2 as essential contributors to these cellular processes. Mutations in these genes result in altered root and hypocotyl gravitropism. In roots, this abnormal growth behavior is associated with a lack of PIN3 relocalization within the statocytes and an absence of preferential downward auxin transport upon gravistimulation. These two genes encode paralogous J-domain proteins that are associated with the plasma membrane and other membranes of the vesicular trafficking pathway, and appear to modulate protein trafficking within the statocytes. An analysis of the root gravitropic phenotypes associated with different double mutant configurations affecting ARG1, ARL2 and PIN3 suggest that all three proteins function in a common gravity-signaling pathway. Surprisingly, when a mutation that affects starch biosynthesis (pgm) is introgressed into an arg1-2 mutant, the gravitropic defects are dramatically enhanced relative to

  17. A novel chondroitin sulfate hydrogel for nerve repair

    NASA Astrophysics Data System (ADS)

    Conovaloff, Aaron William

    Brachial plexus injuries affect numerous patients every year, with very debilitating results. The majority of these cases are very severe, and involve damage to the nerve roots. To date, repair strategies for these injuries address only gross tissue damage, but do not supply cells with adequate regeneration signals. As a result, functional recovery is often severely lacking. Therefore, a chondroitin sulfate hydrogel that delivers neurotrophic signals to damaged neurons is proposed as a scaffold to support nerve root regeneration. Capillary electrophoresis studies revealed that chondroitin sulfate can physically bind with a variety of neurotrophic factors, and cultures of chick dorsal root ganglia demonstrated robust neurite outgrowth in chondroitin sulfate hydrogels. Outgrowth in chondroitin sulfate gels was greater than that observed in control gels of hyaluronic acid. Furthermore, the chondroitin sulfate hydrogel's binding activity with nerve growth factor could be enhanced by incorporation of a synthetic bioactive peptide, as revealed by fluorescence recovery after photobleaching. This enhanced binding was observed only in chondroitin sulfate gels, and not in hyaluronic acid control gels. This enhanced binding activity resulted in enhanced dorsal root ganglion neurite outgrowth in chondroitin sulfate gels. Finally, the growth of regenerating dorsal root ganglia in these gels was imaged using label-free coherent anti-Stokes scattering microscopy. This technique generated detailed, high-quality images of live dorsal root ganglion neurites, which were comparable to fixed, F-actin-stained samples. Taken together, these results demonstrate the viability of this chondroitin sulfate hydrogel to serve as an effective implantable scaffold to aid in nerve root regeneration.

  18. Nerve Regeneration Potential of Protocatechuic Acid in RSC96 Schwann Cells by Induction of Cellular Proliferation and Migration through IGF-IR-PI3K-Akt Signaling.

    PubMed

    Ju, Da-Tong; Liao, Hung-En; Shibu, Marthandam Asokan; Ho, Tsung-Jung; Padma, Viswanadha Vijaya; Tsai, Fuu-Jen; Chung, Li-Chin; Day, Cecilia Hsuan; Lin, Chien-Chung; Huang, Chih-Yang

    2015-12-31

    Peripheral nerve injuries, caused by accidental trauma, acute compression or surgery, often result in temporary or life-long neuronal dysfunctions and inflict great economic or social burdens on the patients. Nerve cell proliferation is an essential process to restore injured nerves of adults. Schwann cells play a crucial role in endogenous repair of peripheral nerves due to their ability to proliferate, migrate and provide trophic support to axons via expression of various neurotrophic factors, such as the nerve growth factor (NGF), especially after nerve injury. Protocatechuic acid (PCA) is a dihydroxybenzoic acid, a type of phenolic acid, isolated from the kernels of Alpinia oxyphylla Miq (AOF), a traditional Chinese herbal medicine the fruits of which are widely used as a tonic, aphrodisiac, anti-salivation and anti-diarrheatic. This study investigated the molecular mechanisms by which PCA induces Schwann cell proliferation by activating IGF-IR-PI3K-Akt pathway. Treatment with PCA induces phosphorylation of the insulin-like growth factor-I (IGF-I)-mediated phosphatidylinositol 3 kinase/serine - threonine kinase (PI3K/Akt) pathway, and activates expression of cell nuclear antigen (PCNA) in a dose-dependent manner. Cell cycle analysis after 18 h of treatment showed that proliferation of the RSC96 cells was enhanced by PCA treatment. The PCA induced proliferation was accompanied by modulation in the expressions of cell cycle proteins cyclin D1, cyclin E and cyclin A. Knockdown of PI3K using small interfering RNA (siRNA) and inhibition of IGF-IR receptor resulted in the reduction in cell survival proteins. The results collectively showed that PCA treatment promoted cell proliferation and cell survival via IGF-I signaling.

  19. Low levels of strigolactones in roots as a component of the systemic signal of drought stress in tomato.

    PubMed

    Visentin, Ivan; Vitali, Marco; Ferrero, Manuela; Zhang, Yanxia; Ruyter-Spira, Carolien; Novák, Ondřej; Strnad, Miroslav; Lovisolo, Claudio; Schubert, Andrea; Cardinale, Francesca

    2016-12-01

    Strigolactones (SL) contribute to drought acclimatization in shoots, because SL-depleted plants are hypersensitive to drought due to stomatal hyposensitivity to abscisic acid (ABA). However, under drought, SL biosynthesis is repressed in roots, suggesting organ specificity in their metabolism and role. Because SL can be transported acropetally, such a drop may also affect shoots, as a systemic indication of stress. We investigated this hypothesis by analysing molecularly and physiologically wild-type (WT) tomato (Solanum lycopersicum) scions grafted onto SL-depleted rootstocks, compared with self-grafted WT and SL-depleted genotypes, during a drought time-course. Shoots receiving few SL from the roots behaved as if under mild stress even if irrigated. Their stomata were hypersensitive to ABA (likely via a localized enhancement of SL synthesis in shoots). Exogenous SL also enhanced stomata sensitivity to ABA. As the partial shift of SL synthesis from roots to shoots mimics what happens under drought, a reduction of root-produced SL might represent a systemic signal unlinked from shootward ABA translocation, and sufficient to prime the plant for better stress avoidance.

  20. Effects of sciatic nerve transection on ultrastructure, NADPH-diaphorase reaction and serotonin-, tyrosine hydroxylase-, c-Fos-, glucose transporter 1- and 3-like immunoreactivities in frog dorsal root ganglion

    PubMed Central

    Rigon, F.; Rossato, D.; Auler, V.B.; Dal Bosco, L.; Faccioni-Heuser, M.C.; Partata, W.A.

    2013-01-01

    Frogs have been used as an alternative model to study pain mechanisms. Since we did not find any reports on the effects of sciatic nerve transection (SNT) on the ultrastructure and pattern of metabolic substances in frog dorsal root ganglion (DRG) cells, in the present study, 18 adult male frogs (Rana catesbeiana) were divided into three experimental groups: naive (frogs not subjected to surgical manipulation), sham (frogs in which all surgical procedures to expose the sciatic nerve were used except transection of the nerve), and SNT (frogs in which the sciatic nerve was exposed and transected). After 3 days, the bilateral DRG of the sciatic nerve was collected and used for transmission electron microscopy. Immunohistochemistry was used to detect reactivity for glucose transporter (Glut) types 1 and 3, tyrosine hydroxylase, serotonin and c-Fos, as well as nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase). SNT induced more mitochondria with vacuolation in neurons, satellite glial cells (SGCs) with more cytoplasmic extensions emerging from cell bodies, as well as more ribosomes, rough endoplasmic reticulum, intermediate filaments and mitochondria. c-Fos immunoreactivity was found in neuronal nuclei. More neurons and SGCs surrounded by tyrosine hydroxylase-like immunoreactivity were found. No change occurred in serotonin- and Glut1- and Glut3-like immunoreactivity. NADPH-diaphorase occurred in more neurons and SGCs. No sign of SGC proliferation was observed. Since the changes of frog DRG in response to nerve injury are similar to those of mammals, frogs should be a valid experimental model for the study of the effects of SNT, a condition that still has many unanswered questions. PMID:23739744

  1. Biological roles of anti-GM1 antibodies in patients with Guillain-Barré syndrome for nerve growth factor signaling.

    PubMed

    Tanaka, Toshifumi; Furutama, Daisuke; Sakai, Reiko; Fujita, Atsushi; Kimura, Fumiharu; Tagami, Muneyoshi; Ohsawa, Nakaaki; Hanafusa, Toshiaki

    2007-05-01

    To reveal the biological and pathological roles of anti-GM1 antibody in Guillain-Barré syndrome (GBS), we examined its effects on nerve growth factor (NGF) induced TrkA autophosphorylation (NGF-TrkA signaling) in PC12 cells, a sympathetic nerve cell line. The NGF-TrkA signaling is enhanced by exogenous GM1 ganglioside and this phenomenon is regarded as one of the functional aspects of GM1. The IgGs purified from patients' sera inhibited the NGF-TrkA signaling in GM1 pre-incubated PC12 cells. The degrees of inhibition by IgGs from patients paralleled their immunological reactivity to GM1. In addition, the IgGs also inhibited the neurite outgrowth of NGF-treated PC12 cells. Immunoglobulins in the rabbit sera, which were immunized by GM1, also caused a similar suppressive phenomenon. These results suggested that the anti-GM1 antibody could play roles in pathophysiology in anti-GM1 antibody positive GBS through interfering with the neurotrophic action of NGF and GM1 mediated signal modulation including NGF-TrkA signaling. It is suggested that the modulation of GM1 function is one important action of antibodies and could be one of the important mechanisms in GBS.

  2. CLE-CLAVATA1 peptide-receptor signaling module regulates the expansion of plant root systems in a nitrogen-dependent manner.

    PubMed

    Araya, Takao; Miyamoto, Mayu; Wibowo, Juliarni; Suzuki, Akinori; Kojima, Soichi; Tsuchiya, Yumiko N; Sawa, Shinichiro; Fukuda, Hiroo; von Wirén, Nicolaus; Takahashi, Hideki

    2014-02-04

    Morphological plasticity of root systems is critically important for plant survival because it allows plants to optimize their capacity to take up water and nutrients from the soil environment. Here we show that a signaling module composed of nitrogen (N)-responsive CLE (CLAVATA3/ESR-related) peptides and the CLAVATA1 (CLV1) leucine-rich repeat receptor-like kinase is expressed in the root vasculature in Arabidopsis thaliana and plays a crucial role in regulating the expansion of the root system under N-deficient conditions. CLE1, -3, -4, and -7 were induced by N deficiency in roots, predominantly expressed in root pericycle cells, and their overexpression repressed the growth of lateral root primordia and their emergence from the primary root. In contrast, clv1 mutants showed progressive outgrowth of lateral root primordia into lateral roots under N-deficient conditions. The clv1 phenotype was reverted by introducing a CLV1 promoter-driven CLV1:GFP construct producing CLV1:GFP fusion proteins in phloem companion cells of roots. The overaccumulation of CLE2, -3, -4, and -7 in clv1 mutants suggested the amplitude of the CLE peptide signals being feedback-regulated by CLV1. When CLE3 was overexpressed under its own promoter in wild-type plants, the length of lateral roots was negatively correlated with increasing CLE3 mRNA levels; however, this inhibitory action of CLE3 was abrogated in the clv1 mutant background. Our findings identify the N-responsive CLE-CLV1 signaling module as an essential mechanism restrictively controlling the expansion of the lateral root system in N-deficient environments.

  3. Tomato susceptibility to root-knot nematodes requires an intact jasmonic Acid signaling pathway

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Response of tomato (Solanum lycopersicum) to root-knot nematode (RKN; Meloidogyne spp.) infection was monitored using TOM1 cDNA microarray with resistant (‘Motelle’; Mi-1) and susceptible (‘Moneymaker’; mi) tomato at 24 h after RKN infection. The array analysis identified 1497 genes and 750 genes d...

  4. Promoting Roles of Melatonin in Adventitious Root Development of Solanum lycopersicum L. by Regulating Auxin and Nitric Oxide Signaling

    PubMed Central

    Wen, Dan; Gong, Biao; Sun, Shasha; Liu, Shiqi; Wang, Xiufeng; Wei, Min; Yang, Fengjuan; Li, Yan; Shi, Qinghua

    2016-01-01

    Melatonin (MT) plays integral roles in regulating several biological processes including plant growth, seed germination, flowering, senescence, and stress responses. This study investigated the effects of MT on adventitious root formation (ARF) of de-rooted tomato seedlings. Exogenous MT positively or negatively influenced ARF, which was dependent on the concentration of MT application. In the present experiment, 50 μM MT showed the best effect on inducing ARF. Interestingly, exogenous MT promoted the accumulation of endogenous nitric oxide (NO) by down-regulating the expression of S-nitrosoglutathione reductase (GSNOR). To determine the interaction of MT and NO in ARF, MT synthesis inhibitor p-chlorophenylalanine, NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt as well as GSNOR-overexpression plants with low NO levels were used. The function of MT was removed by NO scavenger or GSNOR-overexpression plants. However, application of MT synthesis inhibitor did little to abolish the function of NO. These results indicate that NO, as a downstream signal, was involved in the MT-induced ARF. Concentrations of indole-3-acetic acid and indole-3-butyric acid, as well as the expression of several genes related to the auxin signaling pathway (PIN1, PIN3, PIN7, IAA19, and IAA24), showed that MT influenced auxin transport and signal transduction as well as auxin accumulation through the NO signaling pathway. Collectively, these strongly suggest that elevated NO levels resulting from inhibited GSNOR activity and auxin signaling were involved in the MT-induced ARF in tomato plants. This can be applied in basic research and breeding. PMID:27252731

  5. H2O2 and ABA signaling are responsible for the increased Na+ efflux and water uptake in Gossypium hirsutum L. roots in the non-saline side under non-uniform root zone salinity.

    PubMed

    Kong, Xiangqiang; Luo, Zhen; Dong, Hezhong; Eneji, A Egrinya; Li, Weijiang

    2016-04-01

    Non-uniform root salinity increases the Na(+)efflux, water use, and growth of the root in non-saline side, which may be regulated by some form of signaling induced by the high-salinity side. However, the signaling and its specific function have remained unknown. Using a split-root system to simulate a non-uniform root zone salinity in Gossypium hirsutum L., we showed that the up-regulated expression of sodium efflux-related genes (SOS1, SOS2, PMA1, and PMA2) and water uptake-related genes (PIP1 and PIP2) was possibly involved in the elevated Na(+) efflux and water use in the the roots in the non-saline side. The increased level of indole acetic acid (IAA) in the non-saline side was the likely cause of the increased root growth. Also, the abscisic acid (ABA) and H2O2 contents in roots in the non-saline side increased, possibly due to the increased expression of their key biosynthesis genes, NCED and RBOHC, and the decreased expression of ABA catabolic CYP707A genes. Exogenous ABA added to the non-saline side induced H2O2 generation by up-regulating the RBOHC gene, but this was decreased by exogenous fluridone. Exogenous H2O2 added to the non-saline side reduced the ABA content by down-regulating NCED genes, which can be induced by diphenylene iodonium (DPI) treatment in the non-saline side, suggesting a feedback mechanism between ABA and H2O2.Both exogenous ABA and H2O2 enhanced the expression of SOS1, PIP1;7 ,PIP2;2, and PIP2;10 genes, but these were down-regulated by fluridone and DPI, suggesting that H2O2 and ABA are important signals for increasing root Na(+) efflux and water uptake in the roots in the non-saline side.

  6. The role of hypothalamic mTORC1 signaling in insulin regulation of food intake, body weight, and sympathetic nerve activity in male mice.

    PubMed

    Muta, Kenjiro; Morgan, Donald A; Rahmouni, Kamal

    2015-04-01

    Insulin action in the brain particularly the hypothalamus is critically involved in the regulation of several physiological processes, including energy homeostasis and sympathetic nerve activity, but the underlying mechanisms are poorly understood. The mechanistic target of rapamycin complex 1 (mTORC1) is implicated in the control of diverse cellular functions, including sensing nutrients and energy status. Here, we examined the role of hypothalamic mTORC1 in mediating the anorectic, weight-reducing, and sympathetic effects of central insulin action. In a mouse hypothalamic cell line (GT1-7), insulin treatment increased mTORC1 activity in a time-dependent manner. In addition, intracerebroventricular (ICV) administration of insulin to mice activated mTORC1 pathway in the hypothalamic arcuate nucleus, a key site of central action of insulin. Interestingly, inhibition of hypothalamic mTORC1 with rapamycin reversed the food intake- and body weight-lowering effects of ICV insulin. Rapamycin also abolished the ability of ICV insulin to cause lumbar sympathetic nerve activation. In GT1-7 cells, we found that insulin activation of mTORC1 pathway requires phosphatidylinositol 3-kinase (PI3K). Consistent with this, genetic disruption of PI3K in mice abolished insulin stimulation of hypothalamic mTORC1 signaling as well as the lumbar sympathetic nerve activation evoked by insulin. These results demonstrate the importance of mTORC1 pathway in the hypothalamus in mediating the action of insulin to regulate energy homeostasis and sympathetic nerve traffic. Our data also highlight the key role of PI3K as a link between insulin receptor and mTORC1 signaling in the hypothalamus.

  7. Oxidative Stress and NO Signalling in the Root Apex as an Early Response to Changes in Gravity Conditions

    PubMed Central

    Mugnai, Sergio; Monetti, Emanuela; Voigt, Boris; Volkmann, Dieter; Mancuso, Stefano

    2014-01-01

    Oxygen influx showed an asymmetry in the transition zone of the root apex when roots were placed horizontally on ground. The influx increased only in the upper side, while no changes were detected in the division and in the elongation zone. Nitric oxide (NO) was also monitored after gravistimulation, revealing a sudden burst only in the transition zone. In order to confirm these results in real microgravity conditions, experiments have been set up by using parabolic flights and drop tower. The production of reactive oxygen species (ROS) was also monitored. Oxygen, NO, and ROS were continuously monitored during normal and hyper- and microgravity conditions in roots of maize seedlings. A distinct signal in oxygen and NO fluxes was clearly detected only in the apex zone during microgravity, with no significant changes in normal and in hypergravity conditions. The same results were obtained by ROS measurement. The detrimental effect of D'orenone, disrupting the polarised auxin transport, on the onset of the oxygen peaks during the microgravity period was also evaluated. Results indicates an active role of NO and ROS as messengers during the gravitropic response, with probable implications in the auxin redistribution. PMID:25197662

  8. Angular-type furocoumarins from the roots of Angelica atropurpurea and their inhibitory activity on the NFAT signal transduction pathway.

    PubMed

    Nagasawa, Azumi; Sakasai, Mitsuyoshi; Sakaguchi, Daishi; Moriwaki, Shigeru; Nishizawa, Yoshinori; Kitahara, Takashi

    2014-12-01

    One new (1) and two known angular-type (2,3) furocoumarins, isoarchangelicin (1), archangelicin (2), and 2'-angeloyl-3'-isovaleryl vaginate (3), were isolated from the roots of Angelica atropurpurea. The structure of the new compound was established on the basis of one- and two-dimensional NMR spectra and other spectroscopic studies. The inhibitory activity of these three compounds and a deacylated form of archangelicin (4) on the nuclear factor of activated T cells (NFAT) signal transduction pathway was tested by NFAT-responsive luciferase reporter gene assay in cultured cells. Although 4 did not exhibit inhibitory activity on NFAT signaling, 1-3 exhibited dose-dependent inhibition with IC50 values of 16.5 (1), 9.0 (2), and 9.2 (3) μM.

  9. Root Hairs

    PubMed Central

    Grierson, Claire; Nielsen, Erik; Ketelaarc, Tijs; Schiefelbein, John

    2014-01-01

    Roots hairs are cylindrical extensions of root epidermal cells that are important for acquisition of nutrients, microbe interactions, and plant anchorage. The molecular mechanisms involved in the specification, differentiation, and physiology of root hairs in Arabidopsis are reviewed here. Root hair specification in Arabidopsis is determined by position-dependent signaling and molecular feedback loops causing differential accumulation of a WD-bHLH-Myb transcriptional complex. The initiation of root hairs is dependent on the RHD6 bHLH gene family and auxin to define the site of outgrowth. Root hair elongation relies on polarized cell expansion at the growing tip, which involves multiple integrated processes including cell secretion, endomembrane trafficking, cytoskeletal organization, and cell wall modifications. The study of root hair biology in Arabidopsis has provided a model cell type for insights into many aspects of plant development and cell biology. PMID:24982600

  10. The time course of long-distance signaling in radiation-induced bystander effect in vivo in Arabidopsis thaliana demonstrated using root micro-grafting.

    PubMed

    Wang, Ting; Li, Fanghua; Xu, Shuyan; Bian, Po; Wu, Yuejin; Wu, Lijun; Yu, Zengliang

    2011-08-01

    The radiation-induced bystander effect has been demonstrated in whole organisms as well as in multicellular tissues in vitro and single-cell culture systems in vitro. However, the time course of bystander signaling, especially in whole organisms, is not clear. Long-distance bystander/abscopal effects in vivo in plants have been demonstrated by our group. Plant grafting is a useful experimental tool for studying the root-shoot signaling of plants. In the present study, we developed a root micro-grafting technique with young seedlings of Arabidopsis thaliana in which the bystander signaling communication of root-to-shoot could easily be stopped or started at specific times after root irradiation. Using this methodology, we demonstrated the time course of long-distance signaling in radiation-induced bystander effects at the level of the organism using the expression level of the AtRAD54 gene as a biological end point. Briefly, an 8-h accumulation of damage signals in bystander parts after irradiation was essential for eliciting a bystander response. The protraction of signal accumulation was not related to the transmission speed of signaling molecules in plants and did not result from the delayed initiation of bystander signals in targeted root cells. It was suggested that the bystander effect might be induced jointly by multiple bystander signals initiated at different stages after irradiation. Moreover, reactive oxygen species (ROS) were shown to be implicated in the response process of bystander cells to radiation damage signals rather than in the generation of bystander signals in targeted cells.

  11. Salt Stress Reduces Root Meristem Size by Nitric Oxide-Mediated Modulation of Auxin Accumulation and Signaling in Arabidopsis1[OPEN

    PubMed Central

    Liu, Wen; Li, Rong-Jun; Han, Tong-Tong; Cai, Wei; Fu, Zheng-Wei

    2015-01-01

    The development of the plant root system is highly plastic, which allows the plant to adapt to various environmental stresses. Salt stress inhibits root elongation by reducing the size of the root meristem. However, the mechanism underlying this process remains unclear. In this study, we explored whether and how auxin and nitric oxide (NO) are involved in salt-mediated inhibition of root meristem growth in Arabidopsis (Arabidopsis thaliana) using physiological, pharmacological, and genetic approaches. We found that salt stress significantly reduced root meristem size by down-regulating the expression of PINFORMED (PIN) genes, thereby reducing auxin levels. In addition, salt stress promoted AUXIN RESISTANT3 (AXR3)/INDOLE-3-ACETIC ACID17 (IAA17) stabilization, which repressed auxin signaling during this process. Furthermore, salt stress stimulated NO accumulation, whereas blocking NO production with the inhibitor Nω-nitro-l-arginine-methylester compromised the salt-mediated reduction of root meristem size, PIN down-regulation, and stabilization of AXR3/IAA17, indicating that NO is involved in salt-mediated inhibition of root meristem growth. Taken together, these findings suggest that salt stress inhibits root meristem growth by repressing PIN expression (thereby reducing auxin levels) and stabilizing IAA17 (thereby repressing auxin signaling) via increasing NO levels. PMID:25818700

  12. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee.

    PubMed

    Rossini, P M; Burke, D; Chen, R; Cohen, L G; Daskalakis, Z; Di Iorio, R; Di Lazzaro, V; Ferreri, F; Fitzgerald, P B; George, M S; Hallett, M; Lefaucheur, J P; Langguth, B; Matsumoto, H; Miniussi, C; Nitsche, M A; Pascual-Leone, A; Paulus, W; Rossi, S; Rothwell, J C; Siebner, H R; Ugawa, Y; Walsh, V; Ziemann, U

    2015-06-01

    These guidelines provide an up-date of previous IFCN report on "Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application" (Rossini et al., 1994). A new Committee, composed of international experts, some of whom were in the panel of the 1994 "Report", was selected to produce a current state-of-the-art review of non-invasive stimulation both for clinical application and research in neuroscience. Since 1994, the international scientific community has seen a rapid increase in non-invasive brain stimulation in studying cognition, brain-behavior relationship and pathophysiology of various neurologic and psychiatric disorders. New paradigms of stimulation and new techniques have been developed. Furthermore, a large number of studies and clinical trials have demonstrated potential therapeutic applications of non-invasive brain stimulation, especially for TMS. Recent guidelines can be found in the literature covering specific aspects of non-invasive brain stimulation, such as safety (Rossi et al., 2009), methodology (Groppa et al., 2012) and therapeutic applications (Lefaucheur et al., 2014). This up-dated review covers theoretical, physiological and practical aspects of non-invasive stimulation of brain, spinal cord, nerve roots and peripheral nerves in the light of more updated knowledge, and include some recent extensions and developments.

  13. Metastasis-associated mts1 (S100A4) protein is selectively expressed in white matter astrocytes and is up-regulated after peripheral nerve or dorsal root injury.

    PubMed

    Kozlova, E N; Lukanidin, E

    1999-09-01

    The S100 family of calcium binding proteins has been shown to be involved in a variety of physiological functions, such as regulation of enzyme function, cell motility, modification of extracellular matrix, and cell proliferation. Several members of the S100 family are expressed in the nervous system, but their functional roles are still largely obscure. The Mts1 gene codes for the S100A4 protein, which has been implicated in the control of cell proliferation and metastasis activity of tumor cells. We have used immunohistochemistry to examine the expression pattern of the Mts1 protein in the adult rat spinal cord and how this expression is influenced by peripheral nerve or dorsal root injury. Mts1 immunoreactivity (IR) was present only in white matter astrocytes in the intact spinal cord. Sciatic nerve as well as dorsal root injury induced a marked and prolonged up-regulation of Mts1-IR in astrocytes in the region of the dorsal funiculus containing the central processes of the injured primary sensory neurons. These findings suggest that Mts1 plays a unique physiological role in white matter astrocytes as well as in the response of astrocytes to degeneration of myelinated axons.

  14. Restoring a Maize Root Signal That Attracts Insect-killing Nematodes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    When attacked by insects, plants emit volatiles that can serve as foraging cues for natural enemies of herbivorous insects. It has been proposed that the emissions of these volatile signals can be manipulated to improve crop protection. Here we demonstrate the full potential of this strategy by re...

  15. AUXIN UP-REGULATED F-BOX PROTEIN1 Regulates the Cross Talk between Auxin Transport and Cytokinin Signaling during Plant Root Growth1[W][OA

    PubMed Central

    Zheng, Xiaohua; Miller, Nathan D.; Lewis, Daniel R.; Christians, Matthew J.; Lee, Kwang-Hee; Muday, Gloria K.; Spalding, Edgar P.; Vierstra, Richard D.

    2011-01-01

    Plant root development is mediated by the concerted action of the auxin and cytokinin phytohormones, with cytokinin serving as an antagonist of auxin transport. Here, we identify the AUXIN UP-REGULATED F-BOX PROTEIN1 (AUF1) and its potential paralog AUF2 as important positive modifiers of root elongation that tether auxin movements to cytokinin signaling in Arabidopsis (Arabidopsis thaliana). The AUF1 mRNA level in roots is strongly up-regulated by auxin but not by other phytohormones. Whereas the auf1 single and auf1 auf2 double mutant roots grow normally without exogenous auxin and respond similarly to the wild type upon auxin application, their growth is hypersensitive to auxin transport inhibitors, with the mutant roots also having reduced basipetal and acropetal auxin transport. The effects of auf1 on auxin movements may be mediated in part by the misexpression of several PIN-FORMED (PIN) auxin efflux proteins, which for PIN2 reduces its abundance on the plasma membrane of root cells. auf1 roots are also hypersensitive to cytokinin and have increased expression of several components of cytokinin signaling. Kinematic analyses of root growth and localization of the cyclin B mitotic marker showed that AUF1 does not affect root cell division but promotes cytokinin-mediated cell expansion in the elongation/differentiation zone. Epistasis analyses implicate the cytokinin regulator ARR1 or its effector(s) as the target of the SKP1-Cullin1-F Box (SCF) ubiquitin ligases assembled with AUF1/2. Given the wide distribution of AUF1/2-type proteins among land plants, we propose that SCFAUF1/2 provides additional cross talk between auxin and cytokinin, which modifies auxin distribution and ultimately root elongation. PMID:21653785

  16. Optical intrinsic signals in rat primary somatosensory cortex during non-noxious and noxious elecrical stimulation of the sciatic nerve

    NASA Astrophysics Data System (ADS)

    Luo, Weihua; Li, Pengcheng; Chen, Shangbin; Luo, Qingming

    2003-12-01

    Optical imaging method was applied into observing the temporal-spatial characteristic of rat primary somatosensory cortex during graded electrical stimulation of the sciatic nerve (5hz,duration of 2s,0.5ms puls,1x,10x and 20x muscle twitch threshold). We found that the temporal and spatial properties of hindlimb somatosensory cortex were modulated by graded intensity electrical stimulation of the sciatic nerve. The magnitude and time course were larger and longer with the intensity raising. And the spatial extent was wider at 20x stimulus than the other two kinds of stimulus. Therefore, our optical imaging was based on 570nm, which only reflect the changes of blood volume. Then our future study will reveal more information of pain modulation in primary somatosensory cortex.

  17. The signal transducer NPH3 integrates the phototropin1 photosensor with PIN2-based polar auxin transport in Arabidopsis root phototropism.

    PubMed

    Wan, Yinglang; Jasik, Jan; Wang, Li; Hao, Huaiqing; Volkmann, Dieter; Menzel, Diedrik; Mancuso, Stefano; Baluška, František; Lin, Jinxing

    2012-02-01

    Under blue light (BL) illumination, Arabidopsis thaliana roots grow away from the light source, showing a negative phototropic response. However, the mechanism of root phototropism is still unclear. Using a noninvasive microelectrode system, we showed that the BL sensor phototropin1 (phot1), the signal transducer NONPHOTOTROPIC HYPOCOTYL3 (NPH3), and the auxin efflux transporter PIN2 were essential for BL-induced auxin flux in the root apex transition zone. We also found that PIN2-green fluorescent protein (GFP) localized to vacuole-like compartments (VLCs) in dark-grown root epidermal and cortical cells, and phot1/NPH3 mediated a BL-initiated pathway that caused PIN2 redistribution to the plasma membrane. When dark-grown roots were exposed to brefeldin A (BFA), PIN2-GFP remained in VLCs in darkness, and BL caused PIN2-GFP disappearance from VLCs and induced PIN2-GFP-FM4-64 colocalization within enlarged compartments. In the nph3 mutant, both dark and BL BFA treatments caused the disappearance of PIN2-GFP from VLCs. However, in the phot1 mutant, PIN2-GFP remained within VLCs under both dark and BL BFA treatments, suggesting that phot1 and NPH3 play different roles in PIN2 localization. In conclusion, BL-induced root phototropism is based on the phot1/NPH3 signaling pathway, which stimulates the shootward auxin flux by modifying the subcellular targeting of PIN2 in the root apex transition zone.

  18. Nicotinic modulation of glutamate receptor function at nerve terminal level: a fine-tuning of synaptic signals.

    PubMed

    Marchi, Mario; Grilli, Massimo; Pittaluga, Anna M

    2015-01-01

    This review focuses on a specific interaction occurring between the nicotinic cholinergic receptors (nAChRs) and the glutamatergic receptors (GluRs) at the nerve endings level. We have employed synaptosomes in superfusion and supplemented and integrated our findings with data obtained using techniques from molecular biology and immuno-cytochemistry, and the assessment of receptor trafficking. In particular, we characterize the following: (1) the direct and unequivocal localization of native α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) glutamatergic receptors on specific nerve terminals, (2) their pharmacological characterization and functional co-localization with nAChRs on the same nerve endings, and (3) the existence of synergistic or antagonistic interactions among them. Indeed, in the rat nucleus accumbens (NAc), the function of some AMPA and NMDA receptors present on the dopaminergic and glutamatergic nerve terminals can be regulated negatively or positively in response to a brief activation of nAChRs. This effect occurs rapidly and involves the trafficking of AMPA and NMDA receptors. The event takes place also at very low concentrations of nicotine and involves the activation of several nAChRs subtypes. This dynamic control by cholinergic nicotinic system of glutamatergic NMDA and AMPA receptors might therefore represent an important neuronal presynaptic adaptation associated with nicotine administration. The understanding of the role of these nicotine-induced functional changes might open new and interesting perspectives both in terms of explaining the mechanisms that underlie some of the effects of nicotine addiction and in the development of new drugs for smoking cessation.

  19. Sirtinol, a Sir2 protein inhibitor, affects stem cell maintenance and root development in Arabidopsis thaliana by modulating auxin-cytokinin signaling components

    PubMed Central

    Singh, Sharmila; Singh, Alka; Yadav, Sandeep; Gautam, Vibhav; Singh, Archita; Sarkar, Ananda K.

    2017-01-01

    In Arabidopsis thaliana, besides several key transcription factors and chromatin modifiers, phytohormones auxin and cytokinin play pivotal role in shoot and root meristem maintenance, and lateral root (LR) development. Sirtinol, a chemical inhibitor of Sir2 proteins, is known to promote some auxin induced phenotypes in Arabidopsis. However, its effect on plant stem cell maintenance or organ formation remained unaddressed. Here we show that sirtinol affects meristem maintenance by altering the expression of key stem cell regulators, cell division and differentiation by modulating both auxin and cytokinin signaling in Arabidopsis thaliana. The expression of shoot stem cell niche related genes WUSCHEL (WUS) and CLAVATA3 (CLV3) was upregulated, whereas SHOOT MERISTEMLESS (STM) was downregulated in sirtinol treated seedlings. The expression level and domain of key root stem cell regulators PLETHORA (PLTs) and WUS-Related Homeobox 5 (WOX5) were altered in sirtinol treated roots. Sirtinol affects LR development by disturbing proper auxin transport and maxima formation, similar to 2,4-dichlorophenoxyacetic acid (2,4-D). Sirtinol also affects LR formation by altering cytokinin biosynthesis and signaling genes in roots. Therefore, sirtinol affects shoot and root growth, meristem maintenance and LR development by altering the expression of cytokinin-auxin signaling components, and regulators of stem cells, meristems, and LRs. PMID:28195159

  20. AHP6 inhibits cytokinin signaling to regulate the orientation of pericycle cell division during lateral root initiation.

    PubMed

    Moreira, Sofia; Bishopp, Anthony; Carvalho, Helena; Campilho, Ana

    2013-01-01

    In Arabidopsis thaliana, lateral roots (LRs) initiate from anticlinal cell divisions of pericycle founder cells. The formation of LR primordia is regulated antagonistically by the phytohormones cytokinin and auxin. It has previously been shown that cytokinin has an inhibitory effect on the patterning events occurring during LR formation. However, the molecular players involved in cytokinin repression are still unknown. In a similar manner to protoxylem formation in Arabidopsis roots, in which AHP6 (ARABIDOPSIS HISTIDINE PHOSPHOTRANSFER PROTEIN 6) acts as a cytokinin inhibitor, we reveal that AHP6 also functions as a cytokinin repressor during early stages of LR development. We show that AHP6 is expressed at different developmental stages during LR formation and is required for the correct orientation of cell divisions at the onset of LR development. Moreover, we demonstrate that AHP6 influences the localization of the auxin efflux carrier PIN1, which is necessary for patterning the LR primordia. In summary, we show that the inhibition of cytokinin signaling through AHP6 is required to establish the correct pattern during LR initiation.

  1. Organizer-Derived WOX5 Signal Maintains Root Columella Stem Cells through Chromatin-Mediated Repression of CDF4 Expression.

    PubMed

    Pi, Limin; Aichinger, Ernst; van der Graaff, Eric; Llavata-Peris, Cristina I; Weijers, Dolf; Hennig, Lars; Groot, Edwin; Laux, Thomas

    2015-06-08

    Stem cells in plants and animals are maintained pluripotent by signals from adjacent niche cells. In plants, WUSCHEL HOMEOBOX (WOX) transcription factors are central regulators of stem cell maintenance in different meristem types, yet their molecular mode of action has remained elusive. Here we show that in the Arabidopsis root meristem, the WOX5 protein moves from the root niche organizer, the quiescent center, into the columella stem cells, where it directly represses the transcription factor gene CDF4. This creates a gradient of CDF4 transcription, which promotes differentiation opposite to the WOX5 gradient, allowing stem cell daughter cells to exit the stem cell state. We further show that WOX5 represses CDF4 transcription by recruiting TPL/TPR co-repressors and the histone deacetylase HDA19, which consequently induces histone deacetylation at the CDF4 regulatory region. Our results show that chromatin-mediated repression of differentiation programs is a common strategy in plant and animal stem cell niches.

  2. Salt stress sensing and early signalling events in plant roots: Current knowledge and hypothesis.

    PubMed

    Shabala, Sergey; Wu, Honghong; Bose, Jayakumar

    2015-12-01

    Soil salinity is a major environmental constraint to crop production. While the molecular identity and functional expression of Na(+) transport systems mediating Na(+) exclusion from the cytosol has been studied in detail, far less is known about the mechanisms by which plants sense high Na(+) levels in the soil and the rapid signalling events that optimise plant performance under saline conditions. This review aims to fill this gap. We first discuss the nature of putative salt stress sensors, candidates which include Na(+) transport systems, mechanosensory proteins, proteins with regulatory Na(+) binding sites, sensing mediated by cyclic nucleotide-gated channels, purine receptors, annexin and voltage gating. We suggest that several transport proteins may be clustered together to form a microdomain in a lipid raft, allowing rapid changes in the activity of an individual protein to be translated into stress-induced Ca(2+) and H2O2 signatures. The pathways of stress signalling to downstream targets are discussed, and the kinetics and specificity of salt stress signalling between glycophytes and halophytes is compared. We argue that these sensing mechanisms operate in parallel, providing plants with a robust system for decoding information about the specific nature and severity of the imposed salt stress.

  3. Microsurgical removal of epidermal and cortical cells: evidence that the gravitropic signal moves through the outer cell layers in primary roots of maize

    NASA Technical Reports Server (NTRS)

    Yang, R. L.; Evans, M. L.; Moore, R.

    1990-01-01

    There is general agreement that during root gravitropism some sort of growth-modifying signal moves from the cap to the elongation zone and that this signal ultimately induces the curvature that leads to reorientation of the root. However, there is disagreement regarding both the nature of the signal and the pathway of its movement from the root cap to the elongation zone. We examined the pathway of movement by testing gravitropism in primary roots of maize (Zea mays L.) from which narrow (0.5 mm) rings of epidermal and cortical tissue were surgically removed from various positions within the elongation zone. When roots were girdled in the apical part of the elongation zone gravitropic curvature occurred apical to the girdle but not basal to the girdle. Filling the girdle with agar allowed curvature basal to the girdle to occur. Shallow girdles, in which only two or three cell layers (epidermis plus one or two cortical cell layers) were removed, prevented or greatly delayed gravitropic curvature basal to the girdle. The results indicate that the gravitropic signal moves basipetally through the outermost cell layers, perhaps through the epidermis itself.

  4. PERK–KIPK–KCBP signalling negatively regulates root growth in Arabidopsis thaliana

    PubMed Central

    Humphrey, Tania V.; Haasen, Katrina E.; Aldea-Brydges, May Grace; Sun, He; Zayed, Yara; Indriolo, Emily; Goring, Daphne R.

    2015-01-01

    The Arabidopsis proline-rich, extensin-like receptor-like kinases (PERKs) are a small group of receptor-like kinases that are thought to act as sensors at the cell wall through their predicted proline-rich extracellular domains. In this study, we focused on the characterization of a subclade of three Arabidopsis predicted PERK genes, PERK8, -9, and -10, for which no functions were known. Yeast two-hybrid interaction studies were conducted with the PERK8,- 9, and -10 cytosolic kinase domains, and two members of the Arabidopsis AGC VIII kinase family were identified as interacting proteins: AGC1-9 and the closely related kinesin-like calmodulin-binding protein (KCBP)-interacting protein kinase (KIPK). As KIPK has been identified previously as an interactor of KCBP, these interactions were also examined further and confirmed in this study. Finally, T-DNA mutants for each gene were screened for altered phenotypes under different conditions, and from these screens, a role for the PERK, KIPK, and KCBP genes in negatively regulating root growth was uncovered. PMID:25262228

  5. Omics of root-to-shoot signaling under salt stress and water deficit.

    PubMed

    Pérez-Alfocea, Francisco; Ghanem, Michel Edmond; Gómez-Cadenas, Aurelio; Dodd, Ian C

    2011-12-01

    Maximizing crop yield depends on the leaves receiving an optimal supply of water, mineral nutrients, small organic molecules, proteins, and hormones from the root system via the xylem. Soil drying and salinization alter these xylem fluxes, and modern omics techniques offer unparalleled opportunities to understand the complexity of these responses. Although absolute xylem concentrations of any constituent depend on the genotype and xylem sap sampling methodology, analysis of the relative changes in concentrations has revealed some conserved behavior. Typically, these stresses increase xylem concentrations of the plant hormone abscisic acid (ABA) that limits crop water loss, but decrease the concentrations of certain cytokinins that stimulate expansive growth and prevent premature leaf senescence. Further understanding of the ionic and biophysical alterations in the rhizosphere environment that cause increased xylem concentrations of the ethylene precursor (ACC) is needed. Interactions of these plant hormones with plant nutrient status and xylem nutrient delivery may be important in tuning plant responses to their environment. Xylem proteomics is an emerging area that will help understand mechanisms of plant stress adaptation. Using omics techniques to underpin rootstock-mediate plant improvement is likely to improve crop yields in dry or saline soil.

  6. Plant phosphatidylcholine-hydrolyzing phospholipases C NPC3 and NPC4 with roles in root development and brassinolide signaling in Arabidopsis thaliana.

    PubMed

    Wimalasekera, Rinukshi; Pejchar, Premysl; Holk, André; Martinec, Jan; Scherer, Günther F E

    2010-05-01

    Phosphatidylcholine-hydrolyzing phospholipase C (PC-PLC) catalyzes the hydrolysis of phosphatidylcholine (PC) to generate phosphocholine and diacylglycerol (DAG). PC-PLC has a long tradition in animal signal transduction to generate DAG as a second messenger besides the classical phosphatidylinositol splitting phospholipase C (PI-PLC). Based on amino acid sequence similarity to bacterial PC-PLC, six putative PC-PLC genes (NPC1 to NPC6) were identified in the Arabidopsis genome. RT-PCR analysis revealed overlapping expression pattern of NPC genes in root, stem, leaf, flower, and silique. In auxin-treated P(NPC3):GUS and P(NPC4):GUS seedlings, strong increase of GUS activity was visible in roots, leaves, and shoots and, to a weaker extent, in brassinolide-treated (BL) seedlings. P(NPC4):GUS seedlings also responded to cytokinin with increased GUS activity in young leaves. Compared to wild-type, T-DNA insertional knockouts npc3 and npc4 showed shorter primary roots and lower lateral root density at low BL concentrations but increased lateral root densities in response to exogenous 0.05-1.0 μM BL. BL-induced expression of TCH4 and LRX2, which are involved in cell expansion, was impaired but not impaired in repression of CPD, a BL biosynthesis gene, in BL-treated npc3 and npc4. These observations suggest NPC3 and NPC4 are important in BL-mediated signaling in root growth. When treated with 0.1 μM BL, DAG accumulation was observed in tobacco BY-2 cell cultures labeled with fluorescent PC as early as 15 min after application. We hypothesize that at least one PC-PLC is a plant signaling enzyme in BL signal transduction and, as shown earlier, in elicitor signal transduction.

  7. Nuclear genomic signals of the 'microturbellarian' roots of platyhelminth evolutionary innovation.

    PubMed

    Laumer, Christopher E; Hejnol, Andreas; Giribet, Gonzalo

    2015-03-12

    Flatworms number among the most diverse invertebrate phyla and represent the most biomedically significant branch of the major bilaterian clade Spiralia, but to date, deep evolutionary relationships within this group have been studied using only a single locus (the rRNA operon), leaving the origins of many key clades unclear. In this study, using a survey of genomes and transcriptomes representing all free-living flatworm orders, we provide resolution of platyhelminth interrelationships based on hundreds of nuclear protein-coding genes, exploring phylogenetic signal through concatenation as well as recently developed consensus approaches. These analyses robustly support a modern hypothesis of flatworm phylogeny, one which emphasizes the primacy of the often-overlooked 'microturbellarian' groups in understanding the major evolutionary transitions within Platyhelminthes: perhaps most notably, we propose a novel scenario for the interrelationships between free-living and vertebrate-parasitic flatworms, providing new opportunities to shed light on the origins and biological consequences of parasitism in these iconic invertebrates.

  8. Ambiguous effect of signals transmitted by the vagus nerve on fibrosarcoma incidence and survival of tumor-bearing rats.

    PubMed

    Mikova, Lucia; Horvathova, Lubica; Ondicova, Katarina; Tillinger, Andrej; Vannucci, Luca E; Bizik, Jozef; Gidron, Yori; Mravec, Boris

    2015-04-23

    While the parasympathetic nervous system appears to be involved in the regulation of tumor progression, its exact role is still unclear. Therefore, using a rat BP6-TU2 fibrosarcoma tumor model, we investigated the effect of (1) reduction of vagal activity produced by subdiaphragmatic vagotomy; and (2) enhancement of vagal activity produced by continuous delivery of electric impulses to the cervical part of the vagus nerve on tumor development and survival of tumor-bearing rats. We also evaluated the expression of cholinergic receptors within in vitro cultivated BP6-TU2 cells. Interestingly, we found that both, vagal stimulation and subdiaphragmatic vagotomy slightly reduced tumor incidence. However, survival of tumor-bearing rats was not affected by any of the experimental approaches. Additionally, we detected mRNA expression of the α1, α2, α5, α7, and α10 subunits of nicotinic receptors and the M1, M3, M4, and M5 subtypes of muscarinic receptors within in vitro cultivated BP6-TU2 cells. Our data indicate that the role of the vagus nerve in modulation of fibrosarcoma development is ambiguous and uncertain and requires further investigation.

  9. Injury signals cooperate with Nf1 loss to relieve the tumor-suppressive environment of adult peripheral nerve.

    PubMed

    Ribeiro, Sara; Napoli, Ilaria; White, Ian J; Parrinello, Simona; Flanagan, Adrienne M; Suter, Ueli; Parada, Luis F; Lloyd, Alison C

    2013-10-17

    Schwann cells are highly plastic cells that dedifferentiate to a progenitor-like state following injury. However, deregulation of this plasticity, may be involved in the formation of neurofibromas, mixed-cell tumors of Schwann cell (SC) origin that arise upon loss of NF1. Here, we show that adult myelinating SCs (mSCs) are refractory to Nf1 loss. However, in the context of injury, Nf1-deficient cells display opposing behaviors along the wounded nerve; distal to the injury, Nf1(-/-) mSCs redifferentiate normally, whereas at the wound site Nf1(-/-) mSCs give rise to neurofibromas in both Nf1(+/+) and Nf1(+/-) backgrounds. Tracing experiments showed that distinct cell types within the tumor derive from Nf1-deficient SCs. This model of neurofibroma formation demonstrates that neurofibromas can originate from adult SCs and that the nerve environment can switch from tumor suppressive to tumor promoting at a site of injury. These findings have implications for both the characterization and treatment of neurofibromas.

  10. Nerve biopsy

    MedlinePlus

    ... Loss of axon tissue Metabolic neuropathies Necrotizing vasculitis Sarcoidosis Risks Allergic reaction to the local anesthetic Discomfort ... Neurosarcoidosis Peripheral neuropathy Primary amyloidosis Radial nerve dysfunction Sarcoidosis Tibial nerve dysfunction Review Date 6/1/2015 ...

  11. Nerves on magnetic resonance imaging.

    PubMed Central

    Collins, J. D.; Shaver, M. L.; Batra, P.; Brown, K.

    1989-01-01

    Nerves are often visualized on magnetic resonance imaging (MRI) studies of the soft tissues on the chest and shoulder girdle. To learn the reasons for the contrast between the nerves and adjacent tissues, the authors obtained a fresh specimen containing part of the brachial plexus nerves from the left axilla and compared MRI with x-ray projections and photomicrographs of histologic sections. The results suggest that the high signals from the nerves stand out in contrast to the low signals from their rich vascular supply. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6A Figure 6B Figure 7 PMID:2733051

  12. OsERF2 controls rice root growth and hormone responses through tuning expression of key genes involved in hormone signaling and sucrose metabolism.

    PubMed

    Xiao, Guiqing; Qin, Hua; Zhou, Jiahao; Quan, Ruidang; Lu, Xiangyang; Huang, Rongfeng; Zhang, Haiwen

    2016-02-01

    Root determines plant distribution, development progresses, stress response, as well as crop qualities and yields, which is under the tight control of genetic programs and environmental stimuli. Ethylene responsive factor proteins (ERFs) play important roles in plant growth and development. Here, the regulatory function of OsERF2 involved in root growth was investigated using the gain-function mutant of OsERF2 (nsf2857) and the artificial microRNA-mediated silenced lines of OsERF2 (Ami-OsERF2). nsf2857 showed short primary roots compared with the wild type (WT), while the primary roots of Ami-OsERF2 lines were longer than those of WT. Consistent with this phenotype, several auxin/cytokinin responsive genes involved in root growth were downregulated in nsf2857, but upregulated in Ami-OsERF2. Then, we found that nsf2857 seedlings exhibited decreased ABA accumulation and sensitivity to ABA and reduced ethylene-mediated root inhibition, while those were the opposite in Ami-ERF2 plants. Moreover, several key genes involved in ABA synthesis were downregulated in nsf2857, but unregulated in Ami-ERF2 lines. In addition, OsERF2 affected the accumulation of sucrose and UDPG by mediating expression of key genes involved in sucrose metabolism. These results indicate that OsERF2 is required for the control of root architecture and ABA- and ethylene-response by tuning expression of series genes involved in sugar metabolism and hormone signaling pathways.

  13. Nuclear genomic signals of the ‘microturbellarian’ roots of platyhelminth evolutionary innovation

    PubMed Central

    Laumer, Christopher E; Hejnol, Andreas; Giribet, Gonzalo

    2015-01-01

    Flatworms number among the most diverse invertebrate phyla and represent the most biomedically significant branch of the major bilaterian clade Spiralia, but to date, deep evolutionary relationships within this group have been studied using only a single locus (the rRNA operon), leaving the origins of many key clades unclear. In this study, using a survey of genomes and transcriptomes representing all free-living flatworm orders, we provide resolution of platyhelminth interrelationships based on hundreds of nuclear protein-coding genes, exploring phylogenetic signal through concatenation as well as recently developed consensus approaches. These analyses robustly support a modern hypothesis of flatworm phylogeny, one which emphasizes the primacy of the often-overlooked ‘microturbellarian’ groups in understanding the major evolutionary transitions within Platyhelminthes: perhaps most notably, we propose a novel scenario for the interrelationships between free-living and vertebrate-parasitic flatworms, providing new opportunities to shed light on the origins and biological consequences of parasitism in these iconic invertebrates. DOI: http://dx.doi.org/10.7554/eLife.05503.001 PMID:25764302

  14. Infraspinatus muscle atrophy from suprascapular nerve compression.

    PubMed

    Cordova, Christopher B; Owens, Brett D

    2014-02-01

    Muscle weakness without pain may signal a nerve compression injury. Because these injuries should be identified and treated early to prevent permanent muscle weakness and atrophy, providers should consider suprascapular nerve compression in patients with shoulder muscle weakness.

  15. Secreted Herpes Simplex Virus-2 Glycoprotein G Modifies NGF-TrkA Signaling to Attract Free Nerve Endings to the Site of Infection

    PubMed Central

    Cabrera, Jorge Rubén; Viejo-Borbolla, Abel; Martinez-Martín, Nadia; Blanco, Soledad; Wandosell, Francisco; Alcamí, Antonio

    2015-01-01

    Herpes simplex virus type 1 (HSV-1) and HSV-2 are highly prevalent viruses that cause a variety of diseases, from cold sores to encephalitis. Both viruses establish latency in peripheral neurons but the molecular mechanisms facilitating the infection of neurons are not fully understood. Using surface plasmon resonance and crosslinking assays, we show that glycoprotein G (gG) from HSV-2, known to modulate immune mediators (chemokines), also interacts with neurotrophic factors, with high affinity. In our experimental model, HSV-2 secreted gG (SgG2) increases nerve growth factor (NGF)-dependent axonal growth of sympathetic neurons ex vivo, and modifies tropomyosin related kinase (Trk)A-mediated signaling. SgG2 alters TrkA recruitment to lipid rafts and decreases TrkA internalization. We could show, with microfluidic devices, that SgG2 reduced NGF-induced TrkA retrograde transport. In vivo, both HSV-2 infection and SgG2 expression in mouse hindpaw epidermis enhance axonal growth modifying the termination zone of the NGF-dependent peptidergic free nerve endings. This constitutes, to our knowledge, the discovery of the first viral protein that modulates neurotrophins, an activity that may facilitate HSV-2 infection of neurons. This dual function of the chemokine-binding protein SgG2 uncovers a novel strategy developed by HSV-2 to modulate factors from both the immune and nervous systems. PMID:25611061

  16. Direct Administration of Nerve-Specific Contrast to Improve Nerve Sparing Radical Prostatectomy

    PubMed Central

    Barth, Connor W.; Gibbs, Summer L.

    2017-01-01

    Nerve damage remains a major morbidity following nerve sparing radical prostatectomy, significantly affecting quality of life post-surgery. Nerve-specific fluorescence guided surgery offers a potential solution by enhancing nerve visualization intraoperatively. However, the prostate is highly innervated and only the cavernous nerve structures require preservation to maintain continence and potency. Systemic administration of a nerve-specific fluorophore would lower nerve signal to background ratio (SBR) in vital nerve structures, making them difficult to distinguish from all nervous tissue in the pelvic region. A direct administration methodology to enable selective nerve highlighting for enhanced nerve SBR in a specific nerve structure has been developed herein. The direct administration methodology demonstrated equivalent nerve-specific contrast to systemic administration at optimal exposure times. However, the direct administration methodology provided a brighter fluorescent nerve signal, facilitating nerve-specific fluorescence imaging at video rate, which was not possible following systemic administration. Additionally, the direct administration methodology required a significantly lower fluorophore dose than systemic administration, that when scaled to a human dose falls within the microdosing range. Furthermore, a dual fluorophore tissue staining method was developed that alleviates fluorescence background signal from adipose tissue accumulation using a spectrally distinct adipose tissue specific fluorophore. These results validate the use of the direct administration methodology for specific nerve visualization with fluorescence image-guided surgery, which would improve vital nerve structure identification and visualization during nerve sparing radical prostatectomy. PMID:28255352

  17. Direct Administration of Nerve-Specific Contrast to Improve Nerve Sparing Radical Prostatectomy.

    PubMed

    Barth, Connor W; Gibbs, Summer L

    2017-01-01

    Nerve damage remains a major morbidity following nerve sparing radical prostatectomy, significantly affecting quality of life post-surgery. Nerve-specific fluorescence guided surgery offers a potential solution by enhancing nerve visualization intraoperatively. However, the prostate is highly innervated and only the cavernous nerve structures require preservation to maintain continence and potency. Systemic administration of a nerve-specific fluorophore would lower nerve signal to background ratio (SBR) in vital nerve structures, making them difficult to distinguish from all nervous tissue in the pelvic region. A direct administration methodology to enable selective nerve highlighting for enhanced nerve SBR in a specific nerve structure has been developed herein. The direct administration methodology demonstrated equivalent nerve-specific contrast to systemic administration at optimal exposure times. However, the direct administration methodology provided a brighter fluorescent nerve signal, facilitating nerve-specific fluorescence imaging at video rate, which was not possible following systemic administration. Additionally, the direct administration methodology required a significantly lower fluorophore dose than systemic administration, that when scaled to a human dose falls within the microdosing range. Furthermore, a dual fluorophore tissue staining method was developed that alleviates fluorescence background signal from adipose tissue accumulation using a spectrally distinct adipose tissue specific fluorophore. These results validate the use of the direct administration methodology for specific nerve visualization with fluorescence image-guided surgery, which would improve vital nerve structure identification and visualization during nerve sparing radical prostatectomy.

  18. Drought and Root Herbivory Interact to Alter the Response of Above-Ground Parasitoids to Aphid Infested Plants and Associated Plant Volatile Signals

    PubMed Central

    Tariq, Muhammad; Wright, Denis J.; Bruce, Toby J. A.; Staley, Joanna T.

    2013-01-01

    Multitrophic interactions are likely to be altered by climate change but there is little empirical evidence relating the responses of herbivores and parasitoids to abiotic factors. Here we investigated the effects of drought on an above/below-ground system comprising a generalist and a specialist aphid species (foliar herbivores), their parasitoids, and a dipteran species (root herbivore).We tested the hypotheses that: (1) high levels of drought stress and below-ground herbivory interact to reduce the performance of parasitoids developing in aphids; (2) drought stress and root herbivory change the profile of volatile organic chemicals (VOCs) emitted by the host plant; (3) parasitoids avoid ovipositing in aphids feeding on plants under drought stress and root herbivory. We examined the effect of drought, with and without root herbivory, on the olfactory response of parasitoids (preference), plant volatile emissions, parasitism success (performance), and the effect of drought on root herbivory. Under drought, percentage parasitism of aphids was reduced by about 40–55% compared with well watered plants. There was a significant interaction between drought and root herbivory on the efficacy of the two parasitoid species, drought stress partially reversing the negative effect of root herbivory on percent parasitism. In the absence of drought, root herbivory significantly reduced the performance (e.g. fecundity) of both parasitoid species developing in foliar herbivores. Plant emissions of VOCs were reduced by drought and root herbivores, and in olfactometer experiments parasitoids preferred the odour from well-watered plants compared with other treatments. The present work demonstrates that drought stress can change the outcome of interactions between herbivores feeding above- and below-ground and their parasitoids, mediated by changes in the chemical signals from plants to parasitoids. This provides a new insight into how the structure of terrestrial communities may

  19. The Arabidopsis bZIP11 transcription factor links low-energy signalling to auxin-mediated control of primary root growth.

    PubMed

    Weiste, Christoph; Pedrotti, Lorenzo; Selvanayagam, Jebasingh; Muralidhara, Prathibha; Fröschel, Christian; Novák, Ondřej; Ljung, Karin; Hanson, Johannes; Dröge-Laser, Wolfgang

    2017-02-01

    Plants have to tightly control their energy homeostasis to ensure survival and fitness under constantly changing environmental conditions. Thus, it is stringently required that energy-consuming stress-adaptation and growth-related processes are dynamically tuned according to the prevailing energy availability. The evolutionary conserved SUCROSE NON-FERMENTING1 RELATED KINASES1 (SnRK1) and the downstream group C/S1 basic leucine zipper (bZIP) transcription factors (TFs) are well-characterised central players in plants' low-energy management. Nevertheless, mechanistic insights into plant growth control under energy deprived conditions remains largely elusive. In this work, we disclose the novel function of the low-energy activated group S1 bZIP11-related TFs as regulators of auxin-mediated primary root growth. Whereas transgenic gain-of-function approaches of these bZIPs interfere with the activity of the root apical meristem and result in root growth repression, root growth of loss-of-function plants show a pronounced insensitivity to low-energy conditions. Based on ensuing molecular and biochemical analyses, we propose a mechanistic model, in which bZIP11-related TFs gain control over the root meristem by directly activating IAA3/SHY2 transcription. IAA3/SHY2 is a pivotal negative regulator of root growth, which has been demonstrated to efficiently repress transcription of major auxin transport facilitators of the PIN-FORMED (PIN) gene family, thereby restricting polar auxin transport to the root tip and in consequence auxin-driven primary root growth. Taken together, our results disclose the central low-energy activated SnRK1-C/S1-bZIP signalling module as gateway to integrate information on the plant's energy status into root meristem control, thereby balancing plant growth and cellular energy resources.

  20. The Arabidopsis bZIP11 transcription factor links low-energy signalling to auxin-mediated control of primary root growth

    PubMed Central

    Weiste, Christoph; Pedrotti, Lorenzo; Muralidhara, Prathibha; Ljung, Karin; Dröge-Laser, Wolfgang

    2017-01-01

    Plants have to tightly control their energy homeostasis to ensure survival and fitness under constantly changing environmental conditions. Thus, it is stringently required that energy-consuming stress-adaptation and growth-related processes are dynamically tuned according to the prevailing energy availability. The evolutionary conserved SUCROSE NON-FERMENTING1 RELATED KINASES1 (SnRK1) and the downstream group C/S1 basic leucine zipper (bZIP) transcription factors (TFs) are well-characterised central players in plants’ low-energy management. Nevertheless, mechanistic insights into plant growth control under energy deprived conditions remains largely elusive. In this work, we disclose the novel function of the low-energy activated group S1 bZIP11-related TFs as regulators of auxin-mediated primary root growth. Whereas transgenic gain-of-function approaches of these bZIPs interfere with the activity of the root apical meristem and result in root growth repression, root growth of loss-of-function plants show a pronounced insensitivity to low-energy conditions. Based on ensuing molecular and biochemical analyses, we propose a mechanistic model, in which bZIP11-related TFs gain control over the root meristem by directly activating IAA3/SHY2 transcription. IAA3/SHY2 is a pivotal negative regulator of root growth, which has been demonstrated to efficiently repress transcription of major auxin transport facilitators of the PIN-FORMED (PIN) gene family, thereby restricting polar auxin transport to the root tip and in consequence auxin-driven primary root growth. Taken together, our results disclose the central low-energy activated SnRK1-C/S1-bZIP signalling module as gateway to integrate information on the plant’s energy status into root meristem control, thereby balancing plant growth and cellular energy resources. PMID:28158182

  1. Drought and root herbivory interact to alter the response of above-ground parasitoids to aphid infested plants and associated plant volatile signals.

    PubMed

    Tariq, Muhammad; Wright, Denis J; Bruce, Toby J A; Staley, Joanna T

    2013-01-01

    Multitrophic interactions are likely to be altered by climate change but there is little empirical evidence relating the responses of herbivores and parasitoids to abiotic factors. Here we investigated the effects of drought on an above/below-ground system comprising a generalist and a specialist aphid species (foliar herbivores), their parasitoids, and a dipteran species (root herbivore).We tested the hypotheses that: (1) high levels of drought stress and below-ground herbivory interact to reduce the performance of parasitoids developing in aphids; (2) drought stress and root herbivory change the profile of volatile organic chemicals (VOCs) emitted by the host plant; (3) parasitoids avoid ovipositing in aphids feeding on plants under drought stress and root herbivory. We examined the effect of drought, with and without root herbivory, on the olfactory response of parasitoids (preference), plant volatile emissions, parasitism success (performance), and the effect of drought on root herbivory. Under drought, percentage parasitism of aphids was reduced by about 40-55% compared with well watered plants. There was a significant interaction between drought and root herbivory on the efficacy of the two parasitoid species, drought stress partially reversing the negative effect of root herbivory on percent parasitism. In the absence of drought, root herbivory significantly reduced the performance (e.g. fecundity) of both parasitoid species developing in foliar herbivores. Plant emissions of VOCs were reduced by drought and root herbivores, and in olfactometer experiments parasitoids preferred the odour from well-watered plants compared with other treatments. The present work demonstrates that drought stress can change the outcome of interactions between herbivores feeding above- and below-ground and their parasitoids, mediated by changes in the chemical signals from plants to parasitoids. This provides a new insight into how the structure of terrestrial communities may be

  2. Silencing the α2 subunit of GABAA receptors in rat dorsal root ganglia reveals its major role in antinociception post-traumatic nerve injury

    PubMed Central

    Obradović, Aleksandar LJ; Scarpa, Joseph; Osuru, Hari P; Weaver, Janelle L; Park, Ji-Yong; Pathirathna, Sriyani; Peterkin, Alexander; Lim, Yunhee; Jagodic, Miljenko M; Todorovic, Slobodan M; Jevtovic-Todorovic, Vesna

    2015-01-01

    Background Neuropathic pain is likely the result of repetitive high frequency bursts of peripheral afferent activity leading to long-lasting changes in synaptic plasticity in the spinal dorsal horn (DH). Drugs that promote GABA activity in the DH provide partial relief of neuropathic symptoms. We examined how in vivo silencing of the GABAA α2 gene in DRG controls of NPP. Methods After crush injury to the right sciatic nerve of female rats, the α2 GABAA antisense and mismatch oligodeoxynucleotides or NO-711 (a GABA uptake inhibitor) were applied to the L5 DRG. In vivo behavioral assessment of nociception was conducted prior to the injury and ensuing 10 days (n=4–10). In vitro quantification of α2 GABAA protein and electrophysiology studies of GABAA currents were performed on acutely dissociated L5 DRG neurons at relevant time-points (n=6–14). Results NPP post-crush injury of a sciatic nerve in adult female rats coincides with significant down-regulation of the α2 subunit expression in the ipsilateral DRG (about 30%). Selective down-regulation of α2 expression in DRGs significantly worsens mechanical (2.55±0.75 to 5.16±1.16) and thermal (7.97±0.96 to 5.51±0.75) hypersensitivity in crush-injured animals and causes development of significant mechanical (2.33±0.40 to 5.00±0.33) and thermal (10.80±0.29 to 7.34±0.81) hypersensitivity in sham animals (data shown as MEAN±SD). Conversely, up-regulation of endogenous GABA via blockade of its uptake in DRG alleviates NPP. Conclusions The GABAA receptor in the DRG plays an important role in pathophysiology of NPP caused by sciatic nerve injury and represent promising target for novel pain therapies. PMID:26164299

  3. ERK1/2-mediated Schwann cell proliferation in the regenerating sciatic nerve by treadmill training.

    PubMed

    Seo, Tae Beom; Oh, Myung-Jin; You, Byoung-Gun; Kwon, Ku-Birm; Chang, In-Ae; Yoon, Jin-Hwan; Lee, Chan-Yong; Namgung, Uk

    2009-10-01

    Proliferation of Schwann cells in the injured peripheral nerve supports axonal regeneration, and physical training in experimental animals has been shown to promote nerve regeneration. Extracellular signal-regulated kinase 1/2 (ERK1/2) activity can mediate neuronal responses to lesion signals, but its role in non-neuronal cells in the injured area is largely unknown. Here we report that treadmill training (TMT) facilitates axonal regeneration via the upregulation of phospho-ERK1/2 protein levels in Schwann cells in the injured sciatic nerve. Low-intensity, but not high-intensity, TMT increased neurite outgrowth of dorsal root ganglion (DRG) sensory neurons and potentiated Schwann cell proliferation. TMT elevated levels of GAP-43 mRNA and protein, and phospho-ERK1/2 protein in the injured sciatic nerves. TMT also enhanced phospho-c-Jun protein levels in the injured nerve. In-vivo administration of the ERK1/2 inhibitor PD98059 eliminated phospho-c-Jun, suggesting ERK1/2 phosphorylation of the c-Jun protein. PD98059 treatment decreased levels of BrdU-labeled proliferating Schwann cells in the distal portion of the injured nerve, and delayed the axonal regrowth that was promoted by TMT. The present data suggest that increased ERK1/2 activity in Schwann cells may play an important role in TMT-mediated enhancement of axonal regeneration in the injured peripheral nerve.

  4. Inhibition of Mammalian Target of Rapamycin (mTOR) Signaling in the Insular Cortex Alleviates Neuropathic Pain after Peripheral Nerve Injury

    PubMed Central

    Kwon, Minjee; Han, Jeongsoo; Kim, Un Jeng; Cha, Myeounghoon; Um, Sun Woo; Bai, Sun Joon; Hong, Seong-Karp; Lee, Bae Hwan

    2017-01-01

    Injury of peripheral nerves can trigger neuropathic pain, producing allodynia and hyperalgesia via peripheral and central sensitization. Recent studies have focused on the role of the insular cortex (IC) in neuropathic pain. Because the IC is thought to store pain-related memories, translational regulation in this structure may reveal novel targets for controlling chronic pain. Signaling via mammalian target of rapamycin (mTOR), which is known to control mRNA translation and influence synaptic plasticity, has been studied at the spinal level in neuropathic pain, but its role in the IC under these conditions remains elusive. Therefore, this study was conducted to determine the role of mTOR signaling in neuropathic pain and to assess the potential therapeutic effects of rapamycin, an inhibitor of mTORC1, in the IC of rats with neuropathic pain. Mechanical allodynia was assessed in adult male Sprague-Dawley rats after neuropathic surgery and following microinjections of rapamycin into the IC on postoperative days (PODs) 3 and 7. Optical recording was conducted to observe the neural responses of the IC to peripheral stimulation. Rapamycin reduced mechanical allodynia and downregulated the expression of postsynaptic density protein 95 (PSD95), decreased neural excitability in the IC, thereby inhibiting neuropathic pain-induced synaptic plasticity. These findings suggest that mTOR signaling in the IC may be a critical molecular mechanism modulating neuropathic pain. PMID:28377693

  5. The retinoic acid signaling pathway regulates anterior/posterior patterning in the nerve cord and pharynx of amphioxus, a chordate lacking neural crest

    NASA Technical Reports Server (NTRS)

    Escriva, Hector; Holland, Nicholas D.; Gronemeyer, Hinrich; Laudet, Vincent; Holland, Linda Z.

    2002-01-01

    Amphioxus, the closest living invertebrate relative of the vertebrates, has a notochord, segmental axial musculature, pharyngeal gill slits and dorsal hollow nerve cord, but lacks neural crest. In amphioxus, as in vertebrates, exogenous retinoic acid (RA) posteriorizes the embryo. The mouth and gill slits never form, AmphiPax1, which is normally downregulated where gill slits form, remains upregulated and AmphiHox1 expression shifts anteriorly in the nerve cord. To dissect the role of RA signaling in patterning chordate embryos, we have cloned the single retinoic acid receptor (AmphiRAR), retinoid X receptor (AmphiRXR) and an orphan receptor (AmphiTR2/4) from amphioxus. AmphiTR2/4 inhibits AmphiRAR-AmphiRXR-mediated transactivation in the presence of RA by competing for DR5 or IR7 retinoic acid response elements (RAREs). The 5' untranslated region of AmphiTR2/4 contains an IR7 element, suggesting possible auto- and RA-regulation. The patterns of AmphiTR2/4 and AmphiRAR expression during embryogenesis are largely complementary: AmphiTR2/4 is strongly expressed in the cerebral vesicle (homologous to the diencephalon plus anterior midbrain), while AmphiRAR expression is high in the equivalent of the hindbrain and spinal cord. Similarly, while AmphiTR2/4 is expressed most strongly in the anterior and posterior thirds of the endoderm, the highest AmphiRAR expression is in the middle third. Expression of AmphiRAR is upregulated by exogenous RA and completely downregulated by the RA antagonist BMS009. Moreover, BMS009 expands the pharynx posteriorly; the first three gill slit primordia are elongated and shifted posteriorly, but do not penetrate, and additional, non-penetrating gill slit primordia are induced. Thus, in an organism without neural crest, initiation and penetration of gill slits appear to be separate events mediated by distinct levels of RA signaling in the pharyngeal endoderm. Although these compounds have little effect on levels of AmphiTR2/4 expression, RA

  6. Overexpression of suppressor of cytokine signaling 3 in dorsal root ganglion attenuates cancer-induced pain in rats

    PubMed Central

    Wei, Jinrong; Li, Meng; Wang, Dieyu; Zhu, Hongyan; Kong, Xiangpeng; Wang, Shusheng; Zhou, You-Lang; Ju, Zhong; Jiang, Guo-Qin

    2017-01-01

    Background Cancer-induced pain (CIP) is one of the most severe types of chronic pain with which clinical treatment remains challenging and the involved mechanisms are largely unknown. Suppressor of cytokine signaling 3 (SOCS3) is an important intracellular protein and provides a classical negative feedback loop, thus involving in a wide variety of processes including inflammation and nociception. However, the role of SOCS3 pathway in CIP is poorly understood. The present study was designed to investigate the role of SOCS3 in dorsal root ganglion (DRG) in the development of CIP. Method CIP was established by injection of Walker 256 mammary gland tumor cells into the rat tibia canal. Whole-cell patch clamping and Western blotting were performed. Results Following the development of bone cancer, SOCS3 expression was significantly downregulated in rat DRGs at L2–L5 segments. Overexpression of SOCS3, using lentiviral-mediated production of SOCS3 at spinal cord level, drastically attenuated mechanical allodynia and body weight-bearing difference, but not thermal hyperalgesia in bone cancer rats. In addition, overexpression of SOCS3 reversed the hyperexcitability of DRG neurons innervating the tibia, and reduced abnormal expression of toll-like receptors 4 in the DRGs. Conclusions These results suggest that SOCS3 might be a key molecular involved in the development of complicated cancer pain and that overexpression of SOCS3 might be an important strategy for treatment for mechanical allodynia associated with bone cancer. PMID:28326931

  7. A gene encoding a peptide with similarity to the plant IDA signaling peptide (AtIDA) is expressed most abundantly in the root-knot nematode (Meloidogyne incognita) soon after root infection.

    PubMed

    Tucker, Mark L; Yang, Ronghui

    2013-06-01

    Small peptides play important roles in intercellular signaling. Inflorescence deficient in abscission (ida) is an Arabidopsis mutant that does not abscise (shed) its flower petals. The IDA gene encodes a small, secreted peptide that putatively binds to two redundant receptor-like kinases (HAESA and HAESA-like2) that initiate a signal transduction pathway. We identified IDA-like (IDL) genes in the genomic sequence for Meloidogyne incognita and Meloidogyne hapla. No orthologous sequences were found in any other genus of nematodes. Transcript for both M. incognita and M. hapla IDLs were found in total RNA isolated from infected root systems of tomato, Solanum lycopersicum. Five and three prime RACE of RNA from M. incognita infected tomato roots revealed a sequence of 392 nt that includes a poly (A) tail of 39 nt. The open reading frame encodes a 47 aa protein with a putative 25 aa N-terminal signal peptide. Expression of MiIDL1 is very low in eggs and pre-parasitic J2 and rapidly increases in the first four days post inoculation (dpi) and then declines at approximately 14 dpi. A proposed role for the root-knot nematode IDL is discussed.

  8. Common peroneal nerve dysfunction

    MedlinePlus

    Neuropathy - common peroneal nerve; Peroneal nerve injury; Peroneal nerve palsy ... type of peripheral neuropathy (damage to nerves outside the brain ... nerve injuries. Damage to the nerve disrupts the myelin sheath ...

  9. Rhizobacterial volatiles and photosynthesis-related signals coordinate MYB72 expression in Arabidopsis roots during onset of induced systemic resistance and iron-deficiency responses.

    PubMed

    Zamioudis, Christos; Korteland, Jolanda; Van Pelt, Johan A; van Hamersveld, Muriël; Dombrowski, Nina; Bai, Yang; Hanson, Johannes; Van Verk, Marcel C; Ling, Hong-Qing; Schulze-Lefert, Paul; Pieterse, Corné M J

    2015-10-01

    In Arabidopsis roots, the transcription factor MYB72 plays a dual role in the onset of rhizobacteria-induced systemic resistance (ISR) and plant survival under conditions of limited iron availability. Previously, it was shown that MYB72 coordinates the expression of a gene module that promotes synthesis and excretion of iron-mobilizing phenolic compounds in the rhizosphere, a process that is involved in both iron acquisition and ISR signaling. Here, we show that volatile organic compounds (VOCs) from ISR-inducing Pseudomonas bacteria are important elicitors of MYB72. In response to VOC treatment, MYB72 is co-expressed with the iron uptake-related genes FERRIC REDUCTION OXIDASE 2 (FRO2) and IRON-REGULATED TRANSPORTER 1 (IRT1) in a manner that is dependent on FER-LIKE IRON DEFICIENCY TRANSCRIPTION FACTOR (FIT), indicating that MYB72 is an intrinsic part of the plant's iron-acquisition response that is typically activated upon iron starvation. However, VOC-induced MYB72 expression is activated independently of iron availability in the root vicinity. Moreover, rhizobacterial VOC-mediated induction of MYB72 requires photosynthesis-related signals, while iron deficiency in the rhizosphere activates MYB72 in the absence of shoot-derived signals. Together, these results show that the ISR- and iron acquisition-related transcription factor MYB72 in Arabidopsis roots is activated by rhizobacterial volatiles and photosynthesis-related signals, and enhances the iron-acquisition capacity of roots independently of the iron availability in the rhizosphere. This work highlights the role of MYB72 in plant processes by which root microbiota simultaneously stimulate systemic immunity and activate the iron-uptake machinery in their host plants.

  10. The Ca(2+) -binding protein PCaP2 located on the plasma membrane is involved in root hair development as a possible signal transducer.

    PubMed

    Kato, Mariko; Aoyama, Takashi; Maeshima, Masayoshi

    2013-05-01

    Plasma membrane-associated Ca(2+) -binding protein-2 (PCaP2) of Arabidopsis thaliana is a novel-type protein that binds to the Ca(2+) /calmodulin complex and phosphatidylinositol phosphates (PtdInsPs) as well as free Ca(2+) . Although the PCaP2 gene is predominantly expressed in root hair cells, it remains unknown how PCaP2 functions in root hair cells via binding to ligands. From biochemical analyses using purified PCaP2 and its variants, we found that the N-terminal basic domain with 23 amino acids (N23) is necessary and sufficient for binding to PtdInsPs and the Ca(2+) /calmodulin complex, and that the residual domain of PCaP2 binds to free Ca(2+) . In mutant analysis, a pcap2 knockdown line displayed longer root hairs than the wild-type. To examine the function of each domain in root hair cells, we over-expressed PCaP2 and its variants using the root hair cell-specific EXPANSIN A7 promoter. Transgenic lines over-expressing PCaP2, PCaP2(G2A) (second glycine substituted by alanine) and ∆23PCaP2 (lacking the N23 domain) exhibited abnormal branched and bulbous root hair cells, while over-expression of the N23 domain suppressed root hair emergence and elongation. The N23 domain was necessary and sufficient for the plasma membrane localization of GFP-tagged PCaP2. These results suggest that the N23 domain of PCaP2 negatively regulates root hair tip growth via processing Ca(2+) and PtdInsP signals on the plasma membrane, while the residual domain is involved in the polarization of cell expansion.

  11. Combinatorial therapy with tamoxifen and trifluoperazine effectively inhibits malignant peripheral nerve sheath tumor growth by targeting complementary signaling cascades.

    PubMed

    Brosius, Stephanie N; Turk, Amy N; Byer, Stephanie J; Longo, Jody Fromm; Kappes, John C; Roth, Kevin A; Carroll, Steven L

    2014-11-01

    Chemotherapeutic agents effective against malignant peripheral nerve sheath tumors (MPNSTs) are urgently needed. We recently found that tamoxifen potently impedes xenograft growth. In vitro, tamoxifen inhibits MPNST proliferation and survival in an estrogen receptor-independent manner; these effects are phenocopied by the calmodulin inhibitor trifluoperazine. The present study was performed to establish the mechanism of action of tamoxifen in vivo and optimize its therapeutic effectiveness. To determine if tamoxifen has estrogen receptor-dependent effects in vivo, we grafted MPNST cells in castrated and ovariectomized mice; xenograft growth was unaffected by reductions in sex hormones. To establish whether tamoxifen and trifluoperazine additively or synergistically impede MPNST growth, mice xenografted with neurofibromatosis type 1-associated or sporadic MPNST cells were treated with tamoxifen, trifluoperazine, or both drugs for 30 days. Both monotherapies inhibited graft growth by 50%, whereas combinatorial treatment maximally reduced graft mass by 90% and enhanced decreases in proliferation and survival. Kinomic analyses showed that tamoxifen and trifluoperazine have both shared and distinct targets in MPNSTs. In addition, trifluoperazine prevented tamoxifen-induced increases in serum/glucocorticoid regulated kinase 1, a protein linked to tamoxifen resistance. These findings suggest that combinatorial therapy with tamoxifen and trifluoperazine is effective against MPNSTs because these agents target complementary pathways that are essential for MPNST pathogenesis.

  12. Influences of neck afferents on sympathetic and respiratory nerve activity.

    PubMed

    Bolton, P S; Kerman, I A; Woodring, S F; Yates, B J

    1998-11-15

    It is well established that the vestibular system influences the sympathetic nervous system and the respiratory system; presumably, vestibulosympathetic and vestibulorespiratory responses participate in maintaining stable blood pressure and blood oxygenation during movement and changes in posture. Many brainstem neurons that generate vestibulospinal reflexes integrate signals from the labyrinth and neck muscles to distinguish between head movements on a stable body and whole body movements. In the present study, responses were recorded from the splanchnic (sympathetic), hypoglossal (inspiratory) and abdominal (expiratory) nerves during stimulation of the C2 dorsal root ganglion or C2 or C3 nerve branches innervating dorsal neck muscles. Stimulation of neck afferents using low current intensities, in many cases less than twice the threshold for producing an afferent volley recordable from the cord dorsum, elicited changes in sympathetic and respiratory nerve activity. These data suggest that head rotation on a stable body would elicit both cervical and vestibular inputs to respiratory motoneurons and sympathetic preganglionic neurons. The effects of cervical afferent stimulation on abdominal, splanchnic and hypoglossal nerve activity were not abolished by transection of the brainstem caudal to the vestibular nuclei; thus, pathways in addition to those involving the vestibular nuclei are involved in relaying cervical inputs to sympathetic preganglionic neurons and respiratory motoneurons. Transection of the C1-3 dorsal roots enhanced responses of the splanchnic and abdominal nerves to pitch head rotations on a fixed body but diminished responses of the hypoglossal nerve. Thus, neck and vestibular afferent influences on activity of respiratory pump muscles and sympathetic outflow appear to be antagonistic, so that responses will occur during whole body movements but not head movements on a stationary trunk. In contrast, neck and vestibular influences on tongue

  13. Hypothalamic mTORC1 signaling controls sympathetic nerve activity and arterial pressure and mediates leptin effects.

    PubMed

    Harlan, Shannon M; Guo, Deng-Fu; Morgan, Donald A; Fernandes-Santos, Caroline; Rahmouni, Kamal

    2013-04-02

    The fundamental importance of the hypothalamus in the regulation of autonomic and cardiovascular functions is well established. However, the molecular processes involved are not well understood. Here, we show that the mammalian (or mechanistic) target of rapamycin (mTOR) signaling in the hypothalamus is tied to the activity of the sympathetic nervous system and to cardiovascular function. Modulation of mTOR complex 1 (mTORC1) signaling caused dramatic changes in sympathetic traffic, blood flow, and arterial pressure. Our data also demonstrate the importance of hypothalamic mTORC1 signaling in transducing the sympathetic and cardiovascular actions of leptin. Moreover, we show that the PI3K pathway links the leptin receptor to mTORC1 signaling and that changes in its activity impact sympathetic traffic and arterial pressure. These findings establish mTORC1 activity in the hypothalamus as a key determinant of sympathetic and cardiovascular regulation and suggest that dysregulated hypothalamic mTORC1 activity may influence the development of cardiovascular diseases.

  14. A re-assessment of sucrose signaling involved in cluster-root formation and function in phosphate-deficient white lupin (Lupinus albus).

    PubMed

    Wang, Zhengrui; Shen, Jianbo; Ludewig, Uwe; Neumann, Günter

    2015-07-01

    Apart from substrate functions, a signaling role of sucrose in root growth regulation is well established. This raised the question whether sucrose signals might also be involved in formation of cluster-roots (CRs) under phosphate (Pi) limitation, mediating exudation of phosphorus (P)-mobilizing root exudates, e.g. in Lupinus albus and members of the Proteaceae. Earlier studies demonstrated that CR formation in L. albus was mimicked to some extent by external application of high sucrose concentrations (25 mM) in the presence of extremely high P supply (1-10 mM), usually suppressing CR formation. In this study, we re-addressed this question using an axenic hydroponic culture system with normal P supply (0.1 mM) and a range of sucrose applications (0.25-25 mM). The 2.5 mM sucrose concentration was comparable with internal sucrose levels in the zone of CR initiation in first-order laterals of P-deficient plants (3.4 mM) and induced the same CR morphology. Similar to earlier studies, high sucrose concentrations (25 mM) resulted in root thickening and inhibition of root elongation, associated with a 10-fold increase of the internal sucrose level. The sucrose analog palatinose and a combination of glucose/fructose failed to stimulate CR formation under P-sufficient conditions, demonstrating a signal function of sucrose and excluding osmotic or carbon source effects. In contrast to earlier findings, sucrose was able to induce CR formation but had no effect on CR functioning with respect to citrate exudation, in vitro activity and expression of genes encoding phosphoenolpyruvate carboxylase, secretory acid phosphatase and MATE transporters, mediating P-mobilizing functions of CRs.

  15. Regulation of Phytosiderophore Release and Antioxidant Defense in Roots Driven by Shoot-Based Auxin Signaling Confers Tolerance to Excess Iron in Wheat

    PubMed Central

    Kabir, Ahmad H.; Khatun, Most A.; Hossain, Mohammad M.; Haider, Syed A.; Alam, Mohammad F.; Paul, Nishit K.

    2016-01-01

    Iron (Fe) is essential but harmful for plants at toxic level. However, how wheat plants tolerate excess Fe remains vague. This study aims at elucidating the mechanisms underlying tolerance to excess Fe in wheat. Higher Fe concentration caused morpho-physiological retardation in BR 26 (sensitive) but not in BR 27 (tolerant). Phytosiderophore and 2-deoxymugineic acid showed no changes in BR 27 but significantly increased in BR 26 due to excess Fe. Further, expression of TaSAMS. TaDMAS1, and TaYSL15 significantly downregulated in BR 27 roots, while these were upregulated in BR 26 under excess Fe. It confirms that inhibition of phytosiderophore directs less Fe accumulation in BR 27. However, phytochelatin and expression of TaPCS1 and TaMT1 showed no significant induction in response to excess Fe. Furthermore, excess Fe showed increased catalase, peroxidase, and glutathione reductase activities along with glutathione, cysteine, and proline accumulation in roots in BR 27. Interestingly, BR 27 self-grafts and plants having BR 26 rootstock attached to BR 27 scion had no Fe-toxicity induced adverse effect on morphology but showed BR 27 type expressions, confirming that shoot-derived signal triggering Fe-toxicity tolerance in roots. Finally, auxin inhibitor applied with higher Fe concentration caused a significant decline in morpho-physiological parameters along with increased TaSAMS and TaDMAS1 expression in roots of BR 27, revealing the involvement of auxin signaling in response to excess Fe. These findings propose that tolerance to excess Fe in wheat is attributed to the regulation of phytosiderophore limiting Fe acquisition along with increased antioxidant defense in roots driven by shoot-derived auxin signaling. PMID:27891139

  16. The Role of DARPP-32, an Intracellular Signaling Molecule, in the Actions of the Nerve Agent Sarin

    DTIC Science & Technology

    2005-08-01

    calmodulin-dependent protein phosphatase signaling cascade, which dephosphorylates phospho-T34-DARPP-32 (Nishi et al., 1999). DARPP-32 is also...32 at Ser-102 (S102) and Ser-137 (S137). For example, S102 on DARPP-32 is phosphorylated by casein kinase II (CK2). In previously published...al., 1989). DARPP-32 is also phosphorylated on amino acid S137 by casein kinase I (CK1). Increases in phosphorylation at this site decrease the rate

  17. Role of hydraulic and chemical signals in leaves, stems and roots in the stomatal behaviour of olive trees under water stress and recovery conditions.

    PubMed

    Torres-Ruiz, Jose M; Diaz-Espejo, Antonio; Perez-Martin, Alfonso; Hernandez-Santana, Virginia

    2015-04-01

    The control of plant transpiration by stomata under water stress and recovery conditions is of paramount importance for plant performance and survival. Although both chemical and hydraulic signals emitted within a plant are considered to play a major role in controlling stomatal dynamics, they have rarely been assessed together. The aims of this study were to evaluate (i) the dynamics of chemical and hydraulic signals at leaf, stem and root level, and (ii) their effect on the regulation of stomatal conductance (gs) during water stress and recovery. Measurements of gs, water potential, abscisic acid (ABA) content and loss of hydraulic functioning at leaf, stem and root level were conducted during a water stress and recovery period imposed on 1-year-old olive plants (Olea europaea L.). Results showed a strong hydraulic segmentation in olive plants, with higher hydraulic functioning losses in roots and leaves than in stems. The dynamics of hydraulic conductance of roots and leaves observed as water stress developed could explain both a protection of the hydraulic functionality of larger organs of the plant (i.e., branches, etc.) and a role in the down-regulation of gs. On the other hand, ABA also increased, showing a similar pattern to gs dynamics, and thus its effect on gs in response to water stress cannot be ruled out. However, neither hydraulic nor non-hydraulic factors were able to explain the delay in the full recovery of gs after soil water availability was restored.

  18. LATERAL ROOT PRIMORDIA 1 of maize acts as a transcriptional activator in auxin signalling downstream of the Aux/IAA gene rootless with undetectable meristem 1.

    PubMed

    Zhang, Yanxiang; von Behrens, Inga; Zimmermann, Roman; Ludwig, Yvonne; Hey, Stefan; Hochholdinger, Frank

    2015-07-01

    Only little is known about target genes of auxin signalling downstream of the Aux/IAA-ARF module. In the present study, it has been demonstrated that maize lateral root primordia 1 (lrp1) encodes a transcriptional activator that is directly regulated by the Aux/IAA protein ROOTLESS WITH UNDETECTABLE MERISTEM 1 (RUM1). Expression of lrp1 is confined to early root primordia and meristems and is auxin-inducible. Based on its primary protein structure, LRP1 is predicted to be a transcription factor. This notion is supported by exclusive LRP1 localization in the nucleus and its ability to activate downstream gene activity. Based on the observation that lrp1 transcription is completely repressed in the semi-dominant gain of function mutant rum1, it was demonstrated that the lrp1 promoter is a direct target of RUM1 proteins. Subsequently, promoter activation assays indicated that RUM1 represses the expression of a GFP reporter fused to the native promoter of lrp1. Constitutive repression of lrp1 in rum1 mutants is a consequence of the stability of mutated rum1 proteins which cannot be degraded by the proteasome and thus constitutively bind to the lrp1 promoter and repress transcription. Taken together, the repression of the transcriptional activator lrp1 by direct binding of RUM1 to its promoter, together with specific expression of lrp1 in root meristems, suggests a function in maize root development via the RUM1-dependent auxin signalling pathway.

  19. Hydraulic Signals from the Roots and Rapid Cell-Wall Hardening in Growing Maize (Zea mays L.) Leaves Are Primary Responses to Polyethylene Glycol-Induced Water Deficits.

    PubMed

    Chazen, O.; Neumann, P. M.

    1994-04-01

    We investigated mechanisms involved in inhibition of maize (Zea mays L.) leaf-elongation growth following addition of non-penetrating osmolyte to the root medium. The elongation rate of the first true leaf remained inhibited for 4 h after addition of polyethylene glycol 6000 (PEG; -0.5 MPa water potential), despite progressive osmotic adjustment in the growing leaf tissues. Thus, inhibition of leaf growth did not appear to be directly related to loss of leaf capacity to maintain osmotic potential gradients. Comparative cell-wall-extension capacities of immature (still expanding) leaf tissues were measured by creep extensiometry using whole plants. Reductions in irreversible (plastic) extension capacity (i.e. wall hardening) were detected minutes and hours after addition of PEG to the roots, by both in vivo and in vitro assay. The onset of the wall-hardening response could be detected by in vitro assay only 2 min after addition of PEG. Thus, initiation of wall hardening appeared to precede transcription-regulated responses. The inhibition of both leaf growth and wall-extension capacity was reversed by removal of PEG after 4 h. Moreover, wall hardening could be induced by other osmolytes (mannitol, NaCl). Thus, the leaf responses did not appear to be related to any specific (toxic) effect of PEG. We conclude that hardening of leaf cell walls is a primary event in the chain of growth regulatory responses to PEG-induced water deficits in maize. The signaling processes by which PEG, which is not expected to penetrate root cell walls or membranes, might cause cell-wall hardening in relatively distant leaves was also investigated. Plants with live or killed roots were exposed to PEG. The killed roots were presumed to be unable to produce hormonal or electrical signals in response to addition of PEG; however, inhibition of leaf elongation and hardening of leaf cell walls were detected with both live and killed roots. Thus, neither hormonal signaling nor signaling via

  20. Overview of Optic Nerve Disorders

    MedlinePlus

    ... where the problem is in the pathway. Visual Pathways and the Consequences of Damage Nerve signals travel ... eyes. Damage to an eye or the visual pathway causes different types of vision loss depending on ...

  1. Small Molecule DFPM Derivative-Activated Plant Resistance Protein Signaling in Roots Is Unaffected by EDS1 Subcellular Targeting Signal and Chemical Genetic Isolation of victr R-Protein Mutants.

    PubMed

    Kunz, Hans-Henning; Park, Jiyoung; Mevers, Emily; García, Ana V; Highhouse, Samantha; Gerwick, William H; Parker, Jane E; Schroeder, Julian I

    2016-01-01

    The small molecule DFPM ([5-(3,4-dichlorophenyl)furan-2-yl]-piperidine-1-ylmethanethione) was recently shown to trigger signal transduction via early effector-triggered immunity signaling genes including EDS1 and PAD4 in Arabidopsis thaliana accession Col-0. Chemical genetic analyses of A. thaliana natural variants identified the plant Resistance protein-like Toll/Interleukin1 Receptor (TIR)-Nucleotide Binding (NB)-Leucine-Rich Repeat (LRR) protein VICTR as required for DFPM-mediated root growth arrest. Here a chemical genetic screen for mutants which disrupt DFPM-mediated root growth arrest in the Col-0 accession identified new mutant alleles of the TIR-NB-LRR gene VICTR. One allele, victr-6, carries a Gly216-to-Asp mutation in the Walker A domain supporting an important function of the VICTR nucleotide binding domain in DFPM responses consistent with VICTR acting as a canonical Resistance protein. The essential nucleo-cytoplasmic regulator of TIR-NB-LRR-mediated effector-triggered immunity, EDS1, was reported to have both nuclear and cytoplasmic actions in pathogen resistance. DFPM was used to investigate the requirements for subcellular EDS1 localization in DFPM-mediated root growth arrest. EDS1-YFP fusions engineered to localize mainly in the cytoplasm or the nucleus by tagging with a nuclear export signal (NES) or a nuclear localization signal (NLS), respectively, were tested. We found that wild-type EDS1-YFP and both the NES and NLS-tagged EDS1 variants were induced by DFPM treatments and fully complemented eds1 mutant plants in root responses to DFPM, suggesting that enrichment of EDS1 in either compartment could confer DFPM-mediated root growth arrest. We further found that a light and O2-dependent modification of DFPM is necessary to mediate DFPM signaling in roots. Chemical analyses including Liquid Chromatography-Mass Spectrometry and High-Resolution Atmospheric Pressure Chemical Ionization Mass Spectrometry identified a DFPM modification product that is

  2. Small Molecule DFPM Derivative-Activated Plant Resistance Protein Signaling in Roots Is Unaffected by EDS1 Subcellular Targeting Signal and Chemical Genetic Isolation of victr R-Protein Mutants

    PubMed Central

    Mevers, Emily; García, Ana V.; Highhouse, Samantha; Gerwick, William H.; Parker, Jane E.; Schroeder, Julian I.

    2016-01-01

    The small molecule DFPM ([5-(3,4-dichlorophenyl)furan-2-yl]-piperidine-1-ylmethanethione) was recently shown to trigger signal transduction via early effector-triggered immunity signaling genes including EDS1 and PAD4 in Arabidopsis thaliana accession Col-0. Chemical genetic analyses of A. thaliana natural variants identified the plant Resistance protein-like Toll/Interleukin1 Receptor (TIR)-Nucleotide Binding (NB)-Leucine-Rich Repeat (LRR) protein VICTR as required for DFPM-mediated root growth arrest. Here a chemical genetic screen for mutants which disrupt DFPM-mediated root growth arrest in the Col-0 accession identified new mutant alleles of the TIR-NB-LRR gene VICTR. One allele, victr-6, carries a Gly216-to-Asp mutation in the Walker A domain supporting an important function of the VICTR nucleotide binding domain in DFPM responses consistent with VICTR acting as a canonical Resistance protein. The essential nucleo-cytoplasmic regulator of TIR-NB-LRR-mediated effector-triggered immunity, EDS1, was reported to have both nuclear and cytoplasmic actions in pathogen resistance. DFPM was used to investigate the requirements for subcellular EDS1 localization in DFPM-mediated root growth arrest. EDS1-YFP fusions engineered to localize mainly in the cytoplasm or the nucleus by tagging with a nuclear export signal (NES) or a nuclear localization signal (NLS), respectively, were tested. We found that wild-type EDS1-YFP and both the NES and NLS-tagged EDS1 variants were induced by DFPM treatments and fully complemented eds1 mutant plants in root responses to DFPM, suggesting that enrichment of EDS1 in either compartment could confer DFPM-mediated root growth arrest. We further found that a light and O2-dependent modification of DFPM is necessary to mediate DFPM signaling in roots. Chemical analyses including Liquid Chromatography-Mass Spectrometry and High-Resolution Atmospheric Pressure Chemical Ionization Mass Spectrometry identified a DFPM modification product that is

  3. The effect of antenatal depression and selective serotonin reuptake inhibitor treatment on nerve growth factor signaling in human placenta.

    PubMed

    Kaihola, Helena; Olivier, Jocelien; Poromaa, Inger Sundström; Åkerud, Helena

    2015-01-01

    Depressive symptoms during pregnancy are common and may have impact on the developing child. Selective serotonin reuptake inhibitors (SSRIs) are the most prescribed antidepressant treatment, but unfortunately, these treatments can also negatively affect the behavioral development and health of a child during pregnancy. In addition, serotonin (5-HT) exerts neurotrophic actions with thus far not fully known effects in the offspring. The neurotrophic growth factor (NGF) is involved in neuronal cell survival and differentiation, and altered placenta levels have been found to increase the risk for pregnancy complications, similar to those found in women treated with SSRIs. We therefore investigated whether the NGF signaling pathway was altered in the placenta from women treated with SSRIs (n = 12) and compared them with placenta from depressed (n = 12) and healthy mothers (n = 12). Results from immunohistochemical stainings revealed that placental NGF protein levels of SSRI-treated women were increased in both trophoblasts and endothelial cells compared with depressed and control women. In addition, downstream of the NGF receptor TrkA, increased levels of the signaling proteins ROCK2 and phosphorylated Raf-1 were found in stromal cells and a tendency towards increased levels of ROCK2 in trophoblasts and endothelial cells in SSRI-treated women when compared to healthy controls. SSRI-treated women also displayed increased levels of phosphorylated ROCK2 in all placental cell types studied in comparison with depressed and control women. Interestingly, in placental endothelial cells from depressed women, NGF levels were significantly lower compared to control women, but ROCK2 levels were increased compared with control and SSRI-treated women. Taken together, these results show that the NGF signaling and downstream pathways in the placenta are affected by SSRI treatment and/or antenatal depression. This might lead to an altered placental function, although the clinical

  4. Influences of age, tongue region, and chorda tympani nerve sectioning on signal detection measures of lingual taste sensitivity.

    PubMed

    Doty, Richard L; Heidt, Julie M; MacGillivray, Michael R; Dsouza, Merle; Tracey, Elisabeth H; Mirza, Natasha; Bigelow, Douglas

    2016-03-01

    Although the ability to taste is critical for ingestion, nutrition, and quality of life, a clear understanding of the influences of age, sex, and chorda tympani (CT) resection on taste function in different regions of the anterior tongue is generally lacking. In this study we employed criterion-free signal detection analysis to assess electric and chemical taste function on multiple tongue regions in normal individuals varying in age and sex and in patients with unilateral CT resections. The subjects were 33 healthy volunteers, ranging from 18 to 87 years of age, and 9 persons, 27 to 77 years of age, with unilateral CT lesions. The influences of age, sex, tongue region, and chorda tympani resections on signal detection sensitivity (d') and response bias (β) measures was assessed in 16 tongue regions to weak electric currents and solutions of sucrose, sodium chloride, and caffeine. Significant age-related decrements in d' were found for sucrose (p=0.012), sodium chloride (p=0.002), caffeine (p=0.006), and electric current (EC) (p=0.0001). Significant posterior to anterior, and medial to lateral, gradients of increasing performance were present for most stimuli. β was larger on the anterior than the posterior tongue for the electrical stimulus in the youngest subjects, whereas the opposite was true for sucrose in the oldest subjects. No sex differences were apparent. d' was depressed ipsilateral to the CT lesion side to varying degrees in all tongue regions, with the weakest influences occurring on the medial and anterior tongue. CT did not meaningfully influence β. This study is the first to employ signal detection analysis to assess the regional sensitivity of the tongue to chemical and electrical stimuli. It clearly demonstrates that tongue regions differ from one another in terms of their age-related sensitivity and their susceptibility to CT lesions.

  5. SEUSS Integrates Gibberellin Signaling with Transcriptional Inputs from the SHR-SCR-SCL3 Module to Regulate Middle Cortex Formation in the Arabidopsis Root.

    PubMed

    Gong, Xue; Flores-Vergara, Miguel A; Hong, Jing Han; Chu, Huangwei; Lim, Jun; Franks, Robert G; Liu, Zhongchi; Xu, Jian

    2016-03-01

    A decade of studies on middle cortex (MC) formation in the root endodermis of Arabidopsis (Arabidopsis thaliana) have revealed a complex regulatory network that is orchestrated by several GRAS family transcription factors, including SHORT-ROOT (SHR), SCARECROW (SCR), and SCARECROW-LIKE3 (SCL3). However, how their functions are regulated remains obscure. Here we show that mutations in the SEUSS (SEU) gene led to a higher frequency of MC formation. seu mutants had strongly reduced expression of SHR, SCR, and SCL3, suggesting that SEU positively regulates these genes. Our results further indicate that SEU physically associates with upstream regulatory sequences of SHR, SCR, and SCL3; and that SEU has distinct genetic interactions with these genes in the control of MC formation, with SCL3 being epistatic to SEU. Similar to SCL3, SEU was repressed by the phytohormone GA and induced by the GA biosynthesis inhibitor paclobutrazol, suggesting that SEU acts downstream of GA signaling to regulate MC formation. Consistently, we found that SEU mediates the regulation of SCL3 by GA signaling. Together, our study identifies SEU as a new critical player that integrates GA signaling with transcriptional inputs from the SHR-SCR-SCL3 module to regulate MC formation in the Arabidopsis root.

  6. SEUSS Integrates Gibberellin Signaling with Transcriptional Inputs from the SHR-SCR-SCL3 Module to Regulate Middle Cortex Formation in the Arabidopsis Root1[OPEN

    PubMed Central

    Gong, Xue; Hong, Jing Han; Chu, Huangwei; Lim, Jun

    2016-01-01

    A decade of studies on middle cortex (MC) formation in the root endodermis of Arabidopsis (Arabidopsis thaliana) have revealed a complex regulatory network that is orchestrated by several GRAS family transcription factors, including SHORT-ROOT (SHR), SCARECROW (SCR), and SCARECROW-LIKE3 (SCL3). However, how their functions are regulated remains obscure. Here we show that mutations in the SEUSS (SEU) gene led to a higher frequency of MC formation. seu mutants had strongly reduced expression of SHR, SCR, and SCL3, suggesting that SEU positively regulates these genes. Our results further indicate that SEU physically associates with upstream regulatory sequences of SHR, SCR, and SCL3; and that SEU has distinct genetic interactions with these genes in the control of MC formation, with SCL3 being epistatic to SEU. Similar to SCL3, SEU was repressed by the phytohormone GA and induced by the GA biosynthesis inhibitor paclobutrazol, suggesting that SEU acts downstream of GA signaling to regulate MC formation. Consistently, we found that SEU mediates the regulation of SCL3 by GA signaling. Together, our study identifies SEU as a new critical player that integrates GA signaling with transcriptional inputs from the SHR-SCR-SCL3 module to regulate MC formation in the Arabidopsis root. PMID:26818732

  7. Activation of microtubule dynamics increases neuronal growth via the nerve growth factor (NGF)- and Gαs-mediated signaling pathways.

    PubMed

    Sarma, Tulika; Koutsouris, Athanasia; Yu, Jiang Zhu; Krbanjevic, Aleksandar; Hope, Thomas J; Rasenick, Mark M

    2015-04-17

    Signals that activate the G protein Gαs and promote neuronal differentiation evoke Gαs internalization in rat pheochromocytoma (PC12) cells. These agents also significantly increase Gαs association with microtubules, resulting in an increase in microtubule dynamics because of the activation of tubulin GTPase by Gαs. To determine the function of Gαs/microtubule association in neuronal development, we used real-time trafficking of a GFP-Gαs fusion protein. GFP-Gαs concentrates at the distal end of the neurites in differentiated living PC12 cells as well as in cultured hippocampal neurons. Gαs translocates to specialized membrane compartments at tips of growing neurites. A dominant-negative Gα chimera that interferes with Gαs binding to tubulin and activation of tubulin GTPase attenuates neurite elongation and neurite number both in PC12 cells and primary hippocampal neurons. This effect is greatest on differentiation induced by activated Gαs. Together, these data suggest that activated Gαs translocates from the plasma membrane and, through interaction with tubulin/microtubules in the cytosol, is important for neurite formation, development, and outgrowth. Characterization of neuronal G protein dynamics and their contribution to microtubule dynamics is important for understanding the molecular mechanisms by which G protein-coupled receptor signaling orchestrates neuronal growth and differentiation.

  8. Nitric oxide mediates strigolactone signaling in auxin and ethylene-sensitive lateral root formation in sunflower seedlings

    PubMed Central

    Bharti, Niharika; Bhatla, Satish C

    2015-01-01

    Strigolactones (SLs) play significant role in shaping root architecture whereby auxin-SL crosstalk has been observed in SL-mediated responses of primary root elongation, lateral root formation and adventitious root (AR) initiation. Whereas GR24 (a synthetic strigolactone) inhibits LR and AR formation, the effect of SL biosynthesis inhibitor (fluridone) is just the opposite (root proliferation). Naphthylphthalamic acid (NPA) leads to LR proliferation but completely inhibits AR development. The diffusive distribution of PIN1 in the provascular cells in the differentiating zone of the roots in response to GR24, fluridone or NPA treatments further indicates the involvement of localized auxin accumulation in LR development responses. Inhibition of LR formation by GR24 treatment coincides with inhibition of ACC synthase activity. Profuse LR development by fluridone and NPA treatments correlates with enhanced [Ca2+]cyt in the apical region and differentiating zones of LR, indicating a critical role of [Ca2+] in LR development in response to the coordinated action of auxins, ethylene and SLs. Significant enhancement of carotenoid cleavage dioxygenase (CCD) activity (enzyme responsible for SL biosynthesis) in tissue homogenates in presence of cPTIO (NO scavenger) indicates the role of endogenous NO as a negative modulator of CCD activity. Differences in the spatial distribution of NO in the primary and lateral roots further highlight the involvement of NO in SL-modulated root morphogenesis in sunflower seedlings. Present work provides new report on the negative modulation of SL biosynthesis through modulation of CCD activity by endogenous nitric oxide during SL-modulated LR development. PMID:26076049

  9. [Lumbosacral nerve bowstring disease].

    PubMed

    Shi, J G; Xu, X M; Sun, J C; Wang, Y; Guo, Y F; Yang, H S; Kong, Q J; Yang, Y; Shi, G D; Yuan, W; Jia, L S

    2017-03-21

    Objective: To define a novel disease-lumbosacral nerve bowstring disease, and propose the diagnostic criteria, while capsule surgery was performed and evaluated in the preliminary study. Methods: From June 2016 to December 2016, a total of 30 patients (22 male and 8 female; mean age of 55.1±9.7 years) with lumbosacral nerve bowstring disease were included in Department of Spine Surgery, Changzheng Hospital, the Second Military Medical University.Lumbosacral nerve bowstring disease was defined as axial hypertension of nerve root and spinal cord caused by congenital anomalies, which could be accompanied by other lesions as lumbar disc herniation, spinal cord stenosis or spondylolisthesis, or aggravated by iatrogenic lesions, resulting in neurological symptoms.This phenomenon is similar to a stretched string, the higher tension on each end the louder sound.Meanwhile, the shape of lumbosacral spine looks like a bow, thus, the disease is nominated as lumbosacral nerve bowstring disease.All the patients underwent capsule surgery and filled out Owestry disability index (ODI) and Tempa scale for kinesiophobia (TSK) before and after surgery. Results: The mean surgery time was (155±36) min, (4.3±0.4) segments were performed surgery.The pre-operative VAS, TSK and ODI scores were (7.6±0.8), (52.0±10.3) and (68.4±12.7), respectively.The post-operative VAS, TSK and ODI scores were (3.3±0.4), ( 24.6±5.2) and (32.1±7.4)(P<0.05, respectively), respectively. Conclusion: The definition and diagnostic criteria of lumbosacral nerve bowstring disease was proposed.Capsule surgery was an effective strategy with most patients acquired excellent outcomes as symptoms relieved and quality of life improved.

  10. Phosphorus deficiency in red clover promotes exudation of orobanchol, the signal for mycorrhizal symbionts and germination stimulant for root parasites.

    PubMed

    Yoneyama, Kaori; Yoneyama, Koichi; Takeuchi, Yasutomo; Sekimoto, Hitoshi

    2007-03-01

    Plant derived sesquiterpene strigolactones, which have previously been characterized as germination stimulants for root parasitic plants, have recently been identified as the branching factors which induce hyphal branching morphogenesis, a critical step in host recognition by arbuscular mycorrhizal (AM) fungi. We show here that, in red clover plants (Trifolium pratense L.), which is known as a host for both AM fungi and the root holoparasitic plant Orobanche minor Sm., reduced supply of phosphorus (P) but not of other elements examined (N, K, Mg, Ca) in the culture medium significantly promotes the release of a strigolactone, orobanchol, by the roots of this plant. In red clover plants, the level of orobanchol exudation appeared to be regulated by P availability and was in good agreement with germination stimulation activity of the root exudates. This implies that under P deficiency, plant roots attract not only symbiotic fungi but also root parasitic plants through the release of strigolactones. This is the first report demonstrating that nutrient availability influences both symbiotic and parasitic interactions in the rhizosphere.

  11. Asarone from Acori Tatarinowii Rhizoma Potentiates the Nerve Growth Factor-Induced Neuronal Differentiation in Cultured PC12 Cells: A Signaling Mediated by Protein Kinase A

    PubMed Central

    Lam, Kelly Y. C.; Chen, Jianping; Lam, Candy T. W.; Wu, Qiyun; Yao, Ping; Dong, Tina T. X.; Lin, Huangquan; Tsim, Karl W. K.

    2016-01-01

    Acori Tatarinowii Rhizoma (ATR), the rhizome of Acorus tatarinowii Schott, is being used clinically to treat neurological disorders. The volatile oil of ATR is being considered as an active ingredient. Here, α-asarone and β-asarone, accounting about 95% of ATR oil, were evaluated for its function in stimulating neurogenesis. In cultured PC12 cells, application of ATR volatile oil, α-asarone or β-asarone, stimulated the expression of neurofilaments, a bio-marker for neurite outgrowth, in a concentration-dependent manner. The co-treatment of ATR volatile oil, α-asarone or β-asarone, with low concentration of nerve growth factor (NGF) potentiated the NGF-induced neuronal differentiation in cultured PC12 cells. In addition, application of protein kinase A inhibitors, H89 and KT5720, in cultures blocked the ATR-induced neurofilament expression, as well as the phosphorylation of cAMP-responsive element binding protein (CREB). In the potentiation of NGF-induced signaling in cultured PC12 cells, α-asarone and β-asarone showed synergistic effects. These results proposed the neurite-promoting asarone, or ATR volatile oil, could be useful in finding potential drugs for treating various neurodegenerative diseases, in which neurotrophin deficiency is normally involved. PMID:27685847

  12. Physiological responses of potato (Solanum tuberosum L.) to partial root-zone drying: ABA signalling, leaf gas exchange, and water use efficiency.

    PubMed

    Liu, Fulai; Shahnazari, Ali; Andersen, Mathias N; Jacobsen, Sven-Erik; Jensen, Christian R

    2006-01-01

    The physiological responses of potato (Solanum tuberosum L. cv. Folva) to partial root-zone drying (PRD) were investigated in potted plants in a greenhouse (GH) and in plants grown in the field under an automatic rain-out-shelter. In the GH, irrigation was applied daily to the whole root system (FI), or to one-half of the root system while the other half was dried, for 9 d. In the field, the plants were drip irrigated either to the whole root system near field capacity (FI) or using 70% water of FI to one side of the roots, and shifted to the other side every 5-10 d (PRD). PRD plants had a similar midday leaf water potential to that of FI, whereas in the GH their root water potential (Psi(r)) was significantly lowered after 5 d. Stomatal conductance (g(s)) was more sensitive to PRD than photosynthesis (A) particularly in the field, leading to greater intrinsic water use efficiency (WUE) (i.e. A/g(s)) in PRD than in FI plants on several days. In PRD, the xylem sap abscisic acid concentration ([ABA](xylem)) increased exponentially with decreasing Psi(r); and the relative [ABA](xylem) (PRD/FI) increased exponentially as the fraction of transpirable soil water (FTSW) in the drying side decreased. In the field, the leaf area index was slightly less in PRD than in FI treatment, while tuber biomass was similar for the two treatments. Compared with FI, PRD treatment saved 30% water and increased crop water use efficiency (WUE) by 59%. Restrictions on leaf area expansion and g(s) by PRD-induced ABA signals might have contributed to reduced water use and increased WUE.

  13. Corticotrigeminal Projections from the Insular Cortex to the Trigeminal Caudal Subnucleus Regulate Orofacial Pain after Nerve Injury via Extracellular Signal-Regulated Kinase Activation in Insular Cortex Neurons.

    PubMed

    Wang, Jian; Li, Zhi-Hua; Feng, Ban; Zhang, Ting; Zhang, Han; Li, Hui; Chen, Tao; Cui, Jing; Zang, Wei-Dong; Li, Yun-Qing

    2015-01-01

    Cortical neuroplasticity alterations are implicated in the pathophysiology of chronic orofacial pain. However, the relationship between critical cortex excitability and orofacial pain maintenance has not been fully elucidated. We recently demonstrated a top-down corticospinal descending pain modulation pathway from the anterior cingulate cortex (ACC) to the spinal dorsal horn that could directly regulate nociceptive transmission. Thus, we aimed to investigate possible corticotrigeminal connections that directly influence orofacial nociception in rats. Infraorbital nerve chronic constriction injury (IoN-CCI) induced significant orofacial nociceptive behaviors as well as pain-related negative emotions such as anxiety/depression in rats. By combining retrograde and anterograde tract tracing, we found powerful evidence that the trigeminal caudal subnucleus (Vc), especially the superficial laminae (I/II), received direct descending projections from granular and dysgranular parts of the insular cortex (IC). Extracellular signal-regulated kinase (ERK), an important signaling molecule involved in neuroplasticity, was significantly activated in the IC following IoN-CCI. Moreover, in IC slices from IoN-CCI rats, U0126, an inhibitor of ERK activation, decreased both the amplitude and the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and reduced the paired-pulse ratio (PPR) of Vc-projecting neurons. Additionally, U0126 also reduced the number of action potentials in the Vc-projecting neurons. Finally, intra-IC infusion of U0126 obviously decreased Fos expression in the Vc, accompanied by the alleviation of both nociceptive behavior and negative emotions. Thus, the corticotrigeminal descending pathway from the IC to the Vc could directly regulate orofacial pain, and ERK deactivation in the IC could effectively alleviate neuropathic pain as well as pain-related negative emotions in IoN-CCI rats, probably through this top-down pathway. These findings may help

  14. Corticotrigeminal Projections from the Insular Cortex to the Trigeminal Caudal Subnucleus Regulate Orofacial Pain after Nerve Injury via Extracellular Signal-Regulated Kinase Activation in Insular Cortex Neurons

    PubMed Central

    Wang, Jian; Li, Zhi-Hua; Feng, Ban; Zhang, Ting; Zhang, Han; Li, Hui; Chen, Tao; Cui, Jing; Zang, Wei-Dong; Li, Yun-Qing

    2015-01-01

    Cortical neuroplasticity alterations are implicated in the pathophysiology of chronic orofacial pain. However, the relationship between critical cortex excitability and orofacial pain maintenance has not been fully elucidated. We recently demonstrated a top-down corticospinal descending pain modulation pathway from the anterior cingulate cortex (ACC) to the spinal dorsal horn that could directly regulate nociceptive transmission. Thus, we aimed to investigate possible corticotrigeminal connections that directly influence orofacial nociception in rats. Infraorbital nerve chronic constriction injury (IoN-CCI) induced significant orofacial nociceptive behaviors as well as pain-related negative emotions such as anxiety/depression in rats. By combining retrograde and anterograde tract tracing, we found powerful evidence that the trigeminal caudal subnucleus (Vc), especially the superficial laminae (I/II), received direct descending projections from granular and dysgranular parts of the insular cortex (IC). Extracellular signal-regulated kinase (ERK), an important signaling molecule involved in neuroplasticity, was significantly activated in the IC following IoN-CCI. Moreover, in IC slices from IoN-CCI rats, U0126, an inhibitor of ERK activation, decreased both the amplitude and the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and reduced the paired-pulse ratio (PPR) of Vc-projecting neurons. Additionally, U0126 also reduced the number of action potentials in the Vc-projecting neurons. Finally, intra-IC infusion of U0126 obviously decreased Fos expression in the Vc, accompanied by the alleviation of both nociceptive behavior and negative emotions. Thus, the corticotrigeminal descending pathway from the IC to the Vc could directly regulate orofacial pain, and ERK deactivation in the IC could effectively alleviate neuropathic pain as well as pain-related negative emotions in IoN-CCI rats, probably through this top–down pathway. These findings may

  15. Influence of nutrient signals and carbon allocation on the expression of phosphate and nitrogen transporter genes in winter wheat (Triticum aestivum L.) roots colonized by arbuscular mycorrhizal fungi

    PubMed Central

    Tian, Hui; Yuan, Xiaolei; Duan, Jianfeng; Li, Wenhu; Zhai, Bingnian; Gao, Yajun

    2017-01-01

    Arbuscular mycorrhizal (AM) colonization of plant roots causes the down-regulation of expression of phosphate (Pi) or nitrogen (N) transporter genes involved in direct nutrient uptake pathways. The mechanism of this effect remains unknown. In the present study, we sought to determine whether the expression of Pi or N transporter genes in roots of winter wheat colonized by AM fungus responded to (1) Pi or N nutrient signals transferred from the AM extra-radical hyphae, or (2) carbon allocation changes in the AM association. A three-compartment culture system, comprising a root compartment (RC), a root and AM hyphae compartment (RHC), and an AM hyphae compartment (HC), was used to test whether the expression of Pi or N transporter genes responded to nutrients (Pi, NH4+ and NO3-) added only to the HC. Different AM inoculation density treatments (roots were inoculated with 0, 20, 50 and 200 g AM inoculum) and light regime treatments (6 hours light and 18 hours light) were established to test the effects of carbon allocation on the expression of Pi or N transporter genes in wheat roots. The expression of two Pi transporter genes (TaPT4 and TaPHT1.2), five nitrate transporter genes (TaNRT1.1, TaNRT1.2, TaNRT2.1, TaNRT2.2, and TaNRT2.3), and an ammonium transporter gene (TaAMT1.2) was quantified using real-time polymerase chain reaction. The expression of TaPT4, TaNRT2.2, and TaAMT1.2 was down-regulated by AM colonization only when roots of host plants received Pi or N nutrient signals. However, the expression of TaPHT1.2, TaNRT2.1, and TaNRT2.3 was down-regulated by AM colonization, regardless of whether there was nutrient transfer from AM hyphae. The expression of TaNRT1.2 was also down-regulated by AM colonization even when there was no nutrient transfer from AM hyphae. The present study showed that an increase in carbon consumption by the AM fungi did not necessarily result in greater down-regulation of expression of Pi or N transporter genes. PMID:28207830

  16. Influence of nutrient signals and carbon allocation on the expression of phosphate and nitrogen transporter genes in winter wheat (Triticum aestivum L.) roots colonized by arbuscular mycorrhizal fungi.

    PubMed

    Tian, Hui; Yuan, Xiaolei; Duan, Jianfeng; Li, Wenhu; Zhai, Bingnian; Gao, Yajun

    2017-01-01

    Arbuscular mycorrhizal (AM) colonization of plant roots causes the down-regulation of expression of phosphate (Pi) or nitrogen (N) transporter genes involved in direct nutrient uptake pathways. The mechanism of this effect remains unknown. In the present study, we sought to determine whether the expression of Pi or N transporter genes in roots of winter wheat colonized by AM fungus responded to (1) Pi or N nutrient signals transferred from the AM extra-radical hyphae, or (2) carbon allocation changes in the AM association. A three-compartment culture system, comprising a root compartment (RC), a root and AM hyphae compartment (RHC), and an AM hyphae compartment (HC), was used to test whether the expression of Pi or N transporter genes responded to nutrients (Pi, NH4+ and NO3-) added only to the HC. Different AM inoculation density treatments (roots were inoculated with 0, 20, 50 and 200 g AM inoculum) and light regime treatments (6 hours light and 18 hours light) were established to test the effects of carbon allocation on the expression of Pi or N transporter genes in wheat roots. The expression of two Pi transporter genes (TaPT4 and TaPHT1.2), five nitrate transporter genes (TaNRT1.1, TaNRT1.2, TaNRT2.1, TaNRT2.2, and TaNRT2.3), and an ammonium transporter gene (TaAMT1.2) was quantified using real-time polymerase chain reaction. The expression of TaPT4, TaNRT2.2, and TaAMT1.2 was down-regulated by AM colonization only when roots of host plants received Pi or N nutrient signals. However, the expression of TaPHT1.2, TaNRT2.1, and TaNRT2.3 was down-regulated by AM colonization, regardless of whether there was nutrient transfer from AM hyphae. The expression of TaNRT1.2 was also down-regulated by AM colonization even when there was no nutrient transfer from AM hyphae. The present study showed that an increase in carbon consumption by the AM fungi did not necessarily result in greater down-regulation of expression of Pi or N transporter genes.

  17. Histamine H3-receptor signaling in cardiac sympathetic nerves: Identification of a novel MAPK-PLA2-COX-PGE2-EP3R pathway.

    PubMed

    Levi, Roberto; Seyedi, Nahid; Schaefer, Ulrich; Estephan, Rima; Mackins, Christina J; Tyler, Eleanor; Silver, Randi B

    2007-04-15

    We hypothesized that the histamine H(3)-receptor (H(3)R)-mediated attenuation of norepinephrine (NE) exocytosis from cardiac sympathetic nerves results not only from a Galpha(i)-mediated inhibition of the adenylyl cyclase-cAMP-PKA pathway, but also from a Gbetagamma(i)-mediated activation of the MAPK-PLA(2) cascade, culminating in the formation of an arachidonate metabolite with anti-exocytotic characteristics (e.g., PGE(2)). We report that in Langendorff-perfused guinea-pig hearts and isolated sympathetic nerve endings (cardiac synaptosomes), H(3)R-mediated attenuation of K(+)-induced NE exocytosis was prevented by MAPK and PLA(2) inhibitors, and by cyclooxygenase and EP(3)-receptor (EP(3)R) antagonists. Moreover, H(3)R activation resulted in MAPK phosphorylation in H(3)R-transfected SH-SY5Y neuroblastoma cells, and in PLA(2) activation and PGE(2) production in cardiac synaptosomes; H(3)R-induced MAPK phosphorylation was prevented by an anti-betagamma peptide. Synergism between H(3)R and EP(3)R agonists (i.e., imetit and sulprostone, respectively) suggested that PGE(2) may be a downstream effector of the anti-exocytotic effect of H(3)R activation. Furthermore, the anti-exocytotic effect of imetit and sulprostone was potentiated by the N-type Ca(2+)-channel antagonist omega-conotoxin GVIA, and prevented by an anti-Gbetagamma peptide. Our findings imply that an EP(3)R Gbetagamma(i)-induced decrease in Ca(2+) influx through N-type Ca(2+)-channels is involved in the PGE(2)/EP(3)R-mediated attenuation of NE exocytosis elicited by H(3)R activation. Conceivably, activation of the Gbetagamma(i) subunit of H(3)R and EP(3)R may also inhibit Ca(2+) entry directly, independent of MAPK intervention. As heart failure, myocardial ischemia and arrhythmic dysfunction are associated with excessive local NE release, attenuation of NE release by H(3)R activation is cardioprotective. Accordingly, this novel H(3)R signaling pathway may ultimately bear therapeutic significance in hyper

  18. Nerve Blocks

    MedlinePlus

    ... Sometimes the needle has to be inserted fairly deep to reach the nerve causing your problem. This ... understanding of the possible charges you will incur. Web page review process: This Web page is reviewed ...

  19. F-actin links Epac-PKC signaling to purinergic P2X3 receptor sensitization in dorsal root ganglia following inflammation

    PubMed Central

    Gu, Yanping; Wang, Congying; Li, GuangWen

    2016-01-01

    Sensitization of purinergic P2X3 receptors (P2X3Rs) contributes to the production of exaggerated nociceptive responses following inflammatory injury. We showed previously that prostaglandin E2 (PGE2) potentiates P2X3R-mediated ATP currents in dorsal root ganglion neurons isolated from both control and complete Freund’s adjuvant-induced inflamed rats. PGE2 potentiation of ATP currents depends only on PKA signaling in control neurons, but it depends on both PKA and PKC signaling in inflamed neurons. We further found that inflammation evokes an increase in exchange proteins directly activated by cAMP (Epacs) in dorsal root ganglions. This increase promotes the activation of PKC to produce a much enhanced PGE2 effect on ATP currents and to elicit Epac-dependent flinch nocifensive behavioral responses in complete Freund’s adjuvant rats. The link between Epac-PKC signaling and P2X3R sensitization remains unexplored. Here, we show that the activation of Epacs promotes the expression of phosphorylated PKC and leads to an increase in the cytoskeleton, F-actin, expression at the cell perimeter. Depolymerization of F-actin blocks PGE2-enhanced ATP currents and inhibits P2X3R-mediated nocifensive responses after inflammation. Thus, F-actin is dynamically involved in the Epac-PKC-dependent P2X3R sensitization. Furthermore, Epacs induce a PKC-dependent increase in the membrane expression of P2X3Rs. This increase is abolished by F-actin depolymerization, suggesting that F-actin mediates Epac-PKC signaling of P2X3R membrane expression. Thus, after inflammation, an Epac-PKC dependent increase in F-actin in dorsal root ganglion neurons enhances the membrane expression of P2X3Rs to bring about sensitization of P2X3Rs and abnormal pain behaviors. PMID:27385722

  20. EXPRESS: F-actin links Epac-PKC signaling to purinergic P2X3 receptors sensitization in dorsal root ganglia following inflammation.

    PubMed

    Gu, Yanping; Wang, Congying; Li, Guangwen; Huang, Li-Yen Mae

    2016-01-01

    Sensitization of purinergic P2X3 receptors (P2X3Rs) contributes to the production of exaggerated nociceptive responses following inflammatory injury. We showed previously that prostaglandin E2 (PGE2) potentiates P2X3R-mediated ATP currents in dorsal root ganglion neurons isolated from both control and complete Freund’s adjuvant-induced inflamed rats. PGE2 potentiation of ATP currents depends only on PKA signaling in control neurons, but it depends on both PKA and PKC signaling in inflamed neurons. We further found that inflammation evokes an increase in exchange proteins directly activated by cAMP (Epacs) in dorsal root ganglions. This increase promotes the activation of PKC to produce a much enhanced PGE2 effect on ATP currents and to elicit Epac-dependent flinch nocifensive behavioral responses in complete Freund’s adjuvant rats. The link between Epac-PKC signaling and P2X3R sensitization remains unexplored. Here, we show that the activation of Epacs promotes the expression of phosphorylated PKC and leads to an increase in the cytoskeleton, F-actin, expression at the cell perimeter. Depolymerization of F-actin blocks PGE2-enhanced ATP currents and inhibits P2X3R-mediated nocifensive responses after inflammation. Thus, F-actin is dynamically involved in the Epac-PKC-dependent P2X3R sensitization. Furthermore, Epacs induce a PKC-dependent increase in the membrane expression of P2X3Rs. This increase is abolished by F-actin depolymerization, suggesting that F-actin mediates Epac-PKC signaling of P2X3R membrane expression. Thus, after inflammation, an Epac-PKC dependent increase in F-actin in dorsal root ganglion neurons enhances the membrane expression of P2X3Rs to bring about sensitization of P2X3Rs and abnormal pain behaviors.

  1. PHYTOCHROME AND FLOWERING TIME1/MEDIATOR25 Regulates Lateral Root Formation via Auxin Signaling in Arabidopsis1[C][W

    PubMed Central

    Raya-González, Javier; Ortiz-Castro, Randy; Ruíz-Herrera, León Francisco; Kazan, Kemal; López-Bucio, José

    2014-01-01

    Root system architecture is a major determinant of water and nutrient acquisition as well as stress tolerance in plants. The Mediator complex is a conserved multiprotein complex that acts as a universal adaptor between transcription factors and the RNA polymerase II. In this article, we characterize possible roles of the MEDIATOR8 (MED8) and MED25 subunits of the plant Mediator complex in the regulation of root system architecture in Arabidopsis (Arabidopsis thaliana). We found that loss-of-function mutations in PHYTOCHROME AND FLOWERING TIME1 (PFT1)/MED25 increase primary and lateral root growth as well as lateral and adventitious root formation. In contrast, PFT1/MED25 overexpression reduces these responses, suggesting that PFT1/MED25 is an important element of meristematic cell proliferation and cell size control in both lateral and primary roots. PFT1/MED25 negatively regulates auxin transport and response gene expression in most parts of the plant, as evidenced by increased and decreased expression of the auxin-related reporters PIN-FORMED1 (PIN1)::PIN1::GFP (for green fluorescent protein), DR5:GFP, DR5:uidA, and BA3:uidA in pft1-2 mutants and in 35S:PFT1 seedlings, respectively. No alterations in endogenous auxin levels could be found in pft1-2 mutants or in 35S:PFT1-overexpressing seedlings. However, detailed analyses of DR5:GFP and DR5:uidA activity in wild-type, pft1-2, and 35S:PFT1 seedlings in response to indole-3-acetic acid, naphthaleneacetic acid, and the polar auxin transport inhibitor 1-N-naphthylphthalamic acid indicated that PFT1/MED25 principally regulates auxin transport and response. These results provide compelling evidence for a new role for PFT1/MED25 as an important transcriptional regulator of root system architecture through auxin-related mechanisms in Arabidopsis. PMID:24784134

  2. Deep Sequencing of the Medicago truncatula Root Transcriptome Reveals a Massive and Early Interaction between Nodulation Factor and Ethylene Signals1[OPEN

    PubMed Central

    Larrainzar, Estíbaliz; Riely, Brendan K.; Kim, Sang Cheol; Carrasquilla-Garcia, Noelia; Yu, Hee-Ju; Hwang, Hyun-Ju; Oh, Mijin; Kim, Goon Bo; Surendrarao, Anandkumar K.; Chasman, Deborah; Siahpirani, Alireza F.; Penmetsa, Ramachandra V.; Lee, Gang-Seob; Kim, Namshin; Roy, Sushmita; Mun, Jeong-Hwan; Cook, Douglas R.

    2015-01-01

    The legume-rhizobium symbiosis is initiated through the activation of the Nodulation (Nod) factor-signaling cascade, leading to a rapid reprogramming of host cell developmental pathways. In this work, we combine transcriptome sequencing with molecular genetics and network analysis to quantify and categorize the transcriptional changes occurring in roots of Medicago truncatula from minutes to days after inoculation with Sinorhizobium medicae. To identify the nature of the inductive and regulatory cues, we employed mutants with absent or decreased Nod factor sensitivities (i.e. Nodulation factor perception and Lysine motif domain-containing receptor-like kinase3, respectively) and an ethylene (ET)-insensitive, Nod factor-hypersensitive mutant (sickle). This unique data set encompasses nine time points, allowing observation of the symbiotic regulation of diverse biological processes with high temporal resolution. Among the many outputs of the study is the early Nod factor-induced, ET-regulated expression of ET signaling and biosynthesis genes. Coupled with the observation of massive transcriptional derepression in the ET-insensitive background, these results suggest that Nod factor signaling activates ET production to attenuate its own signal. Promoter:β-glucuronidase fusions report ET biosynthesis both in root hairs responding to rhizobium as well as in meristematic tissue during nodule organogenesis and growth, indicating that ET signaling functions at multiple developmental stages during symbiosis. In addition, we identified thousands of novel candidate genes undergoing Nod factor-dependent, ET-regulated expression. We leveraged the power of this large data set to model Nod factor- and ET-regulated signaling networks using MERLIN, a regulatory network inference algorithm. These analyses predict key nodes regulating the biological process impacted by Nod factor perception. We have made these results available to the research community through a searchable online

  3. Regulation of Protein Degradation and Protease Expression by Mannose in Maize Root Tips. Pi Sequestration by Mannose May Hinder the Study of Its Signaling Properties

    PubMed Central

    Brouquisse, Renaud; Evrard, Adeline; Rolin, Dominique; Raymond, Philippe; Roby, Claude

    2001-01-01

    The effects of mannose (Man) and glucose (Glc) on central metabolism, proteolysis, and expression of the root starvation-induced protease (RSIP; F. James, R. Brouquisse, C. Suire, A. Pradet, P. Raymond [1996] Biochem J 320: 283–292) were investigated in maize (Zea mays L. cv DEA) root tips. Changes in metabolite concentrations (sugars, ester-phosphates, adenine nucleotides, and amino acids) were monitored using in vivo and in vitro 13C- and 31P-NMR spectroscopy, in parallel with the changes in respiration rates, protein contents, proteolytic activities, and RSIP amounts. The inhibition of proteolysis, the decrease in proteolytic activities, and the repression of RSIP expression triggered by Man, at concentrations usually used to study sugar signaling (2 and 10 mm), were found to be related to a drop of energy metabolism, primarily due to a Man-induced Pi sequestration. However, when supplied at low concentration (2 mm) and with the adequate phosphate concentration (30 mm), energy metabolism was restored and Man repressed proteolysis similarly to Glc, when provided at the same concentration. These results indicate that Man should be used with caution as a Glc analog to study signalization by sugars in plants because possible signaling effects may be hindered by Pi sequestration. PMID:11244127

  4. Lithium Enhances Axonal Regeneration in Peripheral Nerve by Inhibiting Glycogen Synthase Kinase 3β Activation

    PubMed Central

    Su, Huanxing; Yuan, Qiuju; Qin, Dajiang; Yang, Xiaoying; So, Kwok-Fai; Wu, Wutian

    2014-01-01

    Brachial plexus injury often involves traumatic root avulsion resulting in permanent paralysis of the innervated muscles. The lack of sufficient regeneration from spinal motoneurons to the peripheral nerve (PN) is considered to be one of the major causes of the unsatisfactory outcome of various surgical interventions for repair of the devastating injury. The present study was undertaken to investigate potential inhibitory signals which influence axonal regeneration after root avulsion injury. The results of the study showed that root avulsion triggered GSK-3β activation in the injured motoneurons and remaining axons in the ventral funiculus. Systemic application of a clinical dose of lithium suppressed activated GSK-3β in the lesioned spinal cord to the normal level and induced extensive axonal regeneration into replanted ventral roots. Our study suggests that GSK-3β activity is involved in negative regulation for axonal elongation and regeneration and lithium, the specific GSK-3β inhibitor, enhances motoneuron regeneration from CNS to PNS. PMID:24967390

  5. The exocytotic signaling pathway induced by nerve growth factor in the presence of lyso-phosphatidylserine in rat peritoneal mast cells involves a type D phospholipase.

    PubMed

    Seebeck, J; Westenberger, K; Elgeti, T; Ziegler, A; Schütze, S

    2001-12-15

    Nerve growth factor (NGF) has been previously shown to induce exocytosis in rat peritoneal mast cells (RPMCs) in the presence of lyso-phosphatidylserine (lysoPS) by interacting with high-affinity NGF receptors of the TrkA-type. In RPMCs, type D phosphatidylcholine-selective phospholipases (PLDs) have been postulated to be involved in some exocytotic signaling pathways induced by different agonists. The aim of the present study was to assess a putative functional role of PLD for NGF/lysoPS-induced exocytosis in RPMCs. In 1-[14C]palmitoyl-2-lyso-3-phosphatidylcholine-labelled RPMCs, NGF/lysoPS stimulated the formation of diacylglycerol (DAG) and, in the presence of ethanol (1% [v/v]), phosphatidylethanol (PEtOH). These data indicate PLD-activation by NGF/lysoPS in RPMCs. Preincubation of RPMCs for 2 min with ethanol, an inhibitor of PLD-derived DAG-formation, dose-dependently (IC(50): 0.6% [v/v]) and agonist-selectively inhibited the NGF/lysoPS induced release of [3H]serotonin ([3H]5-HT) in [3H]5-HT-loaded RPMCs, confirming the functional importance of PLD-action. Exocytosis and PEtOH-production was potently inhibited by the broad-spectrum serine/threonine kinase inhibitor staurosporine and activated by the protein kinase C(PKC)-activator PMA (phorbol-12-myristate-13-acetate) suggesting a role for PKC as mediator for NGF/lysoPS-induced activation of PLD.

  6. A minocycline derivative reduces nerve injury-induced allodynia, LPS-induced prostaglandin E2 microglial production and signaling via toll-like receptors 2 and 4

    PubMed Central

    Bastos, Leandro F. S.; Godin, Adriana M.; Zhang, Yingning; Jarussophon, Suwatchai; Ferreira, Bruno C. S.; Machado, Renes R.; Maier, Steven F.; Konishi, Yasuo; de Freitas, Rossimiriam P.; Fiebich, Bernd L.; Watkins, Linda R.; Coelho, Márcio M.; Moraes, Márcio F. D.

    2013-01-01

    Many studies have shown that minocycline, an antibacterial tetracycline, suppresses experimental pain. While minocycline’s positive effects on pain resolution suggest that clinical use of such drugs may prove beneficial, minocycline’s antibiotic actions and divalent cation (Ca2+; Mg2+) chelating effects detract from its potential utility. Thus, we tested the antiallodynic effect induced by a non-antibacterial, non-chelating minocycline derivative in a model of neuropathic pain and performed an initial investigation of its anti-inflammatory effects in vitro. Intraperitoneal minocycline (100 mg/kg) and 12S-hydroxy-1,12-pyrazolinominocycline (PMIN; 23.75, 47.50 or 95.00 mg/kg) reduce the mechanical allodynia induced by chronic constriction injury of mouse sciatic nerve. PMIN reduces the LPS-induced production of PGE2 by primary microglial cell cultures. Human embryonic kidney cells were transfected to express human toll-like receptors 2 and 4, and the signaling via both receptors stimulated with PAM3CSK4 or LPS (respectively) was affected either by minocycline or PMIN. Importantly, these treatments did not affect the cell viability, as assessed by MTT test. Altogether, these results reinforce the evidence that the anti-inflammatory and experimental pain suppressive effects induced by tetracyclines are neither necessarily linked to antibacterial nor to Ca2+ chelating activities. This study supports the evaluation of the potential usefulness of PMIN in the management of neuropathic pain, as its lack of antibacterial and Ca2+ chelating activities might confer greater safety over conventional tetracyclines. PMID:23523650

  7. A minocycline derivative reduces nerve injury-induced allodynia, LPS-induced prostaglandin E2 microglial production and signaling via toll-like receptors 2 and 4.

    PubMed

    Bastos, Leandro F S; Godin, Adriana M; Zhang, Yingning; Jarussophon, Suwatchai; Ferreira, Bruno C S; Machado, Renes R; Maier, Steven F; Konishi, Yasuo; de Freitas, Rossimiriam P; Fiebich, Bernd L; Watkins, Linda R; Coelho, Márcio M; Moraes, Márcio F D

    2013-05-24

    Many studies have shown that minocycline, an antibacterial tetracycline, suppresses experimental pain. While minocycline's positive effects on pain resolution suggest that clinical use of such drugs may prove beneficial, minocycline's antibiotic actions and divalent cation (Ca(2+); Mg(2+)) chelating effects detract from its potential utility. Thus, we tested the antiallodynic effect induced by a non-antibacterial, non-chelating minocycline derivative in a model of neuropathic pain and performed an initial investigation of its anti-inflammatory effects in vitro. Intraperitoneal minocycline (100mg/kg) and 12S-hydroxy-1,12-pyrazolinominocycline (PMIN; 23.75 mg/kg, 47.50mg/kg or 95.00 mg/kg) reduce the mechanical allodynia induced by chronic constriction injury of mouse sciatic nerve. PMIN reduces the LPS-induced production of PGE2 by primary microglial cell cultures. Human embryonic kidney cells were transfected to express human toll-like receptors 2 and 4, and the signaling via both receptors stimulated with PAM3CSK4 or LPS (respectively) was affected either by minocycline or PMIN. Importantly, these treatments did not affect the cell viability, as assessed by MTT test. Altogether, these results reinforce the evidence that the anti-inflammatory and experimental pain suppressive effects induced by tetracyclines are neither necessarily linked to antibacterial nor to Ca(2+) chelating activities. This study supports the evaluation of the potential usefulness of PMIN in the management of neuropathic pain, as its lack of antibacterial and Ca(2+) chelating activities might confer greater safety over conventional tetracyclines.

  8. Optic Nerve Decompression

    MedlinePlus

    ... Nerve Decompression Dacryocystorhinostomy (DCR) Disclosure Statement Printer Friendly Optic Nerve Decompression John Lee, MD Introduction Optic nerve decompression is a surgical procedure aimed at ...

  9. Ulnar nerve dysfunction

    MedlinePlus

    Neuropathy - ulnar nerve; Ulnar nerve palsy; Mononeuropathy; Cubital tunnel syndrome ... compressed in the elbow, a problem called cubital tunnel syndrome may result. When damage destroys the nerve ...

  10. Selective breeding of entomopathogenic nematodes for enhanced attraction to a root signal did not reduce their establishment or persistence after field release.

    PubMed

    Hiltpold, Ivan; Baroni, Mariane; Toepfer, Stefan; Kuhlmann, Ulrich; Turlings, Ted C J

    2010-11-01

    We recently showed that the efficacy of an entomopathogenic nematode (EPN) as a biological control agent against a root pest could be enhanced through artificial selection. The EPN Heterorhabditis bacteriophora was selected for higher responsiveness towards (E)-β-caryophyllene (EβC), a sesquiterpene that is emitted by maize roots in response to feeding damage by the western corn rootworm (WCR). EβC is normally only weakly attractive to H. bacteriophora, which is one of the most infectious nematodes against WCR. By selecting H. bacteriophora to move more readily along a EβC gradient we obtained a strain that was almost twice more efficient in controlling WCR population in fields planted with an EβC-producing maize variety. However, artificial selection for one trait may come at a cost for other important traits such as infectiousness, establishment and/or persistence in the field. Indeed, infectiousness was slightly but significantly reduced in the selected strain. Yet, this apparent cost was largely compensated for by the higher responsiveness to the root signal. Here we show that the selection process had no negative effect on establishment and persistence of field-released EPN. This knowledge, combined with the previously reported results, attest to the feasibility of manipulating key traits to improve the efficacy of beneficial organisms.

  11. Selective breeding of entomopathogenic nematodes for enhanced attraction to a root signal did not reduce their establishment or persistence after field release

    PubMed Central

    Hiltpold, Ivan; Baroni, Mariane; Toepfer, Stefan; Kuhlmann, Ulrich

    2010-01-01

    We recently showed that the efficacy of an entomopathogenic nematode (EPN) as a biological control agent against a root pest could be enhanced through artificial selection. The EPN Heterorhabditis bacteriophora was selected for higher responsiveness towards (E)-β-caryophyllene (EβC), a sesquiterpene that is emitted by maize roots in response to feeding damage by the western corn rootworm (WCR). EβC is normally only weakly attractive to H. bacteriophora, which is one of the most infectious nematodes against WCR. By selecting H. bacteriophora to move more readily along a EβC gradient we obtained a strain that was almost twice more efficient in controlling WCR population in fields planted with an EβC-producing maize variety. However, artificial selection for one trait may come at a cost for other important traits such as infectiousness, establishment and/or persistence in the field. Indeed, infectiousness was slightly but significantly reduced in the selected strain. Yet, this apparent cost was largely compensated for by the higher responsiveness to the root signal. Here we show that the selection process had no negative effect on establishment and persistence of field-released EPN. This knowledge, combined with the previously reported results, attest to the feasibility of manipulating key traits to improve the efficacy of beneficial organisms. PMID:21051943

  12. Vagus Nerve Stimulation

    MedlinePlus

    Vagus nerve stimulation Overview By Mayo Clinic Staff Vagus nerve stimulation is a procedure that involves implantation of a device that stimulates the vagus nerve with electrical impulses. There's one vagus nerve on ...

  13. Nerve biopsy (image)

    MedlinePlus

    Nerve biopsy is the removal of a small piece of nerve for examination. Through a small incision, a sample ... is removed and examined under a microscope. Nerve biopsy may be performed to identify nerve degeneration, identify ...

  14. The Root Hair “Infectome” of Medicago truncatula Uncovers Changes in Cell Cycle Genes and Reveals a Requirement for Auxin Signaling in Rhizobial Infection[W][OPEN

    PubMed Central

    Breakspear, Andrew; Liu, Chengwu; Roy, Sonali; Stacey, Nicola; Rogers, Christian; Trick, Martin; Morieri, Giulia; Mysore, Kirankumar S.; Wen, Jiangqi; Oldroyd, Giles E.D.; Downie, J. Allan

    2014-01-01

    Nitrogen-fixing rhizobia colonize legume roots via plant-made intracellular infection threads. Genetics has identified some genes involved but has not provided sufficient detail to understand requirements for infection thread development. Therefore, we transcriptionally profiled Medicago truncatula root hairs prior to and during the initial stages of infection. This revealed changes in the responses to plant hormones, most notably auxin, strigolactone, gibberellic acid, and brassinosteroids. Several auxin responsive genes, including the ortholog of Arabidopsis thaliana Auxin Response Factor 16, were induced at infection sites and in nodule primordia, and mutation of ARF16a reduced rhizobial infection. Associated with the induction of auxin signaling genes, there was increased expression of cell cycle genes including an A-type cyclin and a subunit of the anaphase promoting complex. There was also induction of several chalcone O-methyltransferases involved in the synthesis of an inducer of Sinorhizobium meliloti nod genes, as well as a gene associated with Nod factor degradation, suggesting both positive and negative feedback loops that control Nod factor levels during rhizobial infection. We conclude that the onset of infection is associated with reactivation of the cell cycle as well as increased expression of genes required for hormone and flavonoid biosynthesis and that the regulation of auxin signaling is necessary for initiation of rhizobial infection threads. PMID:25527707

  15. The EXS Domain of PHO1 Participates in the Response of Shoots to Phosphate Deficiency via a Root-to-Shoot Signal1[OPEN

    PubMed Central

    Jung, Ji-Yul; Pradervand, Sylvain

    2016-01-01

    The response of shoots to phosphate (Pi) deficiency implicates long-distance communication between roots and shoots, but the participating components are poorly understood. We have studied the topology of the Arabidopsis (Arabidopsis thaliana) PHOSPHATE1 (PHO1) Pi exporter and defined the functions of its different domains in Pi homeostasis and signaling. The results indicate that the amino and carboxyl termini of PHO1 are both oriented toward the cytosol and that the protein spans the membrane twice in the EXS domain, resulting in a total of six transmembrane α-helices. Using transient expression in Nicotiana benthamiana leaf, we demonstrated that the EXS domain of PHO1 is essential for Pi export activity and proper localization to the Golgi and trans-Golgi network, although the EXS domain by itself cannot mediate Pi export. In contrast, removal of the amino-terminal hydrophilic SPX domain does not affect the Pi export capacity of the truncated PHO1 in N. benthamiana. While the Arabidopsis pho1 mutant has low shoot Pi and shows all the hallmarks associated with Pi deficiency, including poor shoot growth and overexpression of numerous Pi deficiency-responsive genes, expression of only the EXS domain of PHO1 in the roots of the pho1 mutant results in a remarkable improvement of shoot growth despite low shoot Pi. Transcriptomic analysis of pho1 expressing the EXS domain indicates an attenuation of the Pi signaling cascade and the up-regulation of genes involved in cell wall synthesis and the synthesis or response to several phytohormones in leaves as well as an altered expression of genes responsive to abscisic acid in roots. PMID:26546667

  16. Nanofibrous nerve conduit-enhanced peripheral nerve regeneration.

    PubMed

    Jiang, Xu; Mi, Ruifa; Hoke, Ahmet; Chew, Sing Yian

    2014-05-01

    Fibre structures represent a potential class of materials for the formation of synthetic nerve conduits due to their biomimicking architecture. Although the advantages of fibres in enhancing nerve regeneration have been demonstrated, in vivo evaluation of fibre size effect on nerve regeneration remains limited. In this study, we analyzed the effects of fibre diameter of electrospun conduits on peripheral nerve regeneration across a 15-mm critical defect gap in a rat sciatic nerve injury model. By using an electrospinning technique, fibrous conduits comprised of aligned electrospun poly (ε-caprolactone) (PCL) microfibers (981 ± 83 nm, Microfiber) or nanofibers (251 ± 32 nm, Nanofiber) were obtained. At three months post implantation, axons regenerated across the defect gap in all animals that received fibrous conduits. In contrast, complete nerve regeneration was not observed in the control group that received empty, non-porous PCL film conduits (Film). Nanofiber conduits resulted in significantly higher total number of myelinated axons and thicker myelin sheaths compared to Microfiber and Film conduits. Retrograde labeling revealed a significant increase in number of regenerated dorsal root ganglion sensory neurons in the presence of Nanofiber conduits (1.93 ± 0.71 × 10(3) vs. 0.98 ± 0.30 × 10(3) in Microfiber, p < 0.01). In addition, the compound muscle action potential (CMAP) amplitudes were higher and distal motor latency values were lower in the Nanofiber conduit group compared to the Microfiber group. This study demonstrated the impact of fibre size on peripheral nerve regeneration. These results could provide useful insights for future nerve guide designs.

  17. Salt stress-induced Ca2+ waves are associated with rapid, long-distance root-to-shoot signaling in plants

    PubMed Central

    Choi, Won-Gyu; Toyota, Masatsugu; Kim, Su-Hwa; Hilleary, Richard; Gilroy, Simon

    2014-01-01

    Their sessile lifestyle means that plants have to be exquisitely sensitive to their environment, integrating many signals to appropriate developmental and physiological responses. Stimuli ranging from wounding and pathogen attack to the distribution of water and nutrients in the soil are frequently presented in a localized manner but responses are often elicited throughout the plant. Such systemic signaling is thought to operate through the redistribution of a host of chemical regulators including peptides, RNAs, ions, metabolites, and hormones. However, there are hints of a much more rapid communication network that has been proposed to involve signals ranging from action and system potentials to reactive oxygen species. We now show that plants also possess a rapid stress signaling system based on Ca2+ waves that propagate through the plant at rates of up to ∼400 µm/s. In the case of local salt stress to the Arabidopsis thaliana root, Ca2+ wave propagation is channeled through the cortex and endodermal cell layers and this movement is dependent on the vacuolar ion channel TPC1. We also provide evidence that the Ca2+ wave/TPC1 system likely elicits systemic molecular responses in target organs and may contribute to whole-plant stress tolerance. These results suggest that, although plants do not have a nervous system, they do possess a sensory network that uses ion fluxes moving through defined cell types to rapidly transmit information between distant sites within the organism. PMID:24706854

  18. 17β-estradiol impedes Bax-involved mitochondrial apoptosis of retinal nerve cells induced by oxidative damage via the phosphatidylinositol 3-kinase/Akt signal pathway.

    PubMed

    Li, Hongbo; Wang, Baoying; Zhu, Chunhui; Feng, Yan; Wang, Shaolan; Shahzad, Muhammad; Hu, Chenghu; Mo, Mingshu; Du, Fangying; Yu, Xiaorui

    2013-07-01

    Oxidative stress leading to retinal nerve cells (RNCs) apoptosis is a major cause of neurodegenerative disorders of the retina. 17β-Estradiol (E2) has been suggested to be a neuroprotective agent in the central nervous system; however, at present, the underlying mechanisms are not well understood, and the related research on the RNCs is less reported. Here, in order to investigate the protective role and mechanism of E2 against oxidative stress-induced damage on RNCs, the transmission electron microscopy and annexin V-FITC/propidium iodide assay were applied to detect the RNCs apoptosis. Western blot and real-time PCR were used to determine the expression of the critical molecules in Bcl-2 and caspase family associated with apoptosis. The transmission electron microscopy results showed that H(2)O(2) could induce typical features of apoptosis in RNCs, including formation of the apoptosome. E2 could, however, suppress the H(2)O(2)-induced morphological changes of apoptosis. Intriguingly, we observed E2-mediated phagocytic scavenging of apoptosome. In response to H(2)O(2)-induced apoptosis, Bax, acting as one of the pivotal pro-apoptotic members of Bcl-2 family, increased significantly, which directly resulted in an increased ratio of Bax to anti-apoptotic protein Bcl-2 (Bax/Bcl-2). Additionally, caspases 9 and 3, which are the critical molecules of the mitochondrial apoptosis pathway, were activated by H(2)O(2). In contrast, E2 exerted anti-apoptotic effects by reducing the expression of Bax to decrease the ratio of Bax/Bcl-2 and impeded the caspases 9/3 activation. Moreover, LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, could sharply block the effect of E2 in reducing the percentage of apoptotic cells resistance to H(2)O(2). And the attenuation of Bax, the reduced activities of caspases 9/3 and the impeded release of mitochondrial cytochrome c mediated by E2 resistance to H(2)O(2) damage were significantly retrieved by LY294002 administration. Taken

  19. Lumbar nerve root: the enigmatic eponyms.

    PubMed

    Dyck, P

    1984-01-01

    Man's quest for recognition has not escaped the physician, whose contributions to medicine perpetuate his name in print. It is a final grasp for professional immortality, which for men like Imhotep and Hippocrates, has prevailed for millennia. This fervor was particularly evident in the latter 19th century, which created a flurry of eponyms, often two or more physicians publishing the same clinical observation. This article reviews the eponym epidemic as it relates to lumbar radiculopathy.

  20. Optic Nerve.

    PubMed

    Gordon, Lynn K

    2016-10-28

    Optic nerve diseases arise from many different etiologies including inflammatory, neoplastic, genetic, infectious, ischemic, and idiopathic. Understanding some of the characteristics of the most common optic neuropathies along with therapeutic approaches to these diseases is helpful in designing recommendations for individual patients. Although many optic neuropathies have no specific treatment, some do, and it is those potentially treatable or preventable conditions which need to be recognized in order to help patients regain their sight or develop a better understanding of their own prognosis. In this chapter several diseases are discussed including idiopathic intracranial hypertension, optic neuritis, ischemic optic neuropathies, hereditary optic neuropathies, trauma, and primary tumors of the optic nerve. For each condition there is a presentation of the signs and symptoms of the disease, in some conditions the evaluation and diagnostic criteria are highlighted, and where possible, current therapy or past trials are discussed.

  1. Potential regulatory phosphorylation sites in a Medicago truncatula plasma membrane proton pump implicated during early symbiotic signaling in roots.

    PubMed

    Nguyen, Thao T; Volkening, Jeremy D; Rose, Christopher M; Venkateshwaran, Muthusubramanian; Westphall, Michael S; Coon, Joshua J; Ané, Jean-Michel; Sussman, Michael R

    2015-08-04

    In plants and fungi the plasma membrane proton pump generates a large proton-motive force that performs essential functions in many processes, including solute transport and the control of cell elongation. Previous studies in yeast and higher plants have indicated that phosphorylation of an auto-inhibitory domain is involved in regulating pump activity. In this report we examine the Medicago truncatula plasma membrane proton pump gene family, and in particular MtAHA5. Yeast complementation assays with phosphomimetic mutations at six candidate sites support a phosphoregulatory role for two residues, suggesting a molecular model to explain early Nod factor-induced changes in the plasma membrane proton-motive force of legume root cells.

  2. Liming can decrease legume crop yield and leaf gas exchange by enhancing root to shoot ABA signalling.

    PubMed

    Rothwell, Shane A; Elphinstone, E David; Dodd, Ian C

    2015-04-01

    To meet future requirements for food production, sustainable intensive agricultural systems need to optimize nutrient availability to maximize yield, traditionally achieved by maintaining soil pH within an optimal range (6-6.5) by applying lime (calcium carbonate). However, a field trial that applied recommended liming rates to a sandy loam soil (increasing soil pH from 5.5 to 6.2) decreased pod yield of field bean (Vicia faba L. cv. Fuego) by ~30%. Subsequent pot trials, with liming that raised soil pH to 6.3-6.7, reduced stomatal conductance (g(s)) by 63, 26, and 59% in V. faba, bean (Phaseolus vulgaris), and pea (Pisum sativum), respectively. Furthermore, liming reduced shoot dry biomass by 16-24% in these species. Ionomic analysis of root xylem sap and leaf tissue revealed a decrease in phosphorus concentration that was correlated with decreased g(s): both reductions were partially reversed by adding superphosphate fertilizer. Further analysis of pea suggests that leaf gas exchange was reduced by a systemic increase (roots, xylem sap, and leaves) in the phytohormone abscisic acid (ABA) in response to lime-induced suboptimal plant phosphorus concentrations. Supplying synthetic ABA via the transpiration stream to detached pea leaves, at the same xylem sap concentrations induced by liming, decreased transpiration. Furthermore, the g(s) of the ABA-deficient mutant pea wilty was unresponsive to liming, apparently confirming that ABA mediates some responses to low phosphorus availability caused by liming. This research provides a detailed mechanistic understanding of the physiological processes by which lime application can limit crop yields, and questions the suitability of current liming recommendations.

  3. Liming can decrease legume crop yield and leaf gas exchange by enhancing root to shoot ABA signalling

    PubMed Central

    Rothwell, Shane A.; Elphinstone, E. David; Dodd, Ian C.

    2015-01-01

    To meet future requirements for food production, sustainable intensive agricultural systems need to optimize nutrient availability to maximize yield, traditionally achieved by maintaining soil pH within an optimal range (6–6.5) by applying lime (calcium carbonate). However, a field trial that applied recommended liming rates to a sandy loam soil (increasing soil pH from 5.5 to 6.2) decreased pod yield of field bean (Vicia faba L. cv. Fuego) by ~30%. Subsequent pot trials, with liming that raised soil pH to 6.3–6.7, reduced stomatal conductance (g s) by 63, 26, and 59% in V. faba, bean (Phaseolus vulgaris), and pea (Pisum sativum), respectively. Furthermore, liming reduced shoot dry biomass by 16–24% in these species. Ionomic analysis of root xylem sap and leaf tissue revealed a decrease in phosphorus concentration that was correlated with decreased g s: both reductions were partially reversed by adding superphosphate fertilizer. Further analysis of pea suggests that leaf gas exchange was reduced by a systemic increase (roots, xylem sap, and leaves) in the phytohormone abscisic acid (ABA) in response to lime-induced suboptimal plant phosphorus concentrations. Supplying synthetic ABA via the transpiration stream to detached pea leaves, at the same xylem sap concentrations induced by liming, decreased transpiration. Furthermore, the g s of the ABA-deficient mutant pea wilty was unresponsive to liming, apparently confirming that ABA mediates some responses to low phosphorus availability caused by liming. This research provides a detailed mechanistic understanding of the physiological processes by which lime application can limit crop yields, and questions the suitability of current liming recommendations. PMID:25740925

  4. Calcium Signaling in Mitral Cell Dendrites of Olfactory Bulbs of Neonatal Rats and Mice during Olfactory Nerve Stimulation and Beta-Adrenoceptor Activation

    ERIC Educational Resources Information Center

    Yuan, Qi; Mutoh, Hiroki; Debarbieux, Franck; Knopfel, Thomas

    2004-01-01

    Synapses formed by the olfactory nerve (ON) provide the source of excitatory synaptic input onto mitral cells (MC) in the olfactory bulb. These synapses, which relay odor-specific inputs, are confined to the distally tufted single primary dendrites of MCs, the first stage of central olfactory processing. Beta-adrenergic modulation of electrical…

  5. Peripheral nerve injury and gabapentin, but not their combinations impair attentional behavior via direct effects on noradrenergic signaling in the brain

    PubMed Central

    Suto, Takashi; Eisenach, James C.; Hayashida, Ken-ichiro

    2014-01-01

    Chronic pain following peripheral nerve damage is often accompanied by a reduction in prefrontal cortex (PFC)-related cognitive functions, which are regulated by noradrenaline, released from efferents originating in the locus coeruleus (LC). L5-L6 spinal nerve ligation (SNL) increased tissue content and extracellular concentrations of noradrenaline in microdialysates from the PFC, and impaired attentional level in the novel object recognition test. Systemic gabapentin, commonly used to treat chronic pain, impaired the novel object recognition task in normal, but not SNL animals. Accordingly, gabapentin increased c-fos expression in LC neurons and noradrenaline release in the PFC in normal animals, but in SNL animals, gabapentin failed to increase c-fos expression in LC neurons projecting to the PFC and failed to increase noradrenaline release in the PFC. In contrast, locally perfused gabapentin reduced noradrenaline release in the PFC in vivo and in PFC synaptosomes in vitro. SNL- and gabapentin-induced impairment of novel object recognition task was reversed by intraperitoneal injection of the α1-adrenoceptor antagonist prazosin. These results suggest that increase in noradrenergic tone, induced by nerve injury or gabapentin, impairs PFC functions possibly via α1-adrenoceptor-mediated mechanisms, that the net effect of gabapentin on noradrenaline release in the PFC would depend on sometimes opposing actions at different sites, and that nerve injury selectively impairs the response to gabapentin in PFC projecting neurons in the LC. PMID:24837843

  6. Fusarium oxysporum f.sp. ciceri Race 1 Induced Redox State Alterations Are Coupled to Downstream Defense Signaling in Root Tissues of Chickpea (Cicer arietinum L.)

    PubMed Central

    Chatterjee, Moniya; Das, Sampa

    2013-01-01

    Reactive oxygen species are known to play pivotal roles in pathogen perception, recognition and downstream defense signaling. But, how these redox alarms coordinate in planta into a defensive network is still intangible. Present study illustrates the role of Fusarium oxysporum f.sp ciceri Race1 (Foc1) induced redox responsive transcripts in regulating downstream defense signaling in chickpea. Confocal microscopic studies highlighted pathogen invasion and colonization accompanied by tissue damage and deposition of callose degraded products at the xylem vessels of infected roots of chickpea plants. Such depositions led to the clogging of xylem vessels in compatible hosts while the resistant plants were devoid of such obstructions. Lipid peroxidation assays also indicated fungal induced membrane injury. Cell shrinkage and gradual nuclear adpression appeared as interesting features marking fungal ingress. Quantitative real time polymerase chain reaction exhibited differential expression patterns of redox regulators, cellular transporters and transcription factors during Foc1 progression. Network analysis showed redox regulators, cellular transporters and transcription factors to coordinate into a well orchestrated defensive network with sugars acting as internal signal modulators. Respiratory burst oxidase homologue, cationic peroxidase, vacuolar sorting receptor, polyol transporter, sucrose synthase, and zinc finger domain containing transcription factor appeared as key molecular candidates controlling important hubs of the defense network. Functional characterization of these hub controllers may prove to be promising in understanding chickpea–Foc1 interaction and developing the case study as a model for looking into the complexities of wilt diseases of other important crop legumes. PMID:24058463

  7. Fusarium oxysporum f.sp. ciceri race 1 induced redox state alterations are coupled to downstream defense signaling in root tissues of chickpea (Cicer arietinum L.).

    PubMed

    Gupta, Sumanti; Bhar, Anirban; Chatterjee, Moniya; Das, Sampa

    2013-01-01

    Reactive oxygen species are known to play pivotal roles in pathogen perception, recognition and downstream defense signaling. But, how these redox alarms coordinate in planta into a defensive network is still intangible. Present study illustrates the role of Fusarium oxysporum f.sp ciceri Race1 (Foc1) induced redox responsive transcripts in regulating downstream defense signaling in chickpea. Confocal microscopic studies highlighted pathogen invasion and colonization accompanied by tissue damage and deposition of callose degraded products at the xylem vessels of infected roots of chickpea plants. Such depositions led to the clogging of xylem vessels in compatible hosts while the resistant plants were devoid of such obstructions. Lipid peroxidation assays also indicated fungal induced membrane injury. Cell shrinkage and gradual nuclear adpression appeared as interesting features marking fungal ingress. Quantitative real time polymerase chain reaction exhibited differential expression patterns of redox regulators, cellular transporters and transcription factors during Foc1 progression. Network analysis showed redox regulators, cellular transporters and transcription factors to coordinate into a well orchestrated defensive network with sugars acting as internal signal modulators. Respiratory burst oxidase homologue, cationic peroxidase, vacuolar sorting receptor, polyol transporter, sucrose synthase, and zinc finger domain containing transcription factor appeared as key molecular candidates controlling important hubs of the defense network. Functional characterization of these hub controllers may prove to be promising in understanding chickpea-Foc1 interaction and developing the case study as a model for looking into the complexities of wilt diseases of other important crop legumes.

  8. Thermally Drawn Fibers as Nerve Guidance Scaffolds

    PubMed Central

    Koppes, Ryan A.; Park, Seongjun; Hood, Tiffany; Jia, Xiaoting; Poorheravi, Negin Abdolrahim; Achyuta, Anilkumar Harapanahalli; Fink, Yoel; Anikeeva, Polina

    2016-01-01

    Synthetic neural scaffolds hold promise to eventually replace nerve autografts for tissue repair following peripheral nerve injury. Despite substantial evidence for the influence of scaffold geometry and dimensions on the rate of axonal growth, systematic evaluation of these parameters remains a challenge due to limitations in materials processing. We have employed fiber drawing to engineer a wide spectrum of polymer-based neural scaffolds with varied geometries and core sizes. Using isolated whole dorsal root ganglia as an in vitro model system we have identified key features enhancing nerve growth within these fiber scaffolds. Our approach enabled straightforward integration of microscopic topography at the scale of nerve fascicles within the scaffold cores, which led to accelerated Schwann cell migration, as well as neurite growth and alignment. Our findings indicate that fiber drawing provides a scalable and versatile strategy for producing nerve guidance channels capable of controlling direction and accelerating the rate of axonal growth. PMID:26717246

  9. Thermally drawn fibers as nerve guidance scaffolds.

    PubMed

    Koppes, Ryan A; Park, Seongjun; Hood, Tiffany; Jia, Xiaoting; Abdolrahim Poorheravi, Negin; Achyuta, Anilkumar Harapanahalli; Fink, Yoel; Anikeeva, Polina

    2016-03-01

    Synthetic neural scaffolds hold promise to eventually replace nerve autografts for tissue repair following peripheral nerve injury. Despite substantial evidence for the influence of scaffold geometry and dimensions on the rate of axonal growth, systematic evaluation of these parameters remains a challenge due to limitations in materials processing. We have employed fiber drawing to engineer a wide spectrum of polymer-based neural scaffolds with varied geometries and core sizes. Using isolated whole dorsal root ganglia as an in vitro model system we have identified key features enhancing nerve growth within these fiber scaffolds. Our approach enabled straightforward integration of microscopic topography at the scale of nerve fascicles within the scaffold cores, which led to accelerated Schwann cell migration, as well as neurite growth and alignment. Our findings indicate that fiber drawing provides a scalable and versatile strategy for producing nerve guidance channels capable of controlling direction and accelerating the rate of axonal growth.

  10. Rehabilitation of the trigeminal nerve

    PubMed Central

    Iro, Heinrich; Bumm, Klaus; Waldfahrer, Frank

    2005-01-01

    When it comes to restoring impaired neural function by means of surgical reconstruction, sensory nerves have always been in the role of the neglected child when compared with motor nerves. Especially in the head and neck area, with its either sensory, motor or mixed cranial nerves, an impaired sensory function can cause severe medical conditions. When performing surgery in the head and neck area, sustaining neural function must not only be highest priority for motor but also for sensory nerves. In cases with obvious neural damage to sensory nerves, an immediate neural repair, if necessary with neural interposition grafts, is desirable. Also in cases with traumatic trigeminal damage, an immediate neural repair ought to be considered, especially since reconstructive measures at a later time mostly require for interposition grafts. In terms of the trigeminal neuralgia, commonly thought to arise from neurovascular brainstem compression, a pharmaceutical treatment is considered as the state of the art in terms of conservative therapy. A neurovascular decompression of the trigeminal root can be an alternative in some cases when surgical treatment is sought after. Besides the above mentioned therapeutic options, alternative treatments are available. PMID:22073060

  11. Inhibition of auxin transport and auxin signaling and treatment with far red light induces root coiling in the phospholipase-A mutant ppla-I-1. Significance for surface penetration?

    PubMed

    Perrineau, F; Wimalasekera, R; Effendi, Y; Scherer, G F E

    2016-06-01

    When grown on a non-penetretable at a surface angle of 45°, Arabidopsis roots form wave-like structures and, in wild type rarely, but in certain mutants the tip root even may form circles. These circles are called coils. The formation of coils depends on the complex interaction of circumnutation, gravitropism and negative thigmotropism where - at least - gravitropism is intimately linked to auxin transport and signaling. The knockout mutant of patatin-related phospholipase-AI-1 (pplaI-1) is an auxin-signaling mutant which forms moderately increased numbers of coils on tilted agar plates. We tested the effects of the auxin efflux transport inhibitor NPA (1-naphthylphtalamic acid) and of the influx transport inhibitor 1-NOA (1-naphthoxyacetic acid) which both further increased root coil formation. The pPLAI-1 inhibitors HELSS (haloenol lactone suicide substrate=E-6-(bromomethylene)tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one) and ETYA (eicosatetraynoic acid) which are auxin signaling inhibitors also increased coil formation. In addition, far red light treatment increased coil formation. The results point out that a disturbance of auxin transport and signaling is one potential cause for root coils. As we show that the mutant pplaI-1 penetrates horizontal agar plates better than wild type plants root movements may help penetrating the soil.

  12. Dandelion root extract affects colorectal cancer proliferation and survival through the activation of multiple death signalling pathways.

    PubMed

    Ovadje, Pamela; Ammar, Saleem; Guerrero, Jose-Antonio; Arnason, John Thor; Pandey, Siyaram

    2016-11-08

    Dandelion extracts have been studied extensively in recent years for its anti-depressant and anti-inflammatory activity. Recent work from our lab, with in-vitro systems, shows the anti-cancer potential of an aqueous dandelion root extract (DRE) in several cancer cell models, with no toxicity to non-cancer cells. In this study, we examined the cancer cell-killing effectiveness of an aqueous DRE in colon cancer cell models. Aqueous DRE induced programmed cell death (PCD) selectively in > 95% of colon cancer cells, irrespective of their p53 status, by 48 hours of treatment. The anti-cancer efficacy of this extract was confirmed in in-vivo studies, as the oral administration of DRE retarded the growth of human colon xenograft models by more than 90%. We found the activation of multiple death pathways in cancer cells by DRE treatment, as revealed by gene expression analyses showing the expression of genes implicated in programmed cell death. Phytochemical analyses of the extract showed complex multi-component composition of the DRE, including some known bioactive phytochemicals such as α-amyrin, β-amyrin, lupeol and taraxasterol. This suggested that this natural extract could engage and effectively target multiple vulnerabilities of cancer cells. Therefore, DRE could be a non-toxic and effective anti-cancer alternative, instrumental for reducing the occurrence of cancer cells drug-resistance.

  13. Dandelion root extract affects colorectal cancer proliferation and survival through the activation of multiple death signalling pathways

    PubMed Central

    Ovadje, Pamela; Ammar, Saleem; Guerrero, Jose-Antonio; Arnason, John Thor; Pandey, Siyaram

    2016-01-01

    Dandelion extracts have been studied extensively in recent years for its anti-depressant and anti-inflammatory activity. Recent work from our lab, with in-vitro systems, shows the anti-cancer potential of an aqueous dandelion root extract (DRE) in several cancer cell models, with no toxicity to non-cancer cells. In this study, we examined the cancer cell-killing effectiveness of an aqueous DRE in colon cancer cell models. Aqueous DRE induced programmed cell death (PCD) selectively in > 95% of colon cancer cells, irrespective of their p53 status, by 48 hours of treatment. The anti-cancer efficacy of this extract was confirmed in in-vivo studies, as the oral administration of DRE retarded the growth of human colon xenograft models by more than 90%. We found the activation of multiple death pathways in cancer cells by DRE treatment, as revealed by gene expression analyses showing the expression of genes implicated in programmed cell death. Phytochemical analyses of the extract showed complex multi-component composition of the DRE, including some known bioactive phytochemicals such as α-amyrin, β-amyrin, lupeol and taraxasterol. This suggested that this natural extract could engage and effectively target multiple vulnerabilities of cancer cells. Therefore, DRE could be a non-toxic and effective anti-cancer alternative, instrumental for reducing the occurrence of cancer cells drug-resistance. PMID:27564258

  14. Prenatal hypoxia leads to increased muscle sympathetic nerve activity, sympathetic hyperinnervation, premature blunting of neuropeptide Y signaling, and hypertension in adult life.

    PubMed

    Rook, William; Johnson, Christopher D; Coney, Andrew M; Marshall, Janice M

    2014-12-01

    Adverse conditions prenatally increase the risk of cardiovascular disease, including hypertension. Chronic hypoxia in utero (CHU) causes endothelial dysfunction, but whether sympathetic vasoconstrictor nerve functioning is altered is unknown. We, therefore, compared in male CHU and control (N) rats muscle sympathetic nerve activity, vascular sympathetic innervation density, and mechanisms of sympathetic vasoconstriction. In young (Y)-CHU and Y-N rats (≈3 months), baseline arterial blood pressure was similar. However, tonic muscle sympathetic nerve activity recorded focally from arterial vessels of spinotrapezius muscle had higher mean frequency in Y-CHU than in Y-N rats (0.56±0.075 versus 0.33±0.036 Hz), and the proportions of single units with high instantaneous frequencies (1-5 and 6-10 Hz) being greater in Y-CHU rats. Sympathetic innervation density of tibial arteries was ≈50% greater in Y-CHU than in Y-N rats. Increases in femoral vascular resistance evoked by sympathetic stimulation at low frequency (2 Hz for 2 minutes) and bursts at 20 Hz were substantially smaller in Y-CHU than in Y-N rats. In Y-N only, the neuropeptide Y Y1-receptor antagonist BIBP3226 attenuated these responses. By contrast, baseline arterial blood pressure was higher in middle-aged (M)-CHU than in M-N rats (≈9 months; 139±3 versus 126±3 mm Hg, respectively). BIBP3226 had no effect on femoral vascular resistance increases evoked by 2 Hz or 20 Hz bursts in M-N or M-CHU rats. These results indicate that fetal programming induced by prenatal hypoxia causes an increase in centrally generated muscle sympathetic nerve activity in youth and hypertension by middle age. This is associated with blunting of sympathetically evoked vasoconstriction and its neuropeptide Y component that may reflect premature vascular aging and contribute to increased risk of cardiovascular disease.

  15. Natural Variation in Small Molecule–Induced TIR-NB-LRR Signaling Induces Root Growth Arrest via EDS1- and PAD4-Complexed R Protein VICTR in Arabidopsis[C][W

    PubMed Central

    Kim, Tae-Houn; Kunz, Hans-Henning; Bhattacharjee, Saikat; Hauser, Felix; Park, Jiyoung; Engineer, Cawas; Liu, Amy; Ha, Tracy; Parker, Jane E.; Gassmann, Walter; Schroeder, Julian I.

    2012-01-01

    In a chemical genetics screen we identified the small-molecule [5-(3,4-dichlorophenyl)furan-2-yl]-piperidine-1-ylmethanethione (DFPM) that triggers rapid inhibition of early abscisic acid signal transduction via PHYTOALEXIN DEFICIENT4 (PAD4)- and ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1)-dependent immune signaling mechanisms. However, mechanisms upstream of EDS1 and PAD4 in DFPM-mediated signaling remain unknown. Here, we report that DFPM generates an Arabidopsis thaliana accession-specific root growth arrest in Columbia-0 (Col-0) plants. The genetic locus responsible for this natural variant, VICTR (VARIATION IN COMPOUND TRIGGERED ROOT growth response), encodes a TIR-NB-LRR (for Toll-Interleukin1 Receptor–nucleotide binding–Leucine-rich repeat) protein. Analyses of T-DNA insertion victr alleles showed that VICTR is necessary for DFPM-induced root growth arrest and inhibition of abscisic acid–induced stomatal closing. Transgenic expression of the Col-0 VICTR allele in DFPM-insensitive Arabidopsis accessions recapitulated the DFPM-induced root growth arrest. EDS1 and PAD4, both central regulators of basal resistance and effector-triggered immunity, as well as HSP90 chaperones and their cochaperones RAR1 and SGT1B, are required for the DFPM-induced root growth arrest. Salicylic acid and jasmonic acid signaling pathway components are dispensable. We further demonstrate that VICTR associates with EDS1 and PAD4 in a nuclear protein complex. These findings show a previously unexplored association between a TIR-NB-LRR protein and PAD4 and identify functions of plant immune signaling components in the regulation of root meristematic zone-targeted growth arrest. PMID:23275581

  16. Nerve conduction velocity

    MedlinePlus

    ... polyneuropathy Tibial nerve dysfunction Ulnar nerve dysfunction Any peripheral neuropathy can cause abnormal results. Damage to the spinal ... Herniated disk Lambert-Eaton syndrome Mononeuropathy Multiple ... azotemia Primary amyloidosis Radial nerve dysfunction Sciatica ...

  17. Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-kappaB and MAPK signaling pathways.

    PubMed

    Zhou, Ping; Gross, Shimon; Liu, Ji-Hua; Yu, Bo-Yang; Feng, Ling-Ling; Nolta, Jan; Sharma, Vijay; Piwnica-Worms, David; Qiu, Samuel X

    2010-12-01

    Kava (Piper methysticum Foster, Piperaceae) organic solvent-extract has been used to treat mild to moderate anxiety, insomnia, and muscle fatigue in Western countries, leading to its emergence as one of the 10 best-selling herbal preparations. However, several reports of severe hepatotoxicity in kava consumers led the U.S. Food and Drug Administration and authorities in Europe to restrict sales of kava-containing products. Herein we demonstrate that flavokawain B (FKB), a chalcone from kava root, is a potent hepatocellular toxin, inducing cell death in HepG2 (LD(50)=15.3 ± 0.2 μM) and L-02 (LD(50)=32 μM) cells. Hepatocellular toxicity of FKB is mediated by induction of oxidative stress, depletion of reduced glutathione (GSH), inhibition of IKK activity leading to NF-κB transcriptional blockade, and constitutive TNF-α-independent activation of mitogen-activated protein kinase (MAPK) signaling pathways, namely, ERK, p38, and JNK. We further demonstrate by noninvasive bioluminescence imaging that oral consumption of FKB leads to inhibition of hepatic NF-κB transcriptional activity in vivo and severe liver damage. Surprisingly, replenishment with exogenous GSH normalizes both TNF-α-dependent NF-κB as well as MAPK signaling and rescues hepatocytes from FKB-induced death. Our data identify FKB as a potent GSH-sensitive hepatotoxin, levels of which should be specifically monitored and controlled in kava-containing herb products.

  18. Root Zone Soil Moisture (RZSM) Estimates Using VHF (240-270 MHZ) Antenna for SoOp (Signal of Opportunity) Receiver for 6U CubeSat Platforms

    NASA Astrophysics Data System (ADS)

    Joseph, A. T.

    2015-12-01

    The main goal of this research is to develop VHF antennas for 6U Cubesat platforms to enable validation of root zone soil moisture (RZSM) estimation algorithms for signal of opportunity (SoOp) remote sensing over the 240-270 MHz frequency band. This study provides a strong foundation for establishing a path for maturing truly global direct surface soil moisture (SM) and RZSM measurement system over a variety of land covers with limited density restrictions. In SoOp methodology, signals transmitted by already existing transmitters, in this case the Military Satellite Communication (MilSatCom) System's UHF Follow-On program, are utilized to measure properties of reflecting targets by recording reflected signals using a simple passive microwave receiver. We developed and will test VHF (240-270 MHz) antenna technology for SoOp receivers for 6U Cubesat platforms and perform measurement of SM and RZSM using the proposed antennas deployed on a ground-based Soil Moisture Active Passive (SMAP) simulator boom truck. We will validate the RZSM and SM estimation algorithms from measured data (where RZSM is defined as the volumetric SM contained in the top 1 m of the soil column). Knowledge of RZSM up to a depth of 1 m and surface SM up to a depth of 0.05 m on a global scale, at a spatial resolution of 1-10 km through moderate-to-heavy vegetation, is critical to understanding global water resources and the vertical moisture gradient in the Earth's surface layer which controls moisture interactions between the soil, vegetation, and atmosphere. Current observations of surface SM from space by L-band radiometers and radars are limited to measurements of surface SM up to a depth of ~0.05 m through moderate amounts of vegetation. Developing bi-static reflectometry using VHF geostationary satellite SoOp creates the potential of directly observing SM and RZSM on a truly global basis from a constellation of small satellite-based receivers in low earth orbit. The technique provides the

  19. Coculture system of keratinocytes and dorsal-root-ganglion-derived cells for screening neurotrophic factors involved in guidance of neuronal axon growth in the skin.

    PubMed

    Kumamoto, Jun-Ichi; Nakatani, Masashi; Tsutsumi, Moe; Goto, Makiko; Denda, Sumiko; Takei, Kentaro; Denda, Mitsuhiro

    2014-01-01

    The density of peripheral nerve fibres is increased in atopic dermatitis. Moreover, reduction in the fibres in a mouse model of atopic dermatitis reduces scratching behaviour. Thus, regulation of nerve fibre extension could be an effective strategy to reduce itching in pruritus dermatosis. In this study, we established a new coculture system of keratinocytes and dorsal-root-ganglion-derived cells using an apparatus, AXIS(™) , which consists of two different channels connected via a set of microgrooves, through which signalling molecules and axons, but not living cells, can pass. When we seeded keratinocytes in one chamber, extension of nerve fibres was observed from dorsal root ganglion cells seeded in the other chamber. Addition of anti-BDNF antibody in the keratinocyte-seeded chamber significantly reduced the extension. Application of Semaphorin 3A also reduced the extension by approximately 50%. We suggest that this coculture system may be useful for screening of anti-itching drugs.

  20. KLF7-transfected Schwann cell graft transplantation promotes sciatic nerve regeneration.

    PubMed

    Wang, Ying; Li, Wen-Yuan; Jia, Hua; Zhai, Feng-Guo; Qu, Wen-Rui; Cheng, Yong-Xia; Liu, Yan-Cui; Deng, Ling-Xiao; Guo, Su-Fen; Jin, Zai-Shun

    2017-01-06

    Our former study demonstrated that Krüppel-like Factor 7 (KLF7) is a transcription factor that stimulates axonal regeneration after peripheral nerve injury. Currently, we used a gene therapy approach to overexpress KLF7 in Schwann cells (SCs) and assessed whether KLF7-transfected SCs graft could promote sciatic nerve regeneration. SCs were transfected by adeno-associated virus 2 (AAV2)-KLF7 in vitro. Mice were allografted by an acellular nerve (ANA) with either an injection of DMEM (ANA group), SCs (ANA+SCs group) or AAV2-KLF7-transfected SCs (ANA+KLF7-SCs group) to assess repair of a sciatic nerve gap. The results indicate that KLF7 overexpression promoted the proliferation of both transfected SCs and native SCs. The neurite length of the dorsal root ganglia (DRG) explants was enhanced. Several beneficial effects were detected in the ANA+KLF7-SCs group including an increase in the compound action potential amplitude, sciatic function index score, enhanced expression of PKH26-labeling transplant SCs, peripheral myelin protein 0, neurofilaments, S-100, and myelinated regeneration nerve. Additionally, HRP-labeled motoneurons in the spinal cord, CTB-labeled sensory neurons in the DRG, motor endplate density and the weight ratios of target muscles were increased by the treatment while thermal hyperalgesia was diminished. Finally, expression of KLF7, NGF, GAP43, TrkA and TrkB were enhanced in the grafted SCs, which may indicate that several signal pathways may be involved in conferring the beneficial effects from KLF7 overexpression. We concluded that KLF7-overexpressing SCs promoted axonal regeneration of the peripheral nerve and enhanced myelination, which collectively proved KLF-SCs as a novel therapeutic strategy for injured nerves.

  1. Nerve Impulses in Plants

    ERIC Educational Resources Information Center

    Blatt, F. J.

    1974-01-01

    Summarizes research done on the resting and action potential of nerve impulses, electrical excitation of nerve cells, electrical properties of Nitella, and temperature effects on action potential. (GS)

  2. Facial nerve paralysis after cervical traction.

    PubMed

    So, Edmund Cheung

    2010-10-01

    Cervical traction is a frequently used treatment in rehabilitation clinics for cervical spine problems. This modality works, in principle, by decompressing the spinal cord or its nerve roots by applying traction on the cervical spine through a harness placed over the mandible (Olivero et al., Neurosurg Focus 2002;12:ECP1). Previous reports on treatment complications include lumbar radicular discomfort, muscle injury, neck soreness, and posttraction pain (LaBan et al., Arch Phys Med Rehabil 1992;73:295-6; Lee et al., J Biomech Eng 1996;118:597-600). Here, we report the first case of unilateral facial nerve paralysis developed after 4 wks of intermittent cervical traction therapy. Nerve conduction velocity examination revealed a peripheral-type facial nerve paralysis. Symptoms of facial nerve paralysis subsided after prednisolone treatment and suspension of traction therapy. It is suspected that a misplaced or an overstrained harness may have been the cause of facial nerve paralysis in this patient. Possible causes were (1) direct compression by the harness on the right facial nerve near its exit through the stylomastoid foramen; (2) compression of the right external carotid artery by the harness, causing transient ischemic injury at the geniculate ganglion; or (3) coincidental herpes zoster virus infection or idiopathic Bell's palsy involving the facial nerve.

  3. Mitogen-activated protein kinase signal transduction and DNA repair network are involved in aluminum-induced DNA damage and adaptive response in root cells of Allium cepa L.

    PubMed Central

    Panda, Brahma B.; Achary, V. Mohan M.

    2014-01-01

    In the current study, we studied the role of signal transduction in aluminum (Al3+)-induced DNA damage and adaptive response in root cells of Allium cepa L. The root cells in planta were treated with Al3+ (800 μM) for 3 h without or with 2 h pre-treatment of inhibitors of mitogen-activated protein kinase (MAPK), and protein phosphatase. Also, root cells in planta were conditioned with Al3+ (10 μM) for 2 h and then subjected to genotoxic challenge of ethyl methane sulfonate (EMS; 5 mM) for 3 h without or with the pre-treatment of the aforementioned inhibitors as well as the inhibitors of translation, transcription, DNA replication and repair. At the end of treatments, roots cells were assayed for cell death and/or DNA damage. The results revealed that Al3+ (800 μM)-induced significant DNA damage and cell death. On the other hand, conditioning with low dose of Al3+ induced adaptive response conferring protection of root cells from genotoxic stress caused by EMS-challenge. Pre-treatment of roots cells with the chosen inhibitors prior to Al3+-conditioning prevented or reduced the adaptive response to EMS genotoxicity. The results of this study suggested the involvement of MAPK and DNA repair network underlying Al-induced DNA damage and adaptive response to genotoxic stress in root cells of A. cepa. PMID:24926302

  4. Role of puerarin in the signalling of neuropathic pain mediated by P2X3 receptor of dorsal root ganglion neurons.

    PubMed

    Xu, Changshui; Xu, Wenyuan; Xu, Hong; Xiong, Wei; Gao, Yun; Li, Guilin; Liu, Shuangmei; Xie, Jinyan; Tu, Guihua; Peng, Haiying; Qiu, Shuyi; Liang, Shangdong

    2012-01-04

    Tissue injury or inflammation of the nervous system may result in chronic neuropathic pain characterized by sensitivity to painful stimuli. P2X(3) receptors play a crucial role in facilitating pain transmission. Puerarin is an active compound of a traditional Chinese medicine Ge-gen, and Ge-gen soup has anti-inflammatory effects. The present research investigated the role of puerarin in the signalling of chronic neuropathic pain mediated by P2X(3) receptors of rat dorsal root ganglion neurons. Chronic constriction injury (CCI) rat model was adopted. Sprague-Dawley rats were randomly divided into blank control group (Ctrl), sham group (Sham), puerarin-treated control group (Ctrl+PUE), chronic constriction injury (CCI) group and puerarin-treated CCI group (CCI+PUE). Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured by the von-Frey test and the Hargreaves' test respectively. The stain values of P2X(3) protein and mRNA in L4/L5 dorsal root ganglion (DRG) were detected by immunohistochemistry, western blot and in situ hybridization. At day 4-7 after the operation of CCI rats, MWT and TWL in group CCI and CCI+PUE were lower than those in group Ctrl, Sham and Ctrl+PUE, while there was no difference among group Ctrl, Sham and Ctrl+PUE. At day 7-10 after operation, MWT and TWL in group CCI+PUE was higher than those in group CCI, but there was no significant difference between group CCI+PUE and group Ctrl (p>0.05). At day 14 after operation, the stain values of P2X(3) proteins and mRNAs in L4/L5 DRG of group CCI were higher than those in group Ctrl, Sham, Ctrl+PUE and CCI+PUE, while the stain values of P2X(3) proteins and mRNAs in group CCI+PUE were significantly decreased compared with those in group CCI. Therefore, puerarin may alleviate neuropathic pain mediated by P2X(3) receptors in dorsal root ganglion neurons.

  5. Metabolic changes and associated cytokinin signals in response to nitrate assimilation in roots and shoots of Lolium perenne.

    PubMed

    Roche, Jessica; Love, Jonathan; Guo, Qianqian; Song, Jiancheng; Cao, Mingshu; Fraser, Karl; Huege, Jan; Jones, Chris; Novák, Ondřej; Turnbull, Matthew H; Jameson, Paula E

    2016-04-01

    The efficiency of inorganic nitrogen (N) assimilation is a critical component of fertilizer use by plants and of forage production in Lolium perenne, an important pasture species worldwide. We present a spatiotemporal description of nitrate use efficiency in terms of metabolic responses and carbohydrate remobilization, together with components of cytokinin signal transduction following nitrate addition to N-impoverished plants. Perennial ryegrass (L. perenne cv. Grasslands Nui) plants were grown for 10 weeks in unfertilized soil and then treated with nitrate (5 mM) hydroponically. Metabolomic analysis by gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry revealed a dynamic interaction between N and carbon metabolism over a week-long time course represented by the relative abundance of amino acids, tricarboxylic acid intermediates and stored water-soluble carbohydrates (WSCs). The initial response to N addition was characterized by a rapid remobilization of carbon stores from the low-molecular weight WSC, along with an increase in N content and assimilation into free amino acids. Subsequently, the shoot became the main source of carbon through remobilization of a large pool of high-molecular weight WSC. Associated quantification of cytokinin levels and expression profiling of putative cytokinin response regulator genes by quantitative reverse transcription polymerase chain reaction support a role for cytokinin in the mediation of the response to N addition in perennial ryegrass. The presence of high levels of cis-zeatin-type cytokinins is discussed in the context of hormonal homeostasis under the stress of steady-state N deficiency.

  6. The role of peripheral nerve ECM components in the tissue engineering nerve construction.

    PubMed

    Gao, Xupeng; Wang, Yu; Chen, Jifeng; Peng, Jiang

    2013-01-01

    The extracellular matrix (ECM) is the naturally occurring substrate that provides a support structure and an attachment site for cells. It also produces a biological signal, which plays an important role in and has significant impact on cell adhesion, migration, proliferation, differentiation, and gene expression. Peripheral nerve repair is a complicated process involving Schwann cell proliferation and migration, 'bands of Büngner' formation, and newborn nerve extension. In the ECM of peripheral nerves, macromolecules are deposited among cells; these constitute the microenvironment of Schwann cell growth. Such macromolecules include collagen (I, III, IV, V), laminin, fibronectin, chondroitin sulfate proteoglycans (CSPGs), and other nerve factors. Collagen, the main component of ECM, provides structural support and guides newborn neurofilament extension. Laminin, fibronectin, CSPGs, and neurotrophic factors, are promoters or inhibitors, playing different roles in nerve repair after injury. By a chemical decellularization process, acellular nerve allografting eliminates the antigens responsible for allograft rejection and maintains most of the ECM components, which can effectively guide and enhance nerve regeneration. Thus, the composition and features of peripheral nerve ECM suggest its superiority as nerve repair material. This review focuses on the structure, function, and application in the tissue engineering nerve construction of the peripheral nerve ECM components.

  7. Coupling Activity-Based Detection, Target Amplification, Colorimetric and Fluorometric Signal Amplification, for Quantitative Chemosensing of Fluoride Generated from Nerve Agents.

    PubMed

    Sun, Xiaolong; Reuther, James F; Phillips, Scott T; Anslyn, Eric V

    2017-03-17

    The G-class nerve agents, which include sarin, soman, and cyclosarin, react readily with nucleophilic reagents to produce fluoride. Thus, a chemosensing protocol has been designed for these agents that pairs the nucleophilic reactivity of oximates for generating fluoride with an autoinductive target amplification reaction to amplify the quantity of fluoride for facile colorimetric and fluorescent optical quantification. The chemosensing protocol was demonstrated by using the nerve agent surrogate diisopropyl fluorophosphate (DFP) and benzaldoxime as the nucleophile. Autoinductive fluoride amplification responds to fluoride released from DFP by amplifying the fluoride concentration and a yellow reporter molecule. The reporter is a conjugated oligomer with a nominal repeating unit that originates from 4-aminobenzaldehyde. Exposure of the amplified fluoride to a fluoride-specific ratiometric fluorescent reporter provides a fluorescent readout, in which three fluorophores are generated per fluoride. Both colorimetric and fluorescent readouts enable quantitative assays with low micromolar limits of detection for fluoride resulting from DFP. More importantly, this work demonstrates the successful merging of multiple complex reactions for achieving selective, sensitive, and quantitative chemosensing.

  8. Nerve conduction

    MedlinePlus Videos and Cool Tools

    ... peripheral nervous system (PNS). The CNS contains the brain and the spinal cord and the PNS consists ... the axon. Without this insulation, signals from the brain might never reach the outlying muscle groups in ...

  9. Select noxious stimuli induce changes on corneal nerve morphology.

    PubMed

    Hegarty, Deborah M; Hermes, Sam M; Yang, Katherine; Aicher, Sue A

    2017-06-01

    The surface of the cornea contains the highest density of nociceptive nerves of any tissue in the body. These nerves are responsive to a variety of modalities of noxious stimuli and can signal pain even when activated by low threshold stimulation. Injury of corneal nerves can lead to altered nerve morphology, including neuropathic changes which can be associated with chronic pain. Emerging technologies that allow imaging of corneal nerves in vivo are spawning questions regarding the relationship between corneal nerve density, morphology, and function. We tested whether noxious stimulation of the corneal surface can alter nerve morphology and neurochemistry. We used concentrations of menthol, capsaicin, and hypertonic saline that evoked comparable levels of nocifensive eye wipe behaviors when applied to the ocular surface of an awake rat. Animals were sacrificed and corneal nerves were examined using immunocytochemistry and three-dimensional volumetric analyses. We found that menthol and capsaicin both caused a significant reduction in corneal nerve density as detected with β-tubulin immunoreactivity 2 hr after stimulation. Hypertonic saline did not reduce nerve density, but did cause qualitative changes in nerves including enlarged varicosities that were also seen following capsaicin and menthol stimulation. All three types of noxious stimuli caused a depletion of CGRP from corneal nerves, indicating that all modalities of noxious stimuli evoked peptide release. Our findings suggest that studies aimed at understanding the relationship between corneal nerve morphology and chronic disease may also need to consider the effects of acute stimulation on corneal nerve morphology.

  10. Activation of the cAMP-PKA signaling pathway in rat dorsal root ganglion and spinal cord contributes toward induction and maintenance of bone cancer pain.

    PubMed

    Zhu, Gui-Qin; Liu, Su; He, Duan-Duan; Liu, Yue-Peng; Song, Xue-Jun

    2014-08-01

    The objective of this study was to explore the role of cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) signaling in the development of bone cancer pain in rats. Female Sprague-Dawley rats (N=48) were divided randomly into four groups: sham (n=8), tumor cell implantation (TCI) (n=16), TCI+saline (n=8), and TCI+PKA inhibitor (n=16). Bone cancer-induced pain behaviors - thermal hyperalgesia and mechanical allodynia - were tested at postoperative days -3, -1, 1, 3, 5, 7, 10, and 14. A PKA inhibitor, Rp-cAMPS (1 mmol/l/20 μl), was injected intrathecally on postoperative days 3, 4, and 5 (early phase) or 7, 8, and 9 postoperative days (late phase). The expression of PKA mRNA in dorsal root ganglia (DRG) was detected by reverse transcription-PCR. The concentration of cAMP and activity of PKA in DRG and spinal cord were measured by enzyme-linked immunosorbent assay. TCI treatment induced significant pain behaviors, manifested as thermal hyperalgesia and mechanical allodynia. Spinal administration of the PKA inhibitor Rp-cAMPS during the early phase and late phase significantly delayed or reversed, respectively, TCI-induced thermal hyperalgesia and mechanical allodynia. TCI treatment also led to obvious tumor growth and bone destruction. The level of PKA mRNA in the DRG, as well as the concentration of cAMP and the activity of PKA, in both the DRG and spinal cord were significantly increased after TCI treatment (P<0.01). We conclude that the inhibition of the cAMP-PKA signaling pathway may reduce bone cancer pain.

  11. micro RNA 172 (miR172) signals epidermal infection and is expressed in cells primed for bacterial invasion in Lotus japonicus roots and nodules.

    PubMed

    Holt, Dennis B; Gupta, Vikas; Meyer, Dörte; Abel, Nikolaj B; Andersen, Stig U; Stougaard, Jens; Markmann, Katharina

    2015-10-01

    Legumes interact with rhizobial bacteria to form nitrogen-fixing root nodules. Host signalling following mutual recognition ensures a specific response, but is only partially understood. Focusing on the stage of epidermal infection with Mesorhizobium loti, we analysed endogenous small RNAs (sRNAs) of the model legume Lotus japonicus to investigate their involvement in host response regulation. We used Illumina sequencing to annotate the L. japonicus sRNA-ome and isolate infection-responsive sRNAs, followed by candidate-based functional characterization. Sequences from four libraries revealed 219 novel L. japonicus micro RNAs (miRNAs) from 114 newly assigned families, and 76 infection-responsive sRNAs. Unlike infection-associated coding genes such as NODULE INCEPTION (NIN), a micro RNA 172 (miR172) isoform showed strong accumulation in dependency of both Nodulation (Nod) factor and compatible rhizobia. The genetics of miR172 induction support the existence of distinct epidermal and cortical signalling events. MIR172a promoter activity followed a previously unseen pattern preceding infection thread progression in epidermal and cortical cells. Nodule-associated miR172a expression was infection-independent, representing the second of two genetically separable activity waves. The combined data provide a valuable resource for further study, and identify miR172 as an sRNA marking successful epidermal infection. We show that miR172 acts upstream of several APETALA2-type (AP2) transcription factors, and suggest that it has a role in fine-tuning AP2 levels during bacterial symbiosis.

  12. OPT3 is a component of the iron-signaling network between leaves and roots and misregulation of OPT3 leads to an over-accumulation of cadmium in seeds.

    PubMed

    Mendoza-Cózatl, David G; Xie, Qingqing; Akmakjian, Garo Z; Jobe, Timothy O; Patel, Ami; Stacey, Minviluz G; Song, Lihui; Demoin, Dustin Wayne; Jurisson, Silvia S; Stacey, Gary; Schroeder, Julian I

    2014-09-01

    Plants and seeds are the main dietary sources of zinc, iron, manganese, and copper, but are also the main entry point for toxic elements such as cadmium into the food chain. We report here that an Arabidopsis oligopeptide transporter mutant, opt3-2, over-accumulates cadmium (Cd) in seeds and roots but, unexpectedly, under-accumulates Cd in leaves. The cadmium distribution in opt3-2 differs from iron, zinc, and manganese, suggesting a metal-specific mechanism for metal partitioning within the plant. The opt3-2 mutant constitutively up-regulates the Fe/Zn/Cd transporter IRT1 and FRO2 in roots, indicative of an iron-deficiency response. No genetic mutants that impair the shoot-to-root signaling of iron status in leaves have been identified. Interestingly, shoot-specific expression of OPT3 rescues the Cd sensitivity and complements the aberrant expression of IRT1 in opt3-2 roots, suggesting that OPT3 is required to relay the iron status from leaves to roots. OPT3 expression was found in the vasculature with preferential expression in the phloem at the plasma membrane. Using radioisotope experiments, we found that mobilization of Fe from leaves is severely affected in opt3-2, suggesting that Fe mobilization out of leaves is required for proper trace-metal homeostasis. When expressed in yeast, OPT3 does not localize to the plasma membrane, precluding the identification of the OPT3 substrate. Our in planta results show that OPT3 is important for leaf phloem-loading of iron and plays a key role regulating Fe, Zn, and Cd distribution within the plant. Furthermore, ferric chelate reductase activity analyses provide evidence that iron is not the sole signal transferred from leaves to roots in leaf iron status signaling.

  13. OPT3 Is a Component of the Iron-Signaling Network between Leaves and Roots and Misregulation of OPT3 Leads to an Over-Accumulation of Cadmium in Seeds

    PubMed Central

    Mendoza-Cózatl, David G.; Xie, Qingqing; Akmakjian, Garo Z.; Jobe, Timothy O.; Patel, Ami; Stacey, Minviluz G.; Song, Lihui; Demoin, Dustin Wayne; Jurisson, Silvia S.; Stacey, Gary; Schroeder, Julian I.

    2014-01-01

    Plants and seeds are the main dietary sources of zinc, iron, manganese, and copper, but are also the main entry point for toxic elements such as cadmium into the food chain. We report here that an Arabidopsis oligopeptide transporter mutant, opt3-2, over-accumulates cadmium (Cd) in seeds and roots but, unexpectedly, under-accumulates Cd in leaves. The cadmium distribution in opt3-2 differs from iron, zinc, and manganese, suggesting a metal-specific mechanism for metal partitioning within the plant. The opt3-2 mutant constitutively up-regulates the Fe/Zn/Cd transporter IRT1 and FRO2 in roots, indicative of an iron-deficiency response. No genetic mutants that impair the shoot-to-root signaling of iron status in leaves have been identified. Interestingly, shoot-specific expression of OPT3 rescues the Cd sensitivity and complements the aberrant expression of IRT1 in opt3-2 roots, suggesting that OPT3 is required to relay the iron status from leaves to roots. OPT3 expression was found in the vasculature with preferential expression in the phloem at the plasma membrane. Using radioisotope experiments, we found that mobilization of Fe from leaves is severely affected in opt3-2, suggesting that Fe mobilization out of leaves is required for proper trace-metal homeostasis. When expressed in yeast, OPT3 does not localize to the plasma membrane, precluding the identification of the OPT3 substrate. Our in planta results show that OPT3 is important for leaf phloem-loading of iron and plays a key role regulating Fe, Zn, and Cd distribution within the plant. Furthermore, ferric chelate reductase activity analyses provide evidence that iron is not the sole signal transferred from leaves to roots in leaf iron status signaling. PMID:24880337

  14. Secretory leukocyte protease inhibitor reverses inhibition by CNS myelin, promotes regeneration in the optic nerve, and suppresses expression of the TGFβ signaling protein Smad2

    PubMed Central

    Hannila, Sari S.; Siddiq, Mustafa M.; Carmel, Jason B.; Hou, Jianwei; Chaudhry, Nagarathnamma; Bradley, Peter M.J.; Hilaire, Melissa; Richman, Erica L.; Hart, Ronald P.; Filbin, Marie T.

    2013-01-01

    Following CNS injury, axonal regeneration is limited by myelin-associated inhibitors; however, this can be overcome through elevation of intracellular cyclic AMP, as occurs with conditioning lesions of the sciatic nerve. This study reports that expression of secretory leukocyte protease inhibitor (SLPI) is strongly upregulated in response to elevation of cyclic AMP. We also show that SLPI can overcome inhibition by CNS myelin and significantly enhance regeneration of transected retinal ganglion cell axons in rats. Furthermore, regeneration of dorsal column axons does not occur after a conditioning lesion in SLPI null mutant mice, indicating that expression of SLPI is required for the conditioning lesion effect. Mechanistically, we demonstrate that SLPI localizes to the nuclei of neurons, binds to the Smad2 promoter, and reduces levels of Smad2 protein. Adenoviral overexpression of Smad2 also blocked SLPI-induced axonal regeneration. SLPI and Smad2 may therefore represent new targets for therapeutic intervention in CNS injury. PMID:23516280

  15. Chronic vagus nerve stimulation attenuates vascular endothelial impairments and reduces the inflammatory profile via inhibition of the NF-κB signaling pathway in ovariectomized rats.

    PubMed

    Li, Ping; Liu, Huaipu; Sun, Peng; Wang, Xiaoyu; Wang, Chen; Wang, Ling; Wang, Tinghuai

    2016-02-01

    Vagus nerve stimulation (VNS), a method for activating cholinergic anti-inflammatory pathways, could suppress endothelial activation and minimize tissue injury during inflammation. The aim of this study was to investigate the effects of chronic VNS on endothelial impairments and the inflammatory profile in ovariectomized (OVX) rats. Sprague-Dawley rats (7-8 months old) were randomly assigned to the following four groups: sham-OVX, OVX, OVX+sham-VNS, and OVX+VNS. Throughout the experimental period, the OVX+VNS group received VNS for 3h (20.0 Hz, 1.0 mA, and 10.00 ms pulse width) at the same time every other day. After 12 weeks of VNS, blood samples and thoracic aortas were collected for further analyses. Light microscopy and electron microscopy analyses showed that chronic VNS prevented endothelial swelling, desquamation and even necrosis in the OVX rats. In addition, it obviously improved endothelial function in the OVX rats by restoring the endothelial nitric oxide synthase (e-NOS) and serum endothelin-1 level. Increased expression of cell adhesion molecules (VCAM-1, ICAM-1 and E-selectin) in the thoracic aortas and increases in the levels of circulating cytokines (TNF-α, IL-6, MCP-1, and CINC/KC) were also observed in the OVX rats. Chronic VNS significantly restored these detrimental changes partly by increasing the ACh concentrations in vascular walls and blocking NF-κB pathway activity. The results of this in vivo study have shown that the administration of chronic VNS during, in the early stage of estrogen deficiency, protects OVX rats from endothelial impairments and the inflammatory profile. These findings indicate that activation of the vagus nerve could be a promising supplemental therapy for reducing the risks of suffering from further CVDs in postmenopausal women.

  16. Pain Does Not Follow the Boxcar Model: Temporal Dynamics of the BOLD FMRI Signal during Constant Current Painful Electric Nerve Stimulation

    PubMed Central

    Ibinson, JW; Vogt, KM

    2013-01-01

    The temporal dynamics of the blood oxygen level dependent (BOLD) signal, especially for painful stimulations, is not completely understood. In this study, the BOLD signal response to a long painful electrical stimulation (a continuous painful stimulation of 2 minutes) is directly compared to that of a short painful stimulation (four 30-s periods of painful stimulation interleaved with 30-s rest) in an effort to further probe the relationship between the temporal dynamics of the BOLD signal during constant intensity pain stimulation. Time course analysis showed that both stimulation protocols produced three similarly timed peaks in both data sets, suggesting an early and delayed BOLD response to painful stimulation initiation, and a response related to stimulus termination. Despite the continuous stimulation, the BOLD signal returned to baseline in the two-minute task. Even with this signal discrepancy, however, the activation maps of the two pain tasks differed only slightly, suggesting that the bulk of the activation is determined by the sharp rise in BOLD signal with stimulus onset. These findings imply that the BOLD signal response time course is not directly reflective of pain perception. PMID:24135433

  17. α-Synuclein pathology in the cranial and spinal nerves in Lewy body disease.

    PubMed

    Nakamura, Keiko; Mori, Fumiaki; Tanji, Kunikazu; Miki, Yasuo; Toyoshima, Yasuko; Kakita, Akiyoshi; Takahashi, Hitoshi; Yamada, Masahito; Wakabayashi, Koichi

    2016-06-01

    Accumulation of phosphorylated α-synuclein in neurons and glial cells is a histological hallmark of Lewy body disease (LBD) and multiple system atrophy (MSA). Recently, filamentous aggregations of phosphorylated α-synuclein have been reported in the cytoplasm of Schwann cells, but not in axons, in the peripheral nervous system in MSA, mainly in the cranial and spinal nerve roots. Here we conducted an immunohistochemical investigation of the cranial and spinal nerves and dorsal root ganglia of patients with LBD. Lewy axons were found in the oculomotor, trigeminal and glossopharyngeal-vagus nerves, but not in the hypoglossal nerve. The glossopharyngeal-vagus nerves were most frequently affected, with involvement in all of 20 subjects. In the spinal nerve roots, Lewy axons were found in all of the cases examined. Lewy axons in the anterior nerves were more frequent and numerous in the thoracic and sacral segments than in the cervical and lumbar segments. On the other hand, axonal lesions in the posterior spinal nerve roots appeared to increase along a cervical-to-sacral gradient. Although Schwann cell cytoplasmic inclusions were found in the spinal nerves, they were only minimal. In the dorsal root ganglia, axonal lesions were seldom evident. These findings indicate that α-synuclein pathology in the peripheral nerves is axonal-predominant in LBD, whereas it is restricted to glial cells in MSA.

  18. Local erythropoietin signaling enhances regeneration in peripheral axons.

    PubMed

    Toth, C; Martinez, J A; Liu, W Q; Diggle, J; Guo, G F; Ramji, N; Mi, R; Hoke, A; Zochodne, D W

    2008-06-23

    Erythropoietin (EPO) and its receptor (EPO-R), mediate neuroprotection from axonopathy and apoptosis in the peripheral nervous system (PNS). We examined the impact and potential mechanisms of local EPO signaling on regenerating PNS axons in vivo and in vitro. As a consequence of injury, peripheral nerve axons and DRG neurons have a marked increase in the expression of EPO and EPO-R. Local delivery of EPO via conduit over 2 weeks to rat sciatic nerve following crush injury increased the density and maturity of regenerating myelinated axons growing distally from the crush site. In addition, EPO also rescued retrograde degeneration and atrophy of axons. EPO substantially increased the density and intensity of calcitonin gene-related peptide (CGRP) expression within outgrowing axons. Behavioral improvements in sensorimotor function also occurred in rats exposed to near nerve EPO delivery. EPO delivery led to decreased nuclear factor kappaB (NFkB) activation but increased phosphorylation of Akt and STAT3 within nerve and dorsal root ganglia neurons indicating rescue from an injury phenotype. Spinal cord explant studies also demonstrated a similar dose-dependent effect of EPO upon motor axonal outgrowth. Local EPO signaling enhances regenerating peripheral nervous system axons in addition to its known neuroprotection. Exogenous EPO may have a therapeutic role in a large number of peripheral nerve diseases through its impact on regeneration.

  19. Nitrogen deficiency as well as phosphorus deficiency in sorghum promotes the production and exudation of 5-deoxystrigol, the host recognition signal for arbuscular mycorrhizal fungi and root parasites.

    PubMed

    Yoneyama, Kaori; Xie, Xiaonan; Kusumoto, Dai; Sekimoto, Hitoshi; Sugimoto, Yukihiro; Takeuchi, Yasutomo; Yoneyama, Koichi

    2007-12-01

    Strigolactones released from plant roots induce hyphal branching of symbiotic arbuscular mycorrhizal (AM) fungi and germination of root parasitic weeds, Striga and Orobanche spp. We already demonstrated that, in red clover plants (Trifolium pratense L.), a host for both AM fungi and the root holoparasitic plant Orobanche minor Sm., reduced supply of phosphorus (P) but not of other elements examined (N, K, Ca, Mg) in the culture medium significantly promoted the secretion of a strigolactone, orobanchol, by the roots of this plant. Here we show that in the case of sorghum [Sorghum bicolor (L.) Moench], a host of both the root hemiparasitic plant Striga hermonthica and AM fungi, N deficiency as well as P deficiency markedly enhanced the secretion of a strigolactone, 5-deoxystrigol. The 5-deoxystrigol content in sorghum root tissues also increased under both N deficiency and P deficiency, comparable to the increase in the root exudates. These results suggest that strigolactones may be rapidly released after their production in the roots. Unlike the situation in the roots, neither N nor P deficiency affected the low content of 5-deoxystrigol in sorghum shoot tissues.

  20. OZONE EXPOSURE INITIATES A SEQUENTIAL SIGNALING CASCADE IN AIRWAYS INVOLVING INTERLEUKIN-1BETA RELEASE, NERVE GROWTH FACTOR SECRETION, AND SUBSTANCE P UPREGULATION

    PubMed Central

    Barker, Joshua S.; Wu, Zhongxin; Hunter, Dawn D.; Dey, Richard D.

    2015-01-01

    Previous studies demonstrated that interleukin-1β (IL-1β) and nerve growth factor (NGF) increase synthesis of substance P (SP) in airway neurons both after ozone (O3) exposure and by direct application. It was postulated that NGF mediates O3-induced IL-1β effects on SP. The current study specifically focused on the influence of O3 on IL-1β, NGF, and SP levels in mice bronchoalveolar lavage fluid (BALF) and whether these mediators may be linked in an inflammatory-neuronal cascade in vivo. The findings showed that in vivo O3 exposure induced an increase of all three proteins in mouse BALF and that O3-induced elevations in both NGF and SP are mediated by the inflammatory cytokine IL-1β. Further, inhibition of NGF reduced O3 induced increases of SP in both the lung BALF and lung tissue, demonstrating NGF serves as a mediator of IL-1β effects on SP. These data indicate that IL-1β is an early mediator of O3-induced rise in NGF and subsequent SP release in mice in vivo. PMID:25734767

  1. Differences between winter oilseed rape (Brassica napus L.) cultivars in nitrogen starvation-induced leaf senescence are governed by leaf-inherent rather than root-derived signals.

    PubMed

    Koeslin-Findeklee, Fabian; Becker, Martin A; van der Graaff, Eric; Roitsch, Thomas; Horst, Walter J

    2015-07-01

    Nitrogen (N) efficiency of winter oilseed rape (Brassica napus L.) line-cultivars (cvs.), defined as high grain yield under N limitation, has been primarily attributed to maintained N uptake during reproductive growth (N uptake efficiency) in combination with delayed senescence of the older leaves accompanied with maintained photosynthetic capacity (functional stay-green). However, it is not clear whether genotypic variation in N starvation-induced leaf senescence is due to leaf-inherent factors and/or governed by root-mediated signals. Therefore, the N-efficient and stay-green cvs. NPZ-1 and Apex were reciprocally grafted with the N-inefficient and early-senescing cvs. NPZ-2 and Capitol, respectively and grown in hydroponics. The senescence status of older leaves after 12 days of N starvation assessed by SPAD, photosynthesis and the expression of the senescence-specific cysteine protease gene SAG12-1 revealed that the stay-green phenotype of the cvs. NPZ-1 and Apex under N starvation was primarily under the control of leaf-inherent factors. The same four cultivars were submitted to N starvation for up to 12 days in a time-course experiment. The specific leaf contents of biologically active and inactive cytokinins (CKs) and the expression of genes involved in CK homeostasis revealed that under N starvation leaves of early-senescing cultivars were characterized by inactivation of biologically active CKs, whereas in stay-green cultivars synthesis, activation, binding of and response to biologically active CKs were favoured. These results suggest that the homeostasis of biologically active CKs was the predominant leaf-inherent factor for cultivar differences in N starvation-induced leaf senescence and thus N efficiency.

  2. Differences between winter oilseed rape (Brassica napus L.) cultivars in nitrogen starvation-induced leaf senescence are governed by leaf-inherent rather than root-derived signals

    PubMed Central

    Koeslin-Findeklee, Fabian; Becker, Martin A.; van der Graaff, Eric; Roitsch, Thomas; Horst, Walter J.

    2015-01-01

    Nitrogen (N) efficiency of winter oilseed rape (Brassica napus L.) line-cultivars (cvs.), defined as high grain yield under N limitation, has been primarily attributed to maintained N uptake during reproductive growth (N uptake efficiency) in combination with delayed senescence of the older leaves accompanied with maintained photosynthetic capacity (functional stay-green). However, it is not clear whether genotypic variation in N starvation-induced leaf senescence is due to leaf-inherent factors and/or governed by root-mediated signals. Therefore, the N-efficient and stay-green cvs. NPZ-1 and Apex were reciprocally grafted with the N-inefficient and early-senescing cvs. NPZ-2 and Capitol, respectively and grown in hydroponics. The senescence status of older leaves after 12 days of N starvation assessed by SPAD, photosynthesis and the expression of the senescence-specific cysteine protease gene SAG12-1 revealed that the stay-green phenotype of the cvs. NPZ-1 and Apex under N starvation was primarily under the control of leaf-inherent factors. The same four cultivars were submitted to N starvation for up to 12 days in a time-course experiment. The specific leaf contents of biologically active and inactive cytokinins (CKs) and the expression of genes involved in CK homeostasis revealed that under N starvation leaves of early-senescing cultivars were characterized by inactivation of biologically active CKs, whereas in stay-green cultivars synthesis, activation, binding of and response to biologically active CKs were favoured. These results suggest that the homeostasis of biologically active CKs was the predominant leaf-inherent factor for cultivar differences in N starvation-induced leaf senescence and thus N efficiency. PMID:25944925

  3. Nerve Transfer in Delayed Obstetrical Palsy Repair

    PubMed Central

    Sénès, Filippo; Catena, Nunzio; Sénès, Jacopo

    2015-01-01

    Objective  When root avulsions are detected in children suffering from obstetrical brachial plexus palsy (OBPP), neurotization procedures of different nerve trunks are commonly applied in primary brachial plexus repair, to connect distally the nerves of the upper limbs using healthy nerve structures. This article aims to outline our experience of neurotization procedures in OBPP, which involves nerve transfers in the event of delayed repair, when a primary repair has not occurred or has failed. In addition, we propose the opportunity for late repair, focusing on extending the time limit for nerve surgery beyond that which is usually recommended. Although, according to different authors, the time limit is still unclear, it is generally estimated that nerve repair should take place within the first months of life. In fact, microsurgical repair of OBPP is the technique of choice for young children with the condition who would otherwise have an unfavorable outcome. However, in certain cases the recovery process is not clearly defined so not all the patients are direct candidates for primary nerve surgery. Methods  In the period spanning January 2005 through January 2011, among a group of 105 patients suffering from OBPP, ranging from 1 month to 7 years of age, the authors have identified a group of 32 partially recovered patients. All these patients underwent selective neurotization surgery, which was performed in a period ranging from 5 months to 6.6 years of age. Results  Late neurotization of muscular groups achieved considerable functional recovery in these patients, who presented with reduced motor function during early childhood. The said patients, with the exception of five, would initially have avoided surgery because they had not met the criteria for nerve surgery. Conclusion  We have concluded that the execution of late nerve surgical procedures can be effective in children affected by OBPP. PMID:27917233

  4. Biomaterials and strategies for nerve regeneration.

    PubMed

    Huang, Yi-Cheng; Huang, Yi-You

    2006-07-01

    Nerve regeneration is a complex biological phenomenon. Once the nervous system is impaired, its recovery is difficult and malfunctions in other parts of the body may occur because mature neurons do not undergo cell division. To increase the prospects of axonal regeneration and functional recovery, researches have focused on designing "nerve guidance channels" or "nerve conduits." When developing ideal tissue-engineered nerve conduits, several components come to mind. They include a biodegradable and porous channel wall, the ability to deliver bioactive growth factors, incorporation of support cells, an internal oriented matrix to support cell migration, intraluminal channels to mimic the structure of nerve fascicles, and electrical activities. This article reviews the factors that are critical for nerve repair, and the advanced technologies that are explored to fabricate nerve conduits. To more accurately mimic natural repair in the body, recent studies have focused on the use of various advanced approaches to create ideal nerve conduits that combine multiple stimuli in an effort to better mimic the complex signals normally found in the body.

  5. Siatic nerve: beyond the sacral foramen.

    PubMed

    Sanal, Hatice Tuba

    2016-01-01

    Sciatica may result from pathologies affecting the nerve both in its intraspinal and extraspinal course. In daily routine, the vast majority of cases are caused by herniation of the lumbar discs compressing the neural roots. Extraspinal causes of sciatic pain are usually underestimated and the imaging study may be completed after reporting the lumbar MRIs. However, early diagnosis of the exact etiology of sciatica is paramount for both relieving the symptoms and preventing any additional neurologic injury. In this pictorial assay, some relatively rare causes of sciatic neuralgia along the route of the sciatic nerve after leaving the sacral foramen will be displayed.

  6. Sciatic nerve: beyond the sacral foramen

    PubMed Central

    Sanal, Hatice Tuba

    2016-01-01

    Sciatica may result from pathologies affecting the nerve both in its intraspinal and extraspinal course. In daily routine, the vast majority of cases are caused by herniation of the lumbar discs compressing the neural roots. Extraspinal causes of sciatic pain are usually underestimated and the imaging study may be completed after reporting the lumbar MRIs. However, early diagnosis of the exact etiology of sciatica is paramount for both relieving the symptoms and preventing any additional neurologic injury. In this pictorial assay, some relatively rare causes of sciatic neuralgia along the route of the sciatic nerve after leaving the sacral foramen will be displayed. PMID:27670092

  7. Nerve Injuries in Athletes.

    ERIC Educational Resources Information Center

    Collins, Kathryn; And Others

    1988-01-01

    Over a two-year period this study evaluated the condition of 65 athletes with nerve injuries. These injuries represent the spectrum of nerve injuries likely to be encountered in sports medicine clinics. (Author/MT)

  8. Abscisic acid signalling when soil moisture is heterogeneous: decreased photoperiod sap flow from drying roots limits abscisic acid export to the shoots.

    PubMed

    Dodd, Ian C; Egea, Gregorio; Davies, William J

    2008-09-01

    To investigate the contribution of different parts of the root system to total sap flow and leaf xylem abscisic acid (ABA) concentration ([X-ABA](leaf)), individual sunflower (Helianthus annuus L.) shoots were grafted onto the root systems of two plants grown in separate pots and sap flow through each hypocotyl measured below the graft union. During deficit irrigation (DI), both pots received the same irrigation volumes, while during partial root zone drying (PRD) one pot ('wet') was watered and another ('dry') was not. During PRD, once soil water content (theta) decreased below a threshold, the fraction of sap flow from drying roots declined. As theta declined, root xylem ABA concentration increased in both irrigation treatments, and [X-ABA](leaf) increased in DI plants, but [X-ABA](leaf) of PRD plants actually decreased within a certain theta range. A simple model that weighted ABA contributions of wet and dry root systems to [X-ABA](leaf) according to the sap flow from each, better predicted [X-ABA](leaf) of PRD plants than either [X-ABA](dry), [X-ABA](wet) or their mean. Model simulations revealed that [X-ABA](leaf) during PRD exceeded that of DI with moderate soil drying, but continued soil drying (such that sap flow from roots in drying soil ceased) resulted in the opposite effect.

  9. The nerve growth factor alters calreticulin translocation from the endoplasmic reticulum to the cell surface and its signaling pathway in epithelial ovarian cancer cells.

    PubMed

    Vera, Carolina Andrea; Oróstica, Lorena; Gabler, Fernando; Ferreira, Arturo; Selman, Alberto; Vega, Margarita; Romero, Carmen Aurora

    2017-02-28

    Ovarian cancer is the seventh most common cancer among women worldwide, causing approximately 120,000 deaths every year. Immunotherapy, designed to boost the body's natural defenses against cancer, appears to be a promising option against ovarian cancer. Calreticulin (CRT) is an endoplasmic reticulum (ER) resident chaperone that, translocated to the cell membrane after ER stress, allows cancer cells to be recognized by the immune system. The nerve growth factor (NGF) is a pro-angiogenic molecule overexpressed in this cancer. In the present study, we aimed to determine weather NGF has an effect in CRT translocation induced by cytotoxic and ER stress. We treated A2780 ovarian cancer cells with NGF, thapsigargin (Tg), an ER stress inducer and mitoxantrone (Mtx), a chemotherapeutic drug; CRT subcellular localization was analyzed by immunofluorescence followed by confocal microscopy. In order to determine NGF effect on Mtx and Tg-induced CRT translocation from the ER to the cell membrane, cells were preincubated with NGF prior to Mtx or Tg treatment and CRT translocation to the cell surface was determined by flow cytometry. In addition, by western blot analyses, we evaluated proteins associated with the CRT translocation pathway, both in A2780 cells and human ovarian samples. We also measured NGF effect on cell apoptosis induced by Mtx. Our results indicate that Mtx and Tg, but not NGF, induce CRT translocation to the cell membrane. NGF, however, inhibited CRT translocation induced by Mtx, while it had no effect on Tg-induced CRT exposure. NGF also diminished cell death induced by Mtx. NGF effect on CRT translocation could have consequences in immunotherapy, potentially lessening the effectiveness of this type of treatment.

  10. Optic Nerve Pit

    MedlinePlus

    ... Conditions Frequently Asked Questions Español Condiciones Chinese Conditions Optic Nerve Pit What is optic nerve pit? An optic nerve pit is a ... may be seen in both eyes. How is optic pit diagnosed? If the pit is not affecting ...

  11. Inhibition of Brain Mitogen-Activated Protein Kinase Signaling Reduces Central Endoplasmic Reticulum Stress and Inflammation and Sympathetic Nerve Activity in Heart Failure Rats.

    PubMed

    Wei, Shun-Guang; Yu, Yang; Weiss, Robert M; Felder, Robert B

    2016-01-01

    Mitogen-activated protein kinase (MAPK) signaling and endoplasmic reticulum (ER) stress in the brain have been implicated in the pathophysiology of hypertension. This study determined whether ER stress occurs in subfornical organ and hypothalamic paraventricular nucleus in heart failure (HF) and how MAPK signaling interacts with ER stress and other inflammatory mediators. HF rats had significantly higher levels of the ER stress biomarkers (glucose-regulated protein 78, activating transcription factor 6, activating transcription factor 4, X-box binding protein 1, P58(IPK), and C/EBP homologous protein) in subfornical organ and paraventricular nucleus, which were attenuated by a 4-week intracerebroventricular infusion of inhibitors selective for p44/42 MAPK (PD98059), p38 MAPK (SB203580), or c-Jun N-terminal kinase (SP600125). HF rats also had higher mRNA levels of tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, and nuclear factor-κB p65, and a lower mRNA level of IκB-α, in subfornical organ and paraventricular nucleus, compared with SHAM rats, and these indicators of increased inflammation were attenuated in the HF rats treated with the MAPK inhibitors. Plasma norepinephrine level was higher in HF rats than in SHAM rats but was reduced in the HF rats treated with PD98059 and SB203580. A 4-week intracerebroventricular infusion of PD98059 also improved some hemodynamic and anatomic indicators of left ventricular function in HF rats. These data demonstrate that ER stress increases in the subfornical organ and paraventricular nucleus of rats with ischemia-induced HF and that inhibition of brain MAPK signaling reduces brain ER stress and inflammation and decreases sympathetic excitation in HF. An interaction between MAPK signaling and ER stress in cardiovascular regions of the brain may contribute to the development of HF.

  12. Inhibition of brain mitogen-activated protein kinase signaling reduces central endoplasmic reticulum stress and inflammation and sympathetic nerve activity in heart failure rats

    PubMed Central

    Wei, Shun-Guang; Yu, Yang; Weiss, Robert M.; Felder, Robert B.

    2015-01-01

    Mitogen-activated protein kinase (MAPK) signaling and endoplasmic reticulum (ER) stress in the brain have been implicated in the pathophysiological mechanisms in hypertension. The present study determined whether ER stress occurs in subfornical organ (SFO) and hypothalamic paraventricular nucleus (PVN) in heart failure (HF), and how MAPK signaling interacts with ER stress and other inflammatory mediators. HF rats had significantly higher levels of the ER stress biomarkers (GRP78, ATF6, ATF4, XBP-1, P58IPK and CHOP) in SFO and PVN, which were attenuated by a 4-week intracerebroventricular (ICV) infusion of inhibitors selective for p44/42 MAPK (PD98059), p38 MAPK (SB203580) or JNK (SP600125). HF rats also had higher mRNA levels of tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2 and NF-κB p65 and lower mRNA level of IκB-α in SFO and PVN, compared with SHAM rats, and these indicators of increased inflammation were attenuated in the HF rats treated with the MAPK inhibitors. Plasma norepinephrine level was higher in HF than SHAM rats, but was reduced in the HF rats treated with PD98059 and SB203580. A 4-week ICV infusion of PD98059 also improved some hemodynamic and anatomic indicators of left ventricular function in HF rats. These data demonstrate that ER stress increases in the SFO and PVN of rats with ischemia-induced HF, and that inhibition of brain MAPK signaling reduces brain ER stress and inflammation and decreases sympathetic excitation in HF. An interaction between MAPK signaling and ER stress in cardiovascular regions of the brain may contribute to the development of HF. PMID:26573710

  13. Cutting your nerve changes your brain.

    PubMed

    Taylor, Keri S; Anastakis, Dimitri J; Davis, Karen D

    2009-11-01

    Following upper limb peripheral nerve transection and surgical repair, some patients regain good sensorimotor function while others do not. Understanding peripheral and central mechanisms that contribute to recovery may facilitate the development of new therapeutic interventions. Plasticity following peripheral nerve transection has been demonstrated throughout the neuroaxis in animal models of nerve injury. However, the brain changes that occur following peripheral nerve transection and surgical repair in humans have not been examined. Furthermore, the extent to which peripheral nerve regeneration influences functional and structural brain changes has not been characterized. Therefore, we asked whether functional changes are accompanied by grey and/or white matter structural changes and whether these changes relate to sensory recovery? To address these key issues we (i) assessed peripheral nerve regeneration; (ii) measured functional magnetic resonance imaging brain activation (blood oxygen level dependent signal; BOLD) in response to a vibrotactile stimulus; (iii) examined grey and white matter structural brain plasticity; and (iv) correlated sensory recovery measures with grey matter changes in peripheral nerve transection and surgical repair patients. Compared to each patient's healthy contralesional nerve, transected nerves have impaired nerve conduction 1.5 years after transection and repair, conducting with decreased amplitude and increased latency. Compared to healthy controls, peripheral nerve transection and surgical repair patients had altered blood oxygen level dependent signal activity in the contralesional primary and secondary somatosensory cortices, and in a set of brain areas known as the 'task positive network'. In addition, grey matter reductions were identified in several brain areas, including the contralesional primary and secondary somatosensory cortices, in the same areas where blood oxygen level dependent signal reductions were identified

  14. Involvement of MAPK/NF-κB Signaling in the Activation of the Cholinergic Anti-Inflammatory Pathway in Experimental Colitis by Chronic Vagus Nerve Stimulation

    PubMed Central

    Sun, Peng; Zhou, Kewen; Wang, Sheng; Li, Ping; Chen, Sijuan; Lin, Guiping; Zhao, Yan; Wang, Tinghuai

    2013-01-01

    Background Autonomic nervous system dysfunction is implicated in the etiopathogenesis of inflammatory bowel diseases (IBD). Therapies that increase cardiovagal activity, such as Mind-Body interventions, are currently confirmed to be effective in clinical trials in IBD. However, a poor understanding of pathophysiological mechanisms limits the popularization of therapies in clinical practice. The aim of the present study was to explore the mechanisms of these therapies against 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats using a chronic vagus nerve stimulation model in vivo, as well as the lipopolysaccharide (LPS)-induced inflammatory response in human epithelial colorectal adenocarcinoma cells (Caco-2) by acetylcholine in vitro. Methods and Results Colitis was induced in rats with rectal instillation of TNBS, and the effect of chronic VNS (0.25 mA, 20 Hz, 500 ms) on colonic inflammation was evaluated. Inflammatory responses were assessed by disease activity index (DAI), histological scores, myeloperoxidase (MPO) activity, inducible nitric oxide synthase (iNOS), TNF-α and IL-6 production. The expression of Mitogen-activated protein kinases (MAPK) family members, IκB-α, and nuclear NF-κB p65 were studied by immunoblotting. Heart rate variability (HRV) analysis was also applied to assess the sympathetic-vagal balance. DAI, histological scores, MPO activity, iNOS, TNF-α and IL-6 levels were significantly decreased by chronic VNS. Moreover, both VNS and acetylcholine reduced the phosphorylation of MAPKs and prevented the nuclear translocation of NF-κB p65. Methyllycaconitine (MLA) only reversed the inhibitory effect on p-ERK and intranuclear NF-κB p65 expression by ACh in vitro, no significant change was observed in the expression of p-p38 MAPK or p-JNK by MLA. Conclusion Vagal activity modification contributes to the beneficial effects of the cholinergic anti-inflammatory pathway in IBD-related inflamed colonic mucosa based on the activation

  15. Root hydrotropism: an update.

    PubMed

    Cassab, Gladys I; Eapen, Delfeena; Campos, María Eugenia

    2013-01-01

    While water shortage remains the single-most important factor influencing world agriculture, there are very few studies on how plants grow in response to water potential, i.e., hydrotropism. Terrestrial plant roots dwell in the soil, and their ability to grow and explore underground requires many sensors for stimuli such as gravity, humidity gradients, light, mechanical stimulations, temperature, and oxygen. To date, extremely limited information is available on the components of such sensors; however, all of these stimuli are sensed in the root cap. Directional growth of roots is controlled by gravity, which is fixed in direction and intensity. However, other environmental factors, such as water potential gradients, which fluctuate in time, space, direction, and intensity, can act as a signal for modifying the direction of root growth accordingly. Hydrotropism may help roots to obtain water from the soil and at the same time may participate in the establishment of the root system. Current genetic analysis of hydrotropism in Arabidopsis has offered new players, mainly AHR1, NHR1, MIZ1, and MIZ2, which seem to modulate how root caps sense and choose to respond hydrotropically as opposed to other tropic responses. Here we review the mechanism(s) by which these genes and the plant hormones abscisic acid and cytokinins coordinate hydrotropism to counteract the tropic responses to gravitational field, light or touch stimuli. The biological consequence of hydrotropism is also discussed in relation to water stress avoidance.

  16. Activation of rapid signaling pathways and the subsequent transcriptional regulation for the proliferation of breast cancer MCF-7 cells by the treatment with an extract of Glycyrrhiza glabra root.

    PubMed

    Dong, Sijun; Inoue, Akio; Zhu, Yun; Tanji, Masao; Kiyama, Ryoiti

    2007-12-01

    Glycyrrhiza glabra root is one of the common traditional Chinese medicines and used as flavoring and sweetening agents for tobaccos, chewing gums, candies, toothpaste and beverages. While glycyrrhizin is one of the main components in the extract of G. glabra root and has been characterized, the other components have not been well characterized. The mechanism of growth activation of breast cancer MCF-7 cells, including the activation of Erk1/2 and Akt, and the transcriptional regulation of estrogen-responsive genes, was examined by means of sulforhodamine B, luciferase reporter gene, real-time RT-PCR and Western blotting assays after the induction of the cells with the extract of G. glabra root. The extract has similar activity to that induced by 17beta-estradiol (E(2)), although glycyrrhizin did not show such an activity. Moreover, the estrogen receptor alpha-dependent neurite outgrowth induced by the extract was similar to that by E(2), whereas glycyrrhizin had no effect. Furthermore, the expression profile examined by cDNA microarray assay using a set of 120 estrogen-responsive genes, which were related to proliferation, transcription, transport, enzymes and signaling, showed a statistically significant correlation (R=0.47, P<0.0001) between the profiles for E(2) and the extract. However, the expression profile for glycyrrhizin was different from that of the extract and E(2). The results indicate that rapid signaling pathways, including Erk1/2 and Akt, and the subsequent transcriptional regulation are involved in the proliferation of MCF-7 cells induced by the extract of G. glabra root. Furthermore, the extract had estrogenic activity and a distinguishable profile of gene expression, suggesting the presence of potentially useful components other than glycyrrhizin in G. glabra root for hormone and anti-cancer therapies.

  17. Nerve growth factor released from a novel PLGA nerve conduit can improve axon growth

    NASA Astrophysics Data System (ADS)

    Lin, Keng-Min; Shea, Jill; Gale, Bruce K.; Sant, Himanshu; Larrabee, Patti; Agarwal, Jay

    2016-04-01

    Nerve injury can occur due to penetrating wounds, compression, traumatic stretch, and cold exposure. Despite prompt repair, outcomes are dismal. In an attempt to help resolve this challenge, in this work, a poly-lactic-co-glycolic acid (PLGA) nerve conduit with associated biodegradable drug reservoir was designed, fabricated, and tested. Unlike current nerve conduits, this device is capable of fitting various clinical scenarios by delivering different drugs without reengineering the whole system. To demonstrate the potential of this device for nerve repair, a series of experiments were performed using nerve growth factor (NGF). First, an NGF dosage curve was developed to determine the minimum NGF concentration for optimal axonal outgrowth on chick dorsal root ganglia (DRG) cells. Next, PLGA devices loaded with NGF were evaluated for sustained drug release and axon growth enhancement with the released drug. A 20 d in vitro release test was conducted and the nerve conduit showed the ability to meet and maintain the minimum NGF requirement determined previously. Bioactivity assays of the released NGF showed that drug released from the device between the 15th and 20th day could still promote axon growth (76.6-95.7 μm) in chick DRG cells, which is in the range of maximum growth. These novel drug delivery conduits show the ability to deliver NGF at a dosage that efficiently promotes ex vivo axon growth and have the potential for in vivo application to help bridge peripheral nerve gaps.

  18. Rhomboid nerve transfer to the suprascapular nerve for shoulder reanimation in brachial plexus palsy: A clinical report.

    PubMed

    Goubier, J-N; Teboul, F

    2016-10-01

    Recovery of shoulder function is a real challenge in cases of partial brachial plexus palsy. Currently, in C5-C6 root injuries, transfer of the long head of the triceps brachii branch is done to revive the deltoid muscle. Spinal accessory nerve transfer is typically used for reanimation of the suprascapular nerve. We propose an alternative technique in which the nerve of the rhomboid muscles is transferred to the suprascapular nerve. A 33-year-old male patient with a C5-C6 brachial plexus injury with shoulder and elbow flexion palsy underwent surgery 7 months after the injury. The rhomboid nerve was transferred to the suprascapular nerve and the long head of the triceps brachii branch to the axillary nerve for shoulder reanimation. A double transfer of fascicles was performed, from the ulnar and median nerves to the biceps brachii branch and brachialis branch, respectively, for elbow flexion. At 14 months' follow-up, elbow flexion was rated M4. Shoulder elevation was 85 degrees and rated M4, and external rotation was 80 degrees and rated M4. After performing a cadaver study showing that transfer of the rhomboid nerve to the suprascapular nerve is technically possible, here we report and discuss the clinical outcomes of this new transfer technique.

  19. Tumor necrosis factor-α inhibits angiotensin II receptor type 1 expression in dorsal root ganglion neurons via β-catenin signaling.

    PubMed

    Yang, Y; Wu, H; Yan, J-Q; Song, Z-B; Guo, Q-L

    2013-09-17

    Both tumor necrosis factor (TNF)-α and the angiotensin (Ang) II/angiotensin II receptor type 1 (AT1) axis play important roles in neuropathic pain and nociception. In the present study, we explored the interaction between the two systems by examining the mutual effects between TNF-α and the Ang II/AT1 receptor axis in dorsal root ganglion (DRG) neurons. Rat DRG neurons were treated with TNF-α in different concentrations for different lengths of time in the presence or absence of transcription inhibitor actinomycin D, TNF receptor 1 (TNFR1) inhibitor SPD304, β-catenin signaling inhibitor CCT031374, or different kinase inhibitors. TNF-α decreased the AT1 receptor mRNA level as well as the AT1a receptor promoter activity in a dose-dependent manner within 30 h, which led to dose-dependent inhibition of Ang II-binding AT1 receptor level on the cell membrane. Actinomycin D (1 mg/ml), SPD304 (50 μM), p38 mitogen-activated protein kinase (MAPK) inhibitor PD169316 (25 μM), and CCT031374 (50 μM) completely abolished the inhibitory effect of TNF-α on AT1 receptor expression. TNF-α dose-dependently increased soluble β-catenin and phosphorylated GSK-3β levels, which was blocked by SPD304 and PD169316. In DRG neurons treated with AT2 receptor agonist CGP421140, or Ang II with or without AT1 receptor antagonist losartan or AT2 receptor antagonist PD123319 for 30 h, we found that Ang II and Ang II+PD123319 significantly decreased TNF-α expression, whereas CPG421140 and Ang II+losartan increased TNF-α expression. In conclusion, we demonstrate that TNF-α inhibits AT1 receptor expression at the transcription level via TNFR1 in rat DRG neurons by increasing the soluble β-catenin level through the p38 MAPK/GSK-3β pathway. In addition, Ang II appears to inhibit and induce TNF-α expression via the AT1 receptor and the AT2 receptor in DRG neurons, respectively. This is the first evidence of crosstalk between TNF-α and the Ang II/AT receptor axis in DRG neurons.

  20. Endoplasmic reticulum stress increases brain MAPK signaling, inflammation and renin-angiotensin system activity and sympathetic nerve activity in heart failure.

    PubMed

    Wei, Shun-Guang; Yu, Yang; Weiss, Robert M; Felder, Robert B

    2016-10-01

    We previously reported that endoplasmic reticulum (ER) stress is induced in the subfornical organ (SFO) and the hypothalamic paraventricular nucleus (PVN) of heart failure (HF) rats and is reduced by inhibition of mitogen-activated protein kinase (MAPK) signaling. The present study further examined the relationship between brain MAPK signaling, ER stress, and sympathetic excitation in HF. Sham-operated (Sham) and HF rats received a 4-wk intracerebroventricular (ICV) infusion of vehicle (Veh) or the ER stress inhibitor tauroursodeoxycholic acid (TUDCA, 10 μg/day). Lower mRNA levels of the ER stress biomarkers GRP78, ATF6, ATF4, and XBP-1s in the SFO and PVN of TUDCA-treated HF rats validated the efficacy of the TUDCA dose. The elevated levels of phosphorylated p44/42 and p38 MAPK in SFO and PVN of Veh-treated HF rats, compared with Sham rats, were significantly reduced in TUDCA-treated HF rats as shown by Western blot and immunofluorescent staining. Plasma norepinephrine levels were higher in Veh-treated HF rats, compared with Veh-treated Sham rats, and were significantly lower in the TUDCA-treated HF rats. TUDCA-treated HF rats also had lower mRNA levels for angiotensin converting enzyme, angiotensin II type 1 receptor, tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, and NF-κB p65, and a higher mRNA level of IκB-α, in the SFO and PVN than Veh-treated HF rats. These data suggest that ER stress contributes to the augmented sympathetic activity in HF by inducing MAPK signaling, thereby promoting inflammation and renin-angiotensin system activity in key cardiovascular regulatory regions of the brain.

  1. Optic Nerve Elongation

    PubMed Central

    Alvi, Aijaz; Janecka, Ivo P.; Kapadia, Silloo; Johnson, Bruce L.; McVay, William

    1996-01-01

    The length of the optic nerves is a reflection of normal postnatal cranio-orbital development. Unilateral elongation of an optic nerve has been observed in two patients with orbital and skull base neoplasms. In the first case as compared to the patient's opposite, normal optic nerve, an elongated length of the involved optic nerve of 45 mm was present. The involved optic nerve in the second patient was 10 mm longer than the normal opposite optic nerve. The visual and extraocular function was preserved in the second patient. The first patient had only light perception in the affected eye. In this paper, the embryology, anatomy, and physiology of the optic nerve and its mechanisms of stretch and repair are discussed. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7Figure 8Figure 9Figure 10Figure 11Figure 13 PMID:17170975

  2. Morphometric analysis of root shape.

    PubMed

    Grabov, A; Ashley, M K; Rigas, S; Hatzopoulos, P; Dolan, L; Vicente-Agullo, F

    2005-02-01

    Alterations in the root shape in plant mutants indicate defects in hormonal signalling, transport and cytoskeleton function. To quantify the root shape, we introduced novel parameters designated vertical growth index (VGI) and horizontal growth index (HGI). VGI was defined as a ratio between the root tip ordinate and the root length. HGI was the ratio between the root tip abscissa and the root length. To assess the applicability of VGI and HGI for quantification of root shape, we analysed root development in agravitropic Arabidopsis mutants. Statistical analysis indicated that VGI is a sensitive morphometric parameter enabling detection of weak gravitropic defects. VGI dynamics were qualitatively similar in auxin-transport mutants aux1, pin2 and trh1, but different in the auxin-signalling mutant axr2. Analysis of VGI and HGI of roots grown on tilted plates showed that the trh1 mutation affected downstream cellular responses rather than perception of the gravitropic stimulus. All these tests indicate that the VGI and HGI analysis is a versatile and sensitive method for the study of root morphology.

  3. Assessment of nerve morphology in nerve activation during electrical stimulation

    NASA Astrophysics Data System (ADS)

    Gomez-Tames, Jose; Yu, Wenwei

    2013-10-01

    The distance between nerve and stimulation electrode is fundamental for nerve activation in Transcutaneous Electrical Stimulation (TES). However, it is not clear the need to have an approximate representation of the morphology of peripheral nerves in simulation models and its influence in the nerve activation. In this work, depth and curvature of a nerve are investigated around the middle thigh. As preliminary result, the curvature of the nerve helps to reduce the simulation amplitude necessary for nerve activation from far field stimulation.

  4. The distribution of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) in the medulla oblongata, spinal cord, cranial and spinal nerves of frog, Microhyla ornata.

    PubMed

    Jadhao, Arun G; Biswas, Saikat P; Bhoyar, Rahul C; Pinelli, Claudia

    2017-04-01

    Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) enzymatic activity has been reported in few amphibian species. In this study, we report its unusual localization in the medulla oblongata, spinal cord, cranial nerves, spinal nerves, and ganglions of the frog, Microhyla ornata. In the rhombencephalon, at the level of facial and vagus nerves, the NADPH-d labeling was noted in the nucleus of the abducent and facial nerves, dorsal nucleus of the vestibulocochlear nerve, the nucleus of hypoglossus nerve, dorsal and lateral column nucleus, the nucleus of the solitary tract, the dorsal field of spinal grey, the lateral and medial motor fields of spinal grey and radix ventralis and dorsalis (2-10). Many ependymal cells around the lining of the fourth ventricle, both facial and vagus nerves and dorsal root ganglion, were intensely labeled with NADPH-d. Most strikingly the NADPH-d activity was seen in small and large sized motoneurons in both medial and lateral motor neuron columns on the right and left sides of the brain. This is the largest stained group observed from the caudal rhombencephalon up to the level of radix dorsalis 10 in the spinal cord. The neurons were either oval or elongated in shape with long processes and showed significant variation in the nuclear and cellular diameter. A massive NADPH-d activity in the medulla oblongata, spinal cord, and spinal nerves implied an important role of this enzyme in the neuronal signaling as well as in the modulation of motor functions in the peripheral nervous systems of the amphibians.

  5. Pleiotrophin and peripheral nerve injury.

    PubMed

    Jin, Li; Jianghai, Chen; Juan, Liu; Hao, Kang

    2009-10-01

    The proto-oncogene pleiotrophin, discovered in 1989, was considered as a multifunctional growth factor, which played an important role in tumor occurrence, development, and central nervous system. The latest research showed that pleiotrophin signal pathway probably participated in neural repair after peripheral nerve injury, especially in the following critical points, such as the protection of spinal cord neuron, the promotion of the speed of neuron axon regeneration, the guidance of neuron axon regeneration, skeleton muscle reinnervation, and so on. It potentially plays a key role in the guidance of neural axon regeneration in peripheral nervous system and muscle reinnervation. With the deepening of related researches, pleiotrophin gene would become a controllable target for improving the repairing effect of peripheral nerve injury and reconstruction of the neuromuscular junction.

  6. Enhancement of Peripheral Nerve Regrowth by the Purine Nucleoside Analog and Cell Cycle Inhibitor, Roscovitine

    PubMed Central

    Law, Vincent; Dong, Sophie; Rosales, Jesusa L.; Jeong, Myung-Yung; Zochodne, Douglas; Lee, Ki-Young

    2016-01-01

    Peripheral nerve regeneration is a slow process that can be associated with limited outcomes and thus a search for novel and effective therapy for peripheral nerve injury and disease is crucial. Here, we found that roscovitine, a synthetic purine nucleoside analog, enhances neurite outgrowth in neuronal-like PC12 cells. Furthermore, ex vivo analysis of pre-injured adult rat dorsal root ganglion (DRG) neurons showed that roscovitine enhances neurite regrowth in these cells. Likewise, in vivo transected sciatic nerves in rats locally perfused with roscovitine had augmented repopulation of new myelinated axons beyond the transection zone. By mass spectrometry, we found that roscovitine interacts with tubulin and actin. It interacts directly with tubulin and causes a dose-dependent induction of tubulin polymerization as well as enhances Guanosine-5′-triphosphate (GTP)-dependent tubulin polymerization. Conversely, roscovitine interacts indirectly with actin and counteracts the inhibitory effect of cyclin-dependent kinases 5 (Cdk5) on Actin-Related Proteins 2/3 (Arp2/3)-dependent actin polymerization, and thus, causes actin polymerization. Moreover, in the presence of neurotrophic factors such as nerve growth factor (NGF), roscovitine-enhanced neurite outgrowth is mediated by increased activation of the extracellular signal-regulated kinases 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) pathways. Since microtubule and F-actin dynamics are critical for axonal regrowth, the ability of roscovitine to activate the ERK1/2 and p38 MAPK pathways and support polymerization of tubulin and actin indicate a major role for this purine nucleoside analog in the promotion of axonal regeneration. Together, our findings demonstrate a therapeutic potential for the purine nucleoside analog, roscovitine, in peripheral nerve injury. PMID:27799897

  7. Rehabilitation, Using Guided Cerebral Plasticity, of a Brachial Plexus Injury Treated with Intercostal and Phrenic Nerve Transfers

    PubMed Central

    Dahlin, Lars B.; Andersson, Gert; Backman, Clas; Svensson, Hampus; Björkman, Anders

    2017-01-01

    Recovery after surgical reconstruction of a brachial plexus injury using nerve grafting and nerve transfer procedures is a function of peripheral nerve regeneration and cerebral reorganization. A 15-year-old boy, with traumatic avulsion of nerve roots C5–C7 and a non-rupture of C8–T1, was operated 3 weeks after the injury with nerve transfers: (a) terminal part of the accessory nerve to the suprascapular nerve, (b) the second and third intercostal nerves to the axillary nerve, and (c) the fourth to sixth intercostal nerves to the musculocutaneous nerve. A second operation—free contralateral gracilis muscle transfer directly innervated by the phrenic nerve—was done after 2 years due to insufficient recovery of the biceps muscle function. One year later, electromyography showed activation of the biceps muscle essentially with coughing through the intercostal nerves, and of the transferred gracilis muscle by deep breathing through the phrenic nerve. Voluntary flexion of the elbow elicited clear activity in the biceps/gracilis muscles with decreasing activity in intercostal muscles distal to the transferred intercostal nerves (i.e., corresponding to eighth intercostal), indicating cerebral plasticity, where neural control of elbow flexion is gradually separated from control of breathing. To restore voluntary elbow function after nerve transfers, the rehabilitation of patients operated with intercostal nerve transfers should concentrate on transferring coughing function, while patients with phrenic nerve transfers should focus on transferring deep breathing function. PMID:28316590

  8. Comparison of the fastest regenerating motor and sensory myelinated axons in the same peripheral nerve.

    PubMed

    Moldovan, Mihai; Sørensen, Jesper; Krarup, Christian

    2006-09-01

    Functional outcome after peripheral nerve regeneration is often poor, particularly involving nerve injuries far from their targets. Comparison of sensory and motor axon regeneration before target reinnervation is not possible in the clinical setting, and previous experimental studies addressing the question of differences in growth rates of different nerve fibre populations led to conflicting results. We developed an animal model to compare growth and maturation of the fastest growing sensory and motor fibres within the same mixed nerve after Wallerian degeneration. Regeneration of cat tibial nerve after crush (n = 13) and section (n = 7) was monitored for up to 140 days, using implanted cuff electrodes placed around the sciatic and tibial nerves and wire electrodes at plantar muscles. To distinguish between sensory and motor fibres, recordings were carried out from L6-S2 spinal roots using cuff electrodes. The timing of laminectomy was based on the presence of regenerating fibres along the nerve within the tibial cuff. Stimulation of unlesioned tibial nerves (n = 6) evoked the largest motor response in S1 ventral root and the largest sensory response in L7 dorsal root. Growth rates were compared by mapping the regenerating nerve fibres within the tibial nerve cuff to all ventral or dorsal roots and, regardless of the lesion type, the fastest growth was similar in sensory and motor fibres. Maturation was assessed as recovery of the maximum motor and sensory conduction velocities (CVs) within the tibial nerve cuff. Throughout the observation period the CV was approximately 14% faster in regenerated sensory fibres than in motor fibres in accordance with the difference observed in control nerves. Recovery of amplitude was only partial after section, whereas the root distribution pattern was restored. Our data suggest that the fastest growth and maturation rates that can be achieved during regeneration are similar for motor and sensory myelinated fibres.

  9. Lignosus rhinocerotis (Cooke) Ryvarden mimics the neuritogenic activity of nerve growth factor via MEK/ERK1/2 signaling pathway in PC-12 cells

    PubMed Central

    Seow, Syntyche Ling-Sing; Eik, Lee-Fang; Naidu, Murali; David, Pamela; Wong, Kah-Hui; Sabaratnam, Vikineswary

    2015-01-01

    The traditional application of the sclerotium of Lignosus rhinocerotis (tiger’s milk mushroom) by the indigenous folks as tonic and remedy to treat a variety of ailments has been documented in Malaysia. Indigenous communities claimed to have consumed the decoction to boost their alertness during hunting. Mental alertness is believed to be related to neuronal health and neuroactivity. In the present study, the cell viability and neuritogenic effects of L. rhinocerotis sclerotium hot aqueous and ethanolic extracts, and crude polysaccharides on rat pheochromocytoma (PC-12) cells were studied. Interestingly, the hot aqueous extract exhibited neuritogenic activity comparable to NGF in PC-12 cells. However, the extracts and crude polysaccharides stimulated neuritogenesis without stimulating the production of NGF in PC-12 cells. The involvements of the TrkA receptor and MEK/ERK1/2 pathway in hot aqueous extract-stimulated neuritogenesis were examined by Trk (K252a) and MEK/ERK1/2 (U0126 and PD98059) inhibitors. There was no significant difference in protein expression in NGF- and hot aqueous extract-treated cells for both total and phosphorylated p44/42 MAPK. The neuritogenic activity in PC-12 cells stimulated by hot aqueous and ethanolic extracts, and crude polysaccharides of L. rhinocerotis sclerotium mimicking NGF activity via the MEK/ERK1/2 signaling pathway is reported for the first time. PMID:26542212

  10. The spinal nerves that constitute the lumbosacral plexus and their distribution in the chinchilla.

    PubMed

    Martinez-Pereira, M A; Rickes, E M

    2011-09-01

    In this study, the spinal nerves that constitute the lumbosacral plexus (plexus lumbosacrales) (LSP) and its distribution in Chinchilla lanigera were investigated. Ten chinchillas (6 males and 4 females) were used in this research. The spinal nerves that constitute the LSP were dissected and the distribution of pelvic limb nerves originating from the plexus was examined. The iliohypogastric nerve arose from L1 and L2, giving rise to the cranial and caudal nerves, and the ilioinguinal nerve arose from L3. The other branch of L3 gave rise to the genitofemoral nerve and 1 branch from L4 gave rise to the lateral cutaneous femoral nerve. The trunk formed by the union of L4-5 divided into medial (femoral nerve) and lateral branches (obturator nerve). It was found that the LSP was formed by all the ventral branches of L4 at L6 and S1 at S3. At the caudal part of the plexus, a thick branch, the ischiadic plexus, was formed by contributions from L5-6 and S1. This root gave rise to the nerve branches which were disseminated to the posterior limb (cranial and caudal gluteal nerves, caudal cutaneous femoral nerve and ischiadic nerve). The ischiadic nerve divided into the caudal cutaneous surae, lateral cutaneous surae, common fibular and tibial nerve. The pudendal nerve arose from S1-2 and the other branch of S2 and S3 formed the rectal caudal nerve. The results showed that the origins and distribution of spinal nerves that constitute the LSP of chinchillas were similar to those of a few rodents and other mammals.

  11. Light as stress factor to plant roots - case of root halotropism.

    PubMed

    Yokawa, Ken; Fasano, Rossella; Kagenishi, Tomoko; Baluška, František

    2014-01-01

    Despite growing underground, largely in darkness, roots emerge to be very sensitive to light. Recently, several important papers have been published which reveal that plant roots not only express all known light receptors but also that their growth, physiology and adaptive stress responses are light-sensitive. In Arabidopsis, illumination of roots speeds-up root growth via reactive oxygen species-mediated and F-actin dependent process. On the other hand, keeping Arabidopsis roots in darkness alters F-actin distribution, polar localization of PIN proteins as well as polar transport of auxin. Several signaling components activated by phytohormones are overlapping with light-related signaling cascade. We demonstrated that the sensitivity of roots to salinity is altered in the light-grown Arabidopsis roots. Particularly, light-exposed roots are less effective in their salt-avoidance behavior known as root halotropism. Here we discuss these new aspects of light-mediated root behavior from cellular, physiological and evolutionary perspectives.

  12. Branching Out in Roots: Uncovering Form, Function, and Regulation1

    PubMed Central

    Atkinson, Jonathan A.; Rasmussen, Amanda; Traini, Richard; Voß, Ute; Sturrock, Craig; Mooney, Sacha J.; Wells, Darren M.; Bennett, Malcolm J.

    2014-01-01

    Root branching is critical for plants to secure anchorage and ensure the supply of water, minerals, and nutrients. To date, research on root branching has focused on lateral root development in young seedlings. However, many other programs of postembryonic root organogenesis exist in angiosperms. In cereal crops, the majority of the mature root system is composed of several classes of adventitious roots that include crown roots and brace roots. In this Update, we initially describe the diversity of postembryonic root forms. Next, we review recent advances in our understanding of the genes, signals, and mechanisms regulating lateral root and adventitious root branching in the plant models Arabidopsis (Arabidopsis thaliana), maize (Zea mays), and rice (Oryza sativa). While many common signals, regulatory components, and mechanisms have been identified that control the initiation, morphogenesis, and emergence of new lateral and adventitious root organs, much more remains to be done. We conclude by discussing the challenges and opportunities facing root branching research. PMID:25136060

  13. Optical stimulation of peripheral nerves in vivo

    NASA Astrophysics Data System (ADS)

    Wells, Jonathon D.

    This dissertation documents the emergence and validation of a new clinical tool that bridges the fields of biomedical optics and neuroscience. The research herein describes an innovative method for direct neurostimulation with pulsed infrared laser light. Safety and effectiveness of this technique are first demonstrated through functional stimulation of the rat sciatic nerve in vivo. The Holmium:YAG laser (lambda = 2.12 mum) is shown to operate at an optimal wavelength for peripheral nerve stimulation with advantages over standard electrical neural stimulation; including contact-free stimulation, high spatial selectivity, and lack of a stimulation artifact. The underlying biophysical mechanism responsible for transient optical nerve stimulation appears to be a small, absorption driven thermal gradient sustained at the axonal layer of nerve. Results explicitly prove that low frequency optical stimulation can reliably stimulate without resulting in tissue thermal damage. Based on the positive results from animal studies, these optimal laser parameters were utilized to move this research into the clinic with a combined safety and efficacy study in human subjects undergoing selective dorsal rhizotomy. The clinical Holmium:YAG laser was used to effectively stimulate human dorsal spinal roots and elicit functional muscle responses recorded during surgery without evidence of nerve damage. Overall these results predict that this technology can be a valuable clinical tool in various neurosurgical applications.

  14. Genetic ablation of root cap cells in Arabidopsis

    NASA Technical Reports Server (NTRS)

    Tsugeki, R.; Fedoroff, N. V.

    1999-01-01

    The root cap is increasingly appreciated as a complex and dynamic plant organ. Root caps sense and transmit environmental signals, synthesize and secrete small molecules and macromolecules, and in some species shed metabolically active cells. However, it is not known whether root caps are essential for normal shoot and root development. We report the identification of a root cap-specific promoter and describe its use to genetically ablate root caps by directing root cap-specific expression of a diphtheria toxin A-chain gene. Transgenic toxin-expressing plants are viable and have normal aerial parts but agravitropic roots, implying loss of root cap function. Several cell layers are missing from the transgenic root caps, and the remaining cells are abnormal. Although the radial organization of the roots is normal in toxin-expressing plants, the root tips have fewer cytoplasmically dense cells than do wild-type root tips, suggesting that root meristematic activity is lower in transgenic than in wild-type plants. The roots of transgenic plants have more lateral roots and these are, in turn, more highly branched than those of wild-type plants. Thus, root cap ablation alters root architecture both by inhibiting root meristematic activity and by stimulating lateral root initiation. These observations imply that the root caps contain essential components of the signaling system that determines root architecture.

  15. Phenotyping jasmonate regulation of root growth.

    PubMed

    Kellermeier, Fabian; Amtmann, Anna

    2013-01-01

    Root architecture is a complex and highly plastic feature of higher plants. Direct treatments with jasmonates and alterations in jasmonate signaling have been shown to elicit a range of root phenotypes. Here, we describe a fast, noninvasive, and semiautomatic method to monitor root architectural responses to environmental stimuli using plant tissue culture and the software tool EZ-RHIZO.

  16. Structure-Activity Relationship of Nerve-Highlighting Fluorophores

    PubMed Central

    Gibbs, Summer L.; Xie, Yang; Goodwill, Haley L.; Nasr, Khaled A.; Ashitate, Yoshitomo; Madigan, Victoria J.; Siclovan, Tiberiu M.; Zavodszky, Maria; Tan Hehir, Cristina A.; Frangioni, John V.

    2013-01-01

    Nerve damage is a major morbidity associated with numerous surgical interventions. Yet, nerve visualization continues to challenge even the most experienced surgeons. A nerve-specific fluorescent contrast agent, especially one with near-infrared (NIR) absorption and emission, would be of immediate benefit to patients and surgeons. Currently, there are only three classes of small molecule organic fluorophores that penetrate the blood nerve barrier and bind to nerve tissue when administered systemically. Of these three classes, the distyrylbenzenes (DSBs) are particularly attractive for further study. Although not presently in the NIR range, DSB fluorophores highlight all nerve tissue in mice, rats, and pigs after intravenous administration. The purpose of the current study was to define the pharmacophore responsible for nerve-specific uptake and retention, which would enable future molecules to be optimized for NIR optical properties. Structural analogs of the DSB class of small molecules were synthesized using combinatorial solid phase synthesis and commercially available building blocks, which yielded more than 200 unique DSB fluorophores. The nerve-specific properties of all DSB analogs were quantified using an ex vivo nerve-specific fluorescence assay on pig and human sciatic nerve. Results were used to perform quantitative structure-activity relationship (QSAR) modeling and to define the nerve-specific pharmacophore. All DSB analogs with positive ex vivo fluorescence were tested for in vivo nerve specificity in mice to assess the effect of biodistribution and clearance on nerve fluorescence signal. Two new DSB fluorophores with the highest nerve to muscle ratio were tested in pigs to confirm scalability. PMID:24039960

  17. Adjuvant neurotrophic factors in peripheral nerve repair with chondroitin sulfate proteoglycan-reduced acellular nerve allografts

    PubMed Central

    Boyer, Richard B.; Sexton, Kevin W.; Rodriguez-Feo, Charles L.; Nookala, Ratnam; Pollins, Alonda C.; Cardwell, Nancy L.; Tisdale, Keonna Y.; Nanney, Lillian B.; Shack, R. Bruce; Thayer, Wesley P.

    2014-01-01

    Background Acellular nerve allografts are now standard tools in peripheral nerve repair due to decreased donor site morbidity and operative time savings. Preparation of nerve allografts involves several steps of decellularization and modification of extracellular matrix to remove chondroitin sulfate proteoglycans (CSPGs), which have been shown to inhibit neurite outgrowth through a poorly understood mechanism involving RhoA and ECM-integrin interactions. Chondroitinase ABC (ChABC) is an enzyme that degrades CSPG molecules and has been shown to promote neurite outgrowth following injury of the central and peripheral nervous systems. Variable results following chondroitinase ABC treatment make it difficult to predict the effects of this drug in human nerve allografts, especially in the presence of native extracellular signaling molecules. Several studies have shown cross-talk between neurotrophic factor and CSPG signaling pathways, but their interaction remains poorly understood. In this study, we examined the adjuvant effects of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) on neurite outgrowth post-injury in CSPG-reduced substrates and acellular nerve allografts. Materials and Methods E12 chicken DRG explants were cultured in medium containing ChABC, ChABC + NGF, ChABC + GDNF or control media. Explants were imaged at 3 d and neurite outgrowths measured. The rat sciatic nerve injury model involved a 1-cm sciatic nerve gap that was microsurgically repaired with ChABC pre-treated acellular nerve allografts. Prior to implantation, nerve allografts were incubated in NGF, GDNF or sterile water. Nerve histology was evaluated at 5d and 8wk post-injury. Results The addition of GDNF in vitro produced significant increase in sensory neurite length at 3 d compared to ChABC alone (P < 0.01), while NGF was not significantly different from control. In vivo adjuvant NGF produced increases in total myelinated axon count (P < 0.005) and motor axon

  18. Protein expression of sensory and motor nerves: Two-dimensional gel electrophoresis and mass spectrometry.

    PubMed

    Ren, Zhiwu; Wang, Yu; Peng, Jiang; Zhang, Li; Xu, Wenjing; Liang, Xiangdang; Zhao, Qing; Lu, Shibi

    2012-02-15

    The present study utilized samples from bilateral motor branches of the femoral nerve, as well as saphenous nerves, ventral roots, and dorsal roots of the spinal cord, to detect differential protein expression using two-dimensional gel electrophoresis and nano ultra-high performance liquid chromatography electrospray ionization mass spectrometry tandem mass spectrometry techniques. A mass spectrum was identified using the Mascot search. Results revealed differential expression of 11 proteins, including transgelin, Ig kappa chain precursor, plasma glutathione peroxidase precursor, an unnamed protein product (gi|55628), glyceraldehyde-3-phosphate dehydrogenase-like protein, lactoylglutathione lyase, adenylate kinase isozyme 1, two unnamed proteins products (gi|55628 and gi|1334163), and poly(rC)-binding protein 1 in motor and sensory nerves. Results suggested that these proteins played roles in specific nerve regeneration following peripheral nerve injury and served as specific markers for motor and sensory nerves.

  19. C2 and Greater Occipital Nerve: The Anatomic and Functional Implications in Spinal Surgery

    PubMed Central

    Zhou, Peter L; Greenfield, Jeffrey P; Baaj, Ali A; Frempong-Boadu, Anthony

    2017-01-01

    Introduction Posterior C1-C2 fusion is a highly successful treatment for atlantoaxial instability and other pathologies of the cervical spine, with fusion rates approaching 95%-100%. However, poor visualization of the lateral masses of C1 secondary to the course of the C2 nerve root along with blood loss from the venous plexus and compression of the C2 nerve from lateral mass screws are technical obstacles that can arise during surgery. Thus, sacrifice of the C2 nerve root has long since been debated in fusions involving the C1 and C2 vertebral bodies.  Methods Cadaveric dissections on four adult specimens were performed. Both intradural and extradural courses of C2 were studied in detail. The tentative site of C2 nerve root compression during placement of C1 lateral mass screws was studied in detail. Both the indication as well as the ease of C2 neurectomy were studied in relation to postoperative compression and entrapment. Results Four-six dorsal rootlets of C2 nerve were observed while studying the intradural course. The extradural course was studied with respect to the lateral mass of C1. The greater occipital nerve (GON) course was fairly consistent in all specimens. Transection of C2 around its ganglion would allow for proper C1 lateral mass screw placement as the course of C2 nerve interferes with proper placement of instrumentation. Conclusion C2 nerve root transection is associated with occipital numbness but this often has no effect on health-related quality of life (HRQOL). The C2 nerve root preservation is often associated with entrapment neuropathy or occipital neuralgia, which greatly affects HRQOL. The C2 nerve root transection helps in better visualization, aids in optimal placement of C1 lateral mass screws, minimizes estimated blood loss and improves surgical outcome with successful fusion.

  20. Changes in contralateral protein metabolism following unilateral sciatic nerve section

    SciTech Connect

    Menendez, J.A.; Cubas, S.C.

    1990-03-01

    Changes in nerve biochemistry, anatomy, and function following injuries to the contralateral nerve have been repeatedly reported, though their significance is unknown. The most likely mechanisms for their development are either substances carried by axoplasmic flow or electrically transmitted signals. This study analyzes which mechanism underlies the development of a contralateral change in protein metabolism. The incorporation of labelled amino acids (AA) into proteins of both sciatic nerves was assessed by liquid scintillation after an unilateral section. AA were offered locally for 30 min to the distal stump of the sectioned nerves and at homologous levels of the intact contralateral nerves. At various times, from 1 to 24 h, both sciatic nerves were removed and the proteins extracted with trichloroacetic acid (TCA). An increase in incorporation was found in both nerves 14-24 h after section. No difference existed between sectioned and intact nerves, which is consistent with the contralateral effect. Lidocaine, but not colchicine, when applied previously to the nerves midway between the sectioning site and the spinal cord, inhibited the contralateral increase in AA incorporation. It is concluded that electrical signals, crossing through the spinal cord, are responsible for the development of the contralateral effect. Both the nature of the proteins and the significance of the contralateral effect are matters for speculation.

  1. Environmental Control of Root System Biology.

    PubMed

    Rellán-Álvarez, Rubén; Lobet, Guillaume; Dinneny, José R

    2016-04-29

    The plant root system traverses one of the most complex environments on earth. Understanding how roots support plant life on land requires knowing how soil properties affect the availability of nutrients and water and how roots manipulate the soil environment to optimize acquisition of these resources. Imaging of roots in soil allows the integrated analysis and modeling of environmental interactions occurring at micro- to macroscales. Advances in phenotyping of root systems is driving innovation in cross-platform-compatible methods for data analysis. Root systems acclimate to the environment through architectural changes that act at the root-type level as well as through tissue-specific changes that affect the metabolic needs of the root and the efficiency of nutrient uptake. A molecular understanding of the signaling mechanisms that guide local and systemic signaling is providing insight into the regulatory logic of environmental responses and has identified points where crosstalk between pathways occurs.

  2. Nerve Conduction in the Pre-Medical Physics Course

    ERIC Educational Resources Information Center

    Hobbie, Russell K.

    1973-01-01

    Reviews properties of nerves, analogous networks in propagation of electrical signals in axons, and regenerative changes in membrane permeability due to propagation of the action potential, which can be explained in the noncalculus physics course. (CC)

  3. Label-free photoacoustic microscopy of peripheral nerves

    PubMed Central

    Matthews, Thomas Paul; Zhang, Chi; Yao, Da-Kang; Maslov, Konstantin; Wang, Lihong V.

    2014-01-01

    Abstract. Peripheral neuropathy is a common neurological problem that affects millions of people worldwide. Diagnosis and treatment of this condition are often hindered by the difficulties in making objective, noninvasive measurements of nerve fibers. Photoacoustic microscopy (PAM) has the ability to obtain high resolution, specific images of peripheral nerves without exogenous contrast. We demonstrated the first proof-of-concept imaging of peripheral nerves using PAM. As validated by both standard histology and photoacoustic spectroscopy, the origin of photoacoustic signals is myelin, the primary source of lipids in the nerves. An extracted sciatic nerve sandwiched between two layers of chicken tissue was imaged by PAM to mimic the in vivo case. Ordered fibrous structures inside the nerve, caused by the bundles of myelin-coated axons, could be observed clearly. With further technical improvements, PAM can potentially be applied to monitor and diagnose peripheral neuropathies. PMID:24395587

  4. Label-free photoacoustic microscopy of peripheral nerves

    NASA Astrophysics Data System (ADS)

    Matthews, Thomas Paul; Zhang, Chi; Yao, Da-Kang; Maslov, Konstantin; Wang, Lihong V.

    2014-01-01

    Peripheral neuropathy is a common neurological problem that affects millions of people worldwide. Diagnosis and treatment of this condition are often hindered by the difficulties in making objective, noninvasive measurements of nerve fibers. Photoacoustic microscopy (PAM) has the ability to obtain high resolution, specific images of peripheral nerves without exogenous contrast. We demonstrated the first proof-of-concept imaging of peripheral nerves using PAM. As validated by both standard histology and photoacoustic spectroscopy, the origin of photoacoustic signals is myelin, the primary source of lipids in the nerves. An extracted sciatic nerve sandwiched between two layers of chicken tissue was imaged by PAM to mimic the in vivo case. Ordered fibrous structures inside the nerve, caused by the bundles of myelin-coated axons, could be observed clearly. With further technical improvements, PAM can potentially be applied to monitor and diagnose peripheral neuropathies.

  5. Strigolactones fine-tune the root system.

    PubMed

    Rasmussen, Amanda; Depuydt, Stephen; Goormachtig, Sofie; Geelen, Danny

    2013-10-01

    Strigolactones were originally discovered to be involved in parasitic weed germination, in mycorrhizal association and in the control of shoot architecture. Despite their clear role in rhizosphere signaling, comparatively less attention has been given to the belowground function of strigolactones on plant development. However, research has revealed that strigolactones play a key role in the regulation of the root system including adventitious roots, primary root length, lateral roots, root hairs and nodulation. Here, we review the recent progress regarding strigolactone regulation of the root system and the antagonism and interplay with other hormones.

  6. A novel root-to-shoot stomatal response to very high CO2 levels in the soil: electrical, hydraulic and biochemical signalling.

    PubMed

    Lake, Janice A; Walker, Heather J; Cameron, Duncan D; Lomax, Barry H

    2017-04-01

    Investigations were undertaken in the context of the potential environmental impact of carbon capture and storage (CCS) transportation in the form of a hypothetical leak of extreme levels of CO2 into the soil environment and subsequent effects on plant physiology. Laboratory studies using purpose built soil chambers, separating and isolating the soil and aerial environments, were used to introduce high levels of CO2 gas exclusively into the rhizosphere. CO2 concentrations greater than 32% in the isolated soil environment revealed a previously unknown whole plant stomatal response. Time course measurements of stomatal conductance (gs ), leaf temperature and leaf abscisic acid (ABA) show strong coupling between all three variables over a specific period (3 h following CO2 gassing) occurring as a result of CO2 -specific detection by roots. The coupling of gs and ABA subsequently breaks down resulting in a rapid and complete loss of turgor in the shoot. Root access to water is severely restricted as evidenced by the inability to counter turgor loss, however, the plant regains some turgor over time. Recovery of full turgor is not achieved over the longer term. Results suggest an immediate perception and whole plant response as changes in measured parameters (leaf temperature, gs and ABA) occur in the shoot, but the response is solely due to detection of very high CO2 concentration at the root/soil interface which results in loss of stomatal regulation and disruption to control over water uptake.

  7. A flexible microchannel electrode array for peripheral nerves to interface with neural prosthetics

    NASA Astrophysics Data System (ADS)

    Landrith, Ryan; Nothnagle, Caleb; Kim, Young-tae; Wijesundara, Muthu B. J.

    2016-05-01

    In order to control neural prosthetics by recording signals from peripheral nerves with the required specificity, high density electrode arrays that can be easily implanted on very small peripheral nerves (50μm-500μm) are needed. Interfacing with these small nerves is surgically challenging due to their size and fragile nature. To address this problem, a Flexible MicroChannel Electrode Array for interfacing with small diameter peripheral nerves and nerve fasc