Mammary gland development and response to prenatal atrazine exposure in the Sprague Dawley and Long-Evans rats.

EPA Science Inventory

Mammary gland (MG) tumor development in Sprague Dawley (SD) rats is increased by longterm dietary exposure to the chlorotriazine herbicide atrazine (ATR). ATR is proposed to cause these changes in the adult SD rat by altering hormonally-regulated estrous cyclicity. In Long-Evans...

[Influence of microtubule depolymerization of myocardial cells on mitochondria distribution and energy metabolism in adult rats].

PubMed

Dang, Yong-ming; Fang, Ya-dong; Hu, Jiong-yu; Zhang, Jia-ping; Song, Hua-pei; Zhang, Yi-ming; Zhang, Qiong; Huang, Yue-sheng

2010-02-01

To investigate the influence of microtubule depolymerization of myocardial cells on distribution and activity of mitochondria, and energy metabolism of cells in adult rats. Myocardial cells of SD adult rats and SD suckling rats were isolated and cultured. They were divided into adult and suckling rats control groups (AC and SC, normally cultured without any stimulating factor), adult and suckling rats microtubule depolymerization agent groups (AMDA and SMDA, cultured with 8 micromol/L colchicine containing nutrient solution for 30 minutes) according to the random number table. (1) The expression of polymerized beta tubulin in myocardial cells of adult and suckling rats was detected with Western blot. (2) Myocardial cells of rats in AC and AMDA groups were collected. The expression of cytochrome c was detected with Western blot. Distribution of voltage-dependent anion channels (VDAC) and polymerized beta tubulin in myocardial cells were observed with immunofluorescent staining. Mitochondrial inner membrane potential was determined with immunocytochemical method. Activity of myocardial cells was detected with MTT method. Contents of ATP, adenosine diphosphate (ADP), and adenosine monophosphate (AMP) and energy charge of cells were determined with high performance liquid chromatography. (1) The expression of polymerized beta tubulin:in AMDA group it was 0.52 + or - 0.07, which was obviously lower than that (1.25 + or - 0.12) in AC group (F = 31.002, P = 0.000); in SMDA group it was 0.76 + or - 0.12, which was significantly lower than that (1.11 + or - 0.24) in SC group (F = 31.002, P = 0.000), but was obviously higher than that in AMDA group (F = 31.002, P = 0.009). (2) The expression of cytochrome c in AC group was 0.26 + or - 0.03, which was obviously lower than that (1.55 + or - 0.13) in AMDA group (t = -24.056, P = 0.000). (3) Immunofluorescent staining result: in AC group, microtubules of myocardial cells were in linear tubiform, distributed in parallel with

[Morphologic studies of the protective role of catechin on kanamycin otoneurotoxicity in SD rats].

PubMed

Liu, Guo-hui; Xie, Ding-hua; Wu, Wei-jing

2002-12-28

To determine the protection of catechin on aminoglycoside antibiotics otoneurotoxicity in SD rats, and observe the morphologic changes of cochlear efferent nerve terminals and outer hair cells after the injection of kanamycin and the feeding of catechin by the stomach tube. Thirty-eight SD rats were randomly assigned into three experimental groups (KM-treated, catechin-treated, KM and catechin in combination) and one control group. The KM-treated group was given kanamycin in a dose of 500 mg.(kg.d)-1 for 14 days. The catechin-treated group was given catechin once by the stomach tube in a dose of 400 mg.(kg.d)-1. Two kinds of medicine were simultaneously given in the KM+ catechin group. Transmission electron microscopy was utilized to observe the subcellular structure of efferent nerve fibers and outer hair cells. The densities of efferent nerve fibers and terminals were examined and the numbers of efferent nerve fibers and terminals were numerated by the surface preparation using modified histochemical staining for acetylcholinesterase (AchE). The damage in the group protected by catechin was relieved compared with the unprotected group. No damage was found in the catechin-treated alone group and controls. The densities and numbers of efferent nerve fibers and terminals were obviously fewer in the unprotected group than in the protected group and controls(P < 0.05). There was no significant difference in the numbers of efferent nerve fibers and terminals of the group protected by catechin compared with the controls and the catechin-treated group (P > 0.05). Catechin significantly protects MOC efferent nerves in kanamycin otoneurotoxicity.

Development of quercetin-phospholipid complex to improve the bioavailability and protection effects against carbon tetrachloride-induced hepatotoxicity in SD rats.

PubMed

Zhang, Kexia; Zhang, Meiyu; Liu, Ziying; Zhang, Yuanyuan; Gu, Liqiang; Hu, Gaosheng; Chen, Xiaohui; Jia, Jingming

2016-09-01

Quercetin (QT) is a natural flavonoid with various biological activities and pharmacological actions. However, the bioavailability of QT is relatively low due to its low solubility which severely limits its use. In this study, we intended to improve the bioavailability of QT by preparing quercetin-phospholipid complex (QT-PC) and investigate the protective effect of QT-PC against carbon tetrachloride (CCl4) induced acute liver damage in Sprague-Dawley (SD) rats. The physicochemical properties of QT-PC were characterized in terms of infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (XRPD) and water/n-octanol solubility. FTIR, DSC and XRPD data confirmed the formation of QT-PC. The water solubility of QT was improved significantly in the prepared complex, indicating its increased hydrophilicity. Oral bioavailability of QT and QT-PC was evaluated in SD rats, and the plasma QT was estimated by HPLC-MS. QT-PC exhibited higher Cmax (1.58±0.11 vs. 0.67±0.08μg/mL), increased AUC0-∞ (8.60±1.25 vs. 2.41±0.51mg/Lh) and t1/2z (7.76±1.09 vs. 4.81±0.87h) when compared to free QT. The greater absorption of QT-PC group suggested the improved bioavailability. Moreover, biochemical changes and histopathological observations revealed that QT-PC provided better protection to rat liver than free QT at the same dose. Thus, phospholipid complexation might be one of the suitable approaches to improve the oral bioavailability of QT and obtain better protective effects against CCl4 induced acute liver damage in SD rats than free QT at the same dose level. Copyright © 2016 Elsevier B.V. All rights reserved.

[The expression of p53, MDM2 and Ref1 gene in cultured retina neurons of SD rats treated with vitamin B1 and/or elevated pressure].

PubMed

Yang, Zhikuan; Ge, Jian; Yin, Wei; Shen, Huangxuan; Liu, Haiquan; Guo, Yan

2004-12-01

To investigate the expression of p53, MDM2 and Ref1 gene in cultured retina neurons of SD rats treated with Vitamin B1 and (or) elevated pressure. The retinal neuron of postnatal SD rats were cultured in vivo, the elevated pressure was produced after 7 days, and the total RNA was extracted after another 2 days, expression of p53, MDM2 and Ref1 gene were analyzed with RT-PCR. The expression level of p53 and MDM2 gene were increased in elevated pressure group, normal with Ref1 gene expression. But the expression of p53 and MDM2 gene were decreased significantly in elevated pressure group treated with vitamine B1 compare to the elevated group. Apoptosis seem to be a mechanism of cell death in retinal neurons of SD rats with elevated pressure.Vitamine B1 have protect effects against elevated pressure.

Di-(2-ethylhexyl) phthalate could disrupt the insulin signaling pathway in liver of SD rats and L02 cells via PPARγ

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Wang; Shen, Xin-Yue; Zhang, Wen-wen

Di-(2-ethylhexyl)-phthalate (DEHP), a ubiquitous industrial pollutant in our daily life, has been reported to cause adverse effects on glucose homeostasis and insulin sensitivity in epidemiological studies previously. Recently, it has been reported to be an endocrine disrupter and ligand to peroxisome proliferator activated receptor, which could influence the homeostasis of liver metabolic systems and contribute to the development of type-2 diabetes. However, the potential mechanisms are not known yet. This study was designed to solve these problems with male SD rats and normal human hepatocyte line, L02 cells, exposed to DEHP for toxicological experiments. Adult male SD rats were dividedmore » into four groups, normal group fed with regular diets and three DEHP-treated groups (dissolved in olive oil at doses of 0.05, 5 and 500 mg/kg body weight, respectively, once daily through gastric intubations for 15 weeks). L02 cells were divided into 6 groups, normal group with 5, 10, 25, 50, and 100 μmol/l DEHP groups. DEHP-exposed rats exhibited significant liver damage, glucose tolerance, and insulin tolerance along with reduced expression of insulin receptor and GLUT4 proteins in the liver tissues. The results of in vitro experiments could determine that the DEHP-induced activation of peroxisome proliferator activated receptor γ (PPARγ) played a key role in the production of oxidative stress and down-regulated expression of insulin receptor and GLUT4 proteins in L02 cells. This conclusion could be supported by the results of in vitro experiments, in which the cells were exposed to DEHP with GW9662 (PPARγ inhibitor). In general, these results highlight the key role of PPARγ in the process of insulin resistance induced by DEHP. - Highlights: • DEHP exacerbates insulin resistance both in liver tissues and cells. • Expression of insulin receptor and GLUT4 were altered with PPARγ. • DEHP can induce oxidative stress to disrupt the metabolic homeostasis. • The

Enhancement of immune cytokines and splenic CD4+ T cells by electroacupuncture at ST36 acupoint of SD rats.

PubMed

Chen, Longyun; Xu, Anli; Yin, Nina; Zhao, Min; Wang, Zhigang; Chen, Tao; Gao, Yisheng; Chen, Zebin

2017-01-01

Electroacupuncture at the ST36 acupoint can enhance the body's immune function. However, the mechanism for this enhancement has not been fully described. Our study was designed to investigate the effect of electroacupuncture on the immune function of Sprague-Dawley (SD) rats. The rats were randomly divided into three groups: a control group, a non-acupoint group (abdominal muscle acupuntured) and a ST36 acupoint group. Our results showed that successive electroacupuncture at the ST36 acupoint for 3 d significantly enhanced the interferon-γ (IFN-γ) level in the serum of SD rats. The results also showed that the serum and extracts from spleen cells of the ST36 acupoint group contained higher levels of interleukin (IL)-2 and IL-17 compared to those of the other two groups. Immunohistochemical analysis showed that electroacupuncture applied to the ST36 acupoint enhanced the expression level of CD4 in spleen cells. Furthermore, it was observed that CD4 co-localized with transient receptor potential vanilloid (TRPV) channels at the membrane of splenic CD4+ T cells and the expression level of CD4 was related to TRPV channels in the electroacupuncture treatment. These observations indicated that electroacupuncture stimulation at the ST36 acupoint enhanced the level of immune cytokines and splenic CD4+ T cells through TRPV channels in this system.

Enhancement of immune cytokines and splenic CD4+ T cells by electroacupuncture at ST36 acupoint of SD rats

PubMed Central

Yin, Nina; Zhao, Min; Wang, Zhigang; Chen, Tao; Gao, Yisheng; Chen, Zebin

2017-01-01

Electroacupuncture at the ST36 acupoint can enhance the body’s immune function. However, the mechanism for this enhancement has not been fully described. Our study was designed to investigate the effect of electroacupuncture on the immune function of Sprague-Dawley (SD) rats. The rats were randomly divided into three groups: a control group, a non-acupoint group (abdominal muscle acupuntured) and a ST36 acupoint group. Our results showed that successive electroacupuncture at the ST36 acupoint for 3 d significantly enhanced the interferon-γ (IFN-γ) level in the serum of SD rats. The results also showed that the serum and extracts from spleen cells of the ST36 acupoint group contained higher levels of interleukin (IL)-2 and IL-17 compared to those of the other two groups. Immunohistochemical analysis showed that electroacupuncture applied to the ST36 acupoint enhanced the expression level of CD4 in spleen cells. Furthermore, it was observed that CD4 co-localized with transient receptor potential vanilloid (TRPV) channels at the membrane of splenic CD4+ T cells and the expression level of CD4 was related to TRPV channels in the electroacupuncture treatment. These observations indicated that electroacupuncture stimulation at the ST36 acupoint enhanced the level of immune cytokines and splenic CD4+ T cells through TRPV channels in this system. PMID:28406959

Neurocircuitry of fear extinction in adult and juvenile rats.

PubMed

Ganella, Despina E; Nguyen, Ly Dao; Lee-Kardashyan, Luba; Kim, Leah E; Paolini, Antonio G; Kim, Jee Hyun

2018-06-10

In contrast to adult rodents, juvenile rodents fail to show relapse following extinction of conditioned fear. Using different retrograde tracers injected into the infralimbic cortex (IL) and the ventral hippocampus (vHPC) in conjunction with c-Fos and parvalbumin (PV) immunochemistry, we investigated the neurocircuitry of extinction in juvenile and adult rats. Regardless of fear extinction or retrieval, juvenile rats had more c-Fos+ neurons in the basolateral amygdala (BLA) compared to adults, and showed a higher proportion of c-Fos+ IL-projecting neurons. Adult rats had more activated vHPC-projecting BLA neurons following extinction compared to retrieval, a difference not observed in juvenile rats. The number of activated vHPC- or IL-projecting BLA neurons was significantly correlated with freezing levels in adult, but not juvenile, rats. We also identified neurons in the BLA that simultaneously project to the IL and vHPC activated in the retrieval groups at both ages. This study provides novel insight into the neural process underlying extinction, especially in the juvenile period. Copyright © 2018 Elsevier B.V. All rights reserved.

EFFECTS OF 20 WEEK EXPOSURES IN FEMALE SPRAGUE-DAWLEY (S-D) RATS TO DIBROMOACETIC ACID, A DRINKING WATER DISINFECTANT BY-PRODUCT

EPA Science Inventory

Effects of 20 week exposures in female Sprague-Dawley (S-D) rats to the drinking water disinfection by-product dibromoacetic acid. A S Murr and J M Goldman, Endocrinol. Br., RTD, NHEERL, ORD, US EPA, Res. Tri. Pk, NC. Sponsor: Audrey Cummings

The drinking water disinfect...

EFFECTS OF 20 WEEK EXPOSURES IN FEMALE SPRAGUE-DAWLEY (S-D) RATS TO THE DRINKING WATER DISINFECTION BY-PRODUCT DIBROMOACETIC ACID

EPA Science Inventory

Effects of 20 week exposures in female Sprague-Dawley (S-D) rats to the drinking water disinfection by-product dibromoacetic acid. A S Murr and J M Goldman, Endocrinol. Br., RTD, NHEERL, ORD, US EPA, Res. Tri. Pk, NC. Sponsor: Audrey Cummings

The drinking water disinfect...

Lactogenic Activity of an Enzymatic Hydrolysate from Octopus vulgaris and Carica papaya in SD Rats.

PubMed

Cai, Bingna; Chen, Hua; Sun, Han; Sun, Huili; Wan, Peng; Chen, Deke; Pan, Jianyu

2015-11-01

The traditional Chinese medicine theory believes that octopus papaya soup can stimulate milk production in lactating women. The objective of this study was to determine whether dietary supplementation with an enzymatic hydrolysate of Octopus vulgaris and Carica papaya (EHOC) could increase milk production and nutritional indexes in Sprague Dawley (SD) rats. Female SD rats (n = 24) were fed a control diet (n = 8), EHOC-supplemented diet, or a positive control diet (Shengruzhi) from day 10 of pregnancy to day 10 of lactation. Maternal serum, mammary gland (day 10 of lactation), milk, and pup weight (daily) were collected for analysis. Results showed that the EHOC diet obviously elevated daily milk yield and pup weight compared to the control group (P < .05). The EHOC diet was found to increase the concentration of prolactin (PRL), progesterone (P), estradiol (E2), and growth hormone (GH) significantly in the circulation and mammary gland. Mammary glands of EHOC-treated dams showed clear lobuloalveolar development and proliferation of myoepithelial cells, but no striking variations were observed among the groups. Furthermore, the nutrition content and immune globulin concentration in the milk of EHOC-supplemented dams were higher than those of the control group, especially the cholesterol, glucose, and IgG were higher by 44.98% (P < .001), 42.76% (P < .01), and 42.23% (P < .01), respectively. In conclusion, this article demonstrates that EHOC administration has beneficial effects on milk production in the dams and on performance of the dam and pup. These results indicate that EHOC could be explored as a potentially lactogenic nutriment for lactating women.

Single oral dose toxicity test of polycalcium, a mixed composition of polycan and calcium lactate-gluconate 1:9 (G/G) in SD rat.

PubMed

Kim, Joo-Wan; Choi, Jae-Suk; Ha, Yu-Mi; Choi, In Soon; Kim, Ki-Young; Cho, Hyung-rae; Rha, Chae-hun; Ku, Sae-Kwang

2013-11-01

The object of this study was to obtain acute oral toxicity information of Polycalcium, a mixed composition of Polycan and Calcium lactate-gluconate 1:9 (g/g), in Sprague-Dawely (SD) rats. In order to investigate the toxicity and identify target organs, Polycalcium were once orally administered to female and male SD rats at dose levels of 2000, 1000, 500 and 0 (control) mg/kg body weights. The mortality, changes on body weight and clinical signs were monitored during 14 days after treatment with gross observation, changes on the organ weights and histopathology of principle organs and treatment sites based on the recommendation of KFDA Guidelines [2009-116, 2009]. As the results of single oral treatment of Polycalcium, no treatment related mortalities were observed within 14 days after end of treatment up to 2000 mg/kg, the limited dosage of rodents in the both genders. In addition, no Polycalcium treatment related changes on the body and organ weights, clinical signs, necropsy and histopathological findings were detected. The results obtained in this study suggest that the Polycalcium is non-toxic in rats. The LD50 and approximate LD in rats after single oral dose of Polycalcium were considered over 2000 mg/kg in both female and male, respectively.

Fluoxetine augments ventilatory CO2 sensitivity in Brown Norway but not Sprague Dawley rats.

PubMed

Hodges, Matthew R; Echert, Ashley E; Puissant, Madeleine M; Mouradian, Gary C

2013-04-01

The Brown Norway (BN; BN/NHsdMcwi) rat exhibits a deficit in ventilatory CO2 sensitivity and a modest serotonin (5-HT) deficiency. Here, we tested the hypothesis that the selective serotonin reuptake inhibitor fluoxetine would augment CO2 sensitivity in BN but not Sprague Dawley (SD) rats. Ventilation during room air or 7% CO2 exposure was measured before, during and after 3 weeks of daily injections of saline or fluoxetine (10mg/(kgday)) in adult male BN and SD rats. Fluoxetine had minimal effects on room air breathing in BN and SD rats (p>0.05), although tidal volume (VT) was reduced in BN rats (p<0.05). There were also minimal effects of fluoxetine on CO2 sensitivity in SD rats, but fluoxetine increased minute ventilation, breathing frequency and VT during hypercapnia in BN rats (p<0.05). The augmented CO2 response was reversible upon withdrawal of fluoxetine. Brain levels of biogenic amines were largely unaffected, but 5-HIAA and the ratio of 5-HIAA/5-HT were reduced (p<0.05) consistent with selective and effective 5-HT reuptake inhibition. Thus, fluoxetine increases ventilatory CO2 sensitivity in BN but not SD rats, further suggesting altered 5-HT system function may contribute to the inherently low CO2 sensitivity in the BN rat. Copyright © 2013 Elsevier B.V. All rights reserved.

Combined organizational and activational effects of short and long photoperiods on spatial and temporal memory in rats.

PubMed

MacDonald, Christopher J; Cheng, Ruey-Kuang; Williams, Christina L; Meck, Warren H

2007-02-22

The present study examined the effects of photoperiod on spatial and temporal memory in adult Sprague-Dawley rats that were conceived and reared in different day lengths, i.e., short day (SD-8:16 light/dark) and long day (LD-16:8 light/dark). Both male and female LD rats demonstrated increased spatial memory capacity as evidenced by a lower number of choices to criterion in a 12-arm radial maze task relative to the performance of SD rats. SD rats also demonstrated a distortion in the content of temporal memory as evidenced by a proportional rightward shift in the 20 and 60 s temporal criteria trained using the peak-interval procedure that is consistent with reduced cholinergic function. The conclusion is that both spatial and temporal memory are sensitive to photoperiod variation in laboratory rats in a manner similar to that previously observed for reproductive behaviour.

Intrauterine Growth Restricted Rats Exercised at Pregnancy: Maternal-Fetal Repercussions.

PubMed

Corvino, S B; Netto, A O; Sinzato, Y K; Campos, K E; Calderon, I M P; Rudge, M V C; Volpato, G T; Zambrano, E; Damasceno, D C

2015-08-01

To evaluate the effect of swimming in pregnant rats born with intrauterine growth restriction (IUGR) and their offspring, IUGR rats were obtained using the streptozotocin-induced severe diabetic (SD) rats. In this study, the nondiabetic parental generation presented 10 rats and diabetic parental generation presented 116 rats. Of these, the mated nondiabetic female rats were 10 and the number of diabetic rats was 45. In relation to term pregnancy, there were 10 animals in the nondiabetic group and 15 rats in the diabetic group. In the offspring of SD rats (IUGR group), 43 females were classified as small for pregnancy age, 19 rats were classified as appropriate for pregnancy age, and 0 female was classified as large for pregnancy age. The nondiabetic and SD pregnant rats generated offspring with appropriate (control [C]) and small (IUGR) weight for pregnancy age, respectively. At adult life, the C group was maintained as nonexercised C group and IUGR rats were distributed into 2 subgroups, namely, nonexercised (IUGR) and exercised (IUGRex). The rate of mated rats in the IUGR group was reduced compared to the C group. During pregnancy, the IUGR rats presented hyperinsulinemia, impaired reproductive outcomes, decreased body weight, hypertriglyceridemia, and hyperlactacidemia. The IUGRex presented reduced insulin and triglyceride levels. Thus, swimming improved lipid metabolism and increased insulin sensitivity. However, the offspring showed retarded growth, reinforcing the need to stimulate the exercise practice in women under supervision with different professional expertise to promote appropriate gestational conditions and improve perinatal outcomes. © The Author(s) 2015.

Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats

NASA Technical Reports Server (NTRS)

Marsh, D. R.; Criswell, D. S.; Carson, J. A.; Booth, F. W.

1997-01-01

Myogenic factor mRNA expression was examined during muscle regeneration after bupivacaine injection in Fischer 344/Brown Norway F1 rats aged 3, 18, and 31 mo of age (young, adult, and old, respectively). Mass of the tibialis anterior muscle in the young rats had recovered to control values by 21 days postbupivacaine injection but in adult and old rats remained 40% less than that of contralateral controls at 21 and 28 days of recovery. During muscle regeneration, myogenin mRNA was significantly increased in muscles of young, adult, and old rats 5 days after bupivacaine injection. Subsequently, myogenin mRNA levels in young rat muscle decreased to postinjection control values by day 21 but did not return to control values in 28-day regenerating muscles of adult and old rats. The expression of MyoD mRNA was also increased in muscles at day 5 of regeneration in young, adult, and old rats, decreased to control levels by day 14 in young and adult rats, and remained elevated in the old rats for 28 days. In summary, either a diminished ability to downregulate myogenin and MyoD mRNAs in regenerating muscle occurs in old rat muscles, or the continuing myogenic effort includes elevated expression of these mRNAs.

Malignant Mesothelioma in the Thoracic Cavity of a Crj:CD(SD) Rat Characterized by Round Hyalinous Stroma.

PubMed

Doi, Takuya; Kotani, Yuri; Takahashi, Kazuaki; Hashimoto, Satomi; Yamada, Naoaki; Kokoshima, Hiroko; Tomonari, Yuki; Wako, Yumi; Tsuchitani, Minoru

2010-06-01

Spontaneous malignant mesothelioma was found in a 104-week-old male Crj:CD(SD) rat. The tumor was scattered on the surface of the lung, heart, mediastinal pleura and thoracic wall and metastasized to the alveolar septa. Histopathologically, small flattened or cuboidal tumor cells proliferated with stroma, formed almost normal papillary structures and reacted positively to colloidal iron stain and immunohistochemical staining for mesothelin. Round hyalinous stromata were pronounced, which is a characteristic feature, and the possible reason for this is as follows; at first, a small amount of collagen fibers was formed in the center of the clusters of several tumor cells, and then the cell clusters expanded like balloons with an increase in the collagen fibers.

TRIMETHYLTIN DISRUPTS ACOUSTIC STARTLE RESPONDING IN ADULT RATS

EPA Science Inventory

Trimethyltin (TMT) is a limbic-system toxicant which also produces sensory dysfunction in adult animals. In the present experiment, the authors examined the effects of TMT on the acoustic startle response. Adult male, Long-Evans rats (N=12/dose) received a single i.p. injection o...

PROLONGED PERFORMANCE OF A HIGH REPETITION LOW FORCE TASK INDUCES BONE ADAPTATION IN YOUNG ADULT RATS, BUT LOSS IN MATURE RATS

PubMed Central

Massicotte, Vicky S; Frara, Nagat; Harris, Michele Y; Amin, Mamta; Wade, Christine K; Popoff, Steven N; Barbe, Mary F

2015-01-01

We have shown that prolonged repetitive reaching and grasping tasks lead to exposure-dependent changes in bone microarchitecture and inflammatory cytokines in young adult rats. Since aging mammals show increased tissue inflammatory cytokines, we sought here to determine if aging, combined with prolonged performance of a repetitive upper extremity task, enhances bone loss. We examined the radius, forearm flexor muscles, and serum from 16 mature (14–18 mo of age) and 14 young adult (2.5–6.5 mo of age) female rats after performance of a high repetition low force (HRLF) reaching and grasping task for 12 weeks. Young adult HRLF rats showed enhanced radial bone growth (e.g., increased trabecular bone volume, osteoblast numbers, bone formation rate, and mid-diaphyseal periosteal perimeter), compared to age-matched controls. Mature HRLF rats showed several indices of radial bone loss (e.g., decreased trabecular bone volume, and increased cortical bone thinning, porosity, resorptive spaces and woven bone formation), increased osteoclast numbers and inflammatory cytokines, compared to age-matched controls and young adult HRLF rats. Mature rats weighed more yet had lower maximum reflexive grip strength, than young adult rats, although each age group was able to pull at the required reach rate (4 reaches/min) and required submaximal pulling force (30 force-grams) for a food reward. Serum estrogen levels and flexor digitorum muscle size were similar in each age group. Thus, mature rats had increased bone degradative changes than in young adult rats performing the same repetitive task for 12 weeks, with increased inflammatory cytokine responses and osteoclast activity as possible causes. PMID:26517953

Performance on a strategy set shifting task in rats following adult or adolescent cocaine exposure

PubMed Central

Kantak, Kathleen M.; Barlow, Nicole; Tassin, David H.; Brisotti, Madeline F.; Jordan, Chloe J

2014-01-01

Rationale Neuropsychological testing is widespread in adult cocaine abusers, but lacking in teens. Animal models may provide insight into age-related neuropsychological consequences of cocaine exposure. Objectives Determine whether developmental plasticity protects or hinders behavioral flexibility after cocaine exposure in adolescent vs. adult rats. Methods Using a yoked-triad design, one rat controlled cocaine delivery and the other two passively received cocaine or saline. Rats controlling cocaine delivery (1.0 mg/kg) self-administered for 18 sessions (starting P37 or P77), followed by 18 drug-free days. Rats next were tested in a strategy set shifting task, lasting 11–13 sessions. Results Cocaine self-administration did not differ between age groups. During initial set formation, adolescent-onset groups required more trials to reach criterion and made more errors than adult-onset groups. During the set shift phase, rats with adult-onset cocaine self-administration experience had higher proportions of correct trials and fewer perseverative + regressive errors than age-matched yoked-controls or rats with adolescent-onset cocaine self-administration experience. During reversal learning, rats with adult-onset cocaine experience (self-administered or passive) required fewer trials to reach criterion and the self-administering rats made fewer perseverative + regressive errors than yoked-saline rats. Rats receiving adolescent-onset yoked-cocaine had more trial omissions and longer lever press reaction times than age-matched rats self-administering cocaine or receiving yoked-saline. Conclusions Prior cocaine self-administration may impair memory to reduce proactive interference during set shifting and reversal learning in adult-onset but not adolescent-onset rats (developmental plasticity protective). Passive cocaine may disrupt aspects of executive function in adolescent-onset but not adult-onset rats (developmental plasticity hinders). PMID:24800898

Physiological responses during whole body suspension of adult rats

NASA Technical Reports Server (NTRS)

Steffen, J. M.; Fell, R. D.; Musacchia, X. J.

1987-01-01

The objective of this study was to characterize responses of adult rats to one and two weeks of whole body suspension. Body weights and food and water intakes were initially reduced during suspension, but, while intake of food and water returned to presuspension levels, body weight remained depressed. Diuresis was evident, but only during week two. Hindlimb muscle responses were differential, with the soleus exhibiting the greatest atrophy and the EDL a relative hypertrophy. These findings suggest that adult rats respond qualitatively in a manner similar to juveniles during suspension.

Time Course of the Changes in Novel Trioxane Antimalarial 99/411 Pharmacokinetics upon Antiepileptic Drugs Co-Administration in SD Rats.

PubMed

Singh, Yeshwant; Kushwaha, Hari Narayan; Misra, Anamika; Hidau, Mahendra Kumar; Singh, Shio Kumar

2014-01-01

Objective. The study aimed to evaluate the influences of coadministration of antiepileptic drugs (AEDs) on an antimalarial candidate 99/411 pharmacokinetic (PK) profile. Method. For this, single oral dose PK drug interaction studies were conducted between 99/411 and FDA approved AEDs, namely, Phenytoin (PHT), Carbamazepine (CBZ), and Gabapentin (GB) in both male and female SD rats, to assess the coadministered and intersexual influences on 99/411 PK profile. Results. Studies revealed that there were no significant alterations in the PK profile of 99/411 upon PHT and CBZ coadministration in both male and female rats, while systemic exposure of 99/411 was significantly increased by about 80% in female rats upon GB coadministration. In terms of AUC, there was an increase from 2471 ± 586 to 4560 ± 1396 ng·h/mL. Overall, it was concluded that simultaneous administration of AEDs with 99/411 excludes the requirements for dose adjustment, additional therapeutic monitoring, contraindication to concomitant use, and/or other measures to mitigate risk, except for GB coadministration in females. These findings are further helpful to predict such interactions in humans, when potentially applied through proper allometric scaling to extrapolate the data.

Leptin inhibits testosterone secretion from adult rat testis in vitro.

PubMed

Tena-Sempere, M; Pinilla, L; González, L C; Diéguez, C; Casanueva, F F; Aguilar, E

1999-05-01

Leptin, the product of the ob gene, has emerged recently as a pivotal signal in the regulation of fertility. Although the actions of leptin in the control of reproductive function are thought to be exerted mainly at the hypothalamic level, the potential direct effects of leptin at the pituitary and gonadal level have been poorly characterised. In the present study, we first assessed the ability of leptin to regulate testicular testosterone secretion in vitro. Secondly, we aimed to evaluate whether leptin can modulate basal gonadotrophin and prolactin (PRL) release by incubated hemi-pituitaries from fasted male rats. To attain the first goal, testicular slices from prepubertal and adult rats were incubated with increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Assuming that in vitro testicular responsiveness to leptin may be dependent on the background leptin levels, testicular tissue from both food-deprived and normally-fed animals was used. Furthermore, leptin modulation of stimulated testosterone secretion was evaluated by incubation of testicular samples with different doses of leptin in the presence of 10 IU human chorionic gonadotrophin (hCG). In addition, analysis of leptin actions on pituitary function was carried out using hemi-pituitaries from fasted adult male rats incubated in the presence of increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Serum testosterone levels, and basal and hCG-stimulated testosterone secretion by incubated testicular tissue were significantly decreased by fasting in prepubertal and adult male rats. However, a significant reduction in circulating LH levels was only evident in adult fasted rats. Doses of 10(-9)-10(-7) M leptin had no effect on basal or hCG-stimulated testosterone secretion by testes from prepubertal rats, regardless of the nutritional state of the donor animal. In contrast, leptin significantly decreased basal and hCG-induced testosterone secretion by testes from fasted and fed

Encoding of sound envelope transients in the auditory cortex of juvenile rats and adult rats.

PubMed

Lu, Qi; Jiang, Cuiping; Zhang, Jiping

2016-02-01

Accurate neural processing of time-varying sound amplitude and spectral information is vital for species-specific communication. During postnatal development, cortical processing of sound frequency undergoes progressive refinement; however, it is not clear whether cortical processing of sound envelope transients also undergoes age-related changes. We determined the dependence of neural response strength and first-spike latency on sound rise-fall time across sound levels in the primary auditory cortex (A1) of juvenile (P20-P30) rats and adult (8-10 weeks) rats. A1 neurons were categorized as "all-pass", "short-pass", or "mixed" ("all-pass" at high sound levels to "short-pass" at lower sound levels) based on the normalized response strength vs. rise-fall time functions across sound levels. The proportions of A1 neurons within each of the three categories in juvenile rats were similar to that in adult rats. In general, with increasing rise-fall time, the average response strength decreased and the average first-spike latency increased in A1 neurons of both groups. At a given sound level and rise-fall time, the average normalized neural response strength did not differ significantly between the two age groups. However, the A1 neurons in juvenile rats showed greater absolute response strength, longer first-spike latency compared to those in adult rats. In addition, at a constant sound level, the average first-spike latency of juvenile A1 neurons was more sensitive to changes in rise-fall time. Our results demonstrate the dependence of the responses of rat A1 neurons on sound rise-fall time, and suggest that the response latency exhibit some age-related changes in cortical representation of sound envelope rise time. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pharmacokinetics of bisphenol A in neonatal and adult Sprague-Dawley rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doerge, Daniel R., E-mail: daniel.doerge@fda.hhs.go; Twaddle, Nathan C.; Vanlandingham, Michelle

Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA in urine of > 90% of Americans aged 6-60 suggests ubiquitous and frequent exposure. The current study used LC/MS/MS to measure serum pharmacokinetics of aglycone (active) and conjugated (inactive) BPA in adult and neonatal Sprague-Dawley rats by oral and injection routes. Deuterated BPA was used to avoid issues of background contamination. Linear pharmacokinetics were observed in adult rats treated orally in the range of 0-200 {mu}g/kg bw. Evidence for enterohepatic recirculation of conjugated, butmore » not aglycone, BPA was observed in adult rats. Significant inverse relationships were observed between postnatal age and measures of internal exposures to aglycone BPA and its elimination. In neonatal rats treated orally, internal exposures to aglycone BPA were substantially lower than from subcutaneous injection. The results reinforce the critical role for first-pass Phase II metabolism of BPA in gut and liver after oral exposure that attenuates internal exposure to the aglycone form in rats of all ages. The internal exposures to aglycone BPA observed in adult and neonatal rats following a single oral dose of 100 {mu}g/kg bw are inconsistent with effects mediated by classical estrogen receptors based on binding affinities. However, an impact on alternative estrogen signaling pathways that have higher receptor affinity cannot be excluded in neonatal rats. These findings emphasize the importance of matching aglycone BPA internal dosimetry with receptor affinities in experimental animal studies reporting toxicity.« less

Comparative toxicity and tissue distribution of lead acetate in weanling and adult rats.

PubMed Central

Rader, J I; Peeler, J T; Mahaffey, K R

1981-01-01

The relative toxicity of low doses of lead acetate provided steadily in drinking water or by mouth once per week was studied in weanling and adult rats. Free erythrocyte protoporphyrin and urinary delta-aminolevulinic acid levels were measured, as well as lead levels in blood and kidney. The accumulation of lead in brain tissue and in bone (femur) was measured to determine the effect of age and schedule of administration on tissue distribution and retention of lead. Total intakes of lead during the 60-week experimental period were: weanling and adult rats exposed to drinking water supplemented with 200 microgram of lead acetate/ml: 127 +/- 10 mg and 160 +/- 16 mg, respectively; weanling and adult rats dosed with lead acetate orally once per week: 132 mg and 161 mg, respectively. Increased toxic effects of lead in the weanling animals were apparent in most of the parameters measured (urinary delta-aminolevulinic acid and blood, brain, femur and kidney lead levels). This pattern was observed in weanling rats exposed to lead steadily through drinking water or dosed orally with an equivalent quantity of lead once per week. Lead levels in blood were highly correlated with the accumulation of lead in brain, femur, and kidney tissue in both groups of weanling rats. In adult rats, significant correlations between blood lead and kidney lead and between blood lead and femur lead were found only in the rats receiving lead steadily in drinking water. PMID:7333253

Methylphenidate increases glucose uptake in the brain of young and adult rats.

PubMed

Réus, Gislaine Z; Scaini, Giselli; Titus, Stephanie E; Furlanetto, Camila B; Wessler, Leticia B; Ferreira, Gabriela K; Gonçalves, Cinara L; Jeremias, Gabriela C; Quevedo, João; Streck, Emilio L

2015-10-01

Methylphenidate (MPH) is the drug of choice for pharmacological treatment of attention deficit hyperactivity disorder. Studies have pointed to the role of glucose and lactate as well as in the action mechanisms of drugs used to treat these neuropsychiatric diseases. Thus, this study aims to evaluate the effects of MPH administration on lactate release and glucose uptake in the brains of young and adult rats. MPH (1.0, 2.0 and 10.0mg/kg) or saline was injected in young and adult Wistar male rats either acutely (once) or chronically (once daily for 28 days). Then, the levels of lactate release and glucose uptake were assessed in the prefrontal cortex, hippocampus, striatum, cerebellum and cerebral cortex. Chronic MPH treatment increased glucose uptake at the dose of 10.0mg/kg in the prefrontal cortex and striatum, and at the dose of 2.0mg/kg in the cerebral cortex of young rats. In adult rats, an increase in glucose uptake was observed after acute administration of MPH at the dose of 10.0mg/kg in the prefrontal cortex. After chronic treatment, there was an increase in glucose uptake with MPH doses of 2.0 and 10.0mg/kg in the prefrontal cortex, and at an MPH dose of 2.0mg/kg in the striatum of adult rats. The lactate release did not change with either acute or chronic treatments in young or adult rats. These findings indicate that MPH increases glucose consumption in the brain, and that these changes are dependent on age and posology. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Effects of 4-Vinylcyclohexene Diepoxide on Peripubertal and Adult Sprague–Dawley Rats: Ovarian, Clinical, and Pathologic Outcomes

PubMed Central

Muhammad, F Salih; Goode, Amanda K; Kock, Nancy D; Arifin, Esther A; Cline, J Mark; Adams, Michael R; Hoyer, Patricia B; Christian, Patricia J; Isom, Scott; Kaplan, Jay R; Appt, Susan E

2009-01-01

Young rats treated daily with intraperitoneal 4-vinylcyclohexene diepoxide (VCD) undergo selective destruction of primordial follicles, resulting in gradual ovarian failure resembling the menopausal transition in women. To determine whether VCD has similar effects on ovaries of older rats, adult and peripubertal Sprague–Dawley rats were injected intraperitoneally daily for 30 d with vehicle or VCD at 40 or 80 mg/kg. Body weight, food intake, complete blood counts, and markers of liver injury and renal function were measured during VCD treatment. Complete gross necropsy and microscopic observations were performed on day 31, and ovarian follicles were counted. At 80 mg/kg, VCD destroyed primordial and primary follicles to a similar extent in both adult and peripubertal animals, although adult rats likely started with fewer follicles and therefore approached follicle depletion. Treatment with VCD did not affect body weight, but food intake was reduced in both adult and peripubertal rats treated with 80 mg/kg VCD. Adult rats treated with 80 mg/kg VCD had neutrophilia and increased BUN and creatinine; in addition, 4 of these rats were euthanized on days 25 or 26 due to peritonitis. VCD treatment did not increase alanine aminotransferase levels, a marker of liver injury, although the 80-mg/kg dose increased liver weights. In conclusion, VCD effectively destroys small preantral follicles in adult Sprague–Dawley rats, making them a suitable model of the menopausal transition of women. However, because adult rats were more sensitive to the irritant properties of VCD, the use of a lower dose should be considered. PMID:19295054

Dietary modulation of parathion-induced neurotoxicity in adult and juvenile rats.

PubMed

Liu, Jing; Karanth, Subramanya; Pope, Carey

2005-06-01

Previous studies indicated that dietary glucose (15% in drinking water) could markedly exacerbate the toxicity of parathion in adult rats. The present study evaluated the effect of consumption of the commonly used sweetener, high fructose corn syrup (HFCS), on parathion toxicity in adult and juvenile rats. Animals were given free access to either water or 15% HFCS in drinking water for a total of 10 days and challenged with parathion (6 or 18 mg/kg, s.c., for juveniles or adults, respectively) on the 4th day. Signs of cholinergic toxicity, body weight and chow/fluid intake were recorded daily. Acetylcholinesterase (AChE) activity and immunoreactivity (AChE-IR) in frontal cortex and diaphragm were measured at 2, 4, and 7 days after parathion. As HFCS was associated with significant reduction in chow intake, adult rats were also pair-fed to evaluate the effect of similar reduced chow intake alone on parathion toxicity. The results indicated that the cholinergic toxicity of parathion was significantly increased by HFCS feeding in both age groups. The excess sugar consumption, however, did not significantly affect parathion-induced AChE inhibition in either tissue or either age group. Enzyme immunoreactivity in frontal cortex was generally not affected in either age group while diaphragm AChE-IR was significantly reduced by parathion and HFCS alone in adult animals at 2 and 4 days timepoints, and more so by the combination of sugar feeding and parathion exposure in both age groups. Food restriction alone did not exacerbate parathion toxicity. While the mechanism(s) remains unclear, we conclude that voluntary consumption of the common sweetener HFCS can markedly amplify parathion acute toxicity in both juvenile and adult rats.

[Effect of tail-suspension on the reproduction of adult male rats].

PubMed

Zhou, Dang-xia; Qiu, Shu-dong; Wang, Zhi-yong; Zhang, Jie

2006-04-01

To study the effects on the male reproduction in adult male rats and its mechanisms through simulated weightlessness using tail-suspension, in order to do a basic works of exploring the effects on human being's reproduction in outer space. Forty Spraque-Dawley adult male rats were randomly divided into four groups, two experimental groups and two control groups. Rats in the two experimental groups were tail-suspended for 14 d and 28 d respectively, then we examined the weight and morphology of testis, the quality and amount of sperm, also tested the serum hormone by radioimmunoassay and analyzed apoptosis rate of testicular cells by TUNEL in the experimental rats and control rats. After tail-suspension, the weight of testis, the sperm count and sperm motility significantly decreased (P <0.05), while the apoptosis rate of testicular cells and the amount of abnormal sperm markedly increased (P <0.05). The content of testosterone significantly decreased (P <0.05), but the contents of FSH and LH mildly increased (P > 0.05). These changes were not significant between two experimental groups (P > 0.05). In addition, the seminiferous tubules became atrophy with the reduction of the layers of seminiferous epithelium, and sperm amount in lumens of seminiferous tubules decreased in experimental groups. The above were more remarkable in the 28 d experimental group. Simulating weightlessness has a harmful effect on reproduction of adult male rats. These may be caused by inducing apoptosis. The blocking apoptosis of testicular cells may be useful in improving the harmful effect.

Caffeine and Modafinil Ameliorate the Neuroinflammation and Anxious Behavior in Rats during Sleep Deprivation by Inhibiting the Microglia Activation

PubMed Central

Wadhwa, Meetu; Chauhan, Garima; Roy, Koustav; Sahu, Surajit; Deep, Satyanarayan; Jain, Vishal; Kishore, Krishna; Ray, Koushik; Thakur, Lalan; Panjwani, Usha

2018-01-01

Background: Sleep deprivation (SD) plagues modern society due to the professional demands. It prevails in patients with mood and neuroinflammatory disorders. Although growing evidence suggests the improvement in the cognitive performance by psychostimulants during sleep-deprived conditions, the impending involved mechanism is rarely studied. Thus, we hypothesized that mood and inflammatory changes might be due to the glial cells activation induced modulation of the inflammatory cytokines during SD, which could be improved by administering psychostimulants. The present study evaluated the role of caffeine/modafinil on SD-induced behavioral and inflammatory consequences. Methods: Adult male Sprague-Dawley rats were sleep deprived for 48 h using automated SD apparatus. Caffeine (60 mg/kg/day) or modafinil (100 mg/kg/day) were administered orally to rats once every day during SD. Rats were subjected to anxious and depressive behavioral evaluation after SD. Subsequently, blood and brain were collected for biochemical, immunohistochemical and molecular studies. Results: Sleep deprived rats presented an increased number of entries and time spent in closed arms in elevated plus maze test and decreased total distance traveled in the open field (OF) test. Caffeine/modafinil treatment significantly improved these anxious consequences. However, we did not observe substantial changes in immobility and anhedonia in sleep-deprived rats. Caffeine/modafinil significantly down-regulated the pro- and up-regulated the anti-inflammatory cytokine mRNA and protein expression in the hippocampus during SD. Similar outcomes were observed in blood plasma cytokine levels. Caffeine/modafinil treatment significantly decreased the microglial immunoreactivity in DG, CA1 and CA3 regions of the hippocampus during SD, however, no significant increase in immunoreactivity of astrocytes was observed. Sholl analysis signified the improvement in the morphological alterations of astrocytes and microglia

Methylphenidate treatment increases Na(+), K (+)-ATPase activity in the cerebrum of young and adult rats.

PubMed

Scherer, Emilene B S; Matté, Cristiane; Ferreira, Andréa G K; Gomes, Karin M; Comim, Clarissa M; Mattos, Cristiane; Quevedo, João; Streck, Emilio L; Wyse, Angela T S

2009-12-01

Methylphenidate is a central nervous system stimulant used for the treatment of attention-deficit hyperactivity disorder. Na(+), K(+)-ATPase is a membrane-bound enzyme necessary to maintain neuronal excitability. Considering that methylphenidate effects on central nervous system metabolism are poorly known and that Na(+), K(+)-ATPase is essential to normal brain function, the purpose of this study was to evaluate the effect of this drug on Na(+), K(+)-ATPase activity in the cerebrum of young and adult rats. For acute administration, a single injection of methylphenidate (1.0, 2.0, or 10.0 mg/Kg) or saline was given to rats on postnatal day 25 or postnatal day 60, in the young and adult groups, respectively. For chronic administration, methylphenidate (1.0, 2.0, or 10.0 mg/Kg) or saline injections were given to young rats starting at postnatal day 25 once daily for 28 days. In adult rats, the same regimen was performed starting at postnatal day 60. Our results showed that acute methylphenidate administration increased Na(+), K(+)-ATPase activity in hippocampus, prefrontal cortex, and striatum of young and adult rats. In young rats, chronic administration of methylphenidate also enhanced Na(+), K(+)-ATPase activity in hippocampus and prefrontal cortex, but not in striatum. When tested in adult rats, Na(+), K(+)-ATPase activity was increased in all cerebral structures studied. The present findings suggest that increased Na(+), K(+)-ATPase activity may be associated with neuronal excitability caused by methylphenidate.

[Effect of total flavones from Cuscuta chinensis on expression of Fas/FasL, PCNA and HB-EGF in SD rats model with bromocriptine-induced abortion].

PubMed

Ma, Hong-Xia; You, Zhao-Ling; Wang, Xiao-Yun

2008-11-01

To explore the effect of total flavones from cuscuta chinensis (TFCC) on expression of Fas, PCNA and HB-EGF in SD rats model with bromocriptine-induced abortion. The model rats of bromocriptine during 6-8 d of pregnancy induced early abortion was established, adopting respectively herbs in high and low dosage and progesterone affect model rat and after 12 d, Immunohistochemical was applied to determine Fas, HB-EGF and PCNA in deciduas and placenta. Expression of PCNA on trophoblast and deciduas, HB-EGF on trophoblast, PR on deciduas in the model used Semen cuscutae flavonoid, proesterone and normal pregnacy, were significantlly higher than those of the pure model. Expression of Fas on trophoblast and deciduas in above four groups, were significantlly lower than those of the pure model. There were no expression of HB-EGF on deciduas. TFCC regulates the proliferation and apoptosis of the deciduas and cytotrophoblasts and prevents spontaneous abortions.

Prenatal choline availability modulates hippocampal neurogenesis and neurogenic responses to enriching experiences in adult female rats

PubMed Central

Glenn, Melissa J.; Gibson, Erin M.; Kirby, Elizabeth D.; Mellott, Tiffany J.; Blusztajn, Jan K.; Williams, Christina L.

2008-01-01

Increased dietary intake of choline early in life improves performance of adult rats on memory tasks and prevents their age-related memory decline. Because neurogenesis in the adult hippocampus also declines with age, we investigated whether prenatal choline availability affects hippocampal neurogenesis in adult Sprague–Dawley rats and modifies their neurogenic response to environmental stimulation. On embryonic days (ED) 12−17, pregnant rats ate a choline-supplemented (SUP-5 g/kg), choline sufficient (SFF-1.1 g/kg), or choline-free (DEF) semisynthetic diet. Adult offspring either remained in standard housing or were given 21 daily visits to explore a maze. On the last ten exploration days, all rats received daily injections of 5-bromo-2-deoxyuridine (BrdU, 100 mg/kg). The number of BrdU+ cells was significantly greater in the dentate gyrus in SUP rats compared to SFF or DEF rats. While maze experience increased the number of BrdU+ cells in SFF rats to the level seen in the SUP rats, this enriching experience did not alter cell proliferation in DEF rats. Similar patterns of cell proliferation were obtained with immunohistochemical staining for neuronal marker doublecortin, confirming that diet and exploration affected hippocampal neurogenesis. Moreover, hippocampal levels of the brain-derived neurotrophic factor (BDNF) were increased in SUP rats as compared to SFF and DEF animals. We conclude that prenatal choline intake has enduring effects on adult hippocampal neurogenesis, possibly via up-regulation of BDNF levels, and suggest that these alterations of neurogenesis may contribute to the mechanism of life-long changes in cognitive function governed by the availability of choline during gestation. PMID:17445242

Glucoregulatory responses of adult and aged rats after exposure to chronic stress.

PubMed

Odio, M R; Brodish, A

1990-01-01

Stress has been implicated as an environmental factor that may accelerate the process of biological aging. However, this proposal has remained largely anecdotal due to relatively few studies that directly tested this hypothesis. In the present experiments groups of 6-month-old and 20-month-old male F-344 rats were chronically stressed for a six-month period. After the last stress session, when the animals were 12 months of age (adult) and 26 months of age (old), control and chronically stressed rats were tested for their ability to: (a) elicit glucose and insulin responses to an acute, novel stressor; (b) remove a circulatory glucose load elicited either by acute stress exposure or by injection of d-glucose; and (c) raise insulin levels after a glucose challenge. In control rats, we observed a deficit in each of these parameters in old compared to adult rats. Exposure to chronic stress did not exacerbate deterioration of these response mechanisms in either adult or old rats. In fact, the data showed a modest improvement in glucose tolerance in chronically stressed compared to age-matched control rats. We conclude that chronic stress did not exacerbate age-dependent decline of glucoregulatory capacity. From these results and from our earlier work, we speculate that the decline during aging of the functional integrity of systems involved in the response to stress may be sustained by periodic challenges from the organism's external environment.

Interactions of Stress and CRF in Ethanol-Withdrawal Induced Anxiety in Adolescent and Adult Rats

PubMed Central

Wills, Tiffany A.; Knapp, Darin J.; Overstreet, David H.; Breese, George R.

2010-01-01

Background Repeated stress or administration of corticotropin-releasing factor (CRF) prior to ethanol exposure sensitizes anxiety-like behavior in adult rats. Current experiments determined whether adolescent rats were more sensitive to these challenges in sensitizing ethanol withdrawal-induced anxiety and altering CRF levels in brain during withdrawal. Methods Male adult and adolescent Sprague–Dawley rats were restraint stressed (1 hour) twice 1 week apart prior to a single 5-day cycle of ethanol diet (ED; stress/withdrawal paradigm). Other rats received control diet (CD) and three 1-hour restraint stress sessions. Rats were then tested 5, 24, or 48 hours after the final withdrawal for anxiety-like behavior in the social interaction (SI) test. In other experiments, adolescent rats were given two microinjections of CRF icv 1 week apart followed by 5-days of either CD or ED and tested in social interaction 5 hours into withdrawal. Finally, CRF immunoreactivity was measured in the central nucleus of the amygdala (CeA) and paraventricular nucleus (PVN) after rats experienced control diet, repeated ethanol withdrawals, or stress/withdrawal. Results Rats of both ages had reduced SI following the stress/withdrawal paradigm, and this effect recovered within 24 hours. Higher CRF doses were required to reduce SI in adolescents than previously reported in adults. CRF immunohistochemical levels were higher in the PVN and CeA of CD-exposed adolescents. In adolescent rats, repeated ethanol withdrawals decreased CRF in the CeA but was not associated with decreased CRF cell number. There was no change in CRF from adult treatments. Conclusions In the production of anxiety-like behavior, adolescent rats have equal sensitivity with stress and lower sensitivity with CRF compared to adults. Further, adolescents had higher basal levels of CRF within the PVN and CeA and reduced CRF levels following repeated ethanol withdrawals. This reduced CRF within the CeA could indicate increased

The Effects of Inflammatory Tooth Pain on Anxiety in Adult Male Rats

PubMed Central

Raoof, Maryam; Ebrahimnejad, Hamed; Abbasnejad, Mehdi; Amirkhosravi, Ladan; Raoof, Ramin; Esmaeili Mahani, Saeed; Ramazani, Mohsen; Shokouhinejad, Noushin; Khoshkhounejad, Mehrfam

2016-01-01

Introduction: This study aimed to examine the effects of induced inflammatory tooth pain on anxiety level in adult male rats. Methods: The mandibular incisors of 56 adult male rats were cut off and prefabricated crowns were fixed on the teeth. Formalin and capsaicin were injected intradentally to induce inflammatory tooth pain. Diazepam treated group received diazepam 30 minutes before intradental injection. The anxiety-related behavior was evaluated with elevated plus maze test. Results: Intradental application of chemical noxious stimuli, capsaicin and formalin, significantly affected nociceptive behaviors (P<0.001). Capsaicin (P<0.001) and formalin (P<0.01) significantly increased the anxiety levels in rats by decrease in the duration of time spent in open arm and increase in the duration of time spent in closed arm. Rats that received capsaicin made fewer open arm entries compared to the control animals (P<0.05). Capsaicin (P<0.001) and formalin (P<0.01) treated rats showed more stretch attend postures compared to the control and sham operated animals. In diazepampretreated rats, capsaicin induced algesic effect was prevented (P<0.001). Conclusion: Inflammatory pulpal pain has anxiogenic effect on rats, whereas diazepam premedication showed both anxiolytic and pain reducing effects. PMID:27563419

Age related optic nerve axonal loss in adult Brown Norway rats.

PubMed

Cepurna, William O; Kayton, Robert J; Johnson, Elaine C; Morrison, John C

2005-06-01

The effect of age on the number and morphology of optic nerve axons in adult Brown Norway rats (5-31 months old) (n=29) was examined using transmission electron microscopy (TEM). By manually counting every axon in areas representing 60% of the optic nerve cross-section, we found a significant negative correlation between age and axon count (R(2)=0.18, P<0.05). However, when the oldest animals were omitted, the relationship was no longer statistically significant. Simultaneously, the proportion of spontaneously degenerating axons increased at an exponential rate (R(2)=0.79, P<0.05), with significantly more degeneration in the 31-month group than in 5-month-old animals (ANOVA, P<0.05). This study demonstrates, using quantitative TEM methods, that optic nerve axonal numbers are relatively constant throughout the majority of the adult life of the Brown Norway rat, an increasingly popular strain for glaucoma research. Total axonal loss with aging is substantially less than that reported for other strains. The reduction in axonal numbers and the rate of axonal degeneration do not appear significantly altered until the last few months of life, failing to support some studies that have concluded that optic nerve axon loss in adult rats is linear. However, they do agree with other studies in the rat, and a similar study performed in non-human primate eyes, that concluded that aging changes in the optic nerve and retina follow a complex pattern. Therefore, the impact of animal age must be considered when modeling the course and pathophysiology of experimental glaucomatous optic nerve damage in rats.

Extinction of conditioned cues attenuates incubation of cocaine craving in adolescent and adult rats.

PubMed

Madsen, Heather B; Zbukvic, Isabel C; Luikinga, Sophia J; Lawrence, Andrew J; Kim, Jee Hyun

2017-09-01

Relapse to drug use is often precipitated by exposure to drug associated cues that evoke craving. Cue-induced drug craving has been observed in both animals and humans to increase over the first few weeks of abstinence and remain high over extended periods, a phenomenon known as 'incubation of craving'. As adolescence represents a period of vulnerability to developing drug addiction, potentially due to persistent reactivity to drug associated cues, we first compared incubation of cocaine craving in adolescent and adult rats. Adolescent (P35) and adult (P70) rats were trained to lever press to obtain intravenous cocaine, with each drug delivery accompanied by a light cue that served as the conditioned stimulus (CS). Following acquisition of stable responding, rats were tested for cue-induced cocaine-seeking after either 1 or 30days of abstinence. Additional groups of rats were also tested after 30days of abstinence, however these rats were subjected to a cue extinction session 1week into the abstinence period. Rats were injected with aripiprazole, a dopamine 2 receptor (D2R)-like partial agonist, or vehicle, 30min prior to cue extinction. We found that adolescent and adult rats acquired and maintained a similar level of cocaine self-administration, and rats of both ages exhibited a higher level of cue-induced cocaine-seeking if they were tested after 30days of abstinence compared to 1day. Incubation of cocaine craving was significantly reduced to 1day levels in both adults and adolescents that received cue extinction training. Administration of aripiprazole prior to cue extinction did not further reduce cue-induced drug-seeking. These results indicate that cue extinction training during abstinence may effectively reduce cue-induced relapse at a time when cue-induced drug craving is usually high. Copyright © 2016 Elsevier Inc. All rights reserved.

Immunotoxicity of clonazepam in adult albino rats.

PubMed

Rabei, Hanan Mostafa

2013-01-01

Clonazepam as an addictive drug is studied to elucidate its destructive effects on rats' immune system. The aim of the current work was to study the immunologic changes induced by sub-chronic administration of clonazepam for three weeks followed by a withdrawal period in adult male albino rats. Seventy-two Sprague Dawley rats were divided into three equal groups. The first group was used as control; the second and third groups were treated with clonazepam. Six rats from each group were sacrificed weekly. Data showed that clonazepam induced a significant suppression in the level of IFN-gamma cortisol production, total splenocytes count and lymphocytes transformation induced by PHA mitogen along the experimental period especially in the third group. However, subchronic doses of clonazepam increased the production of IL-10 in both treated groups. Moreover, significant DNA damage in the peripheral blood lymphocytes of both treated groups was observed along the duration of the study. In conclusion, the immune system responses can be adversely affected to a greater extent by sub-chronic administration of clonazepam and should be prescribed cautiously as patients may turn addict to it.

Eating high fat chow enhances the locomotor-stimulating effects of cocaine in adolescent and adult female rats.

PubMed

Baladi, Michelle G; Koek, Wouter; Aumann, Megan; Velasco, Fortino; France, Charles P

2012-08-01

Dopamine systems vary through development in a manner that can impact drugs acting on those systems. Dietary factors can also impact the effects of drugs acting on dopamine systems. This study examined whether eating high fat chow alters locomotor effects of cocaine (1-56 mg/kg) in adolescent and adult female rats. Cocaine was studied in rats (n = 6/group) with free access to standard (5.7% fat) or high fat (34.3%) chow or restricted access to high fat chow (body weight matched to rats eating standard chow). After 1 week of eating high fat chow (free or restricted access), sensitivity to cocaine was significantly increased in adolescent and adult rats, compared with rats eating standard chow. Sensitivity to cocaine was also increased in adolescent rats with restricted, but not free, access to high fat chow for 4 weeks. When adolescent and adult rats that previously ate high fat chow ate standard chow, sensitivity to cocaine returned to normal. In adolescent and adult female rats eating high fat chow, but not those eating standard chow, sensitivity to cocaine increased progressively over once weekly tests with cocaine (i.e., sensitization) in a manner that was not statistically different between adolescents and adults. These results show that eating high fat chow alters sensitivity of female rats to acutely administered cocaine and also facilitates the development of sensitization to cocaine. That the type of food consumed can increase drug effects might have relevance to vulnerability to abuse cocaine in the female population.

Analysis of testosterone effects on sonic hedgehog signaling in juvenile, adolescent and adult sprague dawley rat penis.

PubMed

Bond, Christopher W; Angeloni, Nicholas L; Podlasek, Carol A

2010-03-01

Smooth muscle apoptosis is a major contributing factor to erectile dysfunction (ED) development in prostatectomy and diabetic patients and animal models. A critical regulator of penile smooth muscle and apoptosis is Sonic hedgehog (SHH). The SHH protein is decreased in ED models and SHH treatment of cavernous nerve (CN) injured rats prevents smooth muscle apoptosis. A close association between androgen deficiency and ED has been suggested in the literature, but few studies have examined the molecular effects on penile smooth muscle and on known signaling mechanisms that regulate morphology. Aim. Examine testosterone and SHH interaction in eugonadal adult, adolescent and juvenile rats by performing castration studies and treatment with supraphysiological testosterone. The eugonadal adult Sprague Dawley rats were either treated with testosterone for 7 or 14 days (N = 14) or were castrated for 4 or 7 days (N = 12). The juvenile rats were treated with testosterone for 8 days (N = 7). The adolescent rats were castrated and sacrificed at P88 (N = 8). The control rats had empty vehicle (N = 22) or sham surgery (N = 20). The active form of SHH protein and mRNA were quantified by semi-quantitative immunohistochemical analysis and real-time reverse transcriptase polymerase chain reaction (RT-PCR). Testosterone treatment did not alter SHH signaling in juvenile rats. Shh mRNA increased 3.2-fold and SHH protein increased 1.2-fold in rats castrated during puberty. In adult rats, castration decreased Shh mRNA 3.2-fold but did not alter SHH protein. Testosterone supplement in adult rats increased Shh mRNA 2.3-fold and decreased SHH protein 1.3-fold. SHH signaling is independent of testosterone in normal juvenile rats and is sensitive to testosterone during adolescence, while testosterone supplement in the adult adversely impacts SHH signaling in a very similar manner to that observed with CN injury.

Effects of prenatal caffeine exposure on glucose homeostasis of adult offspring rats

NASA Astrophysics Data System (ADS)

Kou, Hao; Wang, Gui-hua; Pei, Lin-guo; Zhang, Li; Shi, Chai; Guo, Yu; Wu, Dong-fang; Wang, Hui

2017-12-01

Epidemiological evidences show that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR). The IUGR offspring also present glucose intolerance and type 2 diabetes mellitus after maturity. We have previously demonstrated that PCE induced IUGR and increased susceptibility to adult metabolic syndrome in rats. This study aimed to further investigate the effects of PCE on glucose homeostasis in adult offspring rats. Pregnant rats were administered caffeine (120 mg/kg/day, intragastrically) from gestational days 11 to 20. PCE offspring presented partial catch-up growth pattern after birth, characterizing by the increased body weight gain rates. Meanwhile, PCE had no significant influences on the basal blood glucose and insulin phenotypes of adult offspring but increased the glucose tolerance, glucose-stimulated insulin section and β cell sensitivity to glucose in female progeny. The insulin sensitivity of both male and female PCE offspring were enhanced accompanied with reduced β cell fraction and mass. Western blotting results revealed that significant augmentation in protein expression of hepatic insulin signaling elements of PCE females, including insulin receptor (INSR), insulin receptor substrate 1 (IRS-1) and the phosphorylation of serine-threonine protein kinase (Akt), was also potentiated. In conclusion, we demonstrated that PCE reduced the pancreatic β mass but increased the glucose tolerance in adult offspring rats, especially for females. The adaptive compensatory enhancement of β cell responsiveness to glucose and elevated insulin sensitivity mainly mediated by upregulated hepatic insulin signaling might coordinately contribute to the increased glucose tolerance.

Effect of different doses of Malaysian honey on reproductive parameters in adult male rats.

PubMed

Mohamed, M; Sulaiman, S A; Jaafar, H; Sirajudeen, K N S

2012-05-01

The aim of this study was to evaluate the effect of different doses of Malaysian honey on male reproductive parameters in adult rats. Thirty-two healthy adult male Sprague-Dawley rats were randomly divided into four groups (eight rats per group). Group 1 (control group) was given 0.5 ml of distilled water. Groups 2, 3 and 4 were given 0.2, 1.2 and 2.4 g kg(-1) body weight of honey respectively. The rats were treated orally by gavage once daily for 4 weeks. Honey did not significantly alter body and male reproductive organs weights. The rats in Group 3 which received honey at 1.2 g kg(-1) had significantly higher epididymal sperm count than those in Groups 1, 2 and 4. No significant differences were found for the percentage of abnormal sperm, elongated spermatid count, reproductive hormonal levels as well as the histology of the testis among the groups. In conclusion, Malaysian honey at a dose of 1.2 g kg(-1) daily significantly increased epididymal sperm count without affecting spermatid count and reproductive hormones. These findings might suggest that oral administration of honey at this dose for 4 weeks may enhance spermiogenesis in adult rats. © 2011 Blackwell Verlag GmbH.

DELAYED PREPUTIAL SEPARATION (PPS) AND SP22 MEASUREMENT IN RATS ADMINISTERED BROMOCHLOROACETIC ACID (BCA) IN DRINKING WATER

EPA Science Inventory

Reproductive effects of BCA were determined in a dose range finding study (DRFS) and definitive two-generational study. Adult male and female CD� (SD) rats were administered BCA in drinking water for two weeks in the DRFS (10/sex/group) and ten weeks in the definitive study (25/s...

Early treatment with metformin induces resistance against tumor growth in adult rats

PubMed Central

Trombini, Amanda B; Franco, Claudinéia CS; Miranda, Rosiane A; de Oliveira, Júlio C; Barella, Luiz F; Prates, Kelly V; de Souza, Aline A; Pavanello, Audrei; Malta, Ananda; Almeida, Douglas L; Tófolo, Laize P; Rigo, Kesia P; Ribeiro, Tatiane AS; Fabricio, Gabriel S; de Sant’Anna, Juliane R; Castro-Prado, Marialba AA; de Souza, Helenir Medri; de Morais, Hely; Mathias, Paulo CF

2015-01-01

It is known that antidiabetic drug metformin, which is used worldwide, has anti-cancer effects and can be used to prevent cancer growth. We tested the hypothesis that tumor cell growth can be inhibited by early treatment with metformin. For this purpose, adult rats chronically treated with metformin in adolescence or in adulthood were inoculated with Walker 256 carcinoma cells. Adult rats that were treated with metformin during adolescence presented inhibition of tumor growth, and animals that were treated during adult life did not demonstrate any changes in tumor growth. Although we do not have data to disclose a molecular mechanism to the preventive metformin effect, we present, for the first time, results showing that cancer growth in adult life is dependent on early life intervention, thus supporting a new therapeutic prevention for cancer. PMID:26024008

Adaptations of young adult rat cortical bone to 14 days of spaceflight

NASA Technical Reports Server (NTRS)

Vailas, A. C.; Vanderby, R., Jr.; Martinez, D. A.; Ashman, R. B.; Ulm, M. J.; Grindeland, R. E.; Durnova, G. N.; Kaplanskii, A.

1992-01-01

To determine whether mature humeral cortical bone would be modified significantly by an acute exposure to weightlessness, adult rats (110 days old) were subjected to 14 days of microgravity on the COSMOS 2044 biosatellite. There were no significant changes in peak force, stiffness, energy to failure, and displacement at failure in the flight rats compared with ground-based controls. Concentrations and contents of hydroxyproline, calcium, and mature stable hydroxylysylpyridinoline and lysylpyridinoline collagen cross-links remained unchanged after spaceflight. Bone lengths, cortical and endosteal areas, and regionl thicknesses showed no significant differences between flight animals and ground controls. The findings suggest that responsiveness of cortical bone to microgravity is less pronounced in adult rats than in previous spaceflight experiments in which young growing animals were used. It is hypothesized that 14 days of spaceflight may not be sufficient to impact the biochemical and biomechanical properties of cortical bone in the mature rat skeleton.

Fertilizability of Superovulated Eggs by Estrous Stage-independent PMSG/hCG Treatment in Adult Wistar-Imamichi Rats

PubMed Central

Kon, Hiroe; Hokao, Ryoji; Shinoda, Motoo

2014-01-01

We investigated the fertilization and developmental ability of superovulated eggs obtained from adult Wistar-Imamichi (WI) rats, by using pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) treatment. Female WI rats, 11–13 weeks of age, were divided into four groups by estrous stage (metestrus [ME], diestrus [DE], proestrus [PE], or estrus [E]). PMSG (150 IU/kg) and hCG (75 IU/kg) were injected at an interval of 48 or 55 h and the female rats were mated with mature male rats. The ovulated eggs were collected 20, 24, and 27 h after hCG injection. Regardless of the estrous stage at the time of PMSG injection, the treated rats mated and ovulated similar to the untreated spontaneously ovulated rats (S group). Although the proportion of fertilized eggs in the E- and PE-treated groups was less than the S group 20 h after hCG injection, the proportion was not different among all treated and S groups 24 h after hCG injection. The proportion of fertilized eggs using in vitro fertilization and the proportion of offspring obtained from 2-cell stage embryo transfer did not differ among the treated and S groups. In comparison with PMSG/hCG-treated immature rats, mating and ovulation rate of adult rats were significantly higher. The proportion of fertilized eggs obtained from mated rats did not differ between immature and adult rats. These results demonstrate that adult WI rats are good egg donors for reproductive biotechnological studies using unfertilized or fertilized eggs. PMID:24770643

Reinstatement of cocaine seeking induced by drugs, cues, and stress in adolescent and adult rats

PubMed Central

Carroll, Marilyn E.

2010-01-01

Rationale In human and animal studies, adolescence marks a period of increased vulnerability to the initiation and subsequent abuse of drugs. Adolescents may be especially vulnerable to relapse, and a critical aspect of drug abuse is that it is a chronically relapsing disorder. However, little is known of how vulnerability factors such as adolescence are related to conditions that induce relapse, triggered by the drug itself, drug-associated cues, or stress. Objective The purpose of this study was to compare adolescent and adult rats on drug-, cue-, and stress-induced reinstatement of cocaine-seeking behavior. Methods On postnatal days 23 (adolescents) and 90 (adults), rats were implanted with intravenous catheters and trained to lever press for i.v. infusions of cocaine (0.4 mg/kg) during two daily 2-h sessions. The rats then self-administered i.v. cocaine for ten additional sessions. Subsequently, visual and auditory stimuli that signaled drug delivery were unplugged, and rats were allowed to extinguish lever pressing for 20 sessions. Rats were then tested on cocaine-, cue-, and yohimbine (stress)-induced cocaine seeking using a within-subject multicomponent reinstatement procedure. Results Results indicated that adolescents had heightened cocaine seeking during maintenance and extinction compared to adults. During reinstatement, adolescents (vs adults) responded more following cocaine- and yohimbine injections, while adults (vs adolescents) showed greater responding following presentations of drug-associated cues. Conclusion These results demonstrated that adolescents and adults differed across several measures of drug-seeking behavior, and adolescents may be especially vulnerable to relapse precipitated by drugs and stress. PMID:19953228

Toluene effects on the motor activity of adolescent, young-adult, middle-age and senescent male Brown Norway rats.

PubMed

MacPhail, R C; Farmer, J D; Jarema, K A

2012-01-01

Life stage is an important risk factor for toxicity. Children and aging adults, for example, are more susceptible to certain chemicals than are young adults. In comparison to children, relatively little is known about susceptibility in older adults. Additionally, few studies have compared toxicant susceptibility across a broad range of life stages. Results are presented for behavioral evaluations of male Brown Norway rats obtained as adolescents (1 month), or young (4 months), middle-age (12 months) and senescent (24 months) adults. Motor activity was evaluated in photocell devices during 30-min sessions. Age-related baseline characteristics and sensitivity to toluene (0, 300, 650, or 1000mg/kg, p.o.) were determined. In Experiment 1, young-adult, middle-age and senescent rats were treated with corn-oil vehicle before five weekly test sessions. Baselines of horizontal and vertical activity decreased with age, but each age-group's averages remained stable across weeks of testing. Baseline activity of older rats was more variable than that of the young adults; older rats were also more variable individually from week to week. Toluene (1000mg/kg) increased horizontal activity proportionately more in senescent rats (ca. 300% of control) than in middle-age or young-adult rats (ca.145-175% of control). Experiment 2 established toluene dose-effect functions in individual adolescent, young-adult, middle-age and senescent rats; each rat received all treatments, counterbalanced across four weekly sessions. Toluene produced dose-related increases in horizontal activity that increased proportionately with age. Experiment 3 replicated the effects of toluene (1000mg/kg) in Experiment 1, showing that toluene-induced increases in horizontal activity were greatest in the oldest rats. Collectively, the results show that aging increased susceptibility to toluene and also increased variability in toluene response. Given the rapid growth of the aged population, further research is

Properties of single motor units in medial gastrocnemius muscles of adult and old rats.

PubMed Central

Kadhiresan, V A; Hassett, C A; Faulkner, J A

1996-01-01

1. The purpose of this study was to determine the role of motor unit remodelling in the deficit that develops in the maximum isometric tetanic force (Fo) of whole medial gastrocnemius (MGN) muscles in old compared with adult rats. The Fo values and morphological data were determined for MGN muscles and eighty-two single motor units in muscles of adult (10-12 months) and sixty-two units in those of old (24-26 months) F344 rats. During an unfused tetanus, fast and slow (S) motor units were identified by the presence and absence of sag, respectively. Fast-fatigable (FF) and fast-fatigue-resistant (FR) units were classified by fatigue indices less than or greater than 0.50, respectively. 2. For old rats, whole MGN muscle Fo was 29% less than the value of 11.2 N measured for adult rats. The deficit in whole muscle Fo of old rats resulted from equivalent decreases in the number of motor units, 16% smaller than the adult value of ninety-seven, and in the mean motor unit Fo value, 14% less than the adult value of 117 mN. 3. With ageing, little motor unit remodelling occurred in FR units, whereas the S and FF motor units demonstrated dramatic, but opposing, changes. For S units, the number of units remained constant, but the number of fibres per motor unit increased 3-fold from 57 to 165. In contrast, the number of FF units decreased by 34% and the number of fibres per motor unit of the remaining units decreased to 86% of the adult value of 333. The age-related remodelling of motor units appeared to involve denervation of fast muscle fibres with reinnervation of denervated fibres by axonal sprouting from slow fibres. PMID:8782115

Contextual fear conditioning differs for infant, adolescent, and adult rats

PubMed Central

Esmorís-Arranz, Francisco J.; Méndez, Cástor; Spear, Norman E.

2009-01-01

Contextual fear conditioning was tested in infant, adolescent, and adult rats in terms of Pavlovian conditioned suppression. When a discrete auditory conditioned stimulus (CS) was paired with footshock (unconditioned stimulus, US) within the largely olfactory context, infants and adolescents conditioned to the context with substantial effectiveness but adult rats did not. When unpaired presentations of the CS and US occurred within the context, contextual fear conditioning was strong for adults, weak for infants, but about as strong for adolescents as when pairings of CS and US occurred in the context. Nonreinforced presentations of either the CS or context markedly reduced contextual fear conditioning in infants, but, in adolescents, CS extinction had no effect on contextual fear conditioning, although context extinction significantly reduced it. Neither CS extinction nor context extinction affected responding to the CS-context compound in infants, suggesting striking discrimination between the compound and its components. Female adolescents showed the same lack of effect of component extinction on response to the compound as infants, but CS extinction reduced responding to the compound in adolescent males, a sex difference seen also in adults. Theoretical implications are discussed for the development of perceptual-cognitive processing and hippocampus role. PMID:18343048

Early life stress impairs social recognition due to a blunted response of vasopressin release within the septum of adult male rats.

PubMed

Lukas, Michael; Bredewold, Remco; Landgraf, Rainer; Neumann, Inga D; Veenema, Alexa H

2011-07-01

Early life stress poses a risk for the development of psychopathologies characterized by disturbed emotional, social, and cognitive performance. We used maternal separation (MS, 3h daily, postnatal days 1-14) to test whether early life stress impairs social recognition performance in juvenile (5-week-old) and adult (16-week-old) male Wistar rats. Social recognition was tested in the social discrimination test and defined by increased investigation by the experimental rat towards a novel rat compared with a previously encountered rat. Juvenile control and MS rats demonstrated successful social recognition at inter-exposure intervals of 30 and 60 min. However, unlike adult control rats, adult MS rats failed to discriminate between a previously encountered and a novel rat after 60 min. The social recognition impairment of adult MS rats was accompanied by a lack of a rise in arginine vasopressin (AVP) release within the lateral septum seen during social memory acquisition in adult control rats. This blunted response of septal AVP release was social stimulus-specific because forced swimming induced a rise in septal AVP release in both control and MS rats. Retrodialysis of AVP (1 μg/ml, 3.3 μl/min, 30 min) into the lateral septum during social memory acquisition restored social recognition in adult MS rats at the 60-min interval. These studies demonstrate that MS impairs social recognition performance in adult rats, which is likely caused by blunted septal AVP activation. Impaired social recognition may be linked to MS-induced changes in other social behaviors like aggression as shown previously. Copyright © 2010 Elsevier Ltd. All rights reserved.

Supplemental dietary choline during development exerts antidepressant-like effects in adult female rats.

PubMed

Glenn, Melissa J; Adams, Raven S; McClurg, Lauren

2012-03-14

Perinatal choline supplementation in rats is neuroprotective against insults such as fetal alcohol exposure, seizures, and advanced age. In the present study we explored whether dietary choline supplementation may also confer protection from psychological challenges, like stress, and act as a natural buffer against stress-linked psychological disorders, like depression. We previously found that choline supplementation increased adult hippocampal neurogenesis, a function compromised by stress, lowered in depression, and boosted by antidepressants; and increased levels of growth factors linked to depression, like brain-derived neurotrophic factor. Together, these were compelling reasons to study the role of choline in depressed mood. To do this, we treated rats with a choline supplemented diet (5 mg/kg choline chloride in AIN76A) prenatally on embryonic days 10-22, on postnatal days (PD) 25-50, or as adults from PD75 onward. Outside of these treatment periods rats were fed a standard diet (1.1 mg/kg choline chloride in AIN76A); control rats consumed only this diet throughout the study. Starting on PD100 rats' anxiety-like responses to an open field, learning in a water maze, and reactivity to forced swimming were assessed. Rats given choline supplementation during pre- or post-natal development, but not adult-treated rats, were less anxious in the open field and less immobile in the forced swim test than control rats. These effects were not mediated by a learning deficit as all groups performed comparably and well in the water maze. Thus, we offer compelling support for the hypothesis that supplemental dietary choline, at least when given during development, may inoculate an individual against stress and major psychological disorders, like depression. Copyright © 2012 Elsevier B.V. All rights reserved.

Prenatal Opiate Exposure Attenuates LPS-Induced Fever in Adult Rats: Role of Interleukin-1β

PubMed Central

Hamilton, Kathryn L.; Franklin, La’Tonyia M.; Roy, Sabita; Schrott, Lisa M.

2009-01-01

Much is known about the immunomodulatory effects of opiate exposure and withdrawal in adult rats. However, little research has delved into understanding the immunological consequences of prenatal opiate exposure and postnatal withdrawal. The purpose of the current study was to measure changes in responding to immune stimulation in adult rats following prenatal opiate exposure. Further, we sought to characterize the role of interleukin (IL)-1β in these changes. Following prenatal exposure to the long-acting opiate l-alpha-acetylmethadol (LAAM), adult male and female rats were assessed for their fever response to lipopolysaccharide (LPS). Blood and tissue samples were collected to measure circulating IL-1β and IL-1β protein in the hypothalamus and spleen. Prenatal LAAM exposure resulted in a blunted fever response to LPS injection without any changes in basal body temperature or in response to saline injection. Circulating IL-1β was not affected by prenatal LAAM exposure, nor was IL-1β protein in the spleen. Interestingly, mature IL-1β protein was elevated in the hypothalamus of prenatally LAAM-treated rats. These results indicate that prenatal opiate exposure blunts the fever response of adult offspring. Direct action of IL-1β is likely not the cause of the dysfunction reported here. However, alterations in signaling mechanisms downstream from IL-1β may play a role in the altered fever response in adult rats treated prenatally with opiates. PMID:17196563

Age-dependent MDPV-induced taste aversions and thermoregulation in adolescent and adult rats.

PubMed

Merluzzi, Andrew P; Hurwitz, Zachary E; Briscione, Maria A; Cobuzzi, Jennifer L; Wetzell, Bradley; Rice, Kenner C; Riley, Anthony L

2014-07-01

Adolescent rats are more sensitive to the rewarding and less sensitive to the aversive properties of various drugs of abuse than their adult counterparts. Given a nationwide increase in use of "bath salts," the present experiment employed the conditioned taste aversion procedure to assess the aversive effects of 3,4-methylenedioxypyrovalerone (MDPV; 0, 1.0, 1.8, or 3.2 mg/kg), a common constituent in "bath salts," in adult and adolescent rats. As similar drugs induce thermoregulatory changes in rats, temperature was recorded following MDPV administration to assess if thermoregulatory changes were related to taste aversion conditioning. Both age groups acquired taste aversions, although these aversions were weaker and developed at a slower rate in the adolescent subjects. Adolescents increased and adults decreased body temperature following MDPV administration with no correlation to aversions. The relative insensitivity of adolescents to the aversive effects of MDPV suggests that MDPV may confer an increased risk in this population. © 2013 Wiley Periodicals, Inc.

Regulation of Peripheral Catecholamine Responses to Acute Stress in Young Adult and Aged F-344 Rats.

PubMed

McCarty; Pacak; Goldstein; Eisenhofer

1997-12-01

Young adult (3-month-old) and aged (24-month-old) Fischer-344 male rats received i.v. infusions of 3H-labeled norepinephrine (NE) and epinephrine (EPI) to examine the effects of aging on the neuronal uptake of NE and sympathoadrenal release of NE and EPI. Spillovers of NE and EPI into plasma and their clearance from the circulation were estimated from plasma concentrations of endogenous and 3H-labeled NE and EPI. The efficiency of neuronal uptake was assessed from changes in plasma clearance of NE and concentrations of its intraneuronal metabolite, dihydroxyphenylglycol (DHPG), during immobilization stress or neuronal uptake blockade with desipramine. Stress-induced increases in plasma NE and higher plasma NE concentrations in aged compared to young adult rats were due to both decreases in NE clearance and increases in NE spillover. EPI spillover and clearance were reduced in aged compared to young adult rats, so that plasma EPI levels did not differ between groups. Young adult and aged rats had similar desipramine-induced decreases in NE clearance, whereas desipramine-sensitive decreases and stress-induced increases in plasma DHPG were larger in aged rats. This indicates that neuronal uptake is intact and that increased NE spillover at rest and during stress in aged rats reflects increased NE release from sympathetic nerves. The results show that aging is associated with divergent decreases in EPI release from the adrenal medulla and increases in NE release from sympathetic nerves. Increased plasma concentrations of NE in aged compared to young adult rats also result from decreased circulatory clearance of NE, but this does not reflect any age-related impairment of NE reuptake.

Differences in susceptibility of rat strains to experimental infection with Taenia teaniaeformis.

PubMed

Williams, J F; Shearer, A M; Ravitch, M M

1981-08-01

Age-matched, outbred, female, Sprague-Dawley-derived rats from different commercial suppliers were compared for their susceptibility to the establishment and growth of Taenia taeniaeformis. Two of the strains, Spb:[SD] and Kng:[SD], gave very similar results, but the third, Hap:[SD]f, was considerably less receptive. Approximately one in eight of the Hap:[SD]f rats proved refractory to infection, and worm growth was slower and more variable than in Spb:[SD] rats. Male Spb:[SD] rats were not detectably different from females in susceptibility or parasite growth rate. Female rats of four different inbred lines all accepted infection, though the proportion of infective eggs giving rise to hepatic cysts differed. These differences, however, were overshadowed by variations observed in susceptibility of inbred rats of the same strain (Wistar-Lewis) purchased from different commercial suppliers. The results emphasize the need for careful standardization of laboratory procedures and rat strains for experimentation with this host-parasite system. In addition, they illustrate the dangers of extrapolation from the extensive literature of the influence of rat strain and sex on susceptibility to infection with T. taeniaeformis.

Effect of two medium chain triglycerides-supplemented diets on synaptic morphology in the cerebellar cortex of late-adult rats.

PubMed

Balietti, Marta; Fattoretti, Patrizia; Giorgetti, Belinda; Casoli, Tiziana; Di Stefano, Giuseppina; Platano, Daniela; Aicardi, Giorgio; Lattanzio, Fabrizia; Bertoni-Freddari, Carlo

2009-12-01

Ketogenic diets (KDs) have shown beneficial effects in experimental models of neurodegeneration, designating aged individuals as possible recipients. However, few studies have investigated their consequences on aging brain. Here, late-adult rats (19 months of age) were fed for 8 weeks with two medium chain triglycerides-supplemented diets (MCT-SDs) and the average area (S), numeric density (Nv(s)), and surface density (S(v)) of synapses, as well as the average volume (V), numeric density (Nv(m)), and volume density (V(v)) of synaptic mitochondria were evaluated in granule cell layer of the cerebellar cortex (GCL-CCx) by computer-assisted morphometric methods. MCT content was 10 or 20%. About 10%MCT-SD induced the early appearance of senescent patterns (decreased Nv(s) and Nv(m); increased V), whereas 20%MCT-SD caused no changes. Recently, we have shown that both MCT-SDs accelerate aging in the stratum moleculare of CA1 (SM CA1), but are "antiaging" in the outer molecular layer of dentate gyrus (OML DG). Since GCL-CCx is more vulnerable to age than OML DG but less than SM CA1, present and previous results suggest that the effects of MCT-SDs in the aging brain critically depend on neuronal vulnerability to age, besides MCT percentage.

Oleamide restores sleep in adult rats that were subjected to maternal separation.

PubMed

Reyes Prieto, Nidia M; Romano López, Antonio; Pérez Morales, Marcel; Pech, Olivia; Méndez-Díaz, Mónica; Ruiz Contreras, Alejandra E; Prospéro-García, Oscar

2012-12-01

Maternal separation (MS) induces a series of changes in rats' behavior; among them a reduction in spontaneous sleep. One potentially impaired system is the endocannabinoid system (eCBs), since it contributes to generate sleep. To investigate if there are situations early in life that affect the eCBs, which would contribute to make rats vulnerable to suffering insomnia, we studied the rodent model of MS. Rats were separated from their mothers for 3h-periods daily, from postnatal day (PND) 2 to PND 16. Once they gained 250g of body weight (adult rats), they were implanted with electrodes to record the sleep-waking cycle (SWC). MS rats and non-MS (NMS) siblings were assigned to one of the following groups: vehicle, oleamide (OLE, an agonist of the cannabinoid receptor 1, CB1R), OLE+AM251 (an antagonist of the CB1R) and AM251 alone. Expression of the CBR1 receptor was also analyzed in the frontal cortex (FCx) and in the hippocampus (HIP) of both NMS and MS rats. Results indicated that MS induced a reduction in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep with the consequent increase in waking (W) as compared to NMS siblings. OLE normalized the SWC, and AM251 blocked such an effect. CB1R expression was reduced in the FCx and in the HIP of MS rats. Our results indicate that MS reduces sleep and CB1R expression and OLE improves sleep in adult rats. Copyright © 2012 Elsevier Inc. All rights reserved.

Event-Related Potential responses to the acute and chronic effects of alcohol in adolescent and adult Wistar rats

PubMed Central

Ehlers, Cindy L.; Desikan, Anita; Wills, Derek N.

2014-01-01

Background The present study explored the hypothesis that adolescent ethanol exposure may cause long lasting changes in ethanol sensitivity by exploring the age-related effects of acute alcohol on intoxication and on event-related potential (ERP) responses to acoustic stimuli in ethanol naïve adolescent and adult male Wistar rats and in adult rats that were exposed to chronic ethanol/control conditions during adolescence. Methods Ethanol naïve adolescent (postnatal day 32 (PD32)) and adult male rats (PD99) were included in the first study. In a second study, rats were exposed to 5 weeks of ethanol vapor (Blood ethanol concentrations @ 175 mg%) or air from PD24 to PD59 and allowed to mature until PD90. In both studies rats were implanted with cortical recording electrodes, and the effects of acute ethanol (0.0, 1.5, and 3.0 g/kg) on behavioral and ERP responses were assessed. Results Adolescents were found to have higher amplitude and longer latency P3a and P3b components at baseline as compared to adult rats, and ethanol was found to produce a robust dose-dependent increase in the latency of the P3a and P3b components of the auditory ERP recorded in cortical sites in both adolescents and adults. However, ethanol produced significantly larger delays in P3a and P3b latencies in adults as compared to adolescents. Acute ethanol administration was also found to produce a robust dose dependent increase in the latency of the P3a and P3b components in adult animals exposed to ethanol vapor as adolescents and air exposed controls; however, larger acute ethanol-induced increases in P3a and P3b latencies were seen in controls as compared to adolescent vapor exposed rats. Conclusions Adolescent rats have a less intense P3 latency response to acute ethanol administration when compared to adult rats. Exposure to chronic ethanol during adolescence can cause “retention” of the adolescent phenotype of reduced P3 latency sensitivity to ethanol. PMID:24483322

Intrauterine programming mechanism for hypercholesterolemia in prenatal caffeine-exposed female adult rat offspring.

PubMed

Xu, Dan; Luo, Hanwen W; Hu, Wen; Hu, Shuwei W; Yuan, Chao; Wang, Guihua H; Zhang, Li; Yu, Hong; Magdalou, Jacques; Chen, Liaobin B; Wang, Hui

2018-05-02

Clinical and animal studies have indicated that hypercholesterolemia and its associated diseases have intrauterine developmental origins. Our previous studies showed that prenatal caffeine exposure (PCE) led to fetal overexposure to maternal glucocorticoids (GCs) and increased serum total cholesterol levels in adult rat offspring. This study further confirms the intrauterine programming of PCE-induced hypercholesterolemia in female adult rat offspring. Pregnant Wistar rats were intragastrically administered caffeine (30, 60, and 120 mg/kg/d) from gestational day (GD)9 to 20. Female rat offspring were euthanized at GD20 and postnatal wk 12; several adult rat offspring were additionally subjected to ice-water swimming stimulation to induce chronic stress prior to death. The effects of GCs on cholesterol metabolism and epigenetic regulation were verified using the L02 cell line. The results showed that PCE induced hypercholesterolemia in adult offspring, which manifested as significantly higher levels of serum total cholesterol and LDL cholesterol (LDL-C) as well as higher ratios of LDL-C/HDL cholesterol. We further found that the cholesterol levels were increased in fetal livers but were decreased in fetal blood, accompanied by increased maternal blood cholesterol levels and reduced placental cholesterol transport. Furthermore, analysis of PCE offspring in the uterus and in a postnatal basal/chronic stress state and the results of in vitro experiments showed that hepatic cholesterol metabolism underwent GC-dependent changes and was associated with cholesterol synthase via abnormalities in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) histone acetylation. We concluded that, to compensate for intrauterine placentally derived decreases in fetal blood cholesterol levels, high intrauterine GC levels activated fetal hepatic CCAAT enhancer binding protein α signaling and down-regulated Sirtuin1 expression, which mediated the high levels of histone acetylation ( via H3K9

Copolymer-1 enhances cognitive performance in young adult rats

PubMed Central

Meneses, Alfredo; Cruz-Martínez, Yolanda; Anaya-Jiménez, Rosa María; Liy-Salmerón, Gustavo; Carvajal, Horacio Guillermo; Ponce-López, Maria Teresa

2018-01-01

Cognitive impairment is a dysfunction observed as a sequel of various neurodegenerative diseases, as well as a concomitant element in the elderly stages of life. In clinical settings, this malfunction is identified as mild cognitive impairment. Previous studies have suggested that cognitive impairment could be the result of a reduction in the expression of brain-derived neurotrophic factor (BDNF) and/or immune dysfunction. Copolymer-1 (Cop-1) is an FDA-approved synthetic peptide capable of inducing the activation of Th2/3 cells, which are able to release BDNF, as well as to migrate and accumulate in the brain. In this study, we evaluated the effect of Cop-1 immunization on improvement of cognition in adult rats. For this purpose, we performed four experiments. We evaluated the effect of Cop-1 immunization on learning/memory using the Morris water maze for spatial memory and autoshaping for associative memory in 3- or 6-month-old rats. BDNF concentrations at the hippocampus were determined by ELISA. Cop-1 immunization induced a significant improvement of spatial memory and associative memory in 6-month-old rats. Likewise, Cop-1 improved spatial memory and associative memory when animals were immunized at 3 months and evaluated at 6 months old. Additionally, Cop-1 induced a significant increase in BDNF levels at the hippocampus. To our knowledge, the present investigation reports the first instance of Cop-1 treatment enhancing cognitive function in normal young adult rats, suggesting that Cop-1 may be a practical therapeutic strategy potentially useful for age- or disease-related cognitive impairment. PMID:29494605

The impact of social stress during adolescence or adulthood and coping strategy on cognitive function of female rats.

PubMed

Snyder, Kevin; Barry, Mark; Plona, Zachary; Ho, Andrew; Zhang, Xiao-Yan; Valentino, Rita J

2015-06-01

The age of stressor exposure can determine its neurobehavioral impact. For example, exposure of adolescent male rats to resident-intruder stress impairs cognitive flexibility in adulthood. The current study examined the impact of this stressor in female rats. Rats were exposed to resident-intruder stress during early adolescence (EA), mid-adolescence (MA) or adulthood (Adult). They were tested in an operant strategy-shifting task for side discrimination (SD), reversal learning (REV) and strategy set-shifting (SHIFT) the following week. Performance varied with age, stress and coping style. MA and EA rats performed SD and SHIFT better than other ages, respectively. Social stress impaired performance in rats depending on their coping strategy as determined by a short (SL) or long (LL) latency to become subordinate. SL rats were impaired in SD and REV, whereas EA-LL rats were impaired in SHIFT. These impairing effects of female adolescent stress did not endure into adulthood. Strategy set-shifting performance for female adolescents was positively correlated with medial prefrontal cortex (mPFC) activation as indicated by c-fos expression suggesting that this region is engaged during task performance. This contrasts with the inverse relationship between these indices reported for male adolescent rats. Together, the results demonstrate that social stress produces cognitive impairments for female rats that depend on age and coping style but unlike males, the impairing effects of female adolescent social stress are immediate and do not endure into adulthood. Sex differences in the impact of adolescent social stress on cognition may reflect differences in mPFC engagement during the task. Copyright © 2015 Elsevier B.V. All rights reserved.

Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained

PubMed Central

Lensu, Sanna; Ahtiainen, Juha P.; Johansson, Petra P.; Koch, Lauren G.; Britton, Steven L.; Kainulainen, Heikki

2016-01-01

Key points Aerobic exercise, such as running, enhances adult hippocampal neurogenesis (AHN) in rodents.Little is known about the effects of high‐intensity interval training (HIT) or of purely anaerobic resistance training on AHN.Here, compared with a sedentary lifestyle, we report a very modest effect of HIT and no effect of resistance training on AHN in adult male rats.We found the most AHN in rats that were selectively bred for an innately high response to aerobic exercise that also run voluntarily and increase maximal running capacity.Our results confirm that sustained aerobic exercise is key in improving AHN. Abstract Aerobic exercise, such as running, has positive effects on brain structure and function, such as adult hippocampal neurogenesis (AHN) and learning. Whether high‐intensity interval training (HIT), referring to alternating short bouts of very intense anaerobic exercise with recovery periods, or anaerobic resistance training (RT) has similar effects on AHN is unclear. In addition, individual genetic variation in the overall response to physical exercise is likely to play a part in the effects of exercise on AHN but is less well studied. Recently, we developed polygenic rat models that gain differentially for running capacity in response to aerobic treadmill training. Here, we subjected these low‐response trainer (LRT) and high‐response trainer (HRT) adult male rats to various forms of physical exercise for 6–8 weeks and examined the effects on AHN. Compared with sedentary animals, the highest number of doublecortin‐positive hippocampal cells was observed in HRT rats that ran voluntarily on a running wheel, whereas HIT on the treadmill had a smaller, statistically non‐significant effect on AHN. Adult hippocampal neurogenesis was elevated in both LRT and HRT rats that underwent endurance training on a treadmill compared with those that performed RT by climbing a vertical ladder with weights, despite their significant gain in strength

Effects of prenatal exposure to a low dose atrazine metabolite mixture onpubertal timing and prostate development of male Long-Evans rats

EPA Science Inventory

Atrazine (ATR) is a chlorotriazine herbicide extensively used in the US and other countries. Studies examining the effects of adult or developmental ATR exposure on the mammary gland (MG) have used either the Sprague Dawley (SD) or Long-Evans (LE) rat, but no strain comparisons h...

Supplemental dietary choline during development exerts antidepressant-like effects in adult female rats

PubMed Central

Glenn, Melissa J.; Adams, Raven S.; McClurg, Lauren

2012-01-01

Perinatal choline supplementation in rats is neuroprotective against insults such as fetal alcohol exposure, seizures, and advanced age. In the present study we explored whether dietary choline supplementation may also confer protection from psychological challenges, like stress, and act as a natural buffer against stress-linked psychological disorders, like depression. We previously found that choline supplementation increased adult hippocampal neurogenesis, a function compromised by stress, lowered in depression, and boosted by antidepressants; and increased levels of growth factors linked to depression, like brain-derived neurotrophic factor. Together, these were compelling reasons to study the role of choline in depressed mood. To do this, we treated rats with a choline supplemented diet (5 mg/kg choline chloride in AIN76A) prenatally on embryonic days 10–22, on postnatal days (PD) 25–50, or as adults from PD75 onward. Outside of these treatment periods rats were fed a standard diet (1.1 mg/kg choline chloride in AIN76A); control rats consumed only this diet throughout the study. Starting on PD100 rats’ anxiety-like responses to an open field, learning in a water maze, and reactivity to forced swimming were assessed. Rats given choline supplementation during pre- or post-natal development, but not adult-treated rats, were less anxious in the open field and less immobile in the forced swim test than control rats. These effects were not mediated by a learning deficit as all groups performed comparably and well in the water maze. Thus, we offer compelling support for the hypothesis that supplemental dietary choline, at least when given during development, may inoculate an individual against stress and major psychological disorders, like depression. PMID:22305146

COMPARING IMMUNOTOXICITY IN RATS AFTER IN UTERO VERSUS AN ADULT EXPOSURE: IS DEVELOPMENTAL EXPOSURE MORE SENSITIVE?

EPA Science Inventory

Using a known immunosuppresant, dexamethasone (DEX), pregnant Sprague Dawley (SD) rats were given subcutaneous (s.c.) injections of DEX (0.0, 0.0375, 0.075, 0.15, 0.3 mg/kg) during gestation days 6 to 21. Both male and female offspring were tested for immune dysfunction. In a ...

Hyperforin alleviates mood deficits of adult rats suffered from early separation.

PubMed

Zhu, Minghui; Liu, Chunhua; Qin, Xuan; Yang, Zhuo

2015-11-03

In this study, we aimed to explore the effect of hyperforin (Hyp) on adult rats suffered from early separation. Wistar infant rats were randomly divided into three groups: control group (CON), early separation from parents group (ESP), and early separation from parents+treatment with 3mg/kg/day Hyp group (ESP+Hyp). Postnatal rats of ESP group and ESP+Hyp group were separated from their mothers for 6h every day on the 14th day after birth, and this separation lasted for 3 weeks, while rats of CON group had no separation. Hyperforin was intragastric administrated on the 21th day after birth, and lasted for 2 weeks in ESP+Hyp group. After separation, adult rats were evaluated by using the open field test (OFT), novelty suppressed feeding test (NSF) and forced swimming test (FST). In OFT, time spent in central grids was much shorter in ESP group compared with that of CON group. After treatment with hyperforin, time spent in central area was much longer compared with that of ESP group. In NSF, the feeding latency of ESP group was much longer than that of CON group. After treatment with hyperforin, the feeding latency was shorter compared with that of ESP group. In FST, score of ESP group was markedly higher than that of CON group. Interestingly, the score was obviously lower in ESP+Hyp group than that of ESP group. In conclusion, these results suggest that hyperforin is able to alleviate anxiety and remit depression in ESP rats. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effect of hypothyroidism on the hypothalamic-pituitary-ovarian axis and reproductive function of pregnant rats.

PubMed

Sun, Jianran; Hui, Cancan; Xia, Tongjia; Xu, Min; Deng, Datong; Pan, Faming; Wang, Youmin

2018-05-24

This study aimed to detect changes in hormone levels in the hypothalamic-pituitary-ovarian axis in Sprague-Dawley (SD) rats with hypothyroidism, and identify differences in the pregnancy and abortion rates of female adult rats. The potential role of gonadotropin releasing hormone (GnRH) as the link between the hypothalamic-pituitary-ovarian axis and reproductive function regulated by thyroid hormones was also investigated. Female SD rats (n = 136) were causally classified into two groups: the normal-drinking-water group (n = 60) and the 0.05% propylthiouracil-drinking-water group (PTU 2 mg/kg/day, n = 76) to establish an adult rat model of hypothyroidism (6 weeks). Female and male rats at a ratio of 1:2 were used to establish a hypothyroidism pregnancy model. GnRH mRNA and GnRH receptor (GnRHR) expression in rats was detected using real time quantitative PCR(qRT-PCR) and immunohistochemistry, respectively. The abortion rate differed significantly between the hypothyroidism pregnancy group and the normal pregnancy group (P < 0.05). No significant differences were found in the distribution of the GnRHR among the five nuclei (hypothalamic arcuate nucleus, hypothalamic ventromedial nucleus, hypothalamic anterior nucleus, paraventricular nucleus of the hypothalamus, and ventral premammillary nucleus) of the hypothalamus and ovary (P > 0.05). Hypothyroidism had no significant effect on GnRH mRNA expression in the hypothalamic-pituitary-ovarian axis in the four groups (normal control group, normal pregnancy group, hypothyroidism pregnancy group, and hypothyroidism group) (P > 0.05). Hypothyroidism had an adverse impact on pregnancy in rats and may affect the distribution of pituitary GnRHR, whereas it did not obviously affect the distribution of GnRHR in the nuclei of the hypothalamus and ovary. Hypothyroidism had no effect on GnRH mRNA expression.

Differential DNA damage in response to the neonatal and adult excitotoxic hippocampal lesion in rats.

PubMed

Khaing, Z Z; Weickert, C S; Weinberger, D R; Lipska, B K

2000-12-01

We examined the developmental profile of excitotoxin-induced nuclear DNA fragmentation using the transferase dUTP nick-end labelling (TUNEL) technique, as a marker of DNA damage and cell death in rats with neonatal and adult excitotoxic lesions of the ventral hippocampus. We hypothesized that infusion of neurotoxin may result in a differential pattern of cell death in neonatally and adult lesioned rats, both in the infusion site and in remote brain regions presumably involved in mediating behavioural changes observed in these animals. Brains of rats lesioned at 7 days of age and in adulthood were collected at several survival times 1-21 days after the lesion. In the lesioned neonates 1-3 days postlesion, marked increases in TUNEL-positive cells occurred in the ventral hippocampus, the site of neurotoxin infusion, and in a wide surrounding area. Adult lesioned brains showed more positive cells than controls only at the infusion site. In the lesioned neonates, TUNEL-labelled cells were also present in the striatum and nucleus accumbens 1 day postlesion but not at later survival times. Our findings indicate that cell death in remote regions is more prominent in immature than adult brains, that it may lead to distinct alterations in development of these brain regions, and thus may be responsible for functional differences between neonatally and adult lesioned rats.

Attenuation of Diabetic Conditions by Sida rhombifolia in Moderately Diabetic Rats and Inability to Produce Similar Effects in Severely Diabetic in Rats.

PubMed

Chaturvedi, Padmaja; Kwape, Tebogo Elvis

2015-12-01

This study was done out to evaluate the effects of Sida rhombifolia methanol extract (SRM) on diabetes in moderately diabetic (MD) and severely diabetic (SD) Sprague-Dawley rats. SRM was prepared by soaking the powdered plant material in 70% methanol and rota evaporating the methanol from the extract. Effective hypoglycemic doses were established by performing oral glucose tolerance tests (OGTTs) in normal rats. Hourly effects of SRM on glucose were observed in the MD and the SD rats. Rats were grouped, five rats to a group, into normal control 1 (NC1), MD control 1 (MDC1), MD experimental 1 (MDE1), SD control 1 (SDC1), and SD experimental 1 (SDE1) groups. All rats in the control groups were administered 1 mL of distilled water (DW). The rats in the MDE1 and the SDE1 groups were administered SRM orally at 200 and 300 mg/kg body weight (BW), respectively, dissolved in 1 mL of DW. Blood was collected initially and at intervals of 1 hour for 6 hours to measure blood glucose. A similar experimental design was followed for the 30-day long-term trial. Finally, rats were sacrificed, and blood was collected to measure blood glucose, lipid profiles, thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH). OGTTs indicated that two doses (200 and 300 mg/kg BW) were effective hypoglycemic doses in normal rats. Both doses reduced glucose levels after 1 hour in the MDE1 and the SDE1 groups. A long-term trial of SRM in the MD group showed a reduced glucose level, a normal lipid profile, and normal GSH and TBARS levels. In SD rats, SRM had no statistically significant effects on these parameters. Normal weight was achieved in the MD rats, but the SD rats showed reduced BW. The study demonstrates that SRM has potential to alleviate the conditions of moderate diabetic, but not severe diabetes.

Attenuation of Diabetic Conditions by Sida rhombifolia in Moderately Diabetic Rats and Inability to Produce Similar Effects in Severely Diabetic in Rats

PubMed Central

Chaturvedi, Padmaja; Kwape, Tebogo Elvis

2015-01-01

Objectives: This study was done out to evaluate the effects of Sida rhombifolia methanol extract (SRM) on diabetes in moderately diabetic (MD) and severely diabetic (SD) Sprague-Dawley rats. Methods: SRM was prepared by soaking the powdered plant material in 70% methanol and rota evaporating the methanol from the extract. Effective hypoglycemic doses were established by performing oral glucose tolerance tests (OGTTs) in normal rats. Hourly effects of SRM on glucose were observed in the MD and the SD rats. Rats were grouped, five rats to a group, into normal control 1 (NC1), MD control 1 (MDC1), MD experimental 1 (MDE1), SD control 1 (SDC1), and SD experimental 1 (SDE1) groups. All rats in the control groups were administered 1 mL of distilled water (DW). The rats in the MDE1 and the SDE1 groups were administered SRM orally at 200 and 300 mg/kg body weight (BW), respectively, dissolved in 1 mL of DW. Blood was collected initially and at intervals of 1 hour for 6 hours to measure blood glucose. A similar experimental design was followed for the 30-day long-term trial. Finally, rats were sacrificed, and blood was collected to measure blood glucose, lipid profiles, thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH). Results: OGTTs indicated that two doses (200 and 300 mg/kg BW) were effective hypoglycemic doses in normal rats. Both doses reduced glucose levels after 1 hour in the MDE1 and the SDE1 groups. A long-term trial of SRM in the MD group showed a reduced glucose level, a normal lipid profile, and normal GSH and TBARS levels. In SD rats, SRM had no statistically significant effects on these parameters. Normal weight was achieved in the MD rats, but the SD rats showed reduced BW. Conclusion: The study demonstrates that SRM has potential to alleviate the conditions of moderate diabetic, but not severe diabetes. PMID:26998385

Di-n-butyl phthalate prompts interruption of spermatogenesis, steroidogenesis, and fertility associated with increased testicular oxidative stress in adult male rats.

PubMed

Nelli, Giribabu; Pamanji, Sreenivasula Reddy

2017-08-01

Di-n-butyl phthalate (DBP) is extensively used as plasticizer, and it was ubiquitary released into the environment. The present study was aimed to investigate the effect of DBP on reproductive competence in adult male rats. Adult male rats were received corn oil or DBP injection intraperitoneally (ip) at 100 and 500 mg/kg body weight on 90, 97, 104, and 111 days. Following completion of the experimental period, adult male rats were cohabitated with untreated proestrus female rats for determination of fertilization capacity. Then, adult male rats were sacrificed, and other reproductive endpoints were determined by histopathology and biochemical analysis. The results revealed significant reduction of fertilization potential by decrease mating, fertility indices with increase pre-implantation and post-implantation losses, and resorptions in normal female rat cohabitation with DBP-treated adult male rats. The testes, seminal vesicle tissue somatic indices, epididymal sperm count, motility, viability, and hypoosmotic swelling (HOS) sperm were significantly decreased with increased sperm morphological abnormalities in DBP-treated adult male rats. The disorientation of spermatogenic cells decreased the diameter and epithelial thickness of seminiferous tubule in the testicular histopathology of DBP-exposed rats. Significant reduction of testicular 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase enzyme levels and serum testosterone with increased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were observed in DBP-treated groups. Higher testicular oxidative stress marker (lipid peroxidation product) with lower antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase levels in DBP-exposed groups was observed. From these results, it can be concluded that DBP increases oxidative stress; it leads to impairment of spermatogenesis, steroidogenesis, and fertility in adult male rats.

Does prenatal methamphetamine exposure affect the drug-seeking behavior of adult male rats?

PubMed

Slamberová, Romana; Schutová, Barbora; Hrubá, Lenka; Pometlová, Marie

2011-10-10

Methamphetamine (MA) is one of the most frequently used illicit drugs worldwide and also one of the most common drugs abused by pregnant women. Repeated administration of psychostimulants induces behavioral sensitization in response to treatment of the same or related drugs in rodents. The effect of prenatal MA exposure on sensitivity to drugs in adulthood is not yet fully determined. Because our most recent studies demonstrated that prenatal MA (5mg/kg) exposure makes adult rats more sensitive to acute injection of the same drug, we were interested whether the increased sensitivity corresponds with the increased drug-seeking behavior. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the conditioned place preference (CPP). The following psychostimulant drugs were used as a challenge in adulthood: MA (5mg/kg), amphetamine (5mg/kg) and cocaine (10mg/kg). All psychostimulant drugs induced increased drug-seeking behavior in adult male rats. However, while MA and amphetamine-induced increase in drug-seeking behavior did not differ based on the prenatal drug exposure, prenatally MA-exposed rats displayed tolerance effect to cocaine in adulthood. In addition, prenatally MA-exposed rats had decreased weight gain after administration of MA or amphetamine, while the weight of prenatally MA-exposed rats stayed unchanged after cocaine administration. Defecation was increased by all the drugs (MA, amphetamine and cocaine), while only amphetamine increased the tail temperature. In conclusion, our results did not confirm our hypothesis that prenatal MA exposure increases drug-seeking behavior in adulthood in the CPP test. Copyright © 2011 Elsevier B.V. All rights reserved.

Substance P Differentially Modulates Firing Rate of Solitary Complex (SC) Neurons from Control and Chronic Hypoxia-Adapted Adult Rats

PubMed Central

Nichols, Nicole L.; Powell, Frank L.; Dean, Jay B.; Putnam, Robert W.

2014-01-01

NK1 receptors, which bind substance P, are present in the majority of brainstem regions that contain CO2/H+-sensitive neurons that play a role in central chemosensitivity. However, the effect of substance P on the chemosensitive response of neurons from these regions has not been studied. Hypoxia increases substance P release from peripheral afferents that terminate in the caudal nucleus tractus solitarius (NTS). Here we studied the effect of substance P on the chemosensitive responses of solitary complex (SC: NTS and dorsal motor nucleus) neurons from control and chronic hypoxia-adapted (CHx) adult rats. We simultaneously measured intracellular pH and electrical responses to hypercapnic acidosis in SC neurons from control and CHx adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. Substance P significantly increased the basal firing rate in SC neurons from control and CHx rats, although the increase was smaller in CHx rats. However, substance P did not affect the chemosensitive response of SC neurons from either group of rats. In conclusion, we found that substance P plays a role in modulating the basal firing rate of SC neurons but the magnitude of the effect is smaller for SC neurons from CHx adult rats, implying that NK1 receptors may be down regulated in CHx adult rats. Substance P does not appear to play a role in modulating the firing rate response to hypercapnic acidosis of SC neurons from either control or CHx adult rats. PMID:24516602

Cognitive and hippocampus biochemical changes following sleep deprivation in the adult male rat.

PubMed

Nabaee, Ebrahim; Kesmati, Mahnaz; Shahriari, Ali; Khajehpour, Lotfollah; Torabi, Mozhgan

2018-05-14

Sleep deprivation (SD) influences physiological processes such as cognitive function. The balance of oxidant and antioxidant markers, neurotrophic factors and magnesium are affected by sleep deprivation but there is no difference between pre and post training sleep deprivation. This study was designed to investigate memory retrieval and biochemical factors such as oxidant and antioxidant enzyme, brain-derived neurotrophic factor (BDNF) and magnesium levels in the hippocampus following pre and post-training sleep deprivation. Male Wistar rats (weighing 200 ± 20 g) in below groups were used: control 1, 24, 48 and 72 h SD before training groups, control2, 24 h SD1 after training (being evaluated 24 h after training) and SD2 24 after training (being evaluated 48 h after training). Memory was evaluated 90 min, 24 h or 48 h after training by step-through passive avoidance apparatus. Multiple platforms method was used to induce SD. Oxidant and antioxidant markers including glutathione (GSH), glutathione reductase (GPx), malonedialdehyde (MDA), Total antioxidant concentration, catalase, superoxide dismutase (SOD), magnesium and BDNF were assessed in the hippocampus or/and brain. 72 h pre-training SD impaired short and long-term memory significantly. There was no significant difference in hippocampus oxidant and antioxidant markers compared to control. Hippocampal BDNF and magnesium did not show any changes in all SD groups. Lack of correlation between memory impairment and levels of BDNF, magnesium and/or oxidant and antioxidant balance in the hippocampus is likely to be related to animal locomotor activity in the multiple platforms method. More research is needed to clarify the role of neurochemical systems. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Neonatal cystitis-induced colonic hypersensitivity in adult rats: a model of viscero-visceral convergence.

PubMed

Miranda, A; Mickle, A; Schmidt, J; Zhang, Z; Shaker, R; Banerjee, B; Sengupta, J N

2011-07-01

The objective of this study was to determine if neonatal cystitis alters colonic sensitivity later in life and to investigate the role of peripheral mechanisms. Neonatal rats received intravesical zymosan, normal saline, or anesthesia only for three consecutive days [(postnatal (PN) days 14-16)]. The estrous cycle phase was determined prior to recording the visceromotor response (VMR) to colorectal distension (CRD) in adult rats. Eosinophils and mast cells were examined from colon and bladder tissues. CRD- or urinary bladder distension (UBD)-sensitive pelvic nerve afferents (PNAs) were identified and their responses to distension were examined. The relative expression of N-methyl-d-aspartic acid (NMDA)-NR1 subunit in the lumbo-sacral (L6-S1) spinal cord was examined using Western blot. The VMR to CRD (≥10mmHg) in the neonatal zymosan group was significantly higher than control in both the diestrus, estrus phase and in all phases combined. There was no difference in the total number of eosinophils, mast cells or number of degranulated mast cells between groups. The spontaneous firing of UBD, but not CRD-sensitive PNAs from the zymosan-treated rats was significantly higher than the saline-treated control. However, the mechanosensitive properties of PNAs to CRD or UBD were no different between groups (P>0.05). The expression of spinal NR1 subunit was significantly higher in zymosan-treated rats compared with saline-treated rats (P<0.05). Neonatal cystitis results in colonic hypersensitivity in adult rats without changing tissue histology or the mechanosensitive properties of CRD-sensitive PNAs. Neonatal cystitis does result in overexpression of spinal NR1 subunit in adult rats. © 2011 Blackwell Publishing Ltd.

Lithium ameliorates lipopolysaccharide-induced neurotoxicity in the cortex and hippocampus of the adult rat brain.

PubMed

Khan, Muhammad Sohail; Ali, Tahir; Abid, Muhammad Noman; Jo, Myeung Hoon; Khan, Amjad; Kim, Min Woo; Yoon, Gwang Ho; Cheon, Eun Woo; Rehman, Shafiq Ur; Kim, Myeong Ok

2017-09-01

Lithium an effective mood stabilizer, primary used in the treatment of bipolar disorders, has been reported as a protective agent in various neurological disorders. In this study, we examined the neuroprotective role of lithium chloride (LiCl) against lipopolysaccharide (LPS) in the cortex and hippocampus of the adult rat brain. We determined that LiCl -attenuated LPS-induced activated toll-like receptor 4 (TLR4) signalling and significantly reduced the nuclear factor- k B (NF- K B) translation factor and various other inflammatory mediators such as interleukin-1 beta (IL-1β) and tumour necrosis factor alpha (TNF-α). We also analyzed that LiCl significantly abrogated activated gliosis via attenuation of specific markers for activated microglia, ionized calcium-binding adaptor molecule (Iba-1) and astrocytes, glial fibrillary acidic protein (GFAP) in both the cortex and hippocampus of the adult rat brain. Furthermore, we also observed that LiCl treatment significantly ameliorated the increase expression level of apoptotic neurodegeneration protein markers Bax/Bcl2, activated caspase-3 and poly (ADP-ribose) polymerase-1 (PARP-1) in the cortex and hippocampus regions of the LPS-treated adult rat brain. In addition, the morphological results of the fluoro-jade B (FJB) and Nissl staining showed that LiCl attenuated the neuronal degeneration in the cortex and hippocampus regions of the LPS-treated adult rat brain. Taken together, our Western blot and morphological results indicated that LiCl significantly prevents the LPS-induced neurotoxicity via attenuation of neuroinflammation and apoptotic neurodegeneration in the cortex and hippocampus of the adult rat brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

Acute and Chronic Effects of Dietary Lactose in Adult Rats Are not Explained by Residual Intestinal Lactase Activity

PubMed Central

van de Heijning, Bert J. M.; Kegler, Diane; Schipper, Lidewij; Voogd, Eline; Oosting, Annemarie; van der Beek, Eline M.

2015-01-01

Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%–75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed. PMID:26184291

Individual and combined effect of chlorpyrifos and cypermethrin on reproductive system of adult male albino rats.

PubMed

Alaa-Eldin, Eman Ahmad; El-Shafei, Dalia Abdallah; Abouhashem, Nehal S

2017-01-01

Commercial mixtures of chlorpyrifos and cypermethrin pesticides are widely used to enhance the toxic effects of cypermethrin on target insects. So, the purpose of the current study was to evaluate the individual and combined toxic effects of chlorpyrifos (CPF) and cypermethrin (CYP) on reproductive system of adult male albino rats. Forty adult male albino rats were randomized into main four groups: group I (control group) included 16 rats, subdivided into negative and positive control; group II (eight rats) received chlorpyrifos 6.75 mg/kg b.w./orally∕daily); group III (eight rats) (received cypermethrin 12.5 mg/kg b.w./orally∕daily); and group IV (eight rats) (received chlorpyrifos and cypermethrin at the same previously mentioned doses). All treatments were given by oral gavage for 12 weeks. We found that single CPF and CYP exposures significantly have adverse effects on reproductive function of adult male albino rats manifested by reduced testicular weight, decreased sperm count, motility and viability, significantly increased percent of morphologically abnormal spermatozoa, and significant increments in sperm DNA fragmentation index (DFI) with respect to control group. Furthermore, serum follicle stimulating hormone, luteinizing hormone, and testosterone levels were decreased significantly compared to control group. This was accompanied with histopathological changes in the testis of rats such as necrosis, degeneration, decreasing number of spermatogenic cells in some seminiferous tubules, edema, congested blood vessels, and exudate in interstitial tissue of the testis. Notably, all these changes were exaggerated in rats treated concomitantly with chlorpyrifos and cypermethrin rendering the mixture more toxic than the additive effects of each compound and causing greater damage on the reproductive system of male albino rats than the individual pesticides.

Influence of neonatally administered capsaicin on baroreceptor and chemoreceptor reflexes in the adult rat.

PubMed Central

Bond, S. M.; Cervero, F.; McQueen, D. S.

1982-01-01

1 Baroreceptor and chemoreceptor reflex activity was studied in anaesthetized adult rats which had been treated neonatally with a single injection of capsaicin (50 mg/kg s.c.). 2 Pressor responses to bilateral carotid artery occlusion were significantly lower in capsaicin-treated rats compared with vehicle-treated controls. Pressor responses to intravenously injected noradrenaline were similar in the two groups of rats. 3 Resting respiratory minute volume and tidal volume were lower in anaesthetized capsaicin-treated animals than in vehicle-treated controls, but there was no significant difference in respiratory frequency. 4 The increases in respiration evoked by intravenous administration of the peripheral arterial chemoreceptor stimulant, sodium cyanide, or by breathing a hypoxic gas mixture, were significantly lower in capsaicin-treated rats compared with the controls. 5 It is concluded that baroreceptor and chemoreceptor reflex activity are significantly reduced in anaesthetized adult rats which had been treated neonatally with capsaicin, and that this is likely to result from the destruction of unmyelinated baro- and chemoreceptor afferent fibres. PMID:6182938

Effects of acute exposure of permethrin in adult and developing Sprague-Dawley rats on acoustic startle response and brain and plasma concentrations.

PubMed

Williams, Michael T; Gutierrez, Arnold; Vorhees, Charles V

2018-06-08

Permethrin is a Type I (non-cyano) pyrethroid that induces tremors at high concentrations and increases acoustic startle responses (ASR) in adult rodents, however its effects in young rats have been investigated to a limited extent. ASR and tremor were assessed in adult and postnatal day (P)15 Sprague-Dawley rats at oral doses of 60, 90, or 120 mg/kg over an 8 h period. Permethrin increased ASR in adults, regardless of dose, and 20% of the high-dose rats showed tremor at later time points. For the P15 rats all doses induced tremor at all time points, and ASR was increased at 2 h in the 90 and 120 mg/kg groups with a trend in the 60 mg/kg group compared with controls. The 60 mg/kg group showed increased ASR at 4 and 6 h, whereas the 90 mg/kg group showed no differences from the controls at these times. The 120 mg/kg group showed decreased ASR from 4-8 h post-treatment. P15 and adult rats both showed plasma and brain cis- and trans-permethrin increases after dosing. After the same dose of permethrin, P15 rats had greater cis- and trans-permethrin in brain and plasma compared with adults. P15 rats had an increased tremor response compared with adults even at comparable brain permethrin concentrations. For ASR, P15 rats responded sooner and showed a biphasic pattern ranging from increased to decreased response as a function of dose and time, unlike adults that only showed increases. Overall, young rats showed greater effects from permethrin compared with adults.

Neonatal nociception elevated baseline blood pressure and attenuated cardiovascular responsiveness to noxious stress in adult rats.

PubMed

Chu, Ya-Chun; Yang, Cheryl C H; Lin, Ho-Tien; Chen, Pin-Tarng; Chang, Kuang-Yi; Yang, Shun-Chin; Kuo, Terry B J

2012-10-01

Neonatal nociception has significant long-term effects on sensory perception in adult animals. Although neonatal adverse experience affect future responsiveness to stressors is documented, little is known about the involvement of early nociceptive experiences in the susceptibility to subsequent nociceptive stress exposure during adulthood. The aim of this study is to explore the developmental change in cardiovascular regulating activity in adult rats that had been subjected to neonatal nociceptive insults. To address this question, we treated neonatal rats with an intraplantar injection of saline (control) or carrageenan at postnatal day 1. The carrageenan-treated rats exhibited generalized hypoalgesia at basal state, and localized hyperalgesia after re-nociceptive challenge induced by intraplantar injections of complete Freund's adjuvant (CFA) as adults. Then we recorded baseline cardiovascular variables and 24-h responsiveness to an injection of CFA in the free-moving adult rats with telemetric technique. The carrageenan-treated rats showed significantly higher basal blood pressures (110.3±3.16 vs. control 97.0±4.28 mmHg). In control animals, baroreceptor reflex sensitivity (BRS) decreased, sympathetic vasomotor activity increased, and parasympathetic activity was inhibited after CFA injection. Blood pressure elevation was evident (107.0±2.75 vs. pre-injection 97.0±4.28 mmHg). Comparatively, the carrageenan-treated rats showed a higher BRS (BrrLF 1.03±0.09 vs. control 0.70±0.06 ms/mmHg) and higher parasympathetic activity [0.93±0.17 vs. control 0.32±0.02 ln(ms²)] after CFA injection. The change in blood pressure is negligible (111.9±4.05 vs. pre-injection 110.3±3.16 mmHg). Our research has shown that neonatal nociception alters future pain sensation, raises basal blood pressure level, and attenuates cardiovascular responsiveness to nociceptive stress in adult rats. Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.

Ontogeny of cocaine-induced behaviors and cocaine pharmacokinetics in male and female neonatal, preweanling, and adult rats.

PubMed

McDougall, Sanders A; Apodaca, Matthew G; Mohd-Yusof, Alena; Mendez, Adrian D; Katz, Caitlin G; Teran, Angie; Garcia-Carachure, Israel; Quiroz, Anthony T; Crawford, Cynthia A

2018-04-18

Ontogenetic differences in the behavioral responsiveness to cocaine have often been attributed to the maturation of dopaminergic elements (e.g., dopamine transporters, D2 High receptors, receptor coupling, etc.). The purpose of this study was to determine whether ontogenetic changes in cocaine pharmacokinetics might contribute to age-dependent differences in behavioral responsiveness. Male and female neonatal (PD 5), preweanling (PD 10 and PD 20), and adult (PD 70) rats were injected (IP) with cocaine or saline and various behaviors (e.g., locomotor activity, forelimb paddle, vertical activity, head-down sniffing, etc.) were measured for 90 min. In a separate experiment, the dorsal striata of young and adult rats were removed at 10 time points (0-210 min) after IP cocaine administration. Peak cocaine values, cocaine half-life, and dopamine levels were determined using HPLC. When converted to percent of saline controls, PD 5 and PD 10 rats were generally more sensitive to cocaine than older rats, but this effect varied according to the behavior being assessed. Peak cocaine values did not differ according to age or sex, but cocaine half-life in brain was approximately 2 times longer in PD 5 and PD 10 rats than adults. Cocaine pharmacokinetics did not differ between PD 20 and PD 70 rats. Differences in the cocaine-induced behavioral responsiveness of very young rats (PD 5 and PD 10) and adults may be attributable, at least in part, to pharmacokinetic factors; whereas, age-dependent behavioral differences between the late preweanling period and adulthood cannot readily be ascribed to cocaine pharmacokinetics.

Time-dependent decreases in nucleus accumbens AMPA/NMDA ratio and incubation of sucrose craving in adolescent and adult rats.

PubMed

Counotte, Danielle S; Schiefer, Christopher; Shaham, Yavin; O'Donnell, Patricio

2014-04-01

There is evidence that cue-induced sucrose seeking progressively increases after cessation of oral sucrose self-administration (incubation of sucrose craving) in both adolescent and adult rats. The synaptic plasticity changes associated with this incubation at different age groups are unknown. We assessed whether incubation of sucrose craving in rats trained to self-administer sucrose as young adolescents, adolescents, or adults is associated with changes in 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid (AMPA)/N-methyl-D-aspartate (NMDA) ratio (a measure of postsynaptic changes in synaptic strength) in nucleus accumbens. Three age groups initiated oral sucrose self-administration training (10 days) on postnatal day (P) 35 (young adolescents), P42 (adolescents), or P70 (adults). They were then tested for cue-induced sucrose seeking (assessed in an extinction test) on abstinence days 1 and 21. Separate groups of rats were trained to self-administer sucrose or water (a control condition), and assessed for AMPA/NMDA ratio in nucleus accumbens on abstinence days 1-3 and 21. Adult rats earned more sucrose rewards, but sucrose intake per body weight was higher in young adolescent rats. Time-dependent increases in cue-induced sucrose seeking (incubation of sucrose craving) were more pronounced in adult rats, less pronounced in adolescents, and not detected in young adolescents. On abstinence day 21, but not days 1-3, AMPA/NMDA ratio in nucleus accumbens were decreased in rats that self-administered sucrose as adults and adolescents, but not young adolescents. Our data demonstrate age-dependent changes in magnitude of incubation of sucrose craving and nucleus accumbens synaptic plasticity after cessation of sucrose self-administration.

The rate of cerebral utilization of glucose, ketone bodies, and oxygen: a comparative in vivo study of infant and adult rats.

PubMed

Dahlquist, G; Persson, B

1976-11-01

Cerebral blood flow (CBF) was measured by means of Celabeled microspheres in infant (20-day-old) and adult (3-month-old) rats, anesthetised with Na-5-ethyl-5-(1-methylpropyl)2-thiobarbituric acid. Cerebral arteriovenous differences of acetoacetate, D-beta-hydroxybutyrate, glucose, lactate, and oxygen and brain DNA content were determined in other groups of similarly treated infant and adult animals fed or starved for 48 or 72 hr. The mean CBF values of 0.48+/-0.04 and 0.62+/-0.07 ml/(g X min), +/- SEM, in infant and adult animals, respectively, were not significantly different. CBF was unaffected by starvation. At any given arterial concentration the cerebral arteriovenous difference of acetoacetate was significantly higher in infant than adult rats. The same was true for D-beta-hydroxybutyrate at arterial concentrations above 1 mmol/liter. There was an approximately linear relationship between arterial concentration of acetoacetate and its cerebral arteriovenous difference in both infant and adult rats. A similar relationship was found for D-beta-hydroxybutyrate only in infant animals. In the fed state, the cerebral uptake of glucose and ketone bodies (micromoles per (mg DNA X min)) was not different in infant and adult rats. During starvation, cerebral uptake of ketone bodies expressed as micromoles per (mg DNA X min) was higher in infant than adult rats, indicating a higher rate of utilization of ketone bodies per cell in these animals. For glucose, no such difference was found in either fed or starved groups (Table 3). The average percentage of the total cerebral uptake of substrates (micromoles per min) accounted for by ketone bodies increased in both infant and adult rats during starvation. This percentage value was clearly higher in infant than adult rats during starvation. After 72 hr of starvation the values were 38.8% and 15.2% in infant and adult rats, respectively (Fig. 3). Calculated cerebral metabolic rate for oxygen (CMRO2), assuming complete

Sexual odor discrimination and physiological profiles in adult male rats after a neonatal, short term, reversible nasal obstruction.

PubMed

Thornton, S N; Padzys, G S; Trabalon, M

2014-05-01

The present study was designed to examine behavioral responses (interpreted as preferences) to olfactory cues (nest bedding odor and odors of estrous and anestrus females) in adult male rats after they had a short term reversible, bilateral, nasal obstruction (RbNO) as developing rat pups. These results were compared to behavior of control (untreated) and sham operated male littermates. Behavioral tests and physiological parameters were analyzed 90 days after recovery of nasal breathing. Experiments investigated the time spent in arms or the center of a maze of male rats in response to odors from the nest bedding or from adult females. There were no differences in responses between untreated, sham and RbNO adult male rats to fresh and nest bedding odors. RbNO males spent more time in the center of the maze when given a choice of estrus or anestrus female odors, or bedding odors from untreated or sham operated female rats. In contrast untreated and sham male rats preferred the odors of estrous females and of untreated or sham females. Plasma corticosterone levels in the males increased during the behavioral tests. Plasma testosterone levels were significantly lower in RbNO males compared to untreated males and did not increase during the behavioral tests compared to sham operated males. Males from all groups had similar preferences for the odor of bedding from adult RbNO females. Plasma levels of cholesterol and triglycerides were increased in RbNO adults. In conclusion, short term nasal obstruction in males while juvenile has long term consequences on hormones and behavioral preferences, thus potential partner selection when adult. Copyright © 2014 Elsevier Inc. All rights reserved.

Self-administration of nicotine and cigarette smoke extract in adolescent and adult rats.

PubMed

Gellner, Candice A; Belluzzi, James D; Leslie, Frances M

2016-10-01

Although smoking initiation typically occurs during adolescence, most preclinical studies of tobacco use involve adult animals. Furthermore, their focus is largely on nicotine alone, even though cigarette smoke contains thousands of constituents. The present study therefore aimed to determine whether aqueous constituents in cigarette smoke affect acquisition of nicotine self-administration during adolescence in rats. Adolescent and adult male rats, aged postnatal day (P) 25 and 85, respectively, were food trained on a fixed ratio 1 (FR1) schedule, then allowed to self-administer one of 5 doses of nicotine (0, 3.75, 7.5, 15, or 30 μg/kg) or aqueous cigarette smoke extract (CSE) with equivalent nicotine content. Three progressively more difficult schedules of reinforcement, FR1, FR2, and FR5, were used. Both adolescent and adult rats acquired self-administration of nicotine and CSE. Nicotine and CSE similarly increased non-reinforced responding in adolescents, leading to enhanced overall drug intake as compared to adults. When data were corrected for age-dependent alterations in non-reinforced responding, adolescents responded more for low doses of nicotine and CSE than adults at the FR1 reinforcement schedule. No differences in adolescent responding for the two drugs were seen at this schedule, whereas adults had fewer responses for CSE than for nicotine. However, when the reinforcement schedule was increased to FR5, animals dose-dependently self-administered both nicotine and CSE, but no drug or age differences were observed. These data suggest that non-nicotine tobacco smoke constituents do not influence the reinforcing effect of nicotine in adolescents. Published by Elsevier Ltd.

Adolescent TBI-induced hypopituitarism causes sexual dysfunction in adult male rats.

PubMed

Greco, Tiffany; Hovda, David A; Prins, Mayumi L

2015-02-01

Adolescents are at greatest risk for traumatic brain injury (TBI) and repeat TBI (RTBI). TBI-induced hypopituitarism has been documented in both adults and juveniles and despite the necessity of pituitary function for normal physical and brain development, it is still unrecognized and untreated in adolescents following TBI. TBI induced hormonal dysfunction during a critical developmental window has the potential to cause long-term cognitive and behavioral deficits and the topic currently remains unaddressed. The purpose of this study was to determine if four mild TBIs delivered to adolescent male rats disrupts testosterone production and adult behavioral outcomes. Plasma testosterone was quantified from 72 hrs preinjury to 3 months postinjury and pubertal onset, reproductive organ growth, erectile function and reproductive behaviors were assessed at 1 and 2 months postinjury. RTBI resulted in both acute and chronic decreases in testosterone production and delayed onset of puberty. Significant deficits were observed in reproductive organ growth, erectile function and reproductive behaviors in adult rats at both 1 and 2 months postinjury. These data suggest adolescent RTBI-induced hypopituitarism underlies abnormal behavioral changes observed during adulthood. The impact of undiagnosed hypopituitarism following RTBI in adolescence has significance not only for growth and puberty, but also for brain development and neurobehavioral function as adults. © 2014 Wiley Periodicals, Inc.

Sub-chronic 90-day toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Yanli

Neamine, an inhibitor of angiogenin (ANG), is a new investigative anticancer drug currently in preclinical stage. Here we report the 90-day sub-chronic toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo. Neamine has a No Observed Adverse Effect Level (NOAEL) of 12 and 16 mg·kg{sup −1}·d{sup −1} for female and male rats, respectively. No mortality was found. The adverse effects included increased organ coefficients of spleen and kidney, increased BUN in both female and male rats at high dose, increased CR and decreased organ coefficients of heart and liver in male rats atmore » high dose. All of which, except the kidney coefficient and BUN in males, returned to normal levels after 28-day recovery. Histopathological examination revealed vacuolar degeneration of glomerulus, degeneration of renal tubules and cast in the kidneys, which were also recovered except in males of high-dosing group. These results indicate that kidney is the most susceptible organ for neamine toxicity. Tissue microarray analysis validated that ANG is up-regulated in hepatocellular carcinoma accompanied by increased nuclear translocation, suggesting that ANG is a possible target for drug development in liver cancer treatment. Neamine blocked nuclear translocation of ANG in HUVEC and HepG2 cells, and inhibited ANG-stimulated cell proliferation without affecting basal level cell proliferation. Neamine also inhibited progression of HepG2 xenografts in athymic mice accompanied by decreased angiogenesis and cancer cell proliferation. These results suggest that neamine is a specific ANG inhibitor with low toxicity and high anti-liver cancer efficacy. - Highlights: • The NOAEL of neamine is 12 mg·kg{sup −1}·d{sup −1} for females and 16 mg·kg{sup −}1·d{sup −1} for males. • The most susceptible organ for neamine toxicity is kidney. • Neamine inhibits the progression of xenograft HepG2 liver cancer in athymic mice.« less

Adult neurogenesis and its anatomical context in the hippocampus of three mole-rat species

PubMed Central

Amrein, Irmgard; Becker, Anton S.; Engler, Stefanie; Huang, Shih-hui; Müller, Julian; Slomianka, Lutz; Oosthuizen, Maria K.

2014-01-01

African mole-rats (family Bathyergidae) are small to medium sized, long-lived, and strictly subterranean rodents that became valuable animal models as a result of their longevity and diversity in social organization. The formation and integration of new hippocampal neurons in adult mammals (adult hippocampal neurogenesis, AHN) correlates negatively with age and positively with habitat complexity. Here we present quantitative data on AHN in wild-derived mole-rats of 1 year and older, and briefly describe its anatomical context including markers of neuronal function (calbindin and parvalbumin). Solitary Cape mole-rats (Georychus capensis), social highveld mole-rats (Cryptomys hottentotus pretoriae), and eusocial naked mole-rats (Heterocephalus glaber) were assessed. Compared to other rodents, the hippocampal formation in mole-rats is small, but shows a distinct cytoarchitecture in the dentate gyrus and CA1. Distributions of the calcium-binding proteins differ from those seen in rodents; e.g., calbindin in CA3 of naked mole-rats distributes similar to the pattern seen in early primate development, and calbindin staining extends into the stratum lacunosum-moleculare of Cape mole-rats. Proliferating cells and young neurons are found in low numbers in the hippocampus of all three mole-rat species. Resident granule cell numbers are low as well. Proliferating cells expressed as a percentage of resident granule cells are in the range of other rodents, while the percentage of young neurons is lower than that observed in surface dwelling rodents. Between mole-rat species, we observed no difference in the percentage of proliferating cells. The percentages of young neurons are high in social highveld and naked mole-rats, and low in solitary Cape mole-rats. The findings support that proliferation is regulated independently of average life expectancy and habitat. Instead, neuronal differentiation reflects species-specific demands, which appear lower in subterranean rodents. PMID

Undernutrition during foetal and post-natal life affects testicular structure and reduces the number of Sertoli cells in the adult rat.

PubMed

Genovese, P; Núñez, M E; Pombo, C; Bielli, A

2010-04-01

To test whether undernutrition during foetal to pre-pubertal life would have long lasting effects on testicular histology in adult male offspring, eleven adult Sprague-Dawley pregnant rats were divided into two groups: Control group, n = 4, fed ad libitum, during gestation and lactation (until 25 day post-partum). Underfed group pregnant females (n = 7) were kept in cages where only dams had access to food (standard rat chow, 33.5% of ad libitum intake of Control group pregnant dams). After parturition, litters were adjusted to either 14 (Underfed group) or eight (Control group) pups. Mothers were weighed weekly. At 25 day of age pups were weaned, housed at four animals per cage, fed ad libitum and weighed weekly until euthanized at 100 day of age. Testes were processed for standard histology and morphometrical evaluation. At weaning, mother weight was lower in underfed than in Control group (mean +/- SD): 214.1 +/- 26.2 g vs 361.9 +/- 33.1 g. Body weight at 100 days of age (254 +/- 26.9 g vs 342.4 +/- 10.2 g, p adult life, strongly suggesting lower daily sperm production.

Neonatal tobacco smoke reduces thermogenesis capacity in brown adipose tissue in adult rats.

PubMed

Peixoto, T C; Moura, E G; Oliveira, E; Younes-Rapozo, V; Soares, P N; Rodrigues, V S T; Santos, T R; Peixoto-Silva, N; Carvalho, J C; Calvino, C; Conceição, E P S; Guarda, D S; Claudio-Neto, S; Manhães, A C; Lisboa, P C

2018-01-01

Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT) hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower metabolic rate. We evaluated autonomic nerve activity in BAT and its function in adult rats that were exposed to tobacco smoke during lactation. At birth, litters were adjusted to 3 male and 3 female pups/litter. From postnatal day (PND) 3 to 21, Wistar lactating rats and their pups were divided into SE group, smoke-exposed in a cigarette smoking machine (4 times/day) and C group, exposed to filtered air. Offspring were sacrificed at PND180. Adult SE rats of both genders had lower interscapular BAT autonomic nervous system activity, with higher BAT mass but no change in morphology. BAT UCP1 and CPT1a protein levels were decreased in the SE groups of both genders. Male SE rats had lower β3-AR, TRα1, and TRβ1 expression while females showed lower PGC1α expression. BAT Dio2 mRNA and hypothalamic POMC and MC4R levels were similar between groups. Hypothalamic pAMPK level was higher in SE males and lower in SE females. Thus, neonatal cigarette smoke exposure induces lower BAT thermogenic capacity, which can be obesogenic at adulthood.

Effects of self-administered cocaine in adolescent and adult male rats on orbitofrontal cortex-related neurocognitive functioning

PubMed Central

Harvey, Roxann C.; Dembro, Kimberly A.; Rajagopalan, Kiran; Mutebi, Michael M.; Kantak, Kathleen M.

2010-01-01

Rationale Deficits in amygdala-related stimulus-reward learning are produced following 18 drug-free days of cocaine self-administration or its passive delivery in rats exposed during adulthood. No deficits in stimulus-reward learning are produced by cocaine exposure initiated during adolescence. Objectives To determine if age of initiating cocaine exposure differentially affects behavioral functioning of an additional memory system linked to cocaine addiction, the orbitofrontal cortex. Materials and methods A yoked-triad design (n=8) was used. One rat controlled cocaine delivery and the other two passively received cocaine or saline. Rats controlling drug delivery (1.0 mg/kg) self-administered cocaine from either P37–P59 or P77–P99, and then underwent 18 drug-free days (P60–P77 vs. P100–P117). Rats next were tested for acquisition of odor-delayed win-shift behavior conducted over 15 sessions (P78–P96 vs. P118–P136). Results Cocaine self-administration did not differ between adults and adolescents. During the test phase of the odor-delayed win-shift task (relatively difficult task demands), rats from both drug-onset ages showed learning deficits. Rats with cocaine self-administration experience committed more errors and had longer session latencies compared to rats passively receiving saline or cocaine. Rats with adolescent-onset cocaine self-administration experience showed an additional learning deficit by requiring more sessions to reach criterion levels for task acquisition compared to same-aged passive saline controls or rats with adult-onset cocaine self-administration experience. Rats passively receiving cocaine did not differ from the passive saline control from either age group. Conclusions Rats with adolescent-onset cocaine self-administration experience were more impaired in an orbitofrontal cortex-related learning task than rats with adult-onset cocaine self-administration experience. PMID:19513699

Effects of Chronic Fluoxetine Treatment on Neurogenesis and Tryptophan Hydroxylase Expression in Adolescent and Adult Rats

PubMed Central

Meerhoff, Gideon F.

2014-01-01

The antidepressant drug fluoxetine (Prozac) has been increasingly prescribed to children and adolescents with depressive disorders despite a lack of thorough understanding of its therapeutic effects in the paediatric population and of its putative neurodevelopmental effects. Within the framework of PRIOMEDCHILD ERA-NET, we investigated; a) effects of chronic fluoxetine treatment on adult hippocampal neurogenesis, a structural readout relevant for antidepressant action and hippocampal development; b) effects on tryptophan hydroxylase (TPH) expression, a measure of serotonin synthesis; c) whether treatment effects during adolescence differed from treatment at an adult age, and d) whether they were subregion-specific. Stereological quantification of the number of proliferating (Ki-67+) cells and of the number of young migratory neurons (doublecortin+), revealed a significant age-by-treatment interaction effect, indicating that fluoxetine affects both proliferation and neurogenesis in adolescent-treated rats differently than it does in adult-treated rats. In terms of subregional differences, fluoxetine enhanced proliferation mainly in the dorsal parts of the hippocampus, and neurogenesis in both the suprapyramidal and infrapyramidal blades of the dentate gyrus in adolescent-treated rats, while no such differences were seen in adult-treated rats. Fluoxetine exerted similar age-by-treatment interaction effects on TPH cells mainly in the ventral portion of the dorsal raphe nucleus. We conclude that fluoxetine exerts divergent effects on structural plasticity and serotonin synthesis in adolescent versus adult-treated rats. These preliminary data indicate a differential sensitivity of the adolescent brain to this drug and thus warrant further research into their behavioural and translational aspects. Together with recent related findings, they further call for caution in prescribing these drugs to the adolescent population. PMID:24827731

Effects of chronic fluoxetine treatment on neurogenesis and tryptophan hydroxylase expression in adolescent and adult rats.

PubMed

Klomp, Anne; Václavů, Lena; Meerhoff, Gideon F; Reneman, Liesbeth; Lucassen, Paul J

2014-01-01

The antidepressant drug fluoxetine (Prozac) has been increasingly prescribed to children and adolescents with depressive disorders despite a lack of thorough understanding of its therapeutic effects in the paediatric population and of its putative neurodevelopmental effects. Within the framework of PRIOMEDCHILD ERA-NET, we investigated; a) effects of chronic fluoxetine treatment on adult hippocampal neurogenesis, a structural readout relevant for antidepressant action and hippocampal development; b) effects on tryptophan hydroxylase (TPH) expression, a measure of serotonin synthesis; c) whether treatment effects during adolescence differed from treatment at an adult age, and d) whether they were subregion-specific. Stereological quantification of the number of proliferating (Ki-67+) cells and of the number of young migratory neurons (doublecortin+), revealed a significant age-by-treatment interaction effect, indicating that fluoxetine affects both proliferation and neurogenesis in adolescent-treated rats differently than it does in adult-treated rats. In terms of subregional differences, fluoxetine enhanced proliferation mainly in the dorsal parts of the hippocampus, and neurogenesis in both the suprapyramidal and infrapyramidal blades of the dentate gyrus in adolescent-treated rats, while no such differences were seen in adult-treated rats. Fluoxetine exerted similar age-by-treatment interaction effects on TPH cells mainly in the ventral portion of the dorsal raphe nucleus. We conclude that fluoxetine exerts divergent effects on structural plasticity and serotonin synthesis in adolescent versus adult-treated rats. These preliminary data indicate a differential sensitivity of the adolescent brain to this drug and thus warrant further research into their behavioural and translational aspects. Together with recent related findings, they further call for caution in prescribing these drugs to the adolescent population.

Early Effects of a Low Fat, Fructose-Rich Diet on Liver Metabolism, Insulin Signaling, and Oxidative Stress in Young and Adult Rats

PubMed Central

Crescenzo, Raffaella; Cigliano, Luisa; Mazzoli, Arianna; Cancelliere, Rosa; Carotenuto, Rosa; Tussellino, Margherita; Liverini, Giovanna; Iossa, Susanna

2018-01-01

The increase in the use of refined food, which is rich in fructose, is of particular concern in children and adolescents, since the total caloric intake and the prevalence of metabolic syndrome are increasing continuously in these populations. Nevertheless, the effects of high fructose diet have been mostly investigated in adults, by focusing on the effect of a long-term fructose intake. Notably, some reports evidenced that even short-term fructose intake exerts detrimental effects on metabolism. Therefore, the aim of this study was to compare the metabolic changes induced by the fructose-rich diet in rats of different age, i.e., young (30 days old) and adult (90 days old) rats. The fructose-rich diet increased whole body lipid content in adult, but not in young rats. The analysis of liver markers of inflammation suggests that different mechanisms depending on the age might be activated after the fructose-rich diet. In fact, a pro-inflammatory gene-expression analysis showed just a minor activation of macrophages in young rats compared to adult rats, while other markers of low-grade metabolic inflammation (TNF-alpha, myeloperoxidase, lipocalin, haptoglobin) significantly increased. Inflammation was associated with oxidative damage to hepatic lipids in young and adult rats, while increased levels of hepatic nitrotyrosine and ceramides were detected only in young rats. Interestingly, fructose-induced hepatic insulin resistance was evident in young but not in adult rats, while whole body insulin sensitivity decreased both in fructose-fed young and adult rats. Taken together, the present data indicate that young rats do not increase their body lipids but are exposed to metabolic perturbations, such as hepatic insulin resistance and hepatic oxidative stress, in line with the finding that increased fructose intake may be an important predictor of metabolic risk in young people, independently of weight status. These results indicate the need of corrective nutritional

Early Effects of a Low Fat, Fructose-Rich Diet on Liver Metabolism, Insulin Signaling, and Oxidative Stress in Young and Adult Rats.

PubMed

Crescenzo, Raffaella; Cigliano, Luisa; Mazzoli, Arianna; Cancelliere, Rosa; Carotenuto, Rosa; Tussellino, Margherita; Liverini, Giovanna; Iossa, Susanna

2018-01-01

The increase in the use of refined food, which is rich in fructose, is of particular concern in children and adolescents, since the total caloric intake and the prevalence of metabolic syndrome are increasing continuously in these populations. Nevertheless, the effects of high fructose diet have been mostly investigated in adults, by focusing on the effect of a long-term fructose intake. Notably, some reports evidenced that even short-term fructose intake exerts detrimental effects on metabolism. Therefore, the aim of this study was to compare the metabolic changes induced by the fructose-rich diet in rats of different age, i.e., young (30 days old) and adult (90 days old) rats. The fructose-rich diet increased whole body lipid content in adult, but not in young rats. The analysis of liver markers of inflammation suggests that different mechanisms depending on the age might be activated after the fructose-rich diet. In fact, a pro-inflammatory gene-expression analysis showed just a minor activation of macrophages in young rats compared to adult rats, while other markers of low-grade metabolic inflammation (TNF-alpha, myeloperoxidase, lipocalin, haptoglobin) significantly increased. Inflammation was associated with oxidative damage to hepatic lipids in young and adult rats, while increased levels of hepatic nitrotyrosine and ceramides were detected only in young rats. Interestingly, fructose-induced hepatic insulin resistance was evident in young but not in adult rats, while whole body insulin sensitivity decreased both in fructose-fed young and adult rats. Taken together, the present data indicate that young rats do not increase their body lipids but are exposed to metabolic perturbations, such as hepatic insulin resistance and hepatic oxidative stress, in line with the finding that increased fructose intake may be an important predictor of metabolic risk in young people, independently of weight status. These results indicate the need of corrective nutritional

Use of the light/dark test for anxiety in adult and adolescent male rats

PubMed Central

Arrant, Andrew E.; Schramm-Sapyta, Nicole L.; Kuhn, Cynthia M.

2014-01-01

The light/dark (LD) test is a commonly used rodent test of unconditioned anxiety-like behavior that is based on an approach/avoidance conflict between the drive to explore novel areas and an aversion to brightly lit, open spaces. We used the LD test to investigate developmental differences in behavior between adolescent (postnatal day (PN) 28–34) and adult (PN67–74) male rats. We investigated whether LD behavioral measures reflect anxiety-like behavior similarly in each age group using factor analysis and multiple regression. These analyses showed that time in the light compartment, percent distance in the light, rearing, and latency to emerge into the light compartment were measures of anxiety-like behavior in each age group, while total distance traveled and distance in the dark compartment provided indices of locomotor activity. We then used these measures to assess developmental differences in baseline LD behavior and the response to anxiogenic drugs. Adolescent rats emerged into the light compartment more quickly than adults and made fewer pokes into the light compartment. These age differences could reflect greater risk taking and less risk assessment in adolescent rats than adults. Adolescent rats were less sensitive than adults to the anxiogenic effects of the benzodiazepine inverse agonist N-methyl-β-carboline-3-carboxamide (FG-7142) and the α2 adrenergic antagonist yohimbine on anxiety-like behaviors validated by factor analysis, but locomotor variables were similarly affected. These data support the results of the factor analysis and indicate that GABAergic and noradrenergic modulation of LD anxiety-like behavior may be immature during adolescence. PMID:23721963

A comparative study on the effect of high cholesterol diet on the hippocampal CA1 area of adult and aged rats.

PubMed

Abo El-Khair, Doaa M; El-Safti, Fatma El-Nabawia A; Nooh, Hanaa Z; El-Mehi, Abeer E

2014-06-01

Dementia is one of the most important problems nowadays. Aging is associated with learning and memory impairments. Diet rich in cholesterol has been shown to be detrimental to cognitive performance. This work was carried out to compare the effect of high cholesterol diet on the hippocampus of adult and aged male albino rats. Twenty adult and twenty aged male rats were used in this study. According to age, the rats were randomly subdivided into balanced and high cholesterol diet fed groups. The diet was 15 g/rat/day for adult rats and 20 g/rat/day for aged rats for eight weeks. Serial coronal sections of hippocampus and blood samples were taken from each rat. For diet effect evaluation, Clinical, biochemical, histological, immunohistochemical, and morphometric assessments were done. In compare to a balanced diet fed rat, examination of Cornu Ammonis 1 (CA 1) area in the hippocampus of the high cholesterol diet adult rats showed degeneration, a significant decrease of the pyramidal cells, attenuation and/or thickening of small blood vessels, apparent increase of astrocytes and apparent decrease of Nissl's granules content. Moreover, the high cholesterol diet aged rats showed aggravation of senility changes of the hippocampus together with Alzheimer like pathological changes. In conclusion, the high cholesterol diet has a significant detrimental effect on the hippocampus and aging might pronounce this effect. So, we should direct our attention to limit cholesterol intake in our food to maintain a healthy life style for a successful aging.

How Changes in Anti-SD Sequences Would Affect SD Sequences in Escherichia coli and Bacillus subtilis.

PubMed

Abolbaghaei, Akram; Silke, Jordan R; Xia, Xuhua

2017-05-05

The 3' end of the small ribosomal RNAs (ssu rRNA) in bacteria is directly involved in the selection and binding of mRNA transcripts during translation initiation via well-documented interactions between a Shine-Dalgarno (SD) sequence located upstream of the initiation codon and an anti-SD (aSD) sequence at the 3' end of the ssu rRNA. Consequently, the 3' end of ssu rRNA (3'TAIL) is strongly conserved among bacterial species because a change in the region may impact the translation of many protein-coding genes. Escherichia coli and Bacillus subtilis differ in their 3' ends of ssu rRNA, being GAUC ACCUCCUUA 3' in E. coli and GAUC ACCUCCUU UCU3' or GAUC ACCUCCUU UCUA3' in B. subtilis Such differences in 3'TAIL lead to species-specific SDs (designated SD Ec for E. coli and SD Bs for B. subtilis ) that can form strong and well-positioned SD/aSD pairing in one species but not in the other. Selection mediated by the species-specific 3'TAIL is expected to favor SD Bs against SD Ec in B. subtilis , but favor SD Ec against SD Bs in E. coli Among well-positioned SDs, SD Ec is used more in E. coli than in B. subtilis , and SD Bs more in B. subtilis than in E. coli Highly expressed genes and genes of high translation efficiency tend to have longer SDs than lowly expressed genes and genes with low translation efficiency in both species, but more so in B. subtilis than in E. coli Both species overuse SDs matching the bolded part of the 3'TAIL shown above. The 3'TAIL difference contributes to the host specificity of phages. Copyright © 2017 Abolbaghaei et al.

Exercise to reduce the escalation of cocaine self-administration in adolescent and adult rats.

PubMed

Zlebnik, Natalie E; Anker, Justin J; Carroll, Marilyn E

2012-12-01

Concurrent access to an exercise wheel decreases cocaine self-administration under short access (5 h/day for 5 days) conditions and suppresses cocaine-primed reinstatement in adult rats. The effect of exercise (wheel running) on the escalation of cocaine intake during long access (LgA, 6 h/day for 26 days) conditions was evaluated. Adolescent and adult female rats acquired wheel running, and behavior was allowed to stabilize for 3 days. They were then implanted with an iv catheter and allowed to self-administer cocaine (0.4 mg/kg, iv) during 6-h daily sessions for 16 days with concurrent access to either an unlocked or a locked running wheel. Subsequently, for ten additional sessions, wheel access conditions during cocaine self-administration sessions were reversed (i.e., locked wheels became unlocked and vice versa). In the adolescents, concurrent access to the unlocked exercise wheel decreased responding for cocaine and attenuated escalation of cocaine intake irrespective of whether the locked or unlocked condition came first. However, cocaine intake increased when the wheel was subsequently locked for the adolescents that had initial access to an unlocked wheel. Concurrent wheel access either before or after the locked wheel access did not reduce cocaine intake in adults. Wheel running reduced cocaine intake during LgA conditions in adolescent but not adult rats, and concurrent access to the running wheel was necessary. These results suggest that exercise prevents cocaine seeking and that this effect is more pronounced in adolescents than adults.

Chronic central serotonin depletion attenuates ventilation and body temperature in young but not adult Tph2 knockout rats.

PubMed

Kaplan, Kara; Echert, Ashley E; Massat, Ben; Puissant, Madeleine M; Palygin, Oleg; Geurts, Aron M; Hodges, Matthew R

2016-05-01

Genetic deletion of brain serotonin (5-HT) neurons in mice leads to ventilatory deficits and increased neonatal mortality during development. However, it is unclear if the loss of the 5-HT neurons or the loss of the neurochemical 5-HT led to the observed physiologic deficits. Herein, we generated a mutant rat model with constitutive central nervous system (CNS) 5-HT depletion by mutation of the tryptophan hydroxylase 2 (Tph2) gene in dark agouti (DA(Tph2-/-)) rats. DA(Tph2-/-) rats lacked TPH immunoreactivity and brain 5-HT but retain dopa decarboxylase-expressing raphe neurons. Mutant rats were also smaller, had relatively high mortality (∼50%), and compared with controls had reduced room air ventilation and body temperatures at specific postnatal ages. In adult rats, breathing at rest and hypoxic and hypercapnic chemoreflexes were unaltered in adult male and female DA(Tph2-/-) rats. Body temperature was also maintained in adult DA(Tph2-/-) rats exposed to 4°C, indicating unaltered ventilatory and/or thermoregulatory control mechanisms. Finally, DA(Tph2-/-) rats treated with the 5-HT precursor 5-hydroxytryptophan (5-HTP) partially restored CNS 5-HT and showed increased ventilation (P < 0.05) at a developmental age when it was otherwise attenuated in the mutants. We conclude that constitutive CNS production of 5-HT is critically important to fundamental homeostatic control systems for breathing and temperature during postnatal development in the rat. Copyright © 2016 the American Physiological Society.

Chronic central serotonin depletion attenuates ventilation and body temperature in young but not adult Tph2 knockout rats

PubMed Central

Kaplan, Kara; Echert, Ashley E.; Massat, Ben; Puissant, Madeleine M.; Palygin, Oleg; Geurts, Aron M.

2016-01-01

Genetic deletion of brain serotonin (5-HT) neurons in mice leads to ventilatory deficits and increased neonatal mortality during development. However, it is unclear if the loss of the 5-HT neurons or the loss of the neurochemical 5-HT led to the observed physiologic deficits. Herein, we generated a mutant rat model with constitutive central nervous system (CNS) 5-HT depletion by mutation of the tryptophan hydroxylase 2 (Tph2) gene in dark agouti (DATph2−/−) rats. DATph2−/− rats lacked TPH immunoreactivity and brain 5-HT but retain dopa decarboxylase-expressing raphe neurons. Mutant rats were also smaller, had relatively high mortality (∼50%), and compared with controls had reduced room air ventilation and body temperatures at specific postnatal ages. In adult rats, breathing at rest and hypoxic and hypercapnic chemoreflexes were unaltered in adult male and female DATph2−/− rats. Body temperature was also maintained in adult DATph2−/− rats exposed to 4°C, indicating unaltered ventilatory and/or thermoregulatory control mechanisms. Finally, DATph2−/− rats treated with the 5-HT precursor 5-hydroxytryptophan (5-HTP) partially restored CNS 5-HT and showed increased ventilation (P < 0.05) at a developmental age when it was otherwise attenuated in the mutants. We conclude that constitutive CNS production of 5-HT is critically important to fundamental homeostatic control systems for breathing and temperature during postnatal development in the rat. PMID:26869713

[Morphological signs of survival cultured adult rat cardiomyocytes].

PubMed

Chang, Hui; Zhang, Lin; Yu, Zhi-Bin

2011-02-01

To clarify the key morphological signs for the survival of adult rat cardiomyocytes in primary culture. The adult rat hearts were retrogradely superfused by Langendorff apparatus. Cardiomyocytes were digested by collagenase I and cultured in three groups: (1) Serum free medium + BA (Bongkrekic acid, apoptotic inhibitor), (2) 5% serum medium, and (3) 5% serum medium + BA. The morphological alterations were observed and the percentage of rod-shaped cardiomyocytes, the apoptotic rate of cells, the rate of pseudopodium formation and the nuclear distances of cardiomyocytes were detected during culture. (1) The percentage of rod-shaped cardiomyocytes decreased gradually in the first 3 days of cell culture. The percentage of rod-shaped cardiomyocytes cultured without fetal bovine serum (FBS) decreased more rapidly than those cultured with FBS. No differences were noticed between with and without the addition of apoptotic inhibitor BA. The apoptotic rate of cardiomyocytes increased in the first 3 days of cell culture, and the apoptotic rate of cells cultured without FBS increased more than that cultured with FBS. Also BA had no effect on apoptotic rate. (2) Cardiomyocytes cultured with FBS spread from the intercalated disk and extended pseudopodium on the second or third day of cell culture. Cardiomyocytes with thin membranous pseudopodium developed would survive and spread laterally at the 6th day of culture. Cells with the elongated morphology gradually spread extensively and took on a spheroidal shape. Myofibrils gradually lost their parallel. Cells cultured without FBS had no pseudopodium formation. The intercalated disk of cells gradually changed blunt. There was no effect on the rate of pseudopodium formation when added with apoptotic inhibitor BA. (3) Cytoskeletal remodeling occurred in survived cardiomyocytes. After 6 days of culture, cardiomyocytes exhibited characteristic of redifferentiation. (4) The distance between nuclei decreased in a single cardiomyocyte

Glucocorticoid combined with hyaluronic acid enhance glucocorticoid receptor activity through inhibiting p-38MAPK signal pathway activation in treating acute lung injury in rats.

PubMed

Lv, Q

2016-09-01

In order to seek an effective strategy for clinical treatment of acute lung injury (ALI), we are committed to explore the effect of combination therapy of glucocorticoid and hyaluronic acid on acute lung injury caused by an endotoxin (LPS) and its mechanism. Adult male Sprague-Dawley (SD) rats were divided randomly into 5 groups: normal group (n=8); LPS group (n=8); dexamethasone +LPS group (DXMS group, n=8); hyaluronic acid+ LPS group (HA group, n=8); dexamethasone +hyaluronic acid +LPS group (DXMS+HA group, n=8). Firstly, SD rat model with acute lung injury induced by LPS was established, and injected corresponding drugs according to the plan. Then, the expression of TNF-a, IL-8, IL-10, ICAM-1 and total protein were measured by ELISA, and the HE staining was used for detected the pathological change in lung tissue. Subsequently, the water content, dry and wet ratio and permeability in lung tissues of SD rats was assayed. Finally, the expression level of the glucocorticoid receptor (GR) was detected by RT-PCR, and activation of p-p38MAPK was determined by Western blotting. The results showed that concentration of IL-8, IL-10 and ICAM-1 was significantly increased in BALF after LPS injection, and the results from HE staining showed it had widespread inflammation. However, lung structures in SD rats with inhalation lung injury were improved significantly after the injection of dexamethasone and hyaluronic acid, and the Pa02/Fi02, blood pressure and Cdyn were also increased. Moreover, lung water content, the ratio of wet and dry lung, and lung permeability index (LPI) was decreased after having treated the SD rats with a combination of dexamethasone and hyaluronic acid, and the apoptosis index was also decreased in the rats with LPS-induced ALI. Our data also suggested that TNF-α, IL-8, IL-10, intercellular cell adhesion molecule-1 (ICAM-1) and total protein was significantly declined in bronchoalveolar lavage fluid (BALF) of rats with LPS-induced acute lung injury

Treadmill running frequency on anxiety and hippocampal adenosine receptors density in adult and middle-aged rats.

PubMed

Costa, Marcelo S; Ardais, Ana Paula; Fioreze, Gabriela T; Mioranzza, Sabrina; Botton, Paulo Henrique S; Portela, Luis Valmor; Souza, Diogo O; Porciúncula, Lisiane O

2012-01-10

Physical exercise protocols have varied widely across studies raising the question of whether there is an optimal intensity, duration and frequency that would produce maximal benefits in attenuating symptoms related to anxiety disorders. Although physical exercise causes modifications in neurotransmission systems, the involvement of neuromodulators such as adenosine has not been investigated after chronic exercise training. Anxiety-related behavior was assessed in the elevated plus-maze in adult and middle-aged rats submitted to 8 weeks of treadmill running 1, 3 or 7 days/week. The speed of running was weekly adjusted to maintain moderate intensity. The hippocampal adenosine A1 and A2A receptors densities were also assessed. Treadmill running protocol was efficient in increasing physical exercise capacity in adult and middle-aged rats. All frequencies of treadmill running equally decreased the time spent in the open arms in adult animals. Middle-aged treadmill control rats presented lower time spent in the open arms than adult treadmill control rats. However, treadmill running one day/week reversed this age effect. Adenosine A1 receptor was not changed between groups, but treadmill running counteracted the age-related increase in adenosine A2A receptors. Although treadmill running, independent from frequency, triggered anxiety in adult rats and treadmill running one day/week reversed the age-related anxiety, no consistent relationship was found with hippocampal adenosine receptors densities. Thus, our data suggest that as a complementary therapy in the management of mental disturbances, the frequency and intensity of physical exercise should be taken into account according to age. Besides, this is the first study reporting the modulation of adenosine receptors after chronic physical exercise, which could be important to prevent neurological disorders associated to increase in adenosine A2A receptors. Copyright © 2011. Published by Elsevier Inc.

Synergistic effect of estradiol and fluoxetine in young adult and middle-aged female rats in two models of experimental depression.

PubMed

Récamier-Carballo, Soledad; Estrada-Camarena, Erika; Reyes, Rebeca; Fernández-Guasti, Alonso

2012-08-01

The antidepressant effect of estrogens combined with antidepressants is controversial: some preclinical data showed that estrogens facilitate the effect of antidepressants in the forced swimming test (FST) in young adult rats, while others failed to find such effect in middle-aged rats in the chronic mild stress (CMS) model. In clinics similar differences were reported and may be due to the compounds, the depression model or type of depression, the experimental design, and the age of the subjects or the women's menopause stage. The objective of this study was to analyze the antidepressant-like effect of the combination of 17β-estradiol (E(2)) and fluoxetine (FLX) in young adults (2-4 months) and middle-aged (12-14 months) ovariectomized (OVX) rats in two experimental models: FST and CMS. E(2) (5 and 10 μg/rat) and FLX (2.5 and 10 mg/kg) per se dose-dependently reduced immobility in both age groups and, in young adults both compounds increased swimming, whereas in middle-aged rats they increased swimming and climbing. Analysis of the antidepressant-like effect of the combination of suboptimal doses of FLX (1.25 mg/kg) and E(2) (2.5 μg/rat) showed a decrease in immobility and an increase in swimming in both age groups. In the CMS, chronic E(2) (2.5 μg/rat) with FLX (1.25 mg/kg) augmented relative sucrose intake, but middle-aged rats responded 2 weeks earlier than young adults. These results show that the antidepressant-like effect of the combination of E(2) and FLX in young adult and middle-aged female rats is evidenced in the two animal models of depression: FST and CMS. Copyright © 2012 Elsevier B.V. All rights reserved.

The expression of NFATc1 in adult rat skeletal muscle fibres.

PubMed

Mutungi, Gabriel

2008-03-01

Although numerous studies have recently implicated the calcineurin-nuclear factor of activated T-cells (Cn-NFAT) signalling pathway in the regulation of activity-dependent fibre type switching in adult mammalian skeletal muscles, little is known about the endogenous expression of NFAT proteins in the various fibre types present in these muscles. In this study, the immunolocalization of NFATc1 (also known as NFATc or NFAT2) in the extensor digitorum longus (EDL; a mainly fast-twitch muscle) and the soleus (a predominantly slow-twitch muscle) muscles of adult ( approximately 90-day-old) Wistar rats was investigated. The results show that NFATc1 is expressed only in oxidative fibres (i.e. type I and type IIA fibres) that stain intensely for succinate dehydrogenase activity irrespective of whether they are from the fast- or slow-twitch muscle. Thus, 99 +/- 4% (n = 7 rats) of the muscle fibres in the soleus and 42 +/- 2% (n = 7 rats) of those in the EDL expressed NFATc1. In the soleus muscle fibres, NFATc1 was localized mainly in the fibre nuclei, whereas in the EDL fibres it was localized in both the cytoplasm and the nuclei. However, no difference in its localization was observed between type I and type IIA fibres in both muscles. Western blot experiments showed that the soleus expressed more NFATc1 proteins than the EDL. From these results, we suggest that NFATc1 controls the number and distribution of both type I and type IIA fibres, as well as the oxidative capacity of adult mammalian skeletal muscles.

Perinatal nicotine exposure increases obesity susceptibility by peripheral leptin resistance in adult female rat offspring.

PubMed

Zhang, Wan-Xia; Li, Yin-Ping; Fan, Jie; Chen, Hui-Jian; Li, Gai-Ling; Ouyang, Yan-Qiong; Yan, You-E

2018-02-01

Maternal nicotine (NIC) exposure causes overweight, hyperleptinemia and metabolic disorders in adult offspring. Our study aims to explore the underlying mechanism of perinatal NIC exposure increases obesity susceptibility in adult female rat offspring. In our model, we found that adult NIC-exposed females presented higher body weight and subcutaneous and visceral fat mass, as well as larger adipocytes, while no change was found in food intake. Serum profile showed a higher serum glucose, insulin and leptin levels in NIC-exposed females. In adipose tissue and liver, the leptin signaling pathway was blocked at 26 weeks, presented lower Janus tyrosine kinase 2 and signal transducer and activator of transcription 3 gene expression, higher suppressor of cytokine signaling 3 gene expression (in adipose tissue) and lower leptin receptors gene expression (in liver), indicating that peripheral leptin resistance occurred in NIC-exposed adult females. In female rats, the expression of lipolysis genes was affected dominantly in adipose tissue, but lipogenesis genes was affected in liver. Furthermore, the glucose and insulin tolerance tests showed a delayed glucose clearance and a higher area under the curve in NIC-exposed females. Therefore, perinatal NIC exposure programed female rats for adipocyte hypertrophy and obesity in adult life, through the leptin resistance in peripheral tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of Changes in Global Genes Expression in the Distal Colon of Loperamide-Induced Constipation SD Rats in Response to the Laxative Effects of Liriope platyphylla

PubMed Central

Kim, Ji Eun; Park, So Hae; Kwak, Moon Hwa; Go, Jun; Koh, Eun Kyoung; Song, Sung Hwa; Sung, Ji Eun; Lee, Hee Seob; Hong, Jin Tae; Hwang, Dae Youn

2015-01-01

To characterize the changes in global gene expression in the distal colon of constipated SD rats in response to the laxative effects of aqueous extracts of Liriope platyphylla (AEtLP), including isoflavone, saponin, oligosaccharide, succinic acid and hydroxyproline, the total RNA extracted from the distal colon of AEtLP-treated constipation rats was hybridized to oligonucleotide microarrays. The AEtLP treated rats showed an increase in the number of stools, mucosa thickness, flat luminal surface thickness, mucin secretion, and crypt number. Overall, compared to the controls, 581 genes were up-regulated and 216 genes were down-regulated by the constipation induced by loperamide in the constipated rats. After the AEtLP treatment, 67 genes were up-regulated and 421 genes were down-regulated. Among the transcripts up-regulated by constipation, 89 were significantly down-regulated and 22 were recovered to the normal levels by the AEtLP treatment. The major genes in the down-regulated categories included Slc9a5, klk10, Fgf15, and Alpi, whereas the major genes in the recovered categories were Cyp2b2, Ace, G6pc, and Setbp1. On the other hand, after the AEtLP treatment, ten of these genes down-regulated by constipation were up-regulated significantly and five were recovered to the normal levels. The major genes in the up-regulated categories included Serpina3n, Lcn2 and Slc5a8, whereas the major genes in the recovered categories were Tmem45a, Rerg and Rgc32. These results indicate that several gene functional groups and individual genes as constipation biomarkers respond to an AEtLP treatment in constipated model rats. PMID:26151867

Use of the light/dark test for anxiety in adult and adolescent male rats.

PubMed

Arrant, Andrew E; Schramm-Sapyta, Nicole L; Kuhn, Cynthia M

2013-11-01

The light/dark (LD) test is a commonly used rodent test of unconditioned anxiety-like behavior that is based on an approach/avoidance conflict between the drive to explore novel areas and an aversion to brightly lit, open spaces. We used the LD test to investigate developmental differences in behavior between adolescent (postnatal day (PN) 28-34) and adult (PN67-74) male rats. We investigated whether LD behavioral measures reflect anxiety-like behavior similarly in each age group using factor analysis and multiple regression. These analyses showed that time in the light compartment, percent distance in the light, rearing, and latency to emerge into the light compartment were measures of anxiety-like behavior in each age group, while total distance traveled and distance in the dark compartment provided indices of locomotor activity. We then used these measures to assess developmental differences in baseline LD behavior and the response to anxiogenic drugs. Adolescent rats emerged into the light compartment more quickly than adults and made fewer pokes into the light compartment. These age differences could reflect greater risk taking and less risk assessment in adolescent rats than adults. Adolescent rats were less sensitive than adults to the anxiogenic effects of the benzodiazepine inverse agonist N-methyl-β-carboline-3-carboxamide (FG-7142) and the α₂ adrenergic antagonist yohimbine on anxiety-like behaviors validated by factor analysis, but locomotor variables were similarly affected. These data support the results of the factor analysis and indicate that GABAergic and noradrenergic modulation of LD anxiety-like behavior may be immature during adolescence. Copyright © 2013 Elsevier B.V. All rights reserved.

Neonatal hyperleptinaemia programmes adrenal medullary function in adult rats: effects on cardiovascular parameters

PubMed Central

Trevenzoli, I H; Valle, M M R; Machado, F B; Garcia, R M G; Passos, M C F; Lisboa, P C; Moura, E G

2007-01-01

Epidemiological studies have shown a strong correlation between stressful events (nutritional, hormonal or environmental) in early life and development of adult diseases such as obesity, diabetes and cardiovascular failure. It is known that gestation and lactation are crucial periods for healthy growth in mammals and that the sympathoadrenal system is markedly influenced by environmental conditions during these periods. We previously demonstrated that neonatal hyperleptinaemia in rats programmes higher body weight, higher food intake and hypothalamic leptin resistance in adulthood. Using this model of programming, we investigated adrenal medullary function and effects on cardiovascular parameters in male rats in adulthood. Leptin treatment during the first 10 days of lactation (8μg 100 g−1 day−1, s.c.) resulted in lower body weight (6.5%, P < 0.05), hyperleptinaemia (10-fold, P < 0.05) and higher catecholamine content in adrenal glands (18.5%, P < 0.05) on the last day of treatment. In adulthood (150 days), the rats presented higher body weight (5%, P < 0.05), adrenal catecholamine content (3-fold, P < 0.05), tyrosine hydroxylase expression (35%, P < 0.05) and basal and caffeine-stimulated catecholamine release (53% and 100%, respectively, P < 0.05). Systolic blood pressure and heart rate were also higher in adult rats (7% and 6%, respectively, P < 0.05). Our results show that hyperleptinaemia in early life increases adrenal medullary function in adulthood and that this may alter cardiovascular parameters. Thus, we suggest that imprinting factors which increase leptin and catecholamine levels during the neonatal period could be involved in development of adult chronic diseases. PMID:17218354

Prenatal and early postnatal dietary sodium restriction sensitizes the adult rat to amphetamines.

PubMed

McBride, Shawna M; Culver, Bruce; Flynn, Francis W

2006-10-01

Acute sodium deficiency sensitizes adult rats to psychomotor effects of amphetamine. This study determined whether prenatal and early life manipulation of dietary sodium sensitized adult offspring to psychomotor effects of amphetamine (1 or 3 mg/kg ip) in two strains of rats. Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) dams were fed chow containing low NaCl (0.12%; LN), normal NaCl (1%; NN), or high NaCl (4%; HN) throughout breeding, gestation, and lactation. Male offspring were maintained on the test diet for an additional 3 wk postweaning and then fed standard chow thereafter until testing began. Overall, blood pressure (BP), total fluid intake, salt preference, and adrenal gland weight were greater in SHR than in WKY. WKY LN offspring had greater water intake and adrenal gland weight than did WKY NN and HN offspring, whereas WKY HN offspring had increased BP, salt intake, and salt preference compared with other WKY offspring. SHR HN offspring also had increased BP compared with other SHR offspring; all other measures were similar for SHR offspring. The low-dose amphetamine increased locomotor and stereotypical behavior compared with baseline and saline injection in both WKY and SHR offspring. Dietary sodium history affected the rats' psychomotor response to the higher dose of amphetamine. Injections of 3 mg/kg amphetamine in both strains produced significantly more behavioral activity in the LN offspring than in NN and HN offspring. These results show that early life experience with low-sodium diets produce long-term changes in adult rats' behavioral responses to amphetamine.

Acquisition of i.v. cocaine self-administration in adolescent and adult male rats selectively bred for high and low saccharin intake

PubMed Central

Perry, Jennifer L.; Anderson, Marissa M.; Nelson, Sarah E.; Carroll, Marilyn E.

2009-01-01

Adolescence and excessive intake of saccharin have each been previously associated with enhanced vulnerability to drug abuse. In the present study, we focused on the relationship between these two factors using male adolescent and adult rats bred for high (HiS) and low (LoS) levels of saccharin intake. On postnatal day 25 (adolescents) or 150 (adults), rats were implanted with an intravenous catheter and trained to self-administer cocaine (0.4 mg/kg) using an autoshaping procedure that consisted of two 6-h sessions. In the first 6 h, rats were given noncontingent cocaine infusions at random intervals 10 times per hour, and during the second 6-h session, rats were allowed to self-administer cocaine under a fixed ratio 1 (FR 1) lever-response contingency. Acquisition was defined as a total of at least 250 infusions over 5 consecutive days, and rats were given 30 days to meet the acquisition criterion. Subsequently, saccharin intake was determined by comparing 24-h saccharin and water consumption in two-bottle tests. Adolescent LoS rats had a faster rate of acquisition of cocaine self-administration than adult LoS rats; however, adolescent and adult HiS rats acquired at the same rate. Both HiS and LoS adolescents had significantly higher saccharin preference scores than HiS and LoS adults, respectively. Additionally, saccharin score was negatively correlated with the number of days to meet the acquisition criterion for cocaine self-administration, but this was mostly accounted for by the HiS adolescents. These results suggest that during adolescence, rats have both an increased avidity for sweets and vulnerability to initiate drug abuse compared with adulthood. PMID:17360010

Extremely weak magnetic field exposure may inhibit hippocampal neurogenesis of Sprague Dawley rats

NASA Astrophysics Data System (ADS)

Zhang, B.; Tian, L.; Cai, Y.; Xu, H.; Pan, Y.

2016-12-01

Hippocampal neurogenesis occurs throughout life in mammals brains and can be influenced by animals' age as well as environmental factors. Lines of evidences have shown that the magnetic field is an important physics environmental factor influencing many animals' growth and development, and extremely weak magnetic field exposures have been proved having serious adverse effects on the metabolism and behaviors in some animals, but few studies have examined the response of hippocampal neurogenesis to it. In the present study, we experimentally examined the extremely weak magnetic field effects on neurogenesis of the dentate gyrus (DG) of hippocampus of adult Sprague Dawley (SD) rats. Two types of magnetic fields were used, an extremely weak magnetic field (≤ 0.5μT) and the geomagnetic fields (strength 31-58μT) as controls. Thirty-two SD rats (3-weeks old) were used in this study. New cell survival in hippocampus was assessed at 0, 14, 28, and 42 days after a 7-day intraperitoneal injections of 5-bromo-2'-deoxyuridine (BrdU). Meanwhile, the amounts of immature neurons and mature neurons which are both related to hippocampal neurogenesis, as documented by labeling with doublecortin (DCX) and neuron (NeuN), respectively, were also analyzed at 0, 14, 28, and 42 days. Compared with geomagnetic field exposure groups, numbers of BrdU-, DCX-positive cells of DG of hippocampus in tested rats reduces monotonously and more rapidly after 14 days, and NeuN-positive cells significantly decreases after 28days when exposed in the extremely weak magnetic field condition. Our data suggest that the exposure to an extremely weak magnetic field may suppress the neurogenesis in DG of SD rats.

Single-shot dimension measurements of the mouse eye using SD-OCT.

PubMed

Jiang, Minshan; Wu, Pei-Chang; Fini, M Elizabeth; Tsai, Chia-Ling; Itakura, Tatsuo; Zhang, Xiangyang; Jiao, Shuliang

2012-01-01

The authors demonstrate the feasibility and advantage of spectral-domain optical coherence tomography (SD-OCT) for single-shot ocular biometric measurement during the development of the mouse eye. A high-resolution SD-OCT system was built for single-shot imaging of the whole mouse eye in vivo. The axial resolution and imaging depth of the system are 4.5 μm (in tissue) and 5.2 mm, respectively. The system is capable of acquiring a cross-sectional OCT image consisting of 2,048 depth scans in 85 ms. The imaging capability of the SD-OCT system was validated by imaging the normal ocular growth and experimental myopia model using C57BL/6J mice. The biometric dimensions of the mouse eye can be calculated directly from one snapshot of the SD-OCT image. The biometric parameters of the mouse eye including axial length, corneal thickness, anterior chamber depth, lens thickness, vitreous chamber depth, and retinal thickness were successfully measured by the SD-OCT. In the normal ocular growth group, the axial length increased significantly from 28 to 82 days of age (P < .001). The lens thickness increased and the vitreous chamber depth decreased significantly during this period (P < .001 and P = .001, respectively). In the experimental myopia group, there were significant increases in vitreous chamber depth and axial length in comparison to the control eyes (P = .040 and P < .001, respectively). SD-OCT is capable of providing single-shot direct, fast, and high-resolution measurements of the dimensions of young and adult mouse eyes. As a result, SD-OCT is a potentially powerful tool that can be easily applied to research in eye development and myopia using small animal models. Copyright 2012, SLACK Incorporated.

Elevated androstenedione in young adult but not early adolescent prenatally androgenized female rats.

PubMed

Shah, Ami B; Nivar, Isaac; Speelman, Diana L

2018-01-01

Elevated testosterone (T) is routinely reported as a marker of hyperandrogenemia in rodent models for polycystic ovary syndrome (PCOS). In women with PCOS, elevated serum androstenedione (A4) is associated with more severe phenotypes, including a positive correlation with serum T, DHEAS, free androgen index (FAI), LH, and LH/FSH ratio. Furthermore, A4, along with calculated free T and FAI, was identified as one of the best predictors of PCOS in adult women of all ages (18 to > 50 y). The objective of this study was to investigate serum A4 levels in early adolescent and young adult prenatally androgenized (PNA) female rats, a model for PCOS. Pregnant rats were injected with 5 mg T daily during gestational days 16-19 (PNA rats, experimental group) or an equal volume of vehicle (control group). Female offspring of both groups had tail vein blood drawn for serum analysis at 8 and 16 weeks of age. ELISAs were used to quantify serum A4 and T levels. Serum A4 and T were elevated in 16-week-old PNA rats compared to controls. There was no significant difference in either hormone at 8 weeks of age. The PNA rats demonstrated elevated serum A4 and T in young adulthood, as has been observed in women with PCOS, further validating this as a model for PCOS and underscoring the importance of serum A4 elevation as a parameter inherent to PCOS and a rodent model for the disorder. Significant A4 elevation develops between early adolescence and early adulthood in this PNA rat model.

Ulmus davidiana extract improves lumbar vertebral parameters in ovariectomized osteopenic rats

PubMed Central

Zhuang, Xinming; Fu, Changfeng; Liu, Wanguo; Wang, Yuanyi; Xu, Feng; Zhang, Qi; Liu, Yadong; Liu, Yi

2016-01-01

The aim of this study was to determine the skeletal effect of total ethanolic extract from the stem-bark of Ulmus davidiana (UDE) in a rat model of postmenopausal bone loss. Effective dose of UDE was determined in adult female Sprague-Dawley (SD) rats by measuring bone regeneration at fracture site. UDE (250 mg/kg p.o.) was administered to ovariectomized (OVX) osteopenic SD rats for 12 weeks. OVX rats treated with vehicle or 17β-estradiol, and sham-operated rats treated with vehicle served as various controls. Bone mineral density (BMD), microarchitecture, biomechanical strength, turnover markers, and uterotrophic effect were studied. Bioactive markers in UDE were analyzed by HPLC. Human osteoblasts was used to study the effect of compounds on differentiation by alkaline phosphase assay. One-way ANOVA was used to test significance of effects. OVX+UDE group showed BMD, microarchitectural parameters and compressive strength at lumbar vertebra (L5) comparable to sham. At proximal femur, OVX+UDE group exhibited significantly higher BMD, better microarchitecture and compressive strength compared with OVX+vehicle. OVX-induced decrease in Ca/P ratio was completely restored at both skeletal sites by UDE treatment. Serum procollagen N-terminal propeptide and carboxy-terminal collagen crosslinks were respectively higher and lower in OVX+UDE group compared with OVX+vehicle group. Osteogenic genes were upregulated in L5 and anti-resorptive genes were suppressed in proximal femur of OVX+UDE group compared with OVX+vehicle. UDE had no uterine estrogenicity. Analysis of markers yielded two osteogenic isoforms of catechin. In conclusion, UDE completely restored vertebral trabecular bones and strength in osteopenic rats by an osteogenic mechanism and prevented bone loss at proximal femur. PMID:27158327

Environmental Enrichment Promotes Plasticity and Visual Acuity Recovery in Adult Monocular Amblyopic Rats

PubMed Central

Bonaccorsi, Joyce; Cenni, Maria Cristina; Sale, Alessandro; Maffei, Lamberto

2012-01-01

Loss of visual acuity caused by abnormal visual experience during development (amblyopia) is an untreatable pathology in adults. In some occasions, amblyopic patients loose vision in their better eye owing to accidents or illnesses. While this condition is relevant both for its clinical importance and because it represents a case in which binocular interactions in the visual cortex are suppressed, it has scarcely been studied in animal models. We investigated whether exposure to environmental enrichment (EE) is effective in triggering recovery of vision in adult amblyopic rats rendered monocular by optic nerve dissection in their normal eye. By employing both electrophysiological and behavioral assessments, we found a full recovery of visual acuity in enriched rats compared to controls reared in standard conditions. Moreover, we report that EE modulates the expression of GAD67 and BDNF. The non invasive nature of EE renders this paradigm promising for amblyopia therapy in adult monocular people. PMID:22509358

Airborne particles of the california central valley alter the lungs of healthy adult rats.

PubMed Central

Smith, Kevin R; Kim, Seongheon; Recendez, Julian J; Teague, Stephen V; Ménache, Margaret G; Grubbs, David E; Sioutas, Constantinos; Pinkerton, Kent E

2003-01-01

Epidemiologic studies have shown that airborne particulate matter (PM) with a mass median aerodynamic diameter < 10 microm (PM10) is associated with an increase in respiratory-related disease. However, there is a growing consensus that particles < 2.5 microm (PM2.5), including many in the ultrafine (< 0.1 microm) size range, may elicit greater adverse effects. PM is a complex mixture of organic and inorganic compounds; however, those components or properties responsible for biologic effects on the respiratory system have yet to be determined. During the fall and winter of 2000-2001, healthy adult Sprague-Dawley rats were exposed in six separate experiments to filtered air or combined fine (PM2.5) and ultrafine portions of ambient PM in Fresno, California, enhanced approximately 20-fold above outdoor levels. The intent of these studies was to determine if concentrated fine/ultrafine fractions of PM are cytotoxic and/or proinflammatory in the lungs of healthy adult rats. Exposures were for 4 hr/day for 3 consecutive days. The mean mass concentration of particles ranged from 190 to 847 microg/m3. PM was enriched primarily with ammonium nitrate, organic and elemental carbon, and metals. Viability of cells recovered by bronchoalveolar lavage (BAL) from rats exposed to concentrated PM was significantly decreased during 4 of 6 weeks, compared with rats exposed to filtered air (p< 0.05). Total numbers of BAL cells were increased during 1 week, and neutrophil numbers were increased during 2 weeks. These observations strongly suggest exposure to enhanced concentrations of ambient fine/ultrafine particles in Fresno is associated with mild, but significant, cellular effects in the lungs of healthy adult rats. PMID:12782490

A spaceflight study of synaptic plasticity in adult rat vestibular maculas

NASA Technical Reports Server (NTRS)

Ross, M. D.

1994-01-01

Behavioral signs of vestibular perturbation in altered gravity have not been well correlated with structural modifications in neurovestibular centers. This ultrastructural research investigated synaptic plasticity in hair cells of adult rat utricular maculas exposed to microgravity for nine days on a space shuttle. The hypothesis was that synaptic plasticity would be more evident in type II hair cells because they are part of a distributed modifying macular circuitry. All rats were shared with other investigators and were subjected to treatments unrelated to this experiment. Maculas were obtained from flight and control rats after shuttle return (R + 0) and nine days post-flight (R + 9). R + 9 rats had chromodacryorrhea, a sign of acute stress. Tissues were prepared for ultrastructural study by conventional methods. Ribbon synapses were counted in fifty serial sections from medial utricular macular regions of three rats of each flight and control group. Counts in fifty additional consecutive sections from one sample in each group established method reliability. All synapses were photographed and located to specific cells on mosaics of entire sections. Pooled data were analyzed statistically. Flown rats showed abnormal posture and movement at R + 0. They had statistically significant increases in total ribbon synapses and in sphere-like ribbons in both kinds of hair cells; in type II cells, pairs of synapses nearly doubled and clusters of 3 to 6 synapses increased twelve-fold. At R + 9, behavioral signs were normal. However, synapse counts remained high in both kinds of hair cells of flight maculas and were elevated in control type II cells. Only counts in type I cells showed statistically significant differences at R + 9. High synaptic counts at R + 9 may have resulted from stress due to experimental treatments. The results nevertheless demonstrate that adult maculas retain the potential for synaptic plasticity. Type II cells exhibited more synaptic plasticity, but

[Over-expression of BDNF inhibits angiotensin II-induced apoptosis of cardiomyocytes in SD rats].

PubMed

Cao, Jingli; Wu, Yingfeng; Liu, Geming; Li, Zhenlong

2018-03-01

Objective To investigate the role and molecular mechanism of brain-derived neurotrophic factor (BDNF) against the process of cardiomyocyte hypertrophy and apoptosis. Methods Cardiomyocyte hypertrophy were estabolished by angiotensin II (Ang II) in neonatal cardiomyocytes in vitro and incomplete ligature of abdominal aorta of SD rats in vivo. BDNF over-expressing recombinant vector pcDNA5-BDNF was transfected into cardiomyocytes by liposomes. Immunofluorescence staining was used to detect the effect of BDNF transfection on the surface area of myocardial cells. The effect of BDNF transfection on the apoptosis of cardiomyocytes was assayed by flow cytometry. Real-time fluorescent quantitative PCR was performed to detect the effect of over-expression of BDNF on the expressions of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) mRNAs in cardiomyocytes. Western blot assay was used to observe the changes of BDNF, ANP and BNP, calmodulin kinase 2 (CaMK2) and phosphorylated calmodulin kinase 2 (p-CaMK2), calcineurin (CaN), p-CaN, nuclear factor of activated T cells 3 (NFATC3) and p-NFATC3 protein expressions in the myocardial tissues and cardiomyocytes. Results The expression of BDNF protein increased significantly in cardiac hypertrophy animal and cell models in a time-dependent manner. Compared with the untransfected control cardiomyocytes, the surface area of cardiomyocytes, the rate of apoptosis, the levels of ANP and BNP mRNA and protein expression, the levels of p-CaMK2 and CaN protein in the BDNF over-expressed cardiomyocytes were remarkably reduced, while the level of p-NFATC3 protein rose significantly. Conclusion BDNF inhibits the apoptosis of cardiomyocytes induced by Ang II, and it plays the role by inhibiting CaMK2 and CaN signaling pathways.

17-β-Estradiol induces spreading depression and pain behavior in alert female rats

PubMed Central

Sandweiss, Alexander J.; Cottier, Karissa E.; McIntosh, Mary I.; Dussor, Gregory; Davis, Thomas P.; Vanderah, Todd W.; Largent-Milnes, Tally M.

2017-01-01

Aims Test the putative contribution of 17-β-estradiol in the development of spreading depression (SD) events and head pain in awake, non-restrained rats. Main Methods Female, Sprague-Dawley rats were intact or underwent ovariectomy followed one week later by surgery to place electrodes onto the dura to detect epidural electroencephalographic activity (dEEG). dEEG activity was recorded two days later for 12 hours after systemic administration of 17-β-estradiol (180 μg/kg, i.p.). A separate set of rats were observed for changes in exploratory, ambulatory, fine, and rearing behaviors; periorbital allodynia was also assessed. Key Findings A bolus of 17-β-estradiol significantly elevated serum estrogen levels, increased SD episodes over a 12-hour recording period and decreased rearing behaviors in ovariectomized rats. Pre-administration of ICI 182,780, an estrogen receptor antagonist, blocked 17-β-estradiol-evoked SD events and pain behaviors; similar results were observed when the antimigraine therapeutic sumatriptan was used. Significance These data indicate that an estrogen receptor-mediated mechanism contributes to SD events in ovariectomized rats and pain behaviors in both ovariectomized -and intact- rats. This suggests that estrogen plays a different role in each phenomenon of migraine where intense fluctuations in concentration may influence SD susceptibility. This is the first study to relate estrogen peaks to SD development and pain behaviors in awake, freely moving female rats, establishing a framework for future preclinical migraine studies. PMID:29371973

Effect of Norbinaltorphimine on Δ9-Tetrahydrocannabinol (THC)-Induced Taste Avoidance in Adolescent and Adult Sprague-Dawley Rats

PubMed Central

Flax, Shaun M.; Wakeford, Alison G.P.; Cheng, Kejun; Rice, Kenner C.; Riley, Anthony L.

2017-01-01

Rationale The aversive effects of Δ9-tetrahydrocannabinol (THC) are mediated by activity at the kappa opioid receptor (KOR) as assessed in adult animals; however, no studies have assessed KOR involvement in the aversive effects of THC in adolescents. Given that adolescents have been reported to be insensitive to the aversive effects induced by KOR agonists, a different mechanism might mediate the aversive effects of THC in this age group. Objectives The present study was designed to assess the impact of KOR antagonism on the aversive effects of THC in adolescent and adult rats using the conditioned taste avoidance (CTA) procedure. Methods Following a single pretreatment injection of norbinaltorphimine (norBNI; 15 mg/kg), CTAs induced by THC (0, 0.56, 1.0, 1.8 and 3.2 mg/kg) were assessed in adolescent (n = 84) and adult (n = 83) Sprague Dawley rats. Results The KOR antagonist, norBNI, had weak and inconsistent effects on THC-induced taste avoidance in adolescent rats in that norBNI both attenuated and strengthened taste avoidance dependent on dose and trial. norBNI had limited impact on the final one-bottle avoidance and no effects on the two-bottle preference test. Interestingly, norBNI had no effect on THC-induced taste avoidance in adult rats as well. Conclusions That norBNI had no significant effect on THC-induced avoidance in adults and a minor and inconsistent effect in adolescents demonstrates that the aversive effects of THC are not mediated by KOR activity as assessed by the CTA design in Sprague Dawley rats. PMID:26025420

Effect of norbinaltorphimine on ∆⁹-tetrahydrocannabinol (THC)-induced taste avoidance in adolescent and adult Sprague-Dawley rats.

PubMed

Flax, Shaun M; Wakeford, Alison G P; Cheng, Kejun; Rice, Kenner C; Riley, Anthony L

2015-09-01

The aversive effects of ∆(9)-tetrahydrocannabinol (THC) are mediated by activity at the kappa opioid receptor (KOR) as assessed in adult animals; however, no studies have assessed KOR involvement in the aversive effects of THC in adolescents. Given that adolescents have been reported to be insensitive to the aversive effects induced by KOR agonists, a different mechanism might mediate the aversive effects of THC in this age group. The present study was designed to assess the impact of KOR antagonism on the aversive effects of THC in adolescent and adult rats using the conditioned taste avoidance (CTA) procedure. Following a single pretreatment injection of norbinaltorphimine (norBNI; 15 mg/kg), CTAs induced by THC (0, 0.56, 1.0, 1.8, and 3.2 mg/kg) were assessed in adolescent (n = 84) and adult (n = 83) Sprague-Dawley rats. The KOR antagonist, norBNI, had weak and inconsistent effects on THC-induced taste avoidance in adolescent rats in that norBNI both attenuated and strengthened taste avoidance dependent on dose and trial. norBNI had limited impact on the final one-bottle avoidance and no effects on the two-bottle preference test. Interestingly, norBNI had no effect on THC-induced taste avoidance in adult rats as well. That norBNI had no significant effect on THC-induced avoidance in adults, and a minor and inconsistent effect in adolescents demonstrates that the aversive effects of THC are not mediated by KOR activity as assessed by the CTA design in Sprague-Dawley rats.

Decreased Sensitivity in Adolescent versus Adult Rats to the Locomotor Activating Effects of Toluene

PubMed Central

Bowen, Scott E.; Charlesworth, Jonathan D.; Tokarz, Mary E.; Jerry Wright, M.; Wiley, Jenny L.

2007-01-01

Volatile organic solvent (inhalant) abuse continues to be a major health concern throughout the world. Of particular concern is the abuse of inhalants by adolescents because of its toxicity and link to illicit drug use. Toluene, which is found in many products such as glues and household cleaners, is among the most commonly abused organic solvents. While studies have assessed outcomes of exposure to inhalants in adult male animals, there is little research on the neurobehavioral effects of inhalants in female or younger animals. In attempt to address these shortcomings, we exposed male and female Long-Evans rats to 20 min of 0, 2,000, 4,000, or 8,000 parts per million (ppm) inhaled toluene for 10 days in rats aged postnatal (PN) day 28-39 (adolescent), PN44-PN55, or >PN70 (adult). Animals were observed individually in 29-l transparent glass cylindrical jars equipped with standard photocells that were used to measure locomotor activity. Toluene significantly increased activity as compared to air exposure in all groups of male and female rats with the magnitude of locomotor stimulation produced by 4000 ppm toluene being significantly greater for female adults than during any age of adolescence. The results demonstrate that exposure to abuse patterns of high concentrations of toluene through inhalation can alter spontaneous locomotor behavior in rats and that the expression of these effects appears to depend upon the postnatal age of testing and sex of the animal. PMID:17869480

Impairment of male reproduction in adult rats exposed to hydroxyprogesterone caproate in utero

NASA Astrophysics Data System (ADS)

Pushpalatha, T.; Ramachandra Reddy, P.; Sreenivasula Reddy, P.

Hydroxyprogesterone caproate is one of the most effective and widely used drugs for the treatment of uterine bleeding and threatened miscarriage in women. Hydroxyprogesterone caproate was administered to pregnant rats in order to assess the effect of intraperitoneal exposure to supranormal levels of hydroxyprogesterone caproate on the male reproductive potential in the first generation. The cauda epididymal sperm count and motility decreased significantly in rats exposed to hydroxyprogesterone caproate during embryonic development, when compared with control rats. The levels of serum testosterone decreased with an increase in follicle stimulating hormone and luteinizing hormone in adult rats exposed to hydroxyprogesterone caproate during the embryonic stage. It was suggested that the impairment of male reproductive performance could be mediated through the inhibition of testosterone production.

The transcriptome of the medullary area postrema: the thirsty rat, the hungry rat and the hypertensive rat.

PubMed

Hindmarch, Charles C T; Fry, Mark; Smith, Pauline M; Yao, Song T; Hazell, Georgina G J; Lolait, Stephen J; Paton, Julian F R; Ferguson, Alastair V; Murphy, David

2011-05-01

The area postrema (AP) is a sensory circumventricular organ characterized by extensive fenestrated vasculature and neurons which are capable of detecting circulating signals of osmotic, cardiovascular, immune and metabolic status. The AP can communicate these messages via efferent projections to brainstem and hypothalamic structures that are able to orchestrate an appropriate response. We have used microarrays to profile the transcriptome of the AP in the Sprague-Dawley (SD) and Wistar-Kyoto rat and present here a comprehensive catalogue of gene expression, focusing specifically on the population of ion channels, receptors and G protein-coupled receptors expressed in this sensory tissue; of the G protein-coupled receptors expressed in the rat AP, we identified ∼36% that are orphans, having no established ligand. We have also looked at the ways in which the AP transcriptome responds to the physiological stressors of 72 h dehydration (DSD) and 48 h fasting (FSD) and have performed microarrays in these conditions. Comparison between the DSD and SD or between FSD and SD revealed only a modest number of AP genes that are regulated by these homeostatic challenges. The expression levels of a much larger number of genes are altered in the spontaneously hypertensive rat AP compared with the normotensive Wistar-Kyoto control rat, however. Finally, analysis of these 'hypertension-related' elements revealed genes that are involved in the regulation of both blood pressure and immune function and as such are excellent targets for further study.

Acquisition of i.v. cocaine self-administration in adolescent and adult male rats selectively bred for high and low saccharin intake.

PubMed

Perry, Jennifer L; Anderson, Marissa M; Nelson, Sarah E; Carroll, Marilyn E

2007-05-16

Adolescence and excessive intake of saccharin have each been previously associated with enhanced vulnerability to drug abuse. In the present study, we focused on the relationship between these two factors using male adolescent and adult rats selectively bred for high (HiS) and low (LoS) levels of saccharin intake. On postnatal day 25 (adolescents) or 150 (adults), rats were implanted with an intravenous catheter and trained to self-administer cocaine (0.4 mg/kg) using an autoshaping procedure that consisted of two 6-h sessions. In the first 6 h, rats were given non-contingent cocaine infusions at random intervals 10 times per hour, and during the second 6-h session, rats were allowed to self-administer cocaine under a fixed ratio 1 (FR 1) lever-response contingency. Acquisition was defined as a total of at least 250 infusions over 5 consecutive days, and rats were given 30 days to meet the acquisition criterion. Subsequently, saccharin phenotype scores were determined by comparing 24-h saccharin and water consumption in two-bottle tests to verify HiS/LoS status. Adolescent LoS rats had a faster rate of acquisition of cocaine self-administration than adult LoS rats; however, adolescent and adult HiS rats acquired at the same rate. Both HiS and LoS adolescents had significantly higher saccharin phenotype scores than HiS and LoS adults, respectively. Additionally, saccharin score was negatively correlated with the number of days to meet the acquisition criterion for cocaine self-administration, but this was mostly accounted for by the HiS adolescents. These results suggest that during adolescence, compared with adulthood, rats have both an increased avidity for sweets and vulnerability to initiate drug abuse.

Wistar-Kyoto rats as an animal model of anxiety vulnerability: support for a hypervigilance hypothesis.

PubMed

McAuley, J D; Stewart, A L; Webber, E S; Cromwell, H C; Servatius, R J; Pang, K C H

2009-12-01

Inbred Wistar-Kyoto (WKY) rats have been proposed as a model of anxiety vulnerability as they display behavioral inhibition and a constellation of learning and reactivity abnormalities relative to outbred Sprague-Dawley (SD) rats. Together, the behaviors of the WKY rat suggest a hypervigilant state that may contribute to its anxiety vulnerability. To test this hypothesis, open-field behavior, acoustic startle, pre-pulse inhibition and timing behavior were assessed in WKY and Sprague-Dawley (SD) rats. Timing behavior was evaluated using a modified version of the peak-interval timing procedure. Training and testing of timing first occurred without audio-visual (AV) interference. Following this initial test, AV interference was included on some trials. Overall, WKY rats took much longer to leave the center of the arena, made fewer line crossings, and reared less, than did SD rats. WKY rats showed much greater startle responses to acoustic stimuli and significantly greater pre-pulse inhibition than did the SD rats. During timing conditions without AV interference, timing accuracy for both strains was similar; peak times for WKY and SD rats were not different. During interference conditions, however, the timing behavior of the two strains was very different. Whereas peak times for SD rats were similar between non-interference and interference conditions, peak times for WKY rats were shorter and response rates higher in interference conditions than in non-interference conditions. The enhanced acoustic startle response, greater prepulse inhibition and altered timing behavior with audio-visual interference supports a characterization of WKY strain as hypervigilant and provides further evidence for the use of the WKY strain as a model of anxiety vulnerability.

[Morinda Officinalis How improves cellphone radiation-induced abnormality of LH and LHR in male rats].

PubMed

Li, Rong; Yang, Wei-qun; Chen, Hui-qin; Zhang, Yong-hong

2015-09-01

To investigate the effects of Morina Officinalis How (MOH) on the abnormal levels of serum luteotrophic hormone (LH) and LH receptor (LHR) in the testis tissue induced by cellphone radiation (CPR) in rats. Fifty adult male SD rats were randomly divided into five groups of equal number: sham CPR, untreated CPR, negative double distilled water (DDW) control, aqueous MOH extract, and alcohol MOH extract. All the animals were exposed to mobile phone radiation except those of the sham CPR group. Then, the rats of the latter two groups were treated intragastrically with MOH at 20 g per kg of the body weight per day in water and alcohol, respectively. After 2. weeks of treatment, all the rats were sacrificed for measurement of the levels of serum LH and LHR in the testis tissue. The levels of serum LH and LHR were 30.15 ± 8.71 and 33.28 ± 6.61 in the aqueous MOH group and 0.96 ± 0.06 and 0.94 ± 0.08 in the alcohol MOH group, both significantly decreased as compared with the negative DDW controls (P < 0.05), but with no remarkable difference between the two MOH groups (P > 0.05). MOH can improve CPR-induced abnormality of LH and LHR in adult male rats.

Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Male Rats

EPA Pesticide Factsheets

behavioral measures of learning and memory in adult offspring of rats treated with thyroid hormone synthesis inhibitor, propylthiouracil.Electrophysiological measures of 'memory' in form of plasticity model known as long term potentiation (LTP)Molecular changes induced by LTPThis dataset is associated with the following publication:Gilbert , M., K. Sanchez-Huerta, and C. Wood. Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Make Rats. ENDOCRINOLOGY. Endocrine Society, 157(2): 774-87, (2016).

Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart

PubMed Central

Seeley, Sarah L.; Stoops, Thorne S.; D’Souza, Manoranjan S.

2017-01-01

Background We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury. Methods Adult male and female rats received daily injections of methamphetamine (5 mg/kg) or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. Results Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine. Conclusions Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse. PMID:28575091

Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart.

PubMed

Rorabaugh, Boyd R; Seeley, Sarah L; Stoops, Thorne S; D'Souza, Manoranjan S

2017-01-01

We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury. Adult male and female rats received daily injections of methamphetamine (5 mg/kg) or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine. Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse.

Sexual interactions with unfamiliar females reduce hippocampal neurogenesis among adult male rats.

PubMed

Spritzer, M D; Curtis, M G; DeLoach, J P; Maher, J; Shulman, L M

2016-03-24

Recent experiments have shown that sexual interactions prior to cell proliferation cause an increase in neurogenesis in adult male rats. Because adult neurogenesis is critical for some forms of memory, we hypothesized that sexually induced changes in neurogenesis may be involved in mate recognition. Sexually naive adult male rats were either exposed repeatedly to the same sexual partner (familiar group) or to a series of novel sexual partners (unfamiliar group), while control males never engaged in sexual interactions. Ovariectomized female rats were induced into estrus every four days. Males were given two injections of 5-bromo-2'-deoxyuridine (BrdU) (200mg/kg) to label proliferating cells, and the first sexual interactions occurred three days later. Males in the familiar and unfamiliar groups engaged in four, 30-min sexual interactions at four-day intervals, and brain tissue was collected the day after the last sexual interaction. Immunohistochemistry followed by microscopy was used to quantify BrdU-labeled cells. Sexual interactions with unfamiliar females caused a significant reduction in neurogenesis in the dentate gyrus compared to males that interacted with familiar females and compared to the control group. The familiar group showed no difference in neurogenesis compared to the control group. Males in the familiar group engaged in significantly more sexual behavior (ejaculations and intromissions) than did males in the unfamiliar group, suggesting that level of sexual activity may influence neurogenesis levels. In a second experiment, we tested whether this effect was unique to sexual interactions by replicating the entire procedure using anestrus females. We found that interactions with unfamiliar anestrus females reduced neurogenesis relative to the other groups, but this effect was not statistically significant. In combination, these results indicate that interactions with unfamiliar females reduce adult neurogenesis and the effect is stronger for sexual

Glutamate and CO2 production from glutamine in incubated enterocytes of adult and very old rats.

PubMed

Meynial-Denis, Dominique; Bielicki, Guy; Beaufrère, Anne-Marie; Mignon, Michelle; Mirand, Philippe Patureau; Renou, Jean-Pierre

2013-04-01

Glutamine is the major fuel for enterocytes and promotes the growth of intestinal mucosa. Although oral glutamine exerts a positive effect on intestinal villus height in very old rats, how glutamine is used by enterocytes is unclear. Adult (8 months) and very old (27 months) female rats were exposed to intermittent glutamine supplementation for 50% of their age lifetime. Treated rats received glutamine added to their drinking water, and control rats received water alone. Jejunal epithelial cells (~300×10(6) cells) were incubated in oxygenated Krebs-Henseleit buffer for 30 min containing [1-(13)C] glutamine (~17 M) for analysis of glutamine metabolites by (13)C nuclear magnetic resonance ((13)C NMR). An aliquot fraction was incubated in the presence of [U-(14)C] glutamine to measure produced CO2. Glutamine pretreatment increased glutamate production and decreased CO2 production in very old rats. The ratio CO2/glutamate, which was very high in control very old rats, was similar at both ages after glutamine pretreatment, as if enterocytes from very old rats recovered the metabolic abilities of enterocytes from adult rats. Our results suggest that long-term treatment with glutamine started before advanced age (a) prevented the loss of rat body weight without limiting sarcopenia and (b) had a beneficial effect on enterocytes from very old rats probably by favoring the role of glutamate as a precursor for glutathione, arginine and proline biosynthesis, which was not detected in (13)C NMR spectra in our experimental conditions. Copyright © 2013 Elsevier Inc. All rights reserved.

Increased production of active ghrelin is relevant to hyperphagia in nonobese spontaneously diabetic Torii rats.

PubMed

Mifune, Hiroharu; Nishi, Yoshihiro; Tajiri, Yuji; Masuyama, Taku; Hosoda, Hiroshi; Kangawa, Kenji; Kojima, Masayasu

2012-04-01

An abnormal eating behavior is often associated with diabetes mellitus in individuals. In the present study, we investigated the mechanisms underlying the relationship among uncontrolled diabetes, food intake, and the production of ghrelin, an orexigenic hormone, in spontaneous diabetic Torii (SDT) rats. Male SDT rats and age-matched control Sprague-Dawley (SD) rats were housed from 8 to 38 weeks of age. Body weight and daily food intake were measured weekly, whereas blood and whole stomach samples were obtained at the age of 8, 25, and 38 weeks in both SDT and SD rats. The SDT rats at both 25 and 38 weeks of age demonstrated significantly lower body weights despite almost doubled food consumption compared with the SD rats of the same age. The SDT rats showed overt hyperglycemia at 25 and 38 weeks of age with concomitant hypoinsulinemia. The plasma active ghrelin levels and the ratio to total ghrelin levels of SDT rats at 38 weeks of age were significantly higher than those of SD rats of the same age. Stomach ghrelin and ghrelin O-acyltransferase messenger RNA expression levels were higher in SDT rats than in SD rats after the induction of diabetes, with a concomitant decrease of stomach ghrelin-immunopositive cell numbers in SDT rats at 38 weeks of age. The SDT rats with uncontrolled hyperglycemia show hyperphagia with a concomitant increase of plasma active ghrelin concentration. This report is the first to clarify the relevance of ghrelin to hyperphagia in diabetic state over an extended period. Copyright © 2012 Elsevier Inc. All rights reserved.

Aversive effects of ethanol in adolescent versus adult rats: potential causes and implication for future drinking.

PubMed

Schramm-Sapyta, Nicole L; DiFeliceantonio, Alexandra G; Foscue, Ethan; Glowacz, Susan; Haseeb, Naadeyah; Wang, Nancy; Zhou, Cathy; Kuhn, Cynthia M

2010-12-01

Many people experiment with alcohol and other drugs of abuse during their teenage years. Epidemiological evidence suggests that younger initiates into drug taking are more likely to develop problematic drug seeking behavior, including binge and other high-intake behaviors. The level of drug intake for any individual depends on the balance of rewarding and aversive effects of the drug in that individual. Multiple rodent studies have demonstrated that aversive effects of drugs of abuse are reduced in adolescent compared to adult animals. In this study, we addressed 2 key questions: First, do reduced aversive effects of ethanol in younger rats correlate with increased ethanol consumption? Second, are the reduced aversive effects in adolescents attributable to reduced sensitivity to ethanol's physiologic effects? Adolescent and adult rats were tested for ethanol conditioned taste aversion (CTA) followed by a voluntary drinking period, including postdeprivation consumption. Multivariate regression was used to assess correlations. In separate experiments, adolescent and adult rats were tested for their sensitivity to the hypothermic and sedative effects of ethanol, and for blood ethanol concentrations (BECs). We observed that in adolescent rats but not adults, taste aversion was inversely correlated with postdeprivation consumption. Adolescents also exhibited a greater increase in consumption after deprivation than adults. Furthermore, the age difference in ethanol CTA was not attributable to differences in hypothermia, sedation, or BECs. These results suggest that during adolescence, individuals that are insensitive to aversive effects are most likely to develop problem drinking behaviors. These results underscore the importance of the interaction between developmental stage and individual variation in sensitivity to alcohol. Copyright © 2010 by the Research Society on Alcoholism.

Effects of age on recovery of body weight following REM sleep deprivation of rats.

PubMed

Koban, Michael; Stewart, Craig V

2006-01-30

Chronically enforced rapid eye (paradoxical) movement sleep deprivation (REM-SD) of rats leads to a host of pathologies, of which hyperphagia and loss of body weight are among the most readily observed. In recent years, the etiology of many REM-SD-associated pathologies have been elucidated, but one unexplored area is whether age affects outcomes. In this study, male Sprague-Dawley rats at 2, 6, and 12 months of age were REM sleep-deprived with the platform (flowerpot) method for 10-12 days. Two-month-old rats resided on 7-cm platforms, while 10-cm platforms were used for 6- and 12-month-old rats; rats on 15-cm platforms served as tank controls (TCs). Daily changes in food consumption (g/kg(0.67)) and body weight (g) during baseline, REM-SD or TCs, and post-experiment recovery in home cages were determined. Compared to TCs, REM-SD resulted in higher food intake and decreases in body weight. When returned to home cages, food intake rapidly declined to baseline levels. Of primary interest was that rates of body weight gain during recovery differed between the age groups. Two-month-old rats rapidly restored body weight to pre-REM-SD mass within 5 days; 6-month-old rats were extrapolated by linear regression to have taken about 10 days, and for 12-month-old rats, the estimate was about 35 days. The observation that restoration of body weight following its loss during REM-SD may be age-dependent is in general agreement with the literature on aging effects on how mammals respond to stress.

Prenatal choline availability alters the context sensitivity of Pavlovian conditioning in adult rats

PubMed Central

Lamoureux, Jeffrey A.; Meck, Warren H.; Williams, Christina L.

2008-01-01

The effects of prenatal choline availability on Pavlovian conditioning were assessed in adult male rats (3–4 mo). Neither supplementation nor deprivation of prenatal choline affected the acquisition and extinction of simple Pavlovian conditioned excitation, or the acquisition and retardation of conditioned inhibition. However, prenatal choline availability significantly altered the contextual control of these learned behaviors. Both control and choline-deprived rats exhibited context specificity of conditioned excitation as exhibited by a loss in responding when tested in an alternate context after conditioning; in contrast, choline-supplemented rats showed no such effect. When switched to a different context following extinction, however, both choline-supplemented and control rats showed substantial contextual control of responding, whereas choline-deficient rats did not. These data support the view that configural associations that rely on hippocampal function are selectively sensitive to prenatal manipulations of dietary choline during prenatal development. PMID:19050158

Effects of infrasound on cell proliferation in the dentate gyrus of adult rats.

PubMed

Liu, Juanfang; Lin, Tian; Yan, Xiaodong; Jiang, Wen; Shi, Ming; Ye, Ruidong; Rao, Zhiren; Zhao, Gang

2010-06-02

Adult rats were used to identify the effects of infrasound on neurogenesis in the hippocampal dentate gyrus. After 7 consecutive days' exposure to infrasound of 16 Hz at 130 dB, immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and doublecortin (DCX) was preformed. Compared with those in normal groups, the numbers of BrdU+ and DCX+/BrdU+ cells in the subgranular zone in infrasound groups were significantly decreased at 3, 6, 10 and 14 days and returned to normal at 18 days. The percentage of BrdU+ cells that were co-labeled with DCX showed no significant differences between the infrasound and normal groups. These data suggest that infrasound inhibits the cell proliferation in adult rat dentate gyrus but has no effects on early migration and differentiation of these newborn cells.

Pharmacological properties of various anesthetic protocols in 10-day-old neonatal rats.

PubMed

Tsukamoto, Atsushi; Konishi, Yui; Kawakami, Takako; Koibuchi, Chiharu; Sato, Reiichiro; Kanai, Eiichi; Inomata, Tomo

2017-10-30

In general, the anesthesia in neonates involves high risk. Although hypothermic anesthesia is recommended in rats up to the age of 7 days, neonatal anesthesia for later periods has not been standardized. The present study investigated the pharmacological properties of conventional anesthetic protocols in 10-day-old SD rats. The rats were anesthetized with four anesthetics: a combination of ketamine and xylazine (K/X); a combination of medetomidine, midazolam, and butorphanol (M/M/B); isoflurane; and sevoflurane. Anesthetic depth was scored by reflex response to noxious stimuli. Induction and recovery times were recorded. Vital signs and mortality rate were evaluated for safety assessment. All rats died after administration of K/X at a dose of 60/6 mg/kg, whereas K/X at 40/4 mg/kg resulted in insufficient anesthetic depth, indicating inappropriate for neonatal anesthesia. Although M/M/B at the adult rat dose (0.15/2/2.5 mg/kg) did not provide surgical anesthetic depth, the mouse dose (0.3/4/5 mg/kg) showed sufficient anesthetic depth with relatively stable vital signs. Isoflurane required a long induction period, and caused remarkable respiratory depression and hypothermia, resulted in a 25% mortality rate. In contrast, sevoflurane provided consistent surgical anesthetic depth with rapid induction. Although respiratory rate decrease was markedly observed, all rats survived. Among the anesthetic protocols investigated in the present study, sevoflurane and M/M/B at the mouse dose were recommended for the neonatal anesthesia. Compared with adult rats, the required dose of both anesthetics in neonates was higher, possibly associated with their lower anesthetic sensitivity.

Age dependent in vitro metabolism of bifenthrin in rat and human hepatic microsomes.

PubMed

Nallani, Gopinath C; Chandrasekaran, Appavu; Kassahun, Kelem; Shen, Li; ElNaggar, Shaaban F; Liu, Zhiwei

2018-01-01

Bifenthrin, a pyrethroid insecticide, undergoes oxidative metabolism leading to the formation of 4'-hydroxy-bifenthrin (4'-OH-BIF) and hydrolysis leading to the formation of TFP acid in rat and human hepatic microsomes. In this study, age-dependent metabolism of bifenthrin in rats and humans were determined via the rates of formation of 4'-OH-BIF and TFP acid following incubation of bifenthrin in juvenile and adult rat (PND 15 and PND 90) and human (<5years and >18years) liver microsomes. Furthermore, in vitro hepatic intrinsic clearance (CL int ) of bifenthrin was determined by substrate consumption method in a separate experiment. The mean V max (±SD) for the formation of 4'-OH-BIF in juvenile rat hepatic microsomes was 25.0±1.5pmol/min/mg which was significantly lower (p<0.01) compared to that of adult rats (86.0±17.7pmol/min/mg). However, the mean K m values for juvenile (19.9±6.6μM) and adult (23.9±0.4μM) rat liver microsomes were similar. On the other hand, in juvenile human hepatic microsomes, V max for the formation of 4'-OH-BIF (73.9±7.5pmol/min/mg) was significantly higher (p<0.05) than that of adults (21.6±0.6pmol/min/mg) albeit similar K m values (10.5±2.8μM and 8.9±0.6μM) between the two age groups. The trends in the formation kinetics of TFP acid were similar to those of 4'-OH-BIF between the species and age groups, although the differences between juveniles and adults were less pronounced. The data also show that metabolism of bifenthrin occurs primarily via oxidative pathway with relatively lesser contribution (~30%) from hydrolytic pathway in both rat and human liver microsomes. The CL int values for bifenthrin, determined by monitoring the consumption of substrate, in juvenile and adult rat liver microsomes fortified with NADPH were 42.0±7.2 and 166.7±20.5μl/min/mg, respectively, and the corresponding values for human liver microsomes were 76.0±4.0 and 21.3±1.2μl/min/mg, respectively. The data suggest a major species difference

[Effect of prokinetic agents on the electrical activity of stomach and duodenum in rats].

PubMed

Li, Fujun; Zou, Yiyou; Huang, Tianhui

2009-07-01

To determine the effect of prokinetic agents such as domperidone, mosapride, clarithromycin, and itopride on the electrical activity of the stomach and duodenum in SD rats,and also to explore the mechanism. The organism functional experiment system BL-420E was used to record the myoelectrical activity in the stomach and duodenum of SD rats in all groups using domperidone, mosapride, itopride, clarithromycin, and physiological saline on the interdigestive phase. The effect of the prokinetic agents on the amplitude and frequency of gastric and duodenal electromyogram in the SD rats was compared. The antagonists such as atropine, phentolamine, and propranolol were added to investigate the mechanism of action with all prokinetic agents. All prokinetic agents increased the amplitude and frequency of gastric and duodenal fast waves in the SD rats(P<0.05). The effect of itopride was the most obvious among the 3 groups (P<0.05),and clarithromycin had the weakest effect(P<0.05). The amplitude and frequency of gastric and duodenal fast waves in the SD rats in the groups of clarithromycin,domperidone,mosapride, itopride, and physiological saline were inhibited by atropine(P<0.05),but not by phentolamine and propranolol. Itopride, mosapride, domperidone, and clarithromycin can increase the amplitude and frequency of gastric and duodenal fast waves in the SD rats. The mechanism may be related to cholinergic receptors, but not adrenergic receptors.

Voluntary ethanol consumption differs in adolescent and adult male rats using a modified sucrose-fading paradigm.

PubMed

Maldonado, Antoniette M; Finkbeiner, Lauren M; Alipour, Kent K; Kirstein, Cheryl L

2008-09-01

Initiation of alcohol consumption during adolescence is high, which usually begins with consumption of highly concentrated sweetened alcoholic beverages in adolescent humans. Enhanced voluntary ethanol (EtOH) intake has been observed previously in adolescent relative to adult rats under continuous access conditions using sweetened EtOH solutions. The present set of experiments investigated patterns of voluntary EtOH intake in adolescent and adult rats using sweetened EtOH solutions in a limited access paradigm. Rats were trained with modified sucrose-substitution protocols that ended at either 5% sucrose-20% EtOH (5S/20E) (Exp. 1) or 5% sucrose-10% EtOH (5S/10E) (Exp. 2). Voluntary EtOH consumption differences between the 2 age groups were apparent at higher (i.e., 10 and 20%), but not lower (i.e., 2 and 5%) EtOH concentrations. Adolescent rats consumed more EtOH on a g/kg basis only at 20% EtOH (Exp. 1). Adolescent rats voluntarily consumed more EtOH than adults when maintained at 5S/10E (Exp. 2). To assess whether these age-related differences in voluntary EtOH intake were concentration dependent, rats were trained with 5S/20E and subsequently trained with decreasing EtOH concentrations (i.e., 5S/10E and 5S/5E). Adolescents consumed more EtOH when initially presented with the 5S/10E and 5S/20E EtOH concentrations, and subsequently at the lower 5S/5E EtOH concentration (Exp. 3). There were no differences in preference for the sucrose-only solution, however adolescents tended to consume more sucrose at the 5S sucrose concentration (Exp. 4). Given that adolescents consumed more EtOH at the 5S/10E and 5S/20E, but not at the 5S/5E EtOH concentrations, preference for sucrose does not solely explain the age differences in voluntary EtOH intake observed. Overall, results replicate previous work, demonstrating adolescent rats consume more EtOH relative to adults. However, the present results were observed using sweetened EtOH solutions in a limited access paradigm. The

Tauroursodeoxycholic Acid Enhances Mitochondrial Biogenesis, Neural Stem Cell Pool, and Early Neurogenesis in Adult Rats.

PubMed

Soares, Rita; Ribeiro, Filipa F; Xapelli, Sara; Genebra, Tânia; Ribeiro, Maria F; Sebastião, Ana M; Rodrigues, Cecília M P; Solá, Susana

2018-05-01

Although neurogenesis occurs in restricted regions of the adult mammalian brain, neural stem cells (NSCs) produce very few neurons during ageing or after injury. We have recently discovered that the endogenous bile acid tauroursodeoxycholic acid (TUDCA), a strong inhibitor of mitochondrial apoptosis and a neuroprotective in animal models of neurodegenerative disorders, also enhances NSC proliferation, self-renewal, and neuronal conversion by improving mitochondrial integrity and function of NSCs. In the present study, we explore the effect of TUDCA on regulation of NSC fate in neurogenic niches, the subventricular zone (SVZ) of the lateral ventricles and the hippocampal dentate gyrus (DG), using rat postnatal neurospheres and adult rats exposed to the bile acid. TUDCA significantly induced NSC proliferation, self-renewal, and neural differentiation in the SVZ, without affecting DG-derived NSCs. More importantly, expression levels of mitochondrial biogenesis-related proteins and mitochondrial antioxidant responses were significantly increased by TUDCA in SVZ-derived NSCs. Finally, intracerebroventricular administration of TUDCA in adult rats markedly enhanced both NSC proliferation and early differentiation in SVZ regions, corroborating in vitro data. Collectively, our results highlight a potential novel role for TUDCA in neurologic disorders associated with SVZ niche deterioration and impaired neurogenesis.

Disposition of the Emerging Brominated Flame Retardant, 2-Ethylhexyl 2,3,4,5-Tetrabromobenzoate, in Female SD Rats and Male B6C3F1 Mice: Effects of Dose, Route, and Repeated Administration

PubMed Central

Knudsen, Gabriel A.; Sanders, J. Michael; Birnbaum, Linda S.

2016-01-01

2-Ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB; MW 549.92 g/mol; CAS 183658-27-7) is a brominated component of flame retardant mixtures used as substitutes for some PBDEs. EH-TBB is added to various consumer products, including polyurethane foams, and has been detected in humans. The present study characterized the fate of EH-TBB in rodents. [14C]-labeled EH-TBB was absorbed, metabolized, and eliminated via the urine and feces following single administrations of 0.1–100 µmol/kg (∼0.05–55 mg/kg) or repeated administration (0.1 µmol/kg/day × 5–10 days) by gavage to female Hsd:Sprague DawleySD (SD) rats. Cumulative excretion via feces increased (39–60%) with dose (0.1–10 µmol/kg) with corresponding decreases in urinary excretion (54 to 37%) after 72 h. Delayed excretion of [14C]-radioactivity in urine and feces of a 100 µmol/kg oral dose was noted. Recovery was complete for all doses by 72 h. IV-injected rats excreted more of the 0.1 µmol/kg dose in urine and less in feces than did gavaged rats, indicating partial biliary elimination of systemically available compound. No tissue bioaccumulation was found for rats given 5 oral daily doses of EH-TBB. Parent molecule was not detected in urine whereas 2 metabolites, tetrabromobenzoic acid (TBBA), a TBBA-sulfate conjugate, and a TBBA-glycine conjugate were identified. EH-TBB and TBBA were identified in extracts from feces. Data from gavaged male B6C3F1/Tac mice indicated minimal sex- or species differences are likely for the disposition of EH-TBB. Approximately 85% of a 0.1 µmol/kg dose was absorbed from the gut. Overall absorption of EH-TBB is expected to be even greater at lower levels. PMID:27613714

Prenatal zinc reduces stress response in adult rat offspring exposed to lipopolysaccharide during gestation.

PubMed

Galvão, Marcella C; Chaves-Kirsten, Gabriela P; Queiroz-Hazarbassanov, Nicolle; Carvalho, Virgínia M; Bernardi, Maria M; Kirsten, Thiago B

2015-01-01

Previous investigations by our group have shown that prenatal treatment with lipopolysaccharide (LPS; 100 μg/kg, intraperitoneally) on gestation day (GD) 9.5 in rats, which mimics infections by Gram-negative bacteria, induces short- and long-term behavioral and neuroimmune changes in the offspring. Because LPS induces hypozincemia, dams were treated with zinc after LPS in an attempt to prevent or ameliorate the impairments induced by prenatal LPS exposure. LPS can also interfere with hypothalamic-pituitary-adrenal (HPA) axis development; thus, behavioral and neuroendocrine parameters linked to HPA axis were evaluated in adult offspring after a restraint stress session. We prenatally exposed Wistar rats to LPS (100 μg/kg, intraperitoneally, on GD 9.5). One hour later they received zinc (ZnSO4, 2 mg/kg, subcutaneously). Adult female offspring that were in metestrus/diestrus were submitted to a 2 h restraint stress session. Immediately after the stressor, 22 kHz ultrasonic vocalizations, open field behavior, serum corticosterone and brain-derived neurotrophic factor (BDNF) levels, and striatal and hypothalamic neurotransmitter and metabolite levels were assessed. Offspring that received prenatal zinc after LPS presented longer periods in silence, increased locomotion, and reduced serum corticosterone and striatal norepinephrine turnover compared with rats treated with LPS and saline. Prenatal zinc reduced acute restraint stress response in adult rats prenatally exposed to LPS. Our findings suggest a potential beneficial effect of prenatal zinc, in which the stress response was reduced in offspring that were stricken with infectious/inflammatory processes during gestation. Copyright © 2014 Elsevier Inc. All rights reserved.

Eating High Fat Chow Decreases Dopamine Clearance in Adolescent and Adult Male Rats but Selectively Enhances the Locomotor Stimulating Effects of Cocaine in Adolescents

PubMed Central

Baladi, Michelle G.; Horton, Rebecca E.; Owens, William A.; Daws, Lynette C.

2015-01-01

Background: Feeding conditions can influence dopamine neurotransmission and impact behavioral and neurochemical effects of drugs acting on dopamine systems. This study examined whether eating high fat chow alters the locomotor effects of cocaine and dopamine transporter activity in adolescent (postnatal day 25) and adult (postnatal day 75) male Sprague-Dawley rats. Methods: Dose-response curves for cocaine-induced locomotor activity were generated in rats with free access to either standard or high fat chow or restricted access to high fat chow (body weight matched to rats eating standard chow). Results: Compared with eating standard chow, eating high fat chow increased the sensitivity of adolescent, but not adult, rats to the acute effects of cocaine. When tested once per week, sensitization to the locomotor effects of cocaine was enhanced in adolescent rats eating high fat chow compared with adolescent rats eating standard chow. Sensitization to cocaine was not different among feeding conditions in adults. When adolescent rats that previously ate high fat chow ate standard chow, sensitivity to cocaine returned to normal. As measured by chronoamperometry, dopamine clearance rate in striatum was decreased in both adolescent and adult rats eating high fat chow compared with age-matched rats eating standard chow. Conclusions: These results suggest that high fat diet-induced reductions in dopamine clearance rate do not always correspond to increased sensitivity to the locomotor effects of cocaine, suggesting that mechanisms other than dopamine transporter might play a role. Moreover, in adolescent but not adult rats, eating high fat chow increases sensitivity to cocaine and enhances the sensitization that develops to cocaine. PMID:25805560

Sleep deprivation precipitates the development of amphetamine-induced conditioned place preference in rats.

PubMed

Berro, Laís F; Tufik, Sergio B; Frussa-Filho, Roberto; Andersen, Monica L; Tufik, Sergio

2018-04-03

Sleep deprivation (SD) and amphetamine use are commonly associated conditions. SD shares similar neurobiological effects with psychostimulants, playing an important role in drug addiction, especially through conditioning manipulations. The aim of the present study was to investigate the effects of SD on the development of amphetamine-induced conditioned place preference (CPP) in a protocol with a reduced number of conditioning sessions. Male adult Wistar rats were submitted to 4 conditioning sessions (2 sessions/day) in the CPP apparatus, half with saline (non-drug-paired compartment) and half with 2 mg/kg amphetamine (drug-paired compartment) after control (home-cage maintained) or SD (6 h gentle handling method) conditions. Control animals did not express a preference for the amphetamine-paired compartment, showing that 2 conditioning sessions with the drug were not sufficient to establish CPP. On the other hand, animals submitted to SD during the conditioning sessions expressed a preference for the amphetamine-paired compartment, which was maintained across the entire test session. SD precipitated the development of CPP to amphetamine, showing that lack of sleep can contribute to the establishment of a conditioning between the drug effect and environmental cues. Copyright © 2018 Elsevier B.V. All rights reserved.

Do prenatally methamphetamine-exposed adult male rats display general predisposition to drug abuse in the conditioned place preference test?

PubMed

Šlamberová, R; Pometlová, M; Schutová, B; Hrubá, L; Macúchová, E; Nová, E; Rokyta, R

2012-01-01

Drug abuse of pregnant women is a growing problem. The effect of prenatal drug exposure may have devastating effect on development of the offsprings that may be long-term or even permanent. One of the most common drug abused by pregnant women is methamphetamine (MA), which is also the most frequently abused illicit drug in the Czech Republic. Our previous studies demonstrated that prenatal MA exposure alters behavior, cognition, pain and seizures in adult rats in sex-specific manner. Our most recent studies demonstrate that prenatal MA exposure makes adult rats more sensitive to acute injection of the same or related drugs than their controls. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the Conditioned place preference (CPP). Adult male rats were divided to: prenatally MA-exposed (5 mg/kg daily for the entire prenatal period), prenatally saline-exposed (1 ml/kg of physiological saline) and controls (without maternal injections). The following drugs were used in the CPP test in adulthood: MA (5 mg/kg), amphetamine (5 mg/kg), cocaine (5 and 10 mg/kg), morphine (5 mg/kg), MDMA (5 mg/kg) and THC (2 mg/kg). Our data demonstrated that prenatally MA-exposed rats displayed higher amphetamine-seeking behavior than both controls. MA as well as morphine induced drug-seeking behavior of adult male rats, however this effect did not differ based on the prenatal MA exposure. In contrast, prenatal MA exposure induced rather tolerance to cocaine than sensitization after the conditioning in the CPP. MDMA and THC did not induce significant effects. Even though the present data did not fully confirmed our hypotheses, future studies are planned to test the drug-seeking behavior also in self-administration test.

Completion of the life cycle of Sarcocystis zuoi , a parasite from the Norway rat, Rattus norvegicus.

PubMed

Hu, Jun-Jie; Meng, Yu; Guo, Yan-Mei; Liao, Jie-Ying; Song, Jing-Ling

2012-06-01

Transmission experiments were performed to elucidate the life cycle of Sarcocystis zuoi found in Norway rats ( Rattus norvegicus ) in China. Two king rat snakes ( Elaphe carinata ) fed sarcocysts from the muscles of 4 naturally infected Norway rats shed sporocysts measuring 10.8 ± 0.7 × 8.0 ± 0.7 µm, with a prepatent period of 8-9 days. Sporocysts from the intestine of 2 experimentally infected king rat snakes were given to the laboratory Sprague-Dawley (SD) rats ( R. norvegicus ) and Kunming (KM) mice ( Mus musculus ). Microscopic sarcocysts developed in the skeletal muscles of SD rats. No sarcocysts were observed in KM mice. Characters of ultrastructure and molecule of sarcocysts from SD rats were confirmed as S. zuoi . Our results indicate that king rat snake is the definitive host of S. zuoi .

IL-1 receptor antagonist attenuates neonatal lipopolysaccharide-induced long-lasting learning impairment and hippocampal injury in adult rats

PubMed Central

Pang, Yi; Bhatt, Abhay J.; Fan, Lir-Wan

2015-01-01

We have previously reported that neonatal lipopolysaccharide (LPS) exposure resulted in an increase in interleukin-1β (IL-1β) content, injury to the hippocampus, and cognitive deficits in juvenile male and female rats, as well as female adult rats. The present study aimed to determine whether an antiinflammatory cytokine, interleukin-1 receptor antagonist (IL-1ra), protects against the neonatal LPS exposure-induced inflammatory responses, hippocampal injury, and long-lasting learning deficits in adult rats. LPS (1 mg/kg) or LPS plus IL-1ra (0.1 mg/kg) was injected intracerebrally to Sprague-Dawley male rat pups at postnatal day 5 (P5). Neurobehavioral tests were carried out on P21, P49, and P70, while neuropathological studies were conducted on P71. Our results showed that neonatal LPS exposure resulted in learning deficits in rats at both developmental and adult ages, as demonstrated by a significantly impaired performance in the passive avoidance task (P21, P49, and P70), reduced hippocampal volume, and reduced number of Nissl+ cells in the CA1 region of the middle dorsal hippocampus of P71 rat brain. Those neuropathological and neurobehavioral alterations by LPS exposure were associated with a sustained inflammatory response in the P71 rat hippocampus, indicated by increased number of activated microglia as well as elevated levels of IL-1β. Neonatal administration of IL-1ra significantly attenuated LPS-induced long-lasting learning deficits, hippocampal injury, and sustained inflammatory responses in P71 rats. Our study demonstrates that neonatal LPS exposure leads to a persistent injury to the hippocampus, resulting in long-lasting learning disabilities related to chronic inflammation in rats, and these effects can be attenuated with an IL-1 receptor antagonist. PMID:25665855

Analysis of proteome changes in doxorubicin-treated adult rat cardiomyocyte

PubMed Central

Kumar, Suresh N.; Konorev, Eugene A.; Aggarwal, Deepika; Kalyanaraman, Balaraman

2011-01-01

Doxorubicin-induced cardiomyopathy in cancer patients is well established. The proposed mechanism of cardiac damage includes generation of reactive oxygen species, mitochondrial dysfunction and cardiomyocyte apoptosis. Exposure of adult rat cardiomyocytes to low levels of DOX for 48 h induced apoptosis. Analysis of protein expression showed a differential regulation of several key proteins including the voltage dependent anion selective channel protein 2 and methylmalonate semialdehyde dehydrogenase. In comparison, proteomic evaluation of DOX-treated rat heart showed a slightly different set of protein changes that suggests nuclear accumulation of DOX. Using a new solubilization technique, changes in low abundant protein profiles were monitored. Altered protein expression, modification and function related to oxidative stress response may play an important role in DOX cardiotoxicity. PMID:21338723

Transgenerational Effects of Di(2-ethylhexyl) Phthalate in the SD Male Rat

EPA Science Inventory

In the rat, some phthalates alter sexual differentiation at relatively low dosage levels by altering fetal Leydig cell development and hormone synthesis, thereby inducing abnormalities of the testis, gubernacular ligaments, epididymis and other androgen-dependent tissues. In ...

Effects of long-term construction noise on health of adult female Wistar rats.

PubMed

Zymantiene, J; Zelvyte, R; Pampariene, I; Aniuliene, A; Juodziukyniene, N; Kantautaite, J; Oberauskas, V

2017-03-28

The aim of this study was to investigate the influence of long-term building construction noise from refurbishment, which including vibration, on some physiological parameters and histopathological changes of organs of Wistar rats. Twenty 12 month old female rats were divided into two groups: rats group I (n = 10) were exposed to long-term construction noise and rats group II (n = 10) were kept under normal noise level. Study results revealed that long-term construction noise from building refurbishment has an influence on body weight, haematological and some serum biochemical parameters affects caecal microbiota, and causes histopathological changes in the organs of adult female Wistar rats. It was noticed that rats in group I exihibited significantly higher mean values for total protein, albumin and lower values for glucose, AST, ALT, blood urea nitrogen, haematological and caecal microbiota parameters than rats in group II. The most common pathologies were determined in the kidney, liver and lungs. Other observed pathologies were lymphadenopathy, catarrhal inflammation of the intestines, spleen hyperplasia and mammary gland adenofibroma. Single cases were subcutaneous fibroma in the thoracic region, abortus with uterine inflammation and thymus hyperplasia with formation of cysts were found.

Analgesia for early-life pain prevents deficits in adult anxiety and stress in rats.

PubMed

Victoria, Nicole C; Karom, Mary C; Murphy, Anne Z

2015-01-01

Previous studies in rats have established that inflammatory pain experienced on the day of birth (P0) decreases sensitivity to acute noxious, anxiety- and stress-provoking stimuli. However, to date, the impact of early-life pain on adult responses to chronic stress is not known. Further, the ability of morphine, administered at the time of injury, to mitigate changes in adult behavioral and hormonal responses to acute or chronic stressors has not been examined. P0 male and female Sprague-Dawley rat pups were given an intraplantar injection of 1% carrageenan or handled in an identical manner in the presence or absence of morphine. As adults, rats that experienced early-life pain displayed decreased sensitivity to acute stressors, as indicated by increased time in the inner area of the Open Field, and increased latency to immobility and decreased time immobile in the Forced Swim Test (FST). An accelerated return of corticosterone to baseline was also observed. Morphine administration at the time of injury completely reversed this 'hyporesponsive' phenotype. By contrast, following 7 days of chronic variable stress, injured animals displayed a 'hyperresponsive' phenotype in that they initiated immobility and spent significantly more time immobile in the FST than controls. Responses to chronic stress were also rescued in animals that received morphine at the time of injury. These data suggest that analgesia for early-life pain prevents adult hyposensitivity to acute anxiety- and stress-provoking stimuli and increased vulnerability to chronic stress, and have important clinical implications for the management of pain in infants. © 2014 S. Karger AG, Basel.

High-protein diet selectively reduces fat mass and improves glucose tolerance in Western-type diet-induced obese rats

PubMed Central

Stengel, Andreas; Goebel-Stengel, Miriam; Wang, Lixin; Hu, Eugenia; Karasawa, Hiroshi; Pisegna, Joseph R.

2013-01-01

Obesity is an increasing health problem. Because drug treatments are limited, diets remain popular. High-protein diets (HPD) reduce body weight (BW), although the mechanisms are unclear. We investigated physiological mechanisms altered by switching diet induced obesity (DIO) rats from Western-type diet (WTD) to HPD. Male rats were fed standard (SD) or WTD (45% calories from fat). After developing DIO (50% of rats), they were switched to SD (15% calories from protein) or HPD (52% calories from protein) for up to 4 weeks. Food intake (FI), BW, body composition, glucose tolerance, insulin sensitivity, and intestinal hormone plasma levels were monitored. Rats fed WTD showed an increased FI and had a 25% greater BW gain after 9 wk compared with SD (P < 0.05). Diet-induced obese rats switched from WTD to HPD reduced daily FI by 30% on day 1, which lasted to day 9 (−9%) and decreased BW during the 2-wk period compared with SD/SD (P < 0.05). During these 2 wk, WTD/HPD rats lost 72% more fat mass than WTD/SD (P < 0.05), whereas lean mass was unaltered. WTD/HPD rats had lower blood glucose than WTD/SD at 30 min postglucose gavage (P < 0.05). The increase of pancreatic polypeptide and peptide YY during the 2-h dark-phase feeding was higher in WTD/HPD compared with WTD/SD (P < 0.05). These data indicate that HPD reduces BW in WTD rats, which may be related to decreased FI and the selective reduction of fat mass accompanied by improved glucose tolerance, suggesting relevant benefits of HPD in the treatment of obesity. PMID:23883680

Eating high fat chow decreases dopamine clearance in adolescent and adult male rats but selectively enhances the locomotor stimulating effects of cocaine in adolescents.

PubMed

Baladi, Michelle G; Horton, Rebecca E; Owens, William A; Daws, Lynette C; France, Charles P

2015-03-24

Feeding conditions can influence dopamine neurotransmission and impact behavioral and neurochemical effects of drugs acting on dopamine systems. This study examined whether eating high fat chow alters the locomotor effects of cocaine and dopamine transporter activity in adolescent (postnatal day 25) and adult (postnatal day 75) male Sprague-Dawley rats. Dose-response curves for cocaine-induced locomotor activity were generated in rats with free access to either standard or high fat chow or restricted access to high fat chow (body weight matched to rats eating standard chow). Compared with eating standard chow, eating high fat chow increased the sensitivity of adolescent, but not adult, rats to the acute effects of cocaine. When tested once per week, sensitization to the locomotor effects of cocaine was enhanced in adolescent rats eating high fat chow compared with adolescent rats eating standard chow. Sensitization to cocaine was not different among feeding conditions in adults. When adolescent rats that previously ate high fat chow ate standard chow, sensitivity to cocaine returned to normal. As measured by chronoamperometry, dopamine clearance rate in striatum was decreased in both adolescent and adult rats eating high fat chow compared with age-matched rats eating standard chow. These results suggest that high fat diet-induced reductions in dopamine clearance rate do not always correspond to increased sensitivity to the locomotor effects of cocaine, suggesting that mechanisms other than dopamine transporter might play a role. Moreover, in adolescent but not adult rats, eating high fat chow increases sensitivity to cocaine and enhances the sensitization that develops to cocaine. © The Author 2015. Published by Oxford University Press on behalf of CINP.

PI3-kinase cascade has a differential role in acquisition and extinction of conditioned fear memory in juvenile and adult rats.

PubMed

Slouzkey, Ilana; Maroun, Mouna

2016-12-01

The basolateral amygdala (BLA), medial prefrontal cortex (mPFC) circuit, plays a crucial role in acquisition and extinction of fear memory. Extinction of aversive memories is mediated, at least in part, by the phosphoinositide-3 kinase (PI3K)/Akt pathway in adult rats. There is recent interest in the neural mechanisms that mediate fear and extinction in juvenile animals and whether these mechanisms are distinctive from those in adult animals. In the present study, we examined (1) changes in phosphorylation of Akt in the BLA and mPFC after fear conditioning and extinction in juvenile and adult rats and (2) the effect of BLA and mPFC localized inhibition of the PI3K following acquisition and extinction of contextual fear memory. Our results show that Akt phosphorylation is increased following acquisition of contextual fear learning in the BLA but not in the mPFC in adult and juvenile rats. Extinction learning was not associated with changes in Akt phosphorylation. Although there were no differences in the pattern of phosphorylation of Akt either in adult or juvenile rats, microinjection of the PI3K inhibitor, LY294002, into the BLA or mPFC elicited differential effects on fear memory acquisition and extinction, depending on the site and timing of the microinjection, as well as on the age of the animal. These results suggest that PI3K/Akt has a differential role in formation, retrieval, and extinction of contextual fear memory in juvenile and adult animals, and point to developmental differences between adult and juvenile rats in mechanisms of extinction. © 2016 Slouzkey and Maroun; Published by Cold Spring Harbor Laboratory Press.

Neuroprotective Effect of Melatonin Against PCBs Induced Behavioural, Molecular and Histological Changes in Cerebral Cortex of Adult Male Wistar Rats.

PubMed

Bavithra, S; Selvakumar, K; Sundareswaran, L; Arunakaran, J

2017-02-01

There is ample evidence stating Polychlorinated biphenyls (PCBs) as neurotoxins. In the current study, we have analyzed the behavioural impact of PCBs exposure in adult rats and assessed the simultaneous effect of antioxidant melatonin against the PCBs action. The rats were grouped into four and treated intraperitoneally with vehicle, PCBs, PCBs + melatonin and melatonin alone for 30 days, respectively. After the treatment period the rats were tested for locomotor activity and anxiety behaviour analysis. We confirmed the neuronal damage in the cerebral cortex by molecular and histological analysis. Our data indicates that there is impairment in locomotor activity and behaviour of PCBs treated rats compared to control. The simultaneous melatonin treated rat shows increased motor coordination and less anxiety like behaviour compared to PCBs treated rats. Molecular and histological analysis supports that, the impaired motor coordination in PCBs treated rats is due to neurodegeneration in motor cortex region. The results proved that melatonin treatment improved the motor co-ordination and reduced anxiety behaviour, prevented neurodegeneration in the cerebral cortex of PCBs-exposed adult male rats.

The role of apelin in the modulation of gastric and pancreatic enzymes activity in adult rats.

PubMed

Antuschevich, H; Kapica, M; Krawczynska, A; Herman, A; Kato, I; Kuwahara, A; Zabielski, R

2016-06-01

Apelin is considered as important gut regulatory peptide ligand of APJ receptor with a potential physiological role in gastrointestinal cytoprotection, regulation of food intake and drinking behavior. Circulating apelin inhibits secretion of pancreatic juice through vagal- cholecystokinin-dependent mechanism and reduces local blood flow. Our study was aimed to determine the effect of fundectomy and intraperitoneal or intragastric administration of apelin-13 on pancreatic and gastric enzymes activities in adult rats. Fundectomy is a surgical removal of stomach fundus - maine site apelin synthesis. Three independent experiments were carried out on Wistar rats. In the first and second experiment apelin-13 was given by intragastric or intraperitoneal way twice a day for 10 days (100 nmol/kg b.w.). Control groups received the physiological saline respectively. In the third experiment the group of rats after fundectomy were used. Fundectomized rats did not receive apelin and the rats from control group were 'sham operated'. At the end of experiment rats were sacrificed and blood from rats was withdrawn for apelin and CCK (cholecystokinin) radioimmunoassay analysis and pancreas and stomach tissues were collected for enzyme activity analyses. Intragastric and intraperitoneal administrations of apelin-13 increased basal plasma CCK level and stimulated gastric and pancreatic enzymes activity in rats. In animals after fundectomy decreased activity of studied enzymes was observed, as well as basal plasma apelin and CCK levels. In conclusion, apelin can effects on CCK release and stimulates some gastric and pancreatic enzymes activity in adult rats while fudectomy suppresses those processes. Changes in the level of pancreatic lipase activity point out that apelin may occurs as a regulator of lipase secretion.

Cortex-dependent recovery of unassisted hindlimb locomotion after complete spinal cord injury in adult rats

PubMed Central

Manohar, Anitha; Foffani, Guglielmo; Ganzer, Patrick D; Bethea, John R; Moxon, Karen A

2017-01-01

After paralyzing spinal cord injury the adult nervous system has little ability to ‘heal’ spinal connections, and it is assumed to be unable to develop extra-spinal recovery strategies to bypass the lesion. We challenge this assumption, showing that completely spinalized adult rats can recover unassisted hindlimb weight support and locomotion without explicit spinal transmission of motor commands through the lesion. This is achieved with combinations of pharmacological and physical therapies that maximize cortical reorganization, inducing an expansion of trunk motor cortex and forepaw sensory cortex into the deafferented hindlimb cortex, associated with sprouting of corticospinal axons. Lesioning the reorganized cortex reverses the recovery. Adult rats can thus develop a novel cortical sensorimotor circuit that bypasses the lesion, probably through biomechanical coupling, to partly recover unassisted hindlimb locomotion after complete spinal cord injury. DOI: http://dx.doi.org/10.7554/eLife.23532.001 PMID:28661400

Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kheradmand, Arash, E-mail: arashkheradmand@yahoo.com; Dezfoulian, Omid; Alirezaei, Masoud

Highlights: Black-Right-Pointing-Pointer Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. Black-Right-Pointing-Pointer Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. Black-Right-Pointing-Pointer Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. Black-Right-Pointing-Pointer Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivomore » quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P < 0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals

Effects and interactions of tachykinins and dynorphin on FSH and LH secretion in developing and adult rats.

PubMed

Ruiz-Pino, F; Garcia-Galiano, D; Manfredi-Lozano, M; Leon, S; Sánchez-Garrido, M A; Roa, J; Pinilla, L; Navarro, V M; Tena-Sempere, M

2015-02-01

Kisspeptin/neurokinin B/dynorphin (KNDy) neurons, which coexpress kisspeptins (Kps), neurokinin B (NKB), and dynorphin (Dyn), regulate gonadotropin secretion. The KNDy model proposes that NKB (a stimulator, through NK3R) and Dyn (an inhibitor, through κ-opioid receptor) shape Kp secretion onto GnRH neurons. However, some aspects of this paradigm remain ill defined. Here we aimed to characterize the following: 1) the effects of NKB signaling on FSH secretion and 2) the role of Dyn in gonadotropin secretion after NK3R activation; 3) additionally, we explored the roles of other tachykinin receptors, NK1R and NK2R, on gonadotropin release. Thus, the effects of the NK3R agonist, senktide, on FSH release were explored across postnatal development in male and female rats; gonadotropin responses to agonists of NK1R substance P and NK2R [neurokinin A (NKA)] were also monitored. Moreover, the effects of senktide on gonadotropin secretion were assessed after antagonizing Dyn actions by nor-binaltorphimine didydrochloride. Before puberty, rats of both sexes showed increased FSH secretion to senktide (and Kp-10). Conversely, adult female rats were irresponsive to senktide in terms of FSH, despite proven LH responses, whereas the adult males did not display FSH or LH responses to senktide, even at high doses. In turn, substance P and NKA stimulated gonadotropin secretion in prepubertal rats, whereas in adults modest gonadotropin responses to NKA were detected. By pretreatment with a Dyn antagonist, adult males became responsive to senktide in terms of LH secretion and displayed elevated basal LH and FSH levels; nor-binaltorphimine didydrochloride treatment uncovered FSH responses to senktide in adult females. Furthermore, the expression of Pdyn and Opkr1 (encoding Dyn and κ-opioid receptor, respectively) in the mediobasal hypothalamus was greater in males than in females at prepubertal ages. Overall, our data contribute to refining our understanding on how the elements of the

Sierra/SD User's Notes.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Munday, Lynn Brendon; Day, David M.; Bunting, Gregory

Sierra/SD provides a massively parallel implementation of structural dynamics finite element analysis, required for high fidelity, validated models used in modal, vibration, static and shock analysis of weapons systems. This document provides a users guide to the input for Sierra/SD. Details of input specifications for the different solution types, output options, element types and parameters are included. The appendices contain detailed examples, and instructions for running the software on parallel platforms.

Anxiogenic-like effects of fluoxetine render adult male rats vulnerable to the effects of a novel stress.

PubMed

Gomez, Francisca; García-García, Luis

2017-02-01

Fluoxetine (FLX) has paradoxical anxiogenic-like effects during the acute phase of treatment. In adolescent (35d-old) male rats, the stress-like effects induced by short-term (3d-4d) FLX treatment appear to involve up-regulation of paraventricular nucleus (PVN) arginine vasopressin (AVP) mRNA. However, studies on FLX-induced anxiety-like effects in adult rodents are inconclusive. Herein, we sought to study the response of adult male rats (60-65d-old) to a similar FLX treatment, also investigating how the stressful component, inherent to our experimental conditions, contributed to the responses. We show that FLX acutely increased plasma corticosterone concentrations while it attenuated the stress-induced-hyperthermia (SIH) as well as it reduced (≈40%) basal POMC mRNA expression in the arcuate nucleus (ARC). However, FLX did not alter the basal expression of PVN-corticotrophin-releasing hormone (CRH), anterior pituitary-pro-opiomelanocortin (POMC) and raphe nucleusserotonin transporter (SERT). Nonetheless, some regressions point towards the plausibility that FLX activated the hypothalamic-pituitary-adrenal (HPA). The behavioral study revealed that FLX acutely increased emotional reactivity in the holeboard, effect followed by a body weight loss of ≈2.5% after 24h. Interestingly, i.p. injection with vehicle did not have behavioral effects, furthermore, after experiencing the stressful component of the holeboard, the rats kept eating and gaining weight as normal. By contrast, the stress-naïve rats reduced food intake and gained less weight although maintaining a positive energy state. Therefore, on one hand, repetition of a mild stressor would unchain compensatory mechanisms to restore energy homeostasis after stress increasing the resiliency to novel stressors. On the other hand, FLX might render stressed adult rats vulnerable to novel stressors through the emergence of counter-regulatory changes, involving HPA axis activation and diminished sympathetic output

Adult emotionality and neural plasticity as a function of adolescent nutrient supplementation in male rats.

PubMed

McCall, Nora; Mahadevia, Darshini; Corriveau, Jennifer A; Glenn, Melissa J

2015-03-14

The present study explored the effects of supplementing male rats with either choline, omega-3 fatty acids, or phytoestrogens, from weaning into early adulthood, on emotionality and hippocampal plasticity. Because of the neuroprotective properties of these nutrients, we hypothesized that they would positively affect both behavior and hippocampal function when compared to non-supplemented control rats. To test this hypothesis, male Sprague Dawley rats were assigned to one of four nutrient conditions after weaning: 1) control (normal rat chow); 2) choline (supplemented in drinking water); 3) omega 3 fatty acids (daily oral supplements); or 4) phytoestrogens (supplemented in chow). After 4weeks on their respective diets, a subset of rats began 3weeks of behavioral testing, while the remaining behaviorally naïve rats were sacrificed after 6weeks on the diets to assess numbers of adult-born hippocampal neurons using the immature neuron marker, doublecortin. The results revealed that choline supplementation affected emotional functioning; compared to rats in other diet conditions, rats in this group were less anxious in an open field and after exposure to predator odor and showed less behavioral despair after forced swimming. Similar behavioral findings were evident following supplementation with omega-3 fatty acids and phytoestrogen supplementation, though not on all tests and not to the same magnitude. Histological findings followed a pattern consistent with the behavioral findings: choline supplementation, followed by omega-3 fatty acid supplementation, but not phytoestrogen supplementation, significantly increased the numbers of new-born hippocampal neurons. Choline and omega-3 fatty acids have similar biological functions-affecting cell membranes, growth factor levels, and epigenetically altering gene transcription. Thus, the present findings suggest that targeting nutrients with these effects may be a viable strategy to combat adult psychopathologies. Copyright �

[Comparative study of the long-term behavioral effects of noopept and piracetam in adult male rats and female rats in postnatal period].

PubMed

Voronina, T A; Guzevatykh, L S; Trofimov, S S

2005-01-01

Adult male and female rats were treated with the peptide nootrope drug noopept (daily dose, 0.1 mg/kg) and piracetam (200 mg/kg). In the period from 8th to 20th day, both drugs (cognitive enhancers) suppressed the horizontal and vertical activity and the anxiety in test animals as compared to the control group treated with 0.9 % aqueous NaCl solution. Early postnatal injections of the nootropes influenced neither the morphology development nor the behavior of adult female rats in the plus maze, extrapolational escape, passive avoidance, and pain sensitivity threshold tests. Animals in the "intact" group (having received neither drugs not physiological solution, that is, developing in a poor sensor environment), showed less pronounced habituation in the open field test as compared to the control and drug treated groups.

Adult responses to an ischemic stroke in a rat model of neonatal stress and morphine treatment.

PubMed

Hays, Sarah L; Valieva, Olga A; McPherson, Ronald J; Juul, Sandra E; Gleason, Christine A

2013-02-01

Critically ill newborn infants experience stressors that may alter brain development. Using a rodent model, we previously showed that neonatal stress, morphine, and stress plus morphine treatments each influence early gene expression and may impair neurodevelopment and learning behavior. We hypothesized that the combination of neonatal stress with morphine may alter neonatal angiogenesis and/or adult cerebral blood vessel density and thus increase injury after cerebral ischemia in adulthood. To test this, neonatal Lewis rats underwent 8 h/d maternal separation, plus morning/afternoon hypoxia exposure and either saline or morphine treatment (2 mg/kg s.c.) from postnatal day 3-7. A subset received bromodeoxyuridine to track angiogenesis. Adult brains were stained with collagen IV to quantify cerebral blood vessel density. To examine vulnerability to brain injury, postnatal day 80 adult rats underwent right middle cerebral artery occlusion (MCAO) to produce unilateral ischemic lesions. Brains were removed and processed for histology 48 h after injury. Brain injury was assessed by histological evaluation of hematoxylin and eosin, and silver staining. In contrast to our hypothesis, neither neonatal morphine, stress, nor the combination affected cerebral vessel density or MCAO-induced brain injury. Neonatal angiogenesis was not detected in adult rats possibly due to turnover of endothelial cells. Although unrelated to angiogenesis, hippocampal granule cell neurogenesis was detected and there was a trend (P = 0.073) toward increased bromodeoxyuridine incorporation in rats that underwent neonatal stress. These findings are discussed in contrast to other data concerning the effects of morphine on cerebrovascular function, and acute effects of morphine on hippocampal neurogenesis. Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.

Neurogenesis enhancer RO 25-6981 facilitates repeated spatial learning in adult rats.

PubMed

Soloviova, O A; Proshin, A T; Storozheva, Z I; Sherstnev, V V

2012-09-01

The effects of Ro 25-6981 (selective NMDA receptor blocker) in a dose stimulating neurogenesis on repeated learning, reversal learning, and memory reconsolidation were studied in adult rats in Morris water maze. Ro 25-6981 facilitated repeated learning 13 days after injection, but did not influence reversal learning. The blocker injected directly before reminder did not disturb repeated learning and reversal learning in Morris water maze. These effects of Ro 25-6981 on the dynamics of repeated learning seemed to be due to its effects on neurogenesis processes in adult brain.

Chronic overexpression of angiotensin-(1-7) in rats reduces cardiac reactivity to acute stress and dampens anxious behavior.

PubMed

Moura Santos, Danielle; Ribeiro Marins, Fernanda; Limborço-Filho, Marcelo; de Oliveira, Marilene Luzia; Hamamoto, Daniele; Xavier, Carlos Henrique; Moreira, Fabrício Araújo; Santos, Robson Augusto Souza; Campagnole-Santos, Maria José; Peliky Fontes, Marco Antonio

2017-03-01

Angiotensin II (Ang II) acts as a pro-stress hormone, while other evidence indicates that angiotensin-(1-7) [Ang-(1-7)] attenuates physiological responses to emotional stress. To further test this hypothesis, in groups of 5-6 rats we evaluated autonomic, cardiovascular and behavioral parameters in male Sprague-Dawley (SD) and transgenic TGR(A1-7)3292 (TG) rats chronically overexpressing Ang-(1-7). Compared to SD rats, TG rats showed reduced baseline heart rate (HR; SD 380 ± 16 versus TG 329 ± 9 beats per minute (bpm), mean ± standard error of mean, p < .05) and renal sympathetic discharge (SD 138 ± 4 versus TG 117 ± 5 spikes/second, p < .05). TG rats had an attenuated tachycardic response to acute air-puff stress (ΔHR: SD 51 ± 20 versus TG 1 ± 3 bpm; p < .05), which was reversed by intracerebroventricular injection of the Mas receptor antagonist, A-779 (ΔHR: SD 51 ± 20 versus TG 63 ± 15 bpm). TG rats showed less anxious behavior on the elevated plus maze, as revealed by more entries into open arms (SD 2 ± 2 versus TG 47 ± 5% relative to total entries; p < .05), and more time spent in the open arms (SD 5 ± 4 versus TG 53 ± 9% relative to total time, p < .05). By contrast with SD rats, diazepam (1.5 mg/kg, intraperitoneally) did not further reduce anxious behavior in TG rats, indicating a ceiling anxiolytic effect of Ang-(1-7) overexpression. Ang-(1-7) concentrations in hypothalamus and plasma, measured by mass spectrometry were two- and three-fold greater, respectively, in TG rats than in SD rats. Hence, increased endogenous Ang-(1-7) levels in TG rats diminishes renal sympathetic outflow and attenuates cardiac reactivity to emotional stress, which may be via central Mas receptors, and reduces anxious behavior. Lay summaryWe used a genetically modified rat model that produces above normal amounts of a peptide hormone called angiotensin-(1-7) to test whether this peptide can

Hypothyroidism in the adult rat causes incremental changes in brain-derived neurotrophic factor, neuronal and astrocyte apoptosis, gliosis, and deterioration of postsynaptic density.

PubMed

Cortés, Claudia; Eugenin, Eliseo; Aliaga, Esteban; Carreño, Leandro J; Bueno, Susan M; Gonzalez, Pablo A; Gayol, Silvina; Naranjo, David; Noches, Verónica; Marassi, Michelle P; Rosenthal, Doris; Jadue, Cindy; Ibarra, Paula; Keitel, Cecilia; Wohllk, Nelson; Court, Felipe; Kalergis, Alexis M; Riedel, Claudia A

2012-09-01

Adult hypothyroidism is a highly prevalent condition that impairs processes, such as learning and memory. Even though tetra-iodothyronine (T(4)) treatment can overcome the hypothyroidism in the majority of cases, it cannot fully recover the patient's learning capacity and memory. In this work, we analyzed the cellular and molecular changes in the adult brain occurring with the development of experimental hypothyroidism. Adult male Sprague-Dawley rats were treated with 6-propyl-2-thiouracil (PTU) for 20 days to induce hypothyroidism. Neuronal and astrocyte apoptosis were analyzed in the hippocampus of control and hypothyroid adult rats by confocal microscopy. The content of brain-derived neurotrophic factor (BDNF) was analyzed using enzyme-linked immunosorbent assay (ELISA) and in situ hybridization. The glutamatergic synapse and the postsynaptic density (PSD) were analyzed by electron microscopy. The content of PSD proteins like tyrosine receptor kinase B (TrkB), p75, and N-methyl-D-aspartate receptor (NMDAr) were analyzed by immunoblot. We observed that the hippocampus of hypothyroid adult rats displayed increased apoptosis levels in neurons and astrocyte and reactive gliosis compared with controls. Moreover, we found that the amount of BDNF mRNA was higher in the hippocampus of hypothyroid rats and the content of TrkB, the receptor for BDNF, was reduced at the PSD of the CA3 region of hypothyroid rats, compared with controls. We also observed that the glutamatergic synapses from the stratum radiatum of CA3 from hypothyroid rats, contained thinner PSDs than control rats. This observation was in agreement with a reduced content of NMDAr subunits at the PSD in hypothyroid animals. Our data suggest that adult hypothyroidism affects the hippocampus by a mechanism that alters the composition of PSD, reduces neuronal and astrocyte survival, and alters the content of the signaling neurotrophic factors, such as BDNF.

Effect of chronic hyperoxic exposure on duroquinone reduction in adult rat lungs.

PubMed

Audi, Said H; Bongard, Robert D; Krenz, Gary S; Rickaby, David A; Haworth, Steven T; Eisenhauer, Jessica; Roerig, David L; Merker, Marilyn P

2005-11-01

NAD(P)H:quinone oxidoreductase 1 (NQO1) plays a dominant role in the reduction of the quinone compound 2,3,5,6-tetramethyl-1,4-benzoquinone (duroquinone, DQ) to durohydroquinone (DQH2) on passage through the rat lung. Exposure of adult rats to 85% O2 for > or =7 days stimulates adaptation to the otherwise lethal effects of >95% O2. The objective of this study was to examine whether exposure of adult rats to hyperoxia affected lung NQO1 activity as measured by the rate of DQ reduction on passage through the lung. We measured DQH2 appearance in the venous effluent during DQ infusion at different concentrations into the pulmonary artery of isolated perfused lungs from rats exposed to room air or to 85% O2. We also evaluated the effect of hyperoxia on vascular transit time distribution and measured NQO1 activity and protein in lung homogenate. The results demonstrate that exposure to 85% O2 for 21 days increases lung capacity to reduce DQ to DQH2 and that NQO1 is the dominant DQ reductase in normoxic and hyperoxic lungs. Kinetic analysis revealed that 21-day hyperoxia exposure increased the maximum rate of pulmonary DQ reduction, Vmax, and the apparent Michaelis-Menten constant for DQ reduction, Kma. The increase in Vmax suggests a hyperoxia-induced increase in NQO1 activity of lung cells accessible to DQ from the vascular region, consistent qualitatively but not quantitatively with an increase in lung homogenate NQO1 activity in 21-day hyperoxic lungs. The increase in Kma could be accounted for by approximately 40% increase in vascular transit time heterogeneity in 21-day hyperoxic lungs.

Flux control exerted by overt carnitine palmitoyltransferase over palmitoyl-CoA oxidation and ketogenesis is lower in suckling than in adult rats.

PubMed Central

Krauss, S; Lascelles, C V; Zammit, V A; Quant, P A

1996-01-01

We examined the potential of overt carnitine palmitoyltransferase (CPT I) to control the hepatic catabolism of palmitoyl-CoA in suckling and adult rats, using a conceptually simplified model of fatty acid oxidation and ketogenesis. By applying top-down control analysis, we quantified the control exerted by CPT I over total carbon flux from palmitoyl-CoA to ketone bodies and carbon dioxide. Our results show that in both suckling and adult rat, CPT I exerts very significant control over the pathways under investigation. However, under the sets of conditions we studied, less control is exerted by CPT I over total carbon flux in mitochondria isolated from suckling rats than in those isolated from adult rats. Furthermore the flux control coefficient of CPT I changes with malonyl-CoA concentration and ATP turnover rate. PMID:8912677

Effects of Extremely Low Frequency Electromagnetic Fields on Vascular Permeability of Circumventricular Organs in the Adult Rat

NASA Astrophysics Data System (ADS)

Gutiérrez-Mercado, Y. K.; Cañedo-Dorantes, L.; Bañuelos-Pineda, J.; Serrano-Luna, G.; Feria-Velasco, A.

2008-08-01

The present work deals with the effects of extremely low frequency electromagnetic fields (ELF-EMF) on blood vessels permeability to non liposoluble substances of the circumventricular organs (CVO) of adult rats. Male Wistar adult rats were exposed to ELF-EMF and vascular permeability to colloidal carbon was investigated with the use of histological techniques. Results were compared to corresponding data from sham-exposed and control groups of animals. Exposure to ELF-EMF increased the CVO vascular permeability to colloidal carbon intravascularly injected, particularly in the subfornical organ, the median eminence, the pineal gland and the area postrema.

Transgenerational Effects of Di (2-Ethylhexyl) Phthalate in the Male CRL:CD(SD) Rat: Added Value of Assessing Multiple Offspring per Litter

PubMed Central

Gray, Leon Earl; Barlow, Norman J.; Howdeshell, Kembra L.; Ostby, Joseph S.; Furr, Johnathan R.; Gray, Clark L.

2009-01-01

In the rat, some phthalates alter sexual differentiation at relatively low dosage levels by altering fetal Leydig cell development and hormone synthesis, thereby inducing abnormalities of the testis, gubernacular ligaments, epididymis, and other androgen-dependent tissues. In order to define the dose-response relationship between di(2-ethylhexyl) phthalate (DEHP) and the Phthalate Syndrome of reproductive alterations in F1 male rats, Sprague-Dawley (SD) rat dams were dosed by gavage from gestational day 8 to day 17 of lactation with 0, 11, 33, 100, or 300 mg/kg/day DEHP (71–93 males per dose from 12 to 14 litters per dose). Some of the male offspring continued to be exposed to DEHP via gavage from 18 days of age to necropsy at 63–65 days of age (PUB cohort; 16–20/dose). Remaining males were not exposed after postnatal day 17 (in utero-lactational [IUL] cohort) and were necropsied after reaching full maturity. Anogenital distance, sperm counts and reproductive organ weights were reduced in F1 males in the 300 mg/kg/day group and they displayed retained nipples. In the IUL cohort, seminal vesicle weight also was reduced at 100 mg/kg/day. In contrast, serum testosterone and estradiol levels were unaffected in either the PUB or IUL cohorts at necropsy. A significant percentage of F1 males displayed one or more Phthalate Syndrome lesions at 11 mg/kg/day DEHP and above. We were able to detect effects in the lower dose groups only because we examined all the males in each litter rather than only one male per litter. Power calculations demonstrate how using multiple males versus one male/litter enhances the detection of the effects of DEHP. The results at 11 mg/kg/day confirm those reported from a National Toxicology Program multigenerational study which reported no observed adverse effect levels-lowest observed adverse effect levels of 5 and 10 mg/kg/day DEHP, respectively, via the diet. PMID:19482887

Teaching Adult Rats Spinalized as Neonates to Walk Using Trunk Robotic Rehabilitation: Elements of Success, Failure, and Dependence

PubMed Central

Udoekwere, Ubong I.; Oza, Chintan S.

2016-01-01

Robot therapy promotes functional recovery after spinal cord injury (SCI) in animal and clinical studies. Trunk actions are important in adult rats spinalized as neonates (NTX rats) that walk autonomously. Quadrupedal robot rehabilitation was tested using an implanted orthosis at the pelvis. Trunk cortical reorganization follows such rehabilitation. Here, we test the functional outcomes of such training. Robot impedance control at the pelvis allowed hindlimb, trunk, and forelimb mechanical interactions. Rats gradually increased weight support. Rats showed significant improvement in hindlimb stepping ability, quadrupedal weight support, and all measures examined. Function in NTX rats both before and after training showed bimodal distributions, with “poor” and “high weight support” groupings. A total of 35% of rats initially classified as “poor” were able to increase their weight-supported step measures to a level considered “high weight support” after robot training, thus moving between weight support groups. Recovered function in these rats persisted on treadmill with the robot both actuated and nonactuated, but returned to pretraining levels if they were completely disconnected from the robot. Locomotor recovery in robot rehabilitation of NTX rats thus likely included context dependence and/or incorporation of models of robot mechanics that became essential parts of their learned strategy. Such learned dependence is likely a hurdle to autonomy to be overcome for many robot locomotor therapies. Notwithstanding these limitations, trunk-based quadrupedal robot rehabilitation helped the rats to visit mechanical states they would never have achieved alone, to learn novel coordinations, and to achieve major improvements in locomotor function. SIGNIFICANCE STATEMENT Neonatal spinal transected rats without any weight support can be taught weight support as adults by using robot rehabilitation at trunk. No adult control rats with neonatal spinal

Teaching Adult Rats Spinalized as Neonates to Walk Using Trunk Robotic Rehabilitation: Elements of Success, Failure, and Dependence.

PubMed

Udoekwere, Ubong I; Oza, Chintan S; Giszter, Simon F

2016-08-10

Robot therapy promotes functional recovery after spinal cord injury (SCI) in animal and clinical studies. Trunk actions are important in adult rats spinalized as neonates (NTX rats) that walk autonomously. Quadrupedal robot rehabilitation was tested using an implanted orthosis at the pelvis. Trunk cortical reorganization follows such rehabilitation. Here, we test the functional outcomes of such training. Robot impedance control at the pelvis allowed hindlimb, trunk, and forelimb mechanical interactions. Rats gradually increased weight support. Rats showed significant improvement in hindlimb stepping ability, quadrupedal weight support, and all measures examined. Function in NTX rats both before and after training showed bimodal distributions, with "poor" and "high weight support" groupings. A total of 35% of rats initially classified as "poor" were able to increase their weight-supported step measures to a level considered "high weight support" after robot training, thus moving between weight support groups. Recovered function in these rats persisted on treadmill with the robot both actuated and nonactuated, but returned to pretraining levels if they were completely disconnected from the robot. Locomotor recovery in robot rehabilitation of NTX rats thus likely included context dependence and/or incorporation of models of robot mechanics that became essential parts of their learned strategy. Such learned dependence is likely a hurdle to autonomy to be overcome for many robot locomotor therapies. Notwithstanding these limitations, trunk-based quadrupedal robot rehabilitation helped the rats to visit mechanical states they would never have achieved alone, to learn novel coordinations, and to achieve major improvements in locomotor function. Neonatal spinal transected rats without any weight support can be taught weight support as adults by using robot rehabilitation at trunk. No adult control rats with neonatal spinal transections spontaneously achieve similar changes

Subsecond fear discrimination in rats: adult impairment in adolescent heavy alcohol drinkers.

PubMed

DiLeo, Alyssa; Wright, Kristina M; McDannald, Michael A

2016-11-01

Discriminating safety from danger must be accurate and rapid. Yet, the rapidity with which fear discrimination emerges remains unknown. Rapid fear discrimination in adulthood may be susceptible to impairment by adolescent heavy alcohol drinking, which increases incidence of anxiety disorders. Rats were given voluntary, adolescent alcohol access, and heavy drinkers were identified. In adulthood, rapid fear discrimination of safety, uncertainty, and danger cues was assessed. Normal rats, but not heavy drinkers, showed discriminative fear <1 sec following cue onset. This provides the first demonstration of subsecond fear discrimination and its adult impairment in adolescent heavy alcohol drinkers. © 2016 DiLeo et al.; Published by Cold Spring Harbor Laboratory Press.

Adolescent, but not adult, rats exhibit ethanol-mediated appetitive second-order conditioning

PubMed Central

Pautassi, Ricardo Marcos; Myers, Mallory; Spear, Linda Patia; Molina, Juan Carlos; Spear, Norman E.

2008-01-01

Background Adolescent rats are less sensitive to the sedative effects of ethanol than older animals. They also seem to perceive the reinforcing properties of ethanol. However, unlike neonates or infants, ethanol-mediated appetitive behavior has yet to be clearly shown in adolescents. Appetitive ethanol reinforcement was assessed in adolescent (postnatal day 33, P33) and adult rats (P71) through second-order conditioning (SOC). Methods On P32 or P70 animals were intragastrically administered ethanol (0.5 or 2.0 g/kg) paired with intraoral pulses of sucrose (CS1, first-order conditioning phase). CS1 delivery took place either 5-20 (Early pairing) or 30-45 (Late pairing) min following ethanol. CS1 exposure and ethanol administration were separated by 240 min in unpaired controls. On P33 or P71, animals were presented the CS1 (second-order conditioning phase) while in a distinctive chamber (CS2). Then, they were tested for CS2 preference. Results Early and late paired adolescents, but not adults, had greater preference for the CS2 than controls, a result indicative of ontogenetic variation in ethanol-mediated reinforcement. During the CS1 - CS2 associative phase, paired adolescents given 2.0 g/kg ethanol wall-climbed more than controls. Blood and brain ethanol levels associated with the 0.5 and 2.0 g/kg doses at the onset of each conditioning phase did not differ substantially across age, with mean BECs of 38 and 112 mg %. Conclusions These data indicate age-related differences between adolescent and adult rats in terms of sensitivity to ethanol’s motivational effects. Adolescents exhibit high sensitivity for ethanol’s appetitive effects. These animals also showed EtOH-mediated behavioral activation during the second-order conditioning phase. The SOC preparation provides a valuable conditioning model for assessing ethanol’s motivational effects across ontogeny. PMID:18782343

Attenuated effects of experimenter-administered heroin in adolescent vs. adult male rats: physical withdrawal and locomotor sensitization

PubMed Central

Doherty, James M.; Frantz, Kyle J.

2012-01-01

Objectives Early onset of heroin use during adolescence might increase chances of later drug addiction. Prior work from our laboratory suggests, however, that adolescent male rats are actually less sensitive than adults to some enduring effects of heroin self-administration. In the present study, we tested two likely correlates of sensitivity to behavioral reinforcement in rats: physical withdrawal and locomotor sensitization. Methods Adolescent (35 days old at start) and adult (79 days old) male Sprague-Dawley rats were administered escalating doses of heroin, increasing from 1.0 to 8.0 mg/kg (i.p.) every 12 hr, across 13 days. Somatic signs of spontaneous withdrawal were scored 12 and 24 hr after the last injection, then every 24 hr for 5 days; locomotion was recorded concurrently. Challenge injections of heroin (1 mg/kg i.p.) were given at 4 points: as the first of the escalating doses (day 1), at days 7 and 13 during the escalating regimen, and after 12 days of forced abstinence. Body mass and food intake were measured throughout experimentation. Results A heroin withdrawal syndrome was not observed among adolescents as it was among adults, including somatic signs as well as reduced locomotion, body mass, and food intake. On the other hand, heroin-induced locomotor sensitization did not differ across ages. Conclusion Reduced withdrawal is consistent with the attenuated reinforcing effects of heroin among adolescent male rats that we reported previously. Thus, it is possible that adolescent rats could reveal important neuroprotective factors for use in treatment of heroin dependence. PMID:22941050

Cardiorespiratory effects of gap junction blockade in the locus coeruleus in unanesthetized adult rats.

PubMed

Patrone, Luis G A; Bícego, Kênia Cardoso; Hartzler, Lynn K; Putnam, Robert W; Gargaglioni, Luciane H

2014-01-01

The locus coeruleus (LC) plays an important role in central chemoreception. In young rats (P9 or younger), 85% of LC neurons increase firing rate in response to hypercapnia vs. only about 45% of neurons from rats P10 or older. Carbenoxolone (CARB - gap junction blocker) does not affect the % of LC neurons responding in young rats but it decreases the % responding by half in older animals. We evaluated the participation of gap junctions in the CO2 ventilatory response in unanesthetized adult rats by bilaterally microinjecting CARB (300μM, 1mM or 3mM/100nL), glycyrrhizic acid (GZA, CARB analog, 3mM) or vehicle (aCSF - artificial cerebrospinal fluid) into the LC of Wistar rats. Bilateral gap junction blockade in LC neurons did not affect resting ventilation; however, the increase in ventilation produced by hypercapnia (7% CO2) was reduced by ∼25% after CARB 1mM or 3mM injection (1939.7±104.8mLkg(-1)min(-1) for the aCSF group and 1468.3±122.2mLkg(-1)min(-1) for 1mM CARB, P<0.05; 1939.7±104.8mLkg(-1)min(-1) for the aCSF group and 1540.9±68.4mLkg(-1)min(-1) for the 3mM CARB group, P<0.05) due largely to a decrease in respiratory frequency. GZA injection or CARB injection outside the LC (peri-LC) had no effect on ventilation under any conditions. The results suggest that gap junctions in the LC modulate the hypercapnic ventilatory response of adult rats. Copyright © 2013 Elsevier B.V. All rights reserved.

Prenatal Choline Availability Alters the Context Sensitivity of Pavlovian Conditioning in Adult Rats

ERIC Educational Resources Information Center

Lamoureux, Jeffrey A.; Meck, Warren H.; Williams, Christina L.

2008-01-01

The effects of prenatal choline availability on Pavlovian conditioning were assessed in adult male rats (3-4 mo). Neither supplementation nor deprivation of prenatal choline affected the acquisition and extinction of simple Pavlovian conditioned excitation, or the acquisition and retardation of conditioned inhibition. However, prenatal choline…

Effect of "enriched environment" during development on adult rat behavior and response to the dopamine receptor agonist apomorphine.

PubMed

Hoffmann, L C; Schütte, S R M; Koch, M; Schwabe, K

2009-02-18

Enriched housing conditions (enriched environment, EE) during development has been shown to influence adult rat behavior and transmitter systems, especially dopamine function. We were interested in how different degrees of enrichment during development would affect adult rats' behavior and response to dopamine receptor challenge. Two groups of male Wistar rats (n=11-12) were raised under two different degrees of EE, i.e. "high enriched" and "low enriched" groups. A third group was kept under standard conditions and served as "non-enriched" control. As adults, rats were tested for anxiety (elevated plus-maze), for spatial learning (four-arm-baited eight-arm radial maze), and for motivation (breakpoint of the progressive ratio test). Finally, locomotor activity (activity box) and sensorimotor gating (prepulse inhibition (PPI) of the acoustic startle response (ASR)) were tested with and without challenge with the dopamine receptor agonist apomorphine. The time spent on the open or enclosed arms of the elevated plus-maze did not differ between groups, but the high enriched group showed higher rearing activity on the open arms. The breakpoint did not differ between groups. Learning and memory in the radial maze task only differed on the first few trials, but high enriched rats run faster compared with the other groups. In contrast, in the activity box enriched groups were less active, but apomorphine had the highest effect. Between groups, no difference in PPI and startle amplitude was found, but in the high and low EE group startle amplitude was enhanced after administration of apomorphine, while the PPI deficit induced by this drug was not different between groups. Altogether, we found no evidence that different amounts of environmental enrichment without differences in social EE affect rats' cognitive, emotional or motivational behavior. However, motor activity seems to be enhanced when rats are behaviorally or pharmacologically challenged by dopamine receptor

Expression of developmental myosin and morphological characteristics in adult rat skeletal muscle following exercise-induced injury.

PubMed

Smith, H K; Plyley, M J; Rodgers, C D; McKee, N H

1999-07-01

The extent and stability of the expression of developmental isoforms of myosin heavy chain (MHCd), and their association with cellular morphology, were determined in adult rat skeletal muscle fibres following injury induced by eccentrically-biased exercise. Adult female Wistar rats [274 (10) g] were either assigned as non-exercised controls or subjected to 30 min of treadmill exercise (grade, -16 degrees; speed, 15 m x min(-1)), and then sacrificed following 1, 2, 4, 7, or 12 days of recovery (n = 5-6 per group). Histologically and immunohistologically stained serial, transverse cryosections of the soleus (S), vastus intermedius (VI), and tibialis anterior (TA) muscles were examined using light microscopy and digital imaging. Fibres staining positively for MHCd (MHCd+) were seldom detected in the TA. In the VI and S, higher proportions of MHCd+ fibres (0.8% and 2.5%, respectively) were observed in rats at 4 and 7 days post-exercise, in comparison to all other groups combined (0.2%, 1.2%; P < or = 0.01). In S, MHCd+ fibres were observed less frequently by 12 days (0.7%) than at 7 days (2.6%) following exercise. The majority (85.1%) of the MHCd+ fibres had morphological characteristics indicative of either damage, degeneration, repair or regeneration. Most of the MHCd+ fibres also expressed adult slow, and/or fast myosin heavy chain. Quantitatively, the MHCd+ fibres were smaller (< 2500 microm2) and more angular than fibres not expressing MHCd. Thus, there was a transient increase in a small, but distinct population of MHCd+ fibres following unaccustomed, functional exercise in adult rat S and VI muscles. The observed close coupling of MHCd expression with morphological changes within muscle fibres suggests that these characteristics have a common, initial exercise-induced injury-related stimulus.

Infrasound increases intracellular calcium concentration and induces apoptosis in hippocampi of adult rats.

PubMed

Liu, Zhaohui; Gong, Li; Li, Xiaofang; Ye, Lin; Wang, Bin; Liu, Jing; Qiu, Jianyong; Jiao, Huiduo; Zhang, Wendong; Chen, Jingzao; Wang, Jiuping

2012-01-01

In the present study, we determined the effect of infrasonic exposure on apoptosis and intracellular free Ca²⁺ ([Ca²⁺]i) levels in the hippocampus of adult rats. Adult rats were randomly divided into the control and infrasound exposure groups. For infrasound treatment, animals received infrasonic exposure at 90 (8 Hz) or 130 dB (8 Hz) for 2 h per day. Hippocampi were dissected, and isolated hippocampal neurons were cultured. The [Ca²⁺]i levels in hippocampal neurons from adult rat brains were determined by Fluo-3/AM staining with a confocal microscope system on days 1, 7, 14, 21 and 28 following infrasonic exposure. Apoptosis was evaluated by Annexin V-FITC and propidium iodide double staining. Positive cells were sorted and analyzed by flow cytometry. Elevated [Ca²⁺]i levels were observed on days 14 and 21 after rats received daily treatment with 90 or 130 dB sound pressure level (SPL) infrasonic exposure (p<0.01 vs. control). The highest levels of [Ca²⁺]i were detected in the 130 dB SPL infrasonic exposure group. Meanwhile, apoptosis in hippocampal neurons was found to increase on day 7 following 90 dB SPL infrasound exposure, and significantly increased on day 14. Upon 130 dB infrasound treatment, apoptosis was first observed on day 14, whereas the number of apoptotic cells gradually decreased thereafter. Additionally, a marked correlation between cell apoptosis and [Ca²⁺]i levels was found on day 14 and 21 following daily treatment with 90 and 130 dB SPL, respectively. These results demonstrate that a period of infrasonic exposure induced apoptosis and upregulated [Ca²⁺]i levels in hippocampal neurons, suggesting that infrasound may cause damage to the central nervous system (CNS) through the Ca²⁺‑mediated apoptotic pathway in hippocampal neurons.

Purification and culture of adult rat dorsal root ganglia neurons.

PubMed

Delree, P; Leprince, P; Schoenen, J; Moonen, G

1989-06-01

To study the trophic requirements of adult rat dorsal root ganglia neurons (DRG) in vitro, we developed a purification procedure that yields highly enriched neuronal cultures. Forty to fifty ganglia are dissected from the spinal column of an adult rat. After enzymatic and mechanical dissociation of the ganglia, myelin debris are eliminated by centrifugation on a Percoll gradient. The resulting cell suspension is layered onto a nylon mesh with a pore size of 10 microns. Most of the neurons, the diameter of which ranged from 17 microns to greater than 100 microns, are retained on the upper surface of the sieve; most of the non-neuronal cells with a caliber of less than 10 microns after trypsinization go through it. Recovery of neurons is achieved by reversing the mesh onto a Petri dish containing culture medium. Neurons to non-neurons ratio is 1 to 10 in the initial cell suspension and 1 to 1 after separation. When these purified neurons are seeded at a density of 3,000 neurons/cm2 in 6 mm polyornithine-laminin (PORN-LAM) coated wells, neuronal survival (assessed by the ability to extend neurites), measured after 48 hr of culture, is very low (from 0 to 16%). Addition of nerve growth factor (NGF) does not improve neuronal survival. However, when neurons are cultured in the presence of medium conditioned (CM) by astrocytes or Schwann cells, 60-80% of the seeded, dye-excluding neurons survive. So, purified adult DRG neurons require for their short-term survival and regeneration in culture, a trophic support that is present in conditioned medium from PNS or CNS glia.(ABSTRACT TRUNCATED AT 250 WORDS)

The impact of adult vitamin D deficiency on behaviour and brain function in male Sprague-Dawley rats.

PubMed

Byrne, Jacqueline H; Voogt, Meggie; Turner, Karly M; Eyles, Darryl W; McGrath, John J; Burne, Thomas H J

2013-01-01

Vitamin D deficiency is common in the adult population, and this has been linked to depression and cognitive outcomes in clinical populations. The aim of this study was to investigate the effects of adult vitamin D (AVD) deficiency on behavioural tasks of relevance to neuropsychiatric disorders in male Sprague-Dawley rats. Ten-week old male Sprague-Dawley rats were fed a control or vitamin D deficient diet for 6 weeks prior to, and during behavioural testing. We first examined a range of behavioural domains including locomotion, exploration, anxiety, social behaviour, learned helplessness, sensorimotor gating, and nociception. We then assessed locomotor response to the psychomimetic drugs, amphetamine and MK-801. Attention and vigilance were assessed using the 5 choice serial reaction time task (5C-SRT) and the 5 choice continuous performance task (5C-CPT) and, in a separate cohort, working memory was assessed using the delay match to sample (DMTS) task. We also examined excitatory and inhibitory neurotransmitters in prefrontal cortex and striatum. AVD-deficient rats were deficient in vitamin D3 (<10 nM) and had normal calcium and phosphate levels after 8-10 weeks on the diet. Overall, AVD deficiency was not associated with an altered phenotype across the range of behavioural domains tested. On the 5C-SRT AVD-deficient rats made more premature responses and more head entries during longer inter-trial intervals (ITI) than control rats. On the 5C-CPT AVD-deficient rats took longer to make false alarm (FA) responses than control rats. AVD-deficient rats had increases in baseline GABA levels and the ratio of DOPAC/HVA within the striatum. AVD-deficient rats exhibited no major impairments in any of the behavioural domains tested. Impairments in premature responses in AVD-deficient rats may indicate that these animals have specific alterations in striatal systems governing compulsive or reward-seeking behaviour.

Reproductive toxicity of a single dose of 1,3-dinitrobenzene in two ages of young adult male rats

EPA Science Inventory

These studies evaluated the reproductive response and the possible influence of testicular maturation on the reproductive parameters, in male rats treated with 1,3-dinitrobenzene (m-DNB). Young adult male rats (75 or 105 days of age) were given a single oral dose of 0, 8, 16, 24,...

Developmental vitamin D deficiency alters MK 801-induced hyperlocomotion in the adult rat: An animal model of schizophrenia.

PubMed

Kesby, James P; Burne, Thomas H J; McGrath, John J; Eyles, Darryl W

2006-09-15

Developmental vitamin D (DVD) deficiency has been proposed as a risk factor for schizophrenia. The behavioral phenotype of adult rats subjected to transient low prenatal vitamin D is characterized by spontaneous hyperlocomotion but normal prepulse inhibition of acoustic startle (PPI). The aim of this study was to examine the impact of selected psychotropic agents and one well-known antipsychotic agent on the behavioral phenotype of DVD deplete rats. Control versus DVD deplete adult rats were assessed on holeboard, open field and PPI. In the open field, animals were given MK-801 and/or haloperidol. For PPI, the animals were given apomorphine or MK-801. DVD deplete rats had increased baseline locomotion on the holeboard task and increased locomotion in response to MK-801 compared to control rats. At low doses, haloperidol antagonized the MK-801 hyperactivity of DVD deplete rats preferentially and, at a high dose, resulted in a more pronounced reduction in spontaneous locomotion in DVD deplete rats. DVD depletion did not affect either baseline or drug-mediated PPI response. These results suggest that DVD deficiency is associated with a persistent alteration in neuronal systems associated with motor function but not those associated with sensory motor gating. In light of the putative association between low prenatal vitamin D and schizophrenia, the discrete behavioral differences associated with the DVD model may help elucidate the neurobiological correlates of schizophrenia.

Long-lasting alterations of hippocampal GABAergic neurotransmission in adult rats following perinatal Δ9-THC exposure.

PubMed

Beggiato, Sarah; Borelli, Andrea Celeste; Tomasini, Maria Cristina; Morgano, Lucia; Antonelli, Tiziana; Tanganelli, Sergio; Cuomo, Vincenzo; Ferraro, Luca

2017-03-01

The long-lasting effects of gestational cannabinoids exposure on the adult brain of the offspring are still controversial. It has already been shown that pre- or perinatal cannabinoids exposure induces learning and memory disruption in rat adult offspring, associated with permanent alterations of cortical glutamatergic neurotransmission and cognitive deficits. In the present study, the risk of long-term consequences induced by perinatal exposure to cannabinoids on rat hippocampal GABAergic system of the offspring, has been explored. To this purpose, pregnant rats were treated daily with Delta 9 -tetrahydrocannabinol (Δ 9 -THC; 5mg/kg) or its vehicle. Perinatal exposure to Δ 9 -THC induced a significant reduction (p<0.05) in basal and K + -evoked [ 3 H]-GABA outflow of 90-day-old rat hippocampal slices. These effects were associated with a reduction of hippocampal [ 3 H]-GABA uptake compared to vehicle exposed group. Perinatal exposure to Δ 9 -THC induced a significant reduction of CB1 receptor binding (B max ) in the hippocampus of 90-day-old rats. However, a pharmacological challenge with either Δ 9 -THC (0.1μM) or WIN55,212-2 (2μM), similarly reduced K + -evoked [ 3 H]-GABA outflow in both experimental groups. These reductions were significantly blocked by adding the selective CB1 receptor antagonist SR141716A. These findings suggest that maternal exposure to cannabinoids induces long-term alterations of hippocampal GABAergic system. Interestingly, previous behavioral studies demonstrated that, under the same experimental conditions as in the present study, perinatal cannabinoids exposure induced cognitive impairments in adult rats, thus resembling some effects observed in humans. Although it is difficult and sometimes misleading to extrapolate findings obtained from animal models to humans, the possibility that an alteration of hippocampus aminoacidergic transmission might underlie, at least in part, some of the cognitive deficits affecting the offspring

Novelty-induced locomotion is positively associated with cocaine ingestion in adolescent rats; anxiety is correlated in adults

PubMed Central

Walker, Q. David; Schramm-Sapyta, Nicole L.; Caster, Joseph M.; Waller, Samuel T.; Brooks, Matthew P.; Kuhn, Cynthia M.

2009-01-01

The present studies assessed the roles of sex, age, novelty-seeking and plus-maze behavior on cocaine drinking in rats. Cocaine/saccharin solution was available in three daily, 5-hour sessions then a saccharin-only solution was also available in following sessions. In the one-bottle drinking phase, early and late adolescent males, post-natal day 28 (PN28) and PN42, consumed more cocaine/saccharin solution than young adults (PN65), but females did not exhibit significant age differences. Adolescents of both sexes consumed more cocaine/saccharin than adults during choice drinking. Saccharin availability in the two-bottle trials decreased cocaine/saccharin consumption in PN28 and PN65 rats. After a drug-free period, cocaine-stimulated locomotion was lower in cocaine/saccharin drinking than saccharin-only males, indicating tolerance. We tested the hypothesis that individual differences in pre-screened behavioral traits would correlate with cocaine/saccharin consumption in PN28 and PN65 male rats. High locomotor responses to novelty were associated with greater cocaine/saccharin drinking in adults in one-bottle sessions. In the subsequent choice drinking phase, correlations were age-specific. Adolescents with high novelty-induced locomotion and adults that spent less time on open arms of the elevated plus-maze drank more cocaine/saccharin. Thus, behavioral phenotypes correlated with individual differences in cocaine/saccharin consumption in an age-related manner. PMID:18790706

Spermatogenetic disorders in adult rats exposed to tributyltin chloride during puberty.

PubMed

Yu, Wook Joon; Lee, Beom Jun; Nam, Sang Yoon; Kim, Young Chul; Lee, Yong Soon; Yun, Young Won

2003-12-01

Adverse effects of tributyltin (TBT) chloride were investigated on the reproductive system in male adult rats as exposed during puberty. Fifty Sprague-Dawley rats at the age of 35 days were assigned to five different groups: negative control receiving vehicle, methyltestosterone (10 mg/kg B.W.), and TBT chloride treatments (5, 10, and 20 mg/kg B.W.). Animals were treated by oral gavage for ten consecutive days and sacrificed at 5 weeks after final treatment. The treatment of TBT chloride at the high dose of 20 mg/kg B.W. significantly decreased homogenization-resistant testicular sperm counts (p<0.05). The TBT chloride treatment at the doses of 10 and 20 mg/kg B.W. also significantly decreased caudal epididymal sperm counts (p<0.01). Some of motion kinematic parameters (motility, mean angular displacement, lateral head displacement, and dance) of sperms retrieved from vasa deference were significantly decreased in rats treated with the TBT chloride at the dose of 20 mg/kg B.W. (p<0.05). These results provide a further evidence that an exposure to TBT chloride during pubertal period in male rats produces spermatogenic disorders characterized by decreasing testicular and epididymal sperm counts and some motion parameters of sperms in the vasa deference.

Blood-brain barrier permeability is increased after acute adult stroke but not neonatal stroke in the rat

PubMed Central

Lopez, David Fernandez; Faustino, Joel; Daneman, Richard; Zhou, Lu; Lee, Sarah; Derugin, Nikita; Wendland, Michael F.; Vexler, Zinaida S

2012-01-01

The immaturity of the CNS at birth greatly affects injury after stroke but the contribution of the blood-brain barrier (BBB) to the differential response to stroke in adults and neonates is poorly understood. We asked if the structure and function of the BBB is disrupted differently in neonatal and adult rats by transient middle cerebral artery occlusion. In adult rats, albumin leakage into injured regions was markedly increased during 2–24 h reperfusion but leakage remained low in the neonates. Functional assays employing intravascular tracers in the neonates showed that BBB permeability to both large (70-kDa dextran) and small (3-kDa dextran, Gd-DTPA) tracers remained largely undisturbed 24h after reperfusion. The profoundly different functional integrity of the BBB was associated with the largely nonoverlapping patterns of regulated genes in endothelial cells purified from injured and uninjured adult and neonatal brain at 24h (endothelial transcriptome, 31,042 total probe sets). Within significantly regulated 1,266 probe sets in injured adults and 361 probe sets in neonates, changes in the gene expression of the basal lamina components, adhesion molecules, the tight junction protein occludin, and MMP-9 were among the key differences. The protein expression of collagen-IV, laminin, claudin-5, occludin and ZO-1 was also better preserved in neonatal rats. Neutrophil infiltration remained low in acutely injured neonates but neutralization of CINC-1 in the systemic circulation enhanced neutrophil infiltration, BBB permeability and injury. The markedly more integrant BBB in neonatal brain than in adult brain after acute stroke may have major implications for the treatment of neonatal stroke. PMID:22787045

Effect of seven days of spaceflight on hindlimb muscle protein, RNA and DNA in adult rats

NASA Technical Reports Server (NTRS)

Steffen, J. M.; Musacchia, X. J.

1985-01-01

Effects of seven days of spaceflight on skeletal muscle (soleus, gastrocnemius, EDL) content of protein, RNA and DNA were determined in adult rats. Whereas total protein contents were reduced in parallel with muscle weights, myofibrillar protein appeared to be more affected. There were no significant changes in absolute DNA contents, but a significant (P less than 0.05) increase in DNA concentration (microgram/milligram) in soleus muscles from flight rats. Absolute RNA contents were significantly (P less than 0.025) decreased in the soleus and gastrocnemius muscles of flight rats, with RNA concentrations reduced 15-30 percent. These results agree with previous ground-based observations on the suspended rat with unloaded hindlimbs and support continued use of this model.

The fine structure of intracranial neoplasms induced by the inoculation of avian sarcoma virus in neonatal and adult rats.

PubMed Central

Copeland, D. D.; Talley, F. A.; Bigner, D. D.

1976-01-01

Groups of F-344 rats were inoculated with the Bratislava-77 strain of avian sarcoma virus (B-77 ASV) within 24 hours of birth, at 9 days of age, or between 97 and 119 days of age. Intracranial tumors developed in each age group. Multiple tumors with mixed histologic patterns developed in rats inoculated at 1 or 9 days of age. Solitary tumors with a uniform histologic pattern developed in rats inoculated as adults. On the basis of light and electron microscopic study, the majority of tumors in each age group were classified as astrocytomas and divided into either poorly differentiated, gemistocytic, pilocytic, or polymorphic varieties. The polymorphic astrocytomas were most common among neonatally inoculated rats, while the pilocytic astrocytomas were most common among rats inoculated as adults. Ultrastructural characteristics of astrocytes, including gap junctions and 7- to 9-nm filaments, were present in the majority of tumors in each age groups. Astrocytomas induced in adult rats were remarkable for the presence of extensive basement membrane alone the astrocytic cell surfaces. Intracytoplasmic virus-like particles (R particles) were common in the tumor cells. These virus-like particles are morphologically distinct from C-type B-77 ASV, and no morphologic evidence of C-type virus replication was observed in any of the tumors. Images Figure 16 Figure 17 Figure 1 Figure 2 Figure 18 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 PMID:179328

Ultrafine Particulate Matter Combined With Ozone Exacerbates Lung Injury in Mature Adult Rats With Cardiovascular Disease.

PubMed

Wong, Emily M; Walby, William F; Wilson, Dennis W; Tablin, Fern; Schelegle, Edward S

2018-05-01

Particulate matter (PM) and ozone (O3) are dominant air pollutants that contribute to development and exacerbation of multiple cardiopulmonary diseases. Mature adults with cardiovascular disease (CVD) are particularly susceptible to air pollution-related cardiopulmonary morbidities and mortalities. The aim was to investigate the biologic potency of ultrafine particulate matter (UFPM) combined with O3 in the lungs of mature adult normotensive and spontaneously hypertensive (SH) Wistar-Kyoto rats. Conscious, mature adult male normal Wistar-Kyoto (NW) and SH rats were exposed to one of the following atmospheres: filtered air (FA); UFPM (∼ 250 μg/m3); O3 (1.0 ppm); or UFPM + O3 (∼ 250 μg/m3 + 1.0 ppm) combined for 6 h, followed by an 8 h FA recovery period. Lung sections were evaluated for lesions in the large airways, terminal bronchiolar/alveolar duct regions, alveolar parenchyma, and vasculature. NW and SH rats were similarly affected by the combined-pollutant exposure, displaying severe injury in both large and small airways. SH rats were particularly susceptible to O3 exposure, exhibiting increased injury scores in terminal bronchioles and epithelial degeneration in large airways. UFPM-exposure groups had minimal histologic changes. The chemical composition of UFPM was altered by the addition of O3, indicating that ozonolysis promoted compound degradation. O3 increased the biologic potency of UFPM, resulting in greater lung injury following exposure. Pathologic manifestations of CVD may confer susceptibility to air pollution by impairing normal lung defenses and responses to exposure.

Impaired acclimatization to chronic hypoxia in adult male and female rats following neonatal hypoxia.

PubMed

Lumbroso, Delphine; Joseph, Vincent

2009-08-01

We tested the hypothesis that neonatal exposure to hypoxia alters acclimatization to chronic hypoxia later in life. Rat pups were exposed to normobaric hypoxia (12% O(2); nHx group) in a sealed chamber, or to normoxia (21% O(2); nNx group) from the day before birth to postnatal day 10. The animals were then raised in normal conditions until reaching 12 wk of age. At this age, we assessed ventilatory and hematological acclimatization to chronic hypoxia by exposing male and female nHx and nNx rats for 2 wk to 10% O(2). Minute ventilation, metabolic rate, hypoxic ventilatory response, hematocrit, and hemoglobin levels were measured both before and after acclimatization. We also quantified right ventricular hypertrophy as an index of pulmonary hypertension both before and after acclimatization. There was a significant effect of neonatal hypoxia that decreases ventilatory response (relative to metabolic rate, VE/VCO(2)) to acute hypoxia before acclimatization in males but not in females. nHx rats had an impaired acclimatization to chronic hypoxia characterized by altered respiratory pattern and elevated hematocrit and hemoglobin levels after acclimatization, in both males and females. Right ventricular hypertrophy was present before and after acclimatization in nHx rats, indicating that neonatal hypoxia results in pulmonary hypertension in adults. We conclude that neonatal hypoxia impairs acclimatization to chronic hypoxia in adults and may be a factor contributing to the establishment of chronic mountain sickness in humans living at high altitude.

Maternal High-Fat and High-Salt Diets Have Differential Programming Effects on Metabolism in Adult Male Rat Offspring.

PubMed

Segovia, Stephanie A; Vickers, Mark H; Harrison, Claudia J; Patel, Rachna; Gray, Clint; Reynolds, Clare M

2018-01-01

Maternal high-fat or high-salt diets can independently program adverse cardiometabolic outcomes in offspring. However, there is a paucity of evidence examining their effects in combination on metabolic function in adult offspring. Female Sprague Dawley rats were randomly assigned to either: control (CD; 10% kcal from fat, 1% NaCl), high-salt (SD; 10% kcal from fat, 4% NaCl), high-fat (HF; 45% kcal from fat, 1% NaCl) or high-fat and salt (HFSD; 45% kcal from fat, 4% NaCl) diets 21 days prior to mating and throughout pregnancy and lactation. Male offspring were weaned onto a standard chow diet and were culled on postnatal day 130 for plasma and tissue collection. Adipocyte histology and adipose tissue, liver, and gut gene expression were examined in adult male offspring. HF offspring had significantly greater body weight, impaired insulin sensitivity and hyperleptinemia compared to CD offspring, but these increases were blunted in HFSD offspring. HF offspring had moderate adipocyte hypertrophy and increased expression of the pre-adipocyte marker Dlk1 . There was a significant effect of maternal salt with increased hepatic expression of Dgat1 and Igfb2 . Gut expression of inflammatory ( Il1r1, Tnfα, Il6 , and Il6r ) and renin-angiotensin system ( Agtr1a, Agtr1b ) markers was significantly reduced in HFSD offspring compared to HF offspring. Therefore, salt mitigates some adverse offspring outcomes associated with a maternal HF diet, which may be mediated by altered adipose tissue morphology and gut inflammatory and renin-angiotensin regulation.

Constitutively reduced sensory capacity promotes better recovery after spinal cord-injury (SCI) in blind rats of the dystrophic RCS strain.

PubMed

Rink, Svenja; Bendella, Habib; Alsolivany, Kurdin; Meyer, Carolin; Woehler, Aliona; Jansen, Ramona; Isik, Zeynep; Stein, Gregor; Wennmachers, Sina; Nakamura, Makoto; Angelov, Doychin N

2018-01-01

We compared functional, electrophysiological and morphological parameters after SCI in two groups of rats Sprague Dawley (SD) rats with normal vision and blind rats from a SD-substrain "Royal College of Surgeons" (SD/RCS) who lose their photoreceptor cells after birth due to a genetic defect in the retinal pigment epithelium. For these animals skin-, intramuscular-, and tendon receptors are major available means to resolve spatial information. The purpose of this study was to check whether increased sensitivity in SD/RCS rats would promote an improved recovery after SCI. All rats were subjected to severe compression of the spinal cord at vertebra Th8, spinal cord segment Th10. Recovery of locomotion was analyzed at 1, 3, 6, 9, and 12 weeks after SCI using video recordings of beam walking and inclined ladder climbing. Five functional parameters were studied: foot-stepping angle (FSA), rump-height index (RHI) estimating paw placement and body weight support, respectively, number of correct ladder steps (CLS) assessing skilled hindlimb movements, the BBB-locomotor score and an established urinary bladder score (BS). Sensitivity tests were followed by electrophysiological measurement of M- and H-wave amplitudes from contractions of the plantar musculature after stimulation of the tibial nerve. The closing morphological measurements included lesion volume and expression of astro- and microglia below the lesion. Numerical assessments of BBB, FSA, BS, lesion volume and GFAP-expression revealed no significant differences between both strains. However, compared to SD-rats, the blind SD/RCS animals significantly improved RHI and CLS by 6 - 12 weeks after SCI. To our surprise the withdrawal latencies in the blind SD/RCS rats were longer and the amplitudes of M- and H-waves lower. The expression of IBA1-immunoreactivity in the lumbar enlargement was lower than in the SD-animals. The longer withdrawal latencies suggest a decreased sensitivity in the blind SD/RCS rats, which

6-gingerol ameliorates gentamicin induced renal cortex oxidative stress and apoptosis in adult male albino rats.

PubMed

Hegazy, Ahmed M S; Mosaed, Mohammed M; Elshafey, Saad H; Bayomy, Naglaa A

2016-06-01

Ginger or Zingiber officinale which is used in traditional medicine has been found to possess antioxidant effect that can control the generation of free radicals. Free radicals are the causes of renal cell degeneration that leads to renal failure in case of gentamicin induced toxicity. This study was done to evaluate the possible protective effects of 6-gingerol as natural antioxidant on gentamicin-induced renal cortical oxidative stress and apoptosis in adult male albino rats. Forty adult male albino rats were used in this study and were randomly divided into four groups, control group; 6-gingerol treated group; gentamicin treated group and protected group (given simultaneous 6-gingerol and gentamicin). At the end of the study, blood samples were drawn for biochemical study. Kidney sections were processed for histological, and immunohistochemical examination for caspase-3 to detect apoptosis and anti heat shock protein 47 (HSP47) to detect oxidative damage. Gentamicin treated rats revealed a highly significant increase in renal function tests, tubular dilatation with marked vacuolar degeneration and desquamation of cells, interstitial hemorrhage and cellular infiltration. Immunohistochemically, gentamicin treated rats showed a strong positive immunoreaction for caspase-3 and anti heat shock protein 47 (HSP47). Protected rats showed more or less normal biochemical, histological, and immunohistochemical pictures. In conclusion, co-administration of 6-gingerol during gentamicin 'therapy' has a significant reno-protective effect in a rat model of gentamicin-induced renal damage. It is recommended that administration of ginger with gentamicin might be beneficial in men who receive gentamicin to treat infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dopamine neurons in the ventral tegmental area fire faster in adolescent rats than in adults.

PubMed

McCutcheon, James E; Conrad, Kelly L; Carr, Steven B; Ford, Kerstin A; McGehee, Daniel S; Marinelli, Michela

2012-09-01

Adolescence may be a period of vulnerability to drug addiction. In rats, elevated firing activity of ventral tegmental area (VTA) dopamine neurons predicts enhanced addiction liability. Our aim was to determine if dopamine neurons are more active in adolescents than in adults and to examine mechanisms underlying any age-related difference. VTA dopamine neurons fired faster in adolescents than in adults as measured with in vivo extracellular recordings. Dopamine neuron firing can be divided into nonbursting (single spikes) and bursting activity (clusters of high-frequency spikes). Nonbursting activity was higher in adolescents compared with adults. Frequency of burst events did not differ between ages, but bursts were longer in adolescents than in adults. Elevated dopamine neuron firing in adolescent rats was also observed in cell-attached recordings in ex vivo brain slices. Using whole cell recordings, we found that passive and active membrane properties were similar across ages. Hyperpolarization-activated cation currents and small-conductance calcium-activated potassium channel currents were also comparable across ages. We found no difference in dopamine D2-class autoreceptor function across ages, although the high baseline firing in adolescents resulted in autoreceptor activation being less effective at silencing neurons. Finally, AMPA receptor-mediated spontaneous excitatory postsynaptic currents occurred at lower frequency in adolescents; GABA(A) receptor-mediated spontaneous inhibitory postsynaptic currents occurred at both lower frequency and smaller amplitude in adolescents. In conclusion, VTA dopamine neurons fire faster in adolescence, potentially because GABA tone increases as rats reach adulthood. This elevation of firing rate during adolescence is consistent with it representing a vulnerable period for developing drug addiction.

Effects of restricted maternal contact in neonatal rats on sexual behaviour in the adult.

PubMed

Forsberg, G; Abrahamsson, K; Södersten, P; Eneroth, P

1985-03-01

Rats, deprived of maternal contact and nutrition every alternate day starting on day 5 of life, attained a body weight at 45 days of age which was 50% of that of rats which had free access to maternal contact and nutrition. After 55 days of unrestricted food availability the body weight of the neonatally deprived rats was approximately 15% lower than that of the controls. Malnourished female rats showed normal behavioural oestrous cycles and became pregnant and lactated normally as young adults. After ovariectomy they showed higher lordosis quotients in response to treatment with oestradiol benzoate and progesterone than controls but lost less body weight in response to treatment with oestradiol-filled constant-release implants. Malnourished male rats ejaculated less frequently than controls in tests with sexually receptive female rats but this difference disappeared with repeated testing. The malnourished males showed longer ejaculation latencies and had somewhat higher serum concentrations of LH than controls after castration and treatment with testosterone-filled constant-release implants which reduced serum androgen concentrations to about 30% of the intact level. The results show that rats are capable of sustaining a rather severe neonatal nutritional deprivation without losing the capacity for essentially normal mating behaviour in adulthood.

Neonatal programming with testosterone propionate reduces dopamine transporter expression in nucleus accumbens and methylphenidate-induced locomotor activity in adult female rats.

PubMed

Dib, Tatiana; Martínez-Pinto, Jonathan; Reyes-Parada, Miguel; Torres, Gonzalo E; Sotomayor-Zárate, Ramón

2018-07-02

Research in programming is focused on the study of stimuli that alters sensitive periods in development, such as prenatal and neonatal stages, that can produce long-term deleterious effects. These effects can occur in various organs or tissues such as the brain, affecting brain circuits and related behaviors. Our laboratory has demonstrated that neonatal programming with sex hormones affects the mesocorticolimbic circuitry, increasing the synthesis and release of dopamine (DA) in striatum and nucleus accumbens (NAcc). However, the behavioral response to psychostimulant drugs such as methylphenidate and the possible mechanism(s) involved have not been studied in adult rats exposed to sex hormones during the first hours of life. Thus, the aim of this study was to examine the locomotor activity induced by methylphenidate (5mg/kg i.p.) and the expression of the DA transporter (DAT) in NAcc of adult rats exposed to a single dose of testosterone propionate (TP: 1mg/50μLs.c.) or estradiol valerate (EV: 0.1mg/50μLs.c.) at postnatal day 1. Our results demonstrated that adult female rats treated with TP have a lower methylphenidate-induced locomotor activity compared to control and EV-treated adult female rats. This reduction in locomotor activity is related with a lower NAcc DAT expression. However, neither methylphenidate-induced locomotor activity nor NAcc DAT expression was affected in EV or TP-treated adult male rats. Our results suggest that early exposure to sex hormones affects long-term dopaminergic brain areas involved in the response to psychostimulants, which could be a vulnerability factor to favor the escalating doses of drugs of abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

Creation of Consistent Burn Wounds: A Rat Model

PubMed Central

Cai, Elijah Zhengyang; Ang, Chuan Han; Raju, Ashvin; Tan, Kong Bing; Hing, Eileen Chor Hoong; Loo, Yihua; Wong, Yong Chiat; Lee, Hanjing; Lim, Jane; Moochhala, Shabbir M; Hauser, Charlotte AE

2014-01-01

Background Burn infliction techniques are poorly described in rat models. An accurate study can only be achieved with wounds that are uniform in size and depth. We describe a simple reproducible method for creating consistent burn wounds in rats. Methods Ten male Sprague-Dawley rats were anesthetized and dorsum shaved. A 100 g cylindrical stainless-steel rod (1 cm diameter) was heated to 100℃ in boiling water. Temperature was monitored using a thermocouple. We performed two consecutive toe-pinch tests on different limbs to assess the depth of sedation. Burn infliction was limited to the loin. The skin was pulled upwards, away from the underlying viscera, creating a flat surface. The rod rested on its own weight for 5, 10, and 20 seconds at three different sites on each rat. Wounds were evaluated for size, morphology and depth. Results Average wound size was 0.9957 cm2 (standard deviation [SD] 0.1845) (n=30). Wounds created with duration of 5 seconds were pale, with an indistinct margin of erythema. Wounds of 10 and 20 seconds were well-defined, uniformly brown with a rim of erythema. Average depths of tissue damage were 1.30 mm (SD 0.424), 2.35 mm (SD 0.071), and 2.60 mm (SD 0.283) for duration of 5, 10, 20 seconds respectively. Burn duration of 5 seconds resulted in full-thickness damage. Burn duration of 10 seconds and 20 seconds resulted in full-thickness damage, involving subjacent skeletal muscle. Conclusions This is a simple reproducible method for creating burn wounds consistent in size and depth in a rat burn model. PMID:25075351

SdAb heterodimer formation using leucine zippers

NASA Astrophysics Data System (ADS)

Goldman, Ellen R.; Anderson, George P.; Brozozog-Lee, P. Audrey; Zabetakis, Dan

2013-05-01

Single domain antibodies (sdAb) are variable domains cloned from camel, llama, or shark heavy chain only antibodies, and are among the smallest known naturally derived antigen binding fragments. SdAb derived from immunized llamas are able to bind antigens with high affinity, and most are capable of refolding after heat or chemical denaturation to bind antigen again. We hypothesized that the ability to produce heterodimeric sdAb would enable reagents with the robust characteristics of component sdAb, but with dramatically improved overall affinity through increased avidity. Previously we had constructed multimeric sdAb by genetically linking sdAb that bind non-overlapping epitopes on the toxin, ricin. In this work we explored a more flexible approach; the construction of multivalent binding reagents using multimerization domains. We expressed anti-ricin sdAb that recognize different epitopes on the toxin as fusions with differently charged leucine zippers. When the initially produced homodimers are mixed the leucine zipper domains will pair to produce heterodimers. We used fluorescence resonance energy transfer to confirm heterodimer formation. Surface plasmon resonance, circular dichroism, enzyme linked immunosorbent assays, and fluid array assays were used to characterize the multimer constructs, and evaluate their utility in toxin detection.

Intrauterine proximity to male fetuses affects the morphology of the sexually dimorphic nucleus of the preoptic area in the adult rat brain.

PubMed

Pei, Minjuan; Matsuda, Ken-Ichi; Sakamoto, Hirotaka; Kawata, Mitsuhiro

2006-03-01

Previous studies on polytocous rodents have revealed that the fetal intrauterine position influences its later anatomy, physiology, reproductive performance and behavior. To investigate whether the position of a fetus in the uterus modifies the development of the brain, we examined whether the structure of the sexually dimorphic nucleus of the preoptic area (SDN-POA) of rat brains accorded to their intrauterine positions. Brain sections of adult rats gestated between two male fetuses (2M) and between two female fetuses (2F) in the uterus were analysed for their immunoreactivity to calbindin-D28k, which is a marker of the SDN-POA. The SDN-POA volume of the 2M adult males was greater than that of the 2F adult males, whereas the SDN-POA volume of the 2M and 2F adult females showed no significant difference. This result indicated that contiguous male fetuses have a masculinizing effect on the SDN-POA volume of the male. To further examine whether the increment of SDN-POA volume in adulthood was due to exposure to elevated steroid hormones during fetal life, concentrations of testosterone and 17beta-estradiol in the brain were measured with 2M and 2F fetuses during gestation, respectively. On gestation day 21, the concentrations of testosterone and 17beta-estradiol in the brain were significantly higher in the 2M male rats as compared with the 2F male rats. The results suggested that there was a relationship between the fetal intrauterine position, hormone transfer from adjacent fetuses and the SDN-POA volume in adult rat brains.

Cytoplasm-to-myonucleus ratios and succinate dehydrogenase activities in adult rat slow and fast muscle fibers

NASA Technical Reports Server (NTRS)

Tseng, B. S.; Kasper, C. E.; Edgerton, V. R.

1994-01-01

The relationship between myonuclear number, cellular size, succinate dehydrogenase activity, and myosin type was examined in single fiber segments (n = 54; 9 +/- 3 mm long) mechanically dissected from soleus and plantaris muscles of adult rats. One end of each fiber segment was stained for DNA before quantitative photometric analysis of succinate dehydrogenase activity; the other end was double immunolabeled with fast and slow myosin heavy chain monoclonal antibodies. Mean +/- S.D. cytoplasmic volume/myonucleus ratio was higher in fast and slow plantaris fibers (112 +/- 69 vs. 34 +/- 21 x 10(3) microns3) than fast and slow soleus fibers (40 +/- 20 vs. 30 +/- 14 x 10(3) microns3), respectively. Slow fibers always had small volumes/myonucleus, regardless of fiber diameter, succinate dehydrogenase activity, or muscle of origin. In contrast, smaller diameter (< 70 microns) fast soleus and plantaris fibers with high succinate dehydrogenase activity appeared to have low volumes/myonucleus while larger diameter (> 70 microns) fast fibers with low succinate dehydrogenase activity always had large volume/myonucleus. Slow soleus fibers had significantly greater numbers of myonuclei/mm than did either fast soleus or fast plantaris fibers (116 +/- 51 vs. 55 +/- 22 and 44 +/- 23), respectively. These data suggest that the myonuclear domain is more limited in slow than fast fibers and in the fibers with a high, compared to a low, oxidative metabolic capability.

Neonatal alcohol exposure disrupts hippocampal neurogenesis and contextual fear conditioning in adult rats

PubMed Central

Hamilton, G.F.; Murawski, N.J.; St. Cyr, S.A.; Jablonski, S.A.; Schiffino, F.L.; Stanton, M.E.; Klintsova, A.Y.

2011-01-01

Developmental alcohol exposure can permanently alter brain structures and produce functional impairments in many aspects of behavior, including learning and memory. This study evaluates the effect of neonatal alcohol exposure on adult neurogenesis in the dentate gyrus of the hippocampus and the implications of such exposure for hippocampus-dependent contextual fear conditioning. Alcohol-exposed rats (AE) received 5.25 g/kg/day of alcohol on postnatal days (PD) 4-9 (third trimester in humans), in a binge-like manner. Two control groups were included: sham-intubated (SI) and suckle-control (SC). Animals were housed in social cages (3/cage) after weaning. On PD80, animals were injected with 200 mg/kg BrdU. Half of the animals were sacrificed two hours later. The remainder were sacrificed on PD114 to evaluate cell survival; separate AE, SI, and SC rats not injected with BrdU were tested for the context preexposure facilitation effect (CPFE; ∼PD117). There was no difference in the number of BrdU+ cells in AE, SI and SC groups on PD80. On PD114, cell survival was significantly decreased in AE rats, demonstrating that developmental alcohol exposure damages new cells' ability to incorporate into the network and survive. Behaviorally tested SC and SI groups preexposed to the training context 24h prior to receiving a 1.5mA 2s footshock froze significantly more during the context test than their counterparts preexposed to an alternate context. AE rats failed to show the CPFE. The current study shows the detrimental, long-lasting effects of developmental alcohol exposure on hippocampal adult neurogenesis and contextual fear conditioning. PMID:21816390

Alterations of Hippocampal Myelin Sheath and Axon Sprouting by Status Convulsion and Regulating Lingo-1 Expression with RNA Interference in Immature and Adult Rats.

PubMed

Song, Xiao-Jie; Han, Wei; He, Rong; Li, Tian-Yi; Xie, Ling-Ling; Cheng, Li; Chen, Heng-Sheng; Jiang, Li

2018-03-01

Seizure-induced brain damage is age-dependent, as evidenced by the different alterations of neural physiopathology in developing and mature brains. However, little is known about the age-dependent characteristics of myelinated fiber injury induced by seizures. Considering the critical functions of oligodendrocyte progenitor cells (OPCs) in myelination and Lingo-1 signaling in regulating OPCs' differentiation, the present study aimed to explore the effects of Lingo-1 on myelin and axon in immature and adult rats after status convulsion (SC) induced by lithium-pilocarpine, and the differences between immature and adult brains. Dynamic variations in electrophysiological activity and spontaneous recurrent seizures were recorded by electroencephalogram monitoring after SC. The impaired microstructures of myelin sheaths and decrease in myelin basic protein caused by SC were observed through transmission electron microscopy and western blot analysis respectively, which became more severe in adult rats, but improved gradually in immature rats. Aberrant axon sprouting occurred in adult rats, which was more prominent than in immature rats, as shown by a Timm stain. This damage was improved or negatively affected after down or upregulating Lingo-1 expression. These results demonstrated that in both immature and adult brains, Lingo-1 signaling plays important roles in seizure-induced damage to myelin sheaths and axon growth. The plasticity of the developing brain may provide a potential window of opportunity to prevent the brain from damage.

Effects of severe caloric restriction from birth on the hearts of adult rats.

PubMed

Melo, Dirceu Sousa; Riul, Tania Regina; Esteves, Elizabeth Adriana; Moraes, Patrícia Lanza; Ferreira, Fernanda Oliveira; Gavioli, Mariana; Alves, Márcia Netto Magalhães; Almeida, Pedro William Machado; Guatimosim, Silvia; Ferreira, Anderson José; Dias Peixoto, Marco Fabricio

2013-08-01

There has been increasing evidence suggesting that a severe caloric restriction (SCR) (above 40%) has beneficial effects on the hearts of rats. However, most of the reports have focused on the effects of SCR that started in adulthood. We investigated the consequences of SCR on the hearts of rats subjected to SCR since birth (CR50). From birth to the age of 3 months, CR50 rats were fed 50% of the food that the ad libitum group (AL) was fed. Thereafter, a maximal aerobic test was performed to indirectly evaluate global cardiovascular function. Indices of contractility (+dT/dt) and relaxation (-dT/dt) were analyzed in isolated heart preparation, and cardiomyocyte diameter, number, density, and myocardium collagen content were obtained through histologic analysis. Ventricular myocytes were isolated, using standard methods to evaluate phosphorylated AKT levels, and Ca(2+) handling was evaluated with a combination of Western blot analysis, intracellular Ca(2+) imaging, and confocal microscopy. CR50 rats exhibited increased aerobic performance and cardiac function, as shown by the increase in ±dT/dt. Despite the smaller cardiomyocyte diameter, CR50 rats had an increased heart-body weight ratio, increased cardiomyocyte density and number, and similar levels of myocardium collagen content, compared with AL rats. AKT was hyperphosphorylated in cardiomyocytes from CR50 rats, and there were no significant differences in Ca(2+) transient and SERCA2 levels in cardiomyocytes between CR50 and AL rats. Collectively, these observations reveal the beneficial effects of a 50% caloric restriction on the hearts of adult rats restricted since birth, which might involve cardiomyocyte AKT signaling.

Oral (drinking water) developmental toxicity studies of bromodichloromethane (BDCM) in rats and rabbits.

PubMed

Christian, M S; York, R G; Hoberman, A M; Diener, R M; Fisher, L C

2001-01-01

Crl:CD(SD)IGS BR VAF/Plus (Crl SD) rats and Hra(NZW) SPF rabbits were tested for potential developmental toxicity from bromodichloromethane (BDCM) provided continuously in the drinking water during gestation (gestation days [GDs] 6 to 21 in rats and GDs 6 to 29 in rabbits). Concentrations of 0, 50, 150, 450, or 900 ppm of BDCM were used for rats; 0, 15, 150, 450, or 900 ppm were used for rabbits (in dose range-finding studies, 1350 ppm was excessively maternotoxic to both species). Investigated maternal parameters included viability, clinical signs, water and feed consumption, and body weights. Maternal gross lesions, gravid uterine weights, abnormal placentas, and numbers of corpora lutea, implantation sites, live and dead fetuses, and early and late resorptions were observed at time of Caesarean sectioning (GD 21 in rats; GD 29 in rabbits). Body weights, sex ratios, and morphological abnormalities (external, soft tissue, and skeletal) were noted in the fetuses. Mean consumed doses of BDCM were calculated to be 0, 2.2, 18.4, 45.0, or 82.0 mg/kg/day for the rats, and 0, 1.4, 13.4, 35.6, or 55.3 mg/kg/day for the rabbits (approximate human intake is 0.8 microg/kg/day [0.0008 mg/kg/day] in adults). In pregnant rats, toxicologically important, statistically significant effects included reduced absolute (g/day) and relative (g/kg/day) water consumption values at > or =50 ppm (2.2 mg/kg/day) and reduced body weight gains (also when corrected for gravid uterine weight) and absolute (g/day) and relative (g/kg/day) feed consumption values at >450 ppm (45.0 mg/kg/day). These parameters were also significantly reduced at > or =450 ppm (35.6 mg/kg/day) in pregnant rabbits (significant weight loss occurred in the rabbits at 900 ppm, i.e., 55.3 mg/kg/day). Thus, the maternal no-observable-adverse-effect level (NOAEL) for BDCM was 150 ppm, i.e., 18.4 and 13.4 mg/kg/day in rats and rabbits, respectively. No adverse effects on embryofetal viability, growth, sex ratio, gross

Monosodium Glutamate Dietary Consumption Decreases Pancreatic β-Cell Mass in Adult Wistar Rats

PubMed Central

Boonnate, Piyanard; Waraasawapati, Sakda; Hipkaeo, Wiphawi; Pethlert, Supattra; Sharma, Amod; Selmi, Carlo; Prasongwattana, Vitoon; Cha’on, Ubon

2015-01-01

Background The amount of dietary monosodium glutamate (MSG) is increasing worldwide, in parallel with the epidemics of metabolic syndrome. Parenteral administration of MSG to rodents induces obesity, hyperglycemia, hyperlipidemia, insulin resistance, and type 2 diabetes. However, the impact of dietary MSG is still being debated. We investigated the morphological and functional effects of prolonged MSG consumption on rat glucose metabolism and on pancreatic islet histology. Methods Eighty adult male Wistar rats were randomly subdivided into 4 groups, and test rats in each group were supplemented with MSG for a different duration (1, 3, 6, or 9 months, n=20 for each group). All rats were fed ad libitum with a standard rat chow and water. Ten test rats in each group were provided MSG 2 mg/g body weight/day in drinking water and the 10 remaining rats in each group served as non-MSG treated controls. Oral glucose tolerance tests (OGTT) were performed and serum insulin measured at 9 months. Animals were sacrificed at 1, 3, 6, or 9 months to examine the histopathology of pancreatic islets. Results MSG-treated rats had significantly lower pancreatic β-cell mass at 1, 6 and 9 months of study. Islet hemorrhages increased with age in all groups and fibrosis was significantly more frequent in MSG-treated rats at 1 and 3 months. Serum insulin levels and glucose tolerance in MSG-treated and untreated rats were similar at all time points we investigated. Conclusion Daily MSG dietary consumption was associated with reduced pancreatic β-cell mass and enhanced hemorrhages and fibrosis, but did not affect glucose homeostasis. We speculate that high dietary MSG intake may exert a negative effect on the pancreas and such effect might become functionally significant in the presence or susceptibility to diabetes or NaCl; future experiments will take these crucial cofactors into account. PMID:26121281

Monosodium Glutamate Dietary Consumption Decreases Pancreatic β-Cell Mass in Adult Wistar Rats.

PubMed

Boonnate, Piyanard; Waraasawapati, Sakda; Hipkaeo, Wiphawi; Pethlert, Supattra; Sharma, Amod; Selmi, Carlo; Prasongwattana, Vitoon; Cha'on, Ubon

2015-01-01

The amount of dietary monosodium glutamate (MSG) is increasing worldwide, in parallel with the epidemics of metabolic syndrome. Parenteral administration of MSG to rodents induces obesity, hyperglycemia, hyperlipidemia, insulin resistance, and type 2 diabetes. However, the impact of dietary MSG is still being debated. We investigated the morphological and functional effects of prolonged MSG consumption on rat glucose metabolism and on pancreatic islet histology. Eighty adult male Wistar rats were randomly subdivided into 4 groups, and test rats in each group were supplemented with MSG for a different duration (1, 3, 6, or 9 months, n=20 for each group). All rats were fed ad libitum with a standard rat chow and water. Ten test rats in each group were provided MSG 2 mg/g body weight/day in drinking water and the 10 remaining rats in each group served as non-MSG treated controls. Oral glucose tolerance tests (OGTT) were performed and serum insulin measured at 9 months. Animals were sacrificed at 1, 3, 6, or 9 months to examine the histopathology of pancreatic islets. MSG-treated rats had significantly lower pancreatic β-cell mass at 1, 6 and 9 months of study. Islet hemorrhages increased with age in all groups and fibrosis was significantly more frequent in MSG-treated rats at 1 and 3 months. Serum insulin levels and glucose tolerance in MSG-treated and untreated rats were similar at all time points we investigated. Daily MSG dietary consumption was associated with reduced pancreatic β-cell mass and enhanced hemorrhages and fibrosis, but did not affect glucose homeostasis. We speculate that high dietary MSG intake may exert a negative effect on the pancreas and such effect might become functionally significant in the presence or susceptibility to diabetes or NaCl; future experiments will take these crucial cofactors into account.

A gene catalogue of the Sprague-Dawley rat gut metagenome.

PubMed

Pan, Hudan; Guo, Ruijin; Zhu, Jie; Wang, Qi; Ju, Yanmei; Xie, Ying; Zheng, Yanfang; Wang, Zhifeng; Li, Ting; Liu, Zhongqiu; Lu, Linlin; Li, Fei; Tong, Bin; Xiao, Liang; Xu, Xun; Li, Runze; Yuan, Zhongwen; Yang, Huanming; Wang, Jian; Kristiansen, Karsten; Jia, Huijue; Liu, Liang

2018-05-01

Laboratory rats such as the Sprague-Dawley (SD) rats are an important model for biomedical studies in relation to human physiological or pathogenic processes. Here we report the first catalog of microbial genes in fecal samples from Sprague-Dawley rats. The catalog was established using 98 fecal samples from 49 SD rats, divided in 7 experimental groups, and collected at different time points 30 days apart. The established gene catalog comprises 5,130,167 non-redundant genes with an average length of 750 bp, among which 64.6% and 26.7% were annotated to phylum and genus levels, respectively. Functionally, 53.1%, 21.8%,and 31% of the genes could be annotated to KEGG orthologous groups, modules, and pathways, respectively. A comparison of rat gut metagenome catalogue with human or mouse revealed a higher pairwise overlap between rats and humans (2.47%) than between mice and humans (1.19%) at the gene level. Ninety-seven percent of the functional pathways in the human catalog were present in the rat catalogue, underscoring the potential use of rats for biomedical research.

Neonatal Alcohol Exposure Permanently Disrupts the Circadian Properties and Photic Entrainment of the Activity Rhythm in Adult Rats

PubMed Central

Allen, Gregg C.; West, James R.; Chen, Wei-Jung A.; Earnest, David J.

2009-01-01

Background Alcohol exposure during the period of rapid brain development produces structural damage in different brain regions, including the suprachiasmatic nucleus (SCN), that may have permanent neurobehavioral consequences. Thus, this study examined the long-term effects of neonatal alcohol exposure on circadian behavioral activity in adult rats. Methods Artificially reared Sprague-Dawley rat pups were exposed to alcohol (EtOH; 4.5 g/kg/day) or isocaloric milk formula (gastrostomy control; GC) on postnatal days 4–9. At 2 months of age, rats from the EtOH, GC, and suckle control (SC) groups were housed individually, and properties of the circadian rhythm in wheel-running behavior were continuously analyzed during exposure to a 12-hr light:12-hr dark photoperiod (LD 12:12) or constant darkness (DD). Results Neonatal alcohol exposure had distinctive effects on the rhythmic properties and quantitative parameters of adult wheel-running behavior. EtOH-treated animals were distinguished by unstable and altered entrainment to LD 12:12 such that their daily onsets of activity were highly variable and occurred at earlier times relative to control animals. In DD, circadian regulation of wheel-running behavior was altered by neonatal alcohol exposure such that the free-running period of the activity rhythm was shorter in EtOH-exposed rats than in control animals. Total amount of daily wheel-running activity in EtOH-treated rats was greater than that observed in the SC group. In addition, the circadian activity patterns of EtOH-exposed rats were fragmented such that the duration of the active phase and the number of activity bouts per day were increased. Conclusions These data indicate that neonatal alcohol exposure produces permanent changes in the circadian regulation of the rat activity rhythm and its entrainment to LD cycles. These long-term alterations in circadian behavior, along with the developmental alcohol-induced changes in SCN endogenous rhythmicity, may have

Prenatal choline supplementation attenuates neuropathological response to status epilepticus in the adult rat hippocampus

PubMed Central

Wong-Goodrich, Sarah J. E.; Mellott, Tiffany J.; Glenn, Melissa J.; Blusztajn, Jan K.; Williams, Christina L.

2008-01-01

Prenatal choline supplementation (SUP) protects adult rats against spatial memory deficits observed after excitotoxin-induced status epilepticus (SE). To examine the mechanism underlying this neuroprotection, we determined the effects of SUP on a variety of hippocampal markers known to change in response to SE and thought to underlie ensuing cognitive deficits. Adult offspring from rat dams that received either a Control or SUP diet on embryonic days 12–17 were administered saline or kainic acid (i.p.) to induce SE and were euthanized 16 days later. SUP markedly attenuated seizure-induced hippocampal neurodegeneration, dentate cell proliferation, hippocampal GFAP mRNA expression levels, prevented the loss of hippocampal GAD65 protein and mRNA expression, and altered growth factor expression patterns. SUP also enhanced pre-seizure hippocampal levels of BDNF, NGF, and IGF-1, which may confer a neuroprotective hippocampal microenvironment that dampens the neuropathological response to and/or helps facilitate recovery from SE to protect cognitive function. PMID:18353663

Thymoquinone supplementation ameliorates lead-induced testis function impairment in adult rats.

PubMed

Mabrouk, Aymen; Ben Cheikh, Hassen

2016-06-01

This study was realized to investigate the possible beneficial effect of thymoquinone (TQ), the major active component of volatile oil of Nigella sativa seeds, against lead (Pb)-induced inhibition of rat testicular functions. Adult rats were randomized into four groups: a control group receiving no treatment; a Pb group exposed to 2000 parts per million (ppm) of Pb acetate in drinking water; a Pb-TQ group co-treated with Pb (as in Pb group) plus TQ (5 mg/kg body weight (b.w.)/day, per orally (p.o.)); and a TQ group receiving TQ (5 mg/kg b.w./day, p.o.). All treatments were for 5 weeks. No significant differences were observed for the body weight gain or for relative testes weight among the four groups of animals. Testicular Pb content significantly increased in metal-intoxicated rats compared with that in control rats. TQ supplementation had no effect on this testicular Pb accumulation. Interestingly, when coadministrated with Pb, TQ significantly improved the low plasma testosterone level and the decreased epididymal sperm count caused by Pb. In conclusion, the results suggest, for the first time, that TQ protects against Pb-induced impairment of testicular steroidogenic and spermatogenic functions. This study will open new perspectives for the clinical use of TQ in Pb intoxication. © The Author(s) 2014.

Anti-diabetic properties of rice-based herbal porridges in diabetic Wistar rats.

PubMed

Senadheera, Senadheera Pathirannehelage Anuruddhika Subhashinie; Ekanayake, Sagarika; Wanigatunge, Chandanie

2014-10-01

The present study aims to investigate anti-hyperglycaemic, anti-hyperlipidaemic and toxic effects of long-term consumption of selected green leafy porridges in a streptozotocin-induced diabetic Wistar rat model. Porridges made with Asparagus racemosus Willd. (AR), Hemidesmus indicus (L) R. Br. W. T. Aiton (HI), Scoparia dulcis L. (SD) and coconut milk porridge (CM) were incorporated into diets of diabetic Wistar rats. Diabetic control (DM) and normal control groups (NC) were provided with standard rat diet. Fasting blood glucose (FBG), HbA1c , C reactive protein (CRP), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), liver enzymes and creatinine were measured. Feed and water intake among diabetic groups were significantly high when compared with those of NC (p < 0.05). All rats in SD (mean = 39 ± 19 g) and NC (mean = 114 ± 7 g) groups gained weight, whereas most rats in other diabetic groups lost weight. Among the diabetic groups, SD group had the lowest mean FBG, FBG increment percentage (45%) and HbA1c (5.8 ± 2.1). FBG increment percentage and HbA1c of SD group were not significantly different to those of NC (38%; 4.7 ± 0.7) (p > 0.05). Among the diabetic groups, lowest TC (119 ± 20.6 mg/dL) and highest HDL-C (33 ± 6.3 mg/dL) were also detected in SD group. Alanine transaminase and creatinine were not significantly different (p > 0.05) among diabetic groups but significant when compared with those of NC. When compared with those of NC, aspartate transaminase levels were significantly (p < 0.05) high in SD, CM and DM groups. Body weight : liver weight and body weight : pancreas weight ratios and CRP were not significantly different among all groups. The study proved that SD porridge reduced weight loss, elicited hypoglycaemic and hypolipidaemic properties, and caused no toxicity in diabetes-induced Wistar rats. Copyright © 2014 John Wiley & Sons, Ltd.

Effect of sex on ethanol consumption and conditioned taste aversion in adolescent and adult rats.

PubMed

Schramm-Sapyta, Nicole L; Francis, Reynold; MacDonald, Andrea; Keistler, Colby; O'Neill, Lauren; Kuhn, Cynthia M

2014-04-01

Vulnerability to alcoholism is determined by many factors, including the balance of pleasurable vs. aversive alcohol-induced sensations: pleasurable sensations increase intake, while aversive sensations decrease it. Female sex and adolescent age are associated with lower sensitivity to intake-reducing effects and more rapid development of alcohol abuse. This study assessed voluntary drinking and the aversive effects of alcohol to determine whether these measures are inversely related across the sexes and development. Voluntary drinking of 20 % ethanol in an every-other-day (EOD) availability pattern and the dose-response relationship of ethanol conditioned taste aversion (CTA) were assessed in male and female adolescent and adult rats. CTA was sex specific in adult but not adolescent rats, with adult females exhibiting less aversion. Voluntary ethanol consumption varied according to age and individual differences but was not sex specific. Adolescents initially drank more than adults, exhibited greater day-to-day variation in consumption, were more susceptible to the alcohol deprivation effect, and took longer to establish individual differences in consumption patterns. These results show that the emergence of intake patterns differs between adolescents and adults. Adolescents as a group initiate drinking at high levels but decrease intake as they mature. A subset of adolescents maintained high drinking levels into adulthood. In contrast, most adults consumed at steady, low levels, but a small subset quickly established and maintained high-consumption patterns. Adolescents also showed marked deprivation-induced increases. Sex differences were not observed in EOD drinking during either adolescence or adulthood.

Prenatal exposure to vapors of gasoline-ethanol blends causes few cognitive deficits in adult rats

EPA Science Inventory

Developmental exposure to inhaled ethanol-gasoline fuel blends is a potential public health concern. Here we assessed cognitive functions in adult offspring of pregnant rats that were exposed to vapors of gasoline blended with a range of ethanol concentrations, including gasoli...

Voluntary exercise impact on cognitive impairments in sleep-deprived intact female rats.

PubMed

Rajizadeh, Mohammad Amin; Esmaeilpour, Khadijeh; Masoumi-Ardakani, Yaser; Bejeshk, Mohammad Abbas; Shabani, Mohammad; Nakhaee, Nouzar; Ranjbar, Mohammad Pour; Borzadaran, Fatemeh Mohtashami; Sheibani, Vahid

2018-05-01

Sleep loss is a common problem in modern societies affecting different aspects of individuals' lives. Many studies have reported that sleep deprivation (SD) leads to impairments in various types of learning and memory. Physical exercise has been suggested to attenuate the cognitive impairments induced by sleep deprivation in male rats. Our previous studies have shown that forced exercise by treadmill improved learning and memory impairments following SD. The aim of the current study was to investigate the effects of voluntary exercise by running wheel on cognitive, motor and anxiety-like behavior functions of female rats following 72 h SD. Intact female rats were used in the present study. The multiple platform method was applied for the induction of 72 h SD. The exercise protocol was 4 weeks of running wheel and the cognitive function was evaluated using Morris water maze (MWM), passive avoidance and novel object recognition tests. Open field test and measurement of plasma corticosterone level were performed for evaluation of anxiety-like behaviors. Motor balance evaluation was surveyed by rotarod test. In this study, remarkable learning and long-term memory impairments were observed in sleep deprived rats in comparison to the other groups. Running wheel exercise ameliorated the SD-induced learning and memory impairments. Voluntary and mandatory locomotion and balance situation were not statistically significant among the different groups. Our study confirmed the negative effects of SD on cognitive function and approved protective effects of voluntary exercise on these negative effects. Copyright © 2018 Elsevier Inc. All rights reserved.

[Human umbilical cord blood mononuclear cell transplantation promotes long-term neurobehavioral functional development of newborn SD rats with hypoxic ischemic brain injury].

PubMed

Huang, Hui-zhi; Wen, Xiao-hong; Liu, Hui; Huang, Jin-hua; Liu, Shang-quan; Ren, Wei-hua; Fang, Wen-xiang; Qian, Yin-feng; Hou, Wei-zhu; Yan, Ming-jie; Yao, You-heng; Li, Wei-Zu; Li, Qian-Jin

2013-06-01

To explore the effect of human umbilical cord blood mononuclear cells (UCBMC) promoting nerve behavior function and brain tissue recovery of neonatal SD rat with hypoxic ischemic brain injury (HIBI). A modified newborn rat model that had a combined hypoxic and ischemic brain injury as described by Rice-Vannucci was used, early nervous reflex, the Morris water maze and walking track analysis were used to evaluate nervous behavioral function, and brain MRI, HE staining to evaluate brain damage recovery. Newborn rat Rice-Vannucci model showed significant brain atrophy, obvious hemiplegia of contralateral limbs,e.g right step length [(7.67 ± 0.46) cm vs. (8.22 ± 0.50) cm, F = 1.494] and toe distance [(0.93 ± 0.06) cm vs. (1.12 ± 0.55) cm, F = 0.186] were significantly reduced compared with left side, learning and memory ability was significantly impaired compared with normal control group (P < 0.01); Cliff aversion [(8.44 ± 2.38) s vs.(14.22 ± 5.07) s, t = 4.618] and negative geotaxis reflex time [(7.26 ± 2.00) s vs. (11.76 ± 3.73) s, t = 4.755] on postnatal 14 days of HIBI+ transplantation group were significantly reduced compared with HIBI+NaCl group (P < 0.01) ; the Morris water maze experiment showed escape latency [ (23.11 ± 6.64) s vs. (34.04 ± 12.95) s, t = 3.356] and swimming distance [ (9.12 ± 1.21) cm vs.(12.70 ± 1.53) cm, t = 17.095] of HIBI+transplantation group were significantly reduced compared with those of HIBI+NaCl group (P < 0.01) ; the residual brain volume on postnatal 10 d [ (75.37 ± 4.53)% vs. (67.17 ± 4.08)%, t = -6.017] and 67 d [ (69.05 ± 3.58)% vs.(60.83 ± 3.69)%, t = -7.148]of HIBI+ transplantation group were significantly larger than those of HIBI+NaCl group (P < 0.01); After human UCBMC transplantation, left cortical edema significantly reduced and nerve cell necrosis of HIBI+ transplantation group is not obvious compared with HIBI+NaCl group. Human UCBMC intraperitoneal transplantation significantly promoted recovery of

Whole body gamma radiation and marrow sensitivity: A comparative study between adult rats of eight different strains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, G.S.; Elshafie, M.S.; Abdelrahman, H.G.

1996-10-01

Rats of Fischer-344 strain is quite resistant to whole-body gamma radiation. There is a genetic difference in rat hemoglobin (Hb) {beta}-chain structure, with alternate alleles, A and B, at a single locus. This study was designed to find out whether marrow sensitivity due to sublethal gamma exposure in age matched adult rats is entirely strain specific or a combination of both strain and Hb genotype specific. Eight strains of rats comprising of Hb genotypes AA and BB were studied. Several hematological parameters reflecting marrow evaluation were analyzed and compared. The data to be presented indicate that there is a partialmore » but distinct relationship between radiosensitivity and Hb genotypes.« less

The effects of gonadectomy and binge-like ethanol exposure during adolescence on open field behaviour in adult male rats.

PubMed

Yan, Wensheng; Kang, Jie; Zhang, Guoliang; Li, Shuangcheng; Kang, Yunxiao; Wang, Lei; Shi, Geming

2015-09-14

Binge drinking ethanol exposure during adolescence can lead to long-term neurobehavioural damage. It is not known whether the pubertal surge in testosterone that occurs during adolescence might impact the neurobehavioural effects of early ethanol exposure in adult animals. We examined this hypothesis by performing sham or gonadectomy surgeries on Sprague-Dawley rats around postnatal day (P) 23. From P28-65,the rats were administered 3.0g/kg ethanol using a binge-like model of exposure. Dependent measurements included tests of open field behaviour, blood ethanol concentrations, and testosterone levels. As adults, significant decreases in open field activity were observed in the GX rats. The open field behaviour of the GX rats was restored after testosterone administration. Binge-like ethanol exposure altered most of the parameters of the open field behaviour, suggestive of alcohol-induced anxiety, but rats treated with alcohol in combination with gonadectomy showed less motor behaviour and grooming behaviour and an increase in immobility, suggesting ethanol-induced depression. These results indicated that testosterone is required for ethanol-induced behavioural changes and that testicular hormones are potent stimulators of ethanol-induced behaviours. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Hepatoprotective activity of bacoside A against N-nitrosodiethylamine-induced liver toxicity in adult rats.

PubMed

Janani, Panneerselvam; Sivakumari, Kanakarajan; Parthasarathy, Chandrakesan

2009-10-01

N-Nitrosodiethylamine (DEN) is a notorious carcinogen, present in many environmental factors. DEN induces oxidative stress and cellular injury due to enhanced generation of reactive oxygen species; free radical scavengers protect the membranes from DEN-induced damage. The present study was designed to evaluate the protective effect of bacoside A (the active principle isolated from Bacopa monniera Linn.) on carcinogen-induced damage in rat liver. Adult male albino rats were pretreated with 15 mg/kg body weight/day of bacoside A orally (for 14 days) and then intoxicated with single necrogenic dose of N-nitrosodiethylamine (200 mg/kg bodyweight, intraperitonially) and maintained for 7 days. The liver weight, lipid peroxidation (LPO), and activity of serum marker enzymes (aspartate transaminases, alanine transaminases, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transpeptidase) were markedly increased in carcinogen-administered rats, whereas the activities of marker enzymes were near normal in bacoside A-pretreated rats. Activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutatione-S-transferase, and reduced glutathione) in liver also decreased in carcinogen-administered rats, which were significantly elevated in bacoside A-pretreated rats. It is concluded that pretreatment of bacoside A prevents the elevation of LPO and activity of serum marker enzymes and maintains the antioxidant system and thus protects the rats from DEN-induced hepatotoxicity.

Behavioral Differences Between Late Preweanling and Adult Female Sprague-Dawley Rat Exploration of Animate and Inanimate Stimuli and Food

PubMed Central

Smith, Kiersten S.; Morrell, Joan I.

2010-01-01

The late preweanling rat has potential as a preclinical model for disorders initially manifested in early childhood that are characterized by dysfunctional interactions with specific stimuli (e.g., obsessive-compulsive disorder and autism). No reports, however, of specific-stimulus exploration in the late preweanling rat are found in the literature. We examined the behavioral responses of normal late preweanling (PND 18-19) and adult rats when presented with exemplars of categorically-varied stimuli, including inanimate objects systematically varied in size and interactive properties, biological stimuli, and food. Preweanlings were faster to initiate specific stimulus exploration and were more interactive with most specific stimuli than adults; the magnitude of these preweanling-adult quantitative differences ranged from fairly small to very large depending upon the stimulus. In contrast, preweanlings were adult-like in their interaction with food and prey. Preweanling response to some stimuli, for example to live pups, was qualitatively different from that of adults; the preweanling behavioral repertoire was characterized by pup-seeking while the adult response was characterized by pup-avoidance. The specific stimulus interactions of preweanlings were less impacted than those of adults by the time of day of testing and placement of a stimulus in an anxiety-provoking location. The impact of novelty was stimulus dependent. The differences in interactions of preweanlings versus adults with specific stimuli suggests that CNS systems underlying these behavior patterns are at different stages of immaturity at PND 18 such that there may be an array of developmental trajectories for various categories of specific stimuli. These data provide a basis for the use of the preweanling as a preclinical model for understanding and medicating human disorders during development that are characterized by dysfunctional interactions with specific stimuli. PMID:21056059

Stress-dependent changes in neuroinflammatory markers observed after common laboratory stressors are not seen following acute social defeat of the Sprague Dawley rat.

PubMed

Hueston, Cara M; Barnum, Christopher J; Eberle, Jaime A; Ferraioli, Frank J; Buck, Hollin M; Deak, Terrence

2011-08-03

Exposure to acute stress has been shown to increase the expression of pro-inflammatory cytokines in brain, blood and peripheral organs. However, the nature of the inflammatory response evoked by acute stress varies depending on the stressor used and species examined. The goal of the following series of studies was to characterize the consequences of social defeat in the Sprague Dawley (SD) rat using three different social defeat paradigms. In Experiments 1 and 2, adult male SD rats were exposed to a typical acute resident-intruder paradigm of social defeat (60 min) by placement into the home cage of a larger, aggressive Long Evans rat and brain tissue was collected at multiple time points for analysis of IL-1β protein and gene expression changes in the PVN, BNST and adrenal glands. In subsequent experiments, rats were exposed to once daily social defeat for 7 or 21 days (Experiment 3) or housed continuously with an aggressive partner (separated by a partition) for 7 days (Experiment 4) to assess the impact of chronic social stress on inflammatory measures. Despite the fact that social defeat produced a comparable corticosterone response as other stressors (restraint, forced swim and footshock; Experiment 5), acute social defeat did not affect inflammatory measures. A small but reliable increase in IL-1 gene expression was observed immediately after the 7th exposure to social defeat, while other inflammatory measures were unaffected. In contrast, restraint, forced swim and footshock all significantly increased IL-1 gene expression in the PVN; other inflammatory factors (IL-6, cox-2) were unaffected in this structure. These findings provide a comprehensive evaluation of stress-dependent inflammatory changes in the SD rat, raising intriguing questions regarding the features of the stress challenge that may be predictive of stress-dependent neuroinflammation. Copyright © 2011 Elsevier Inc. All rights reserved.

Importance of neural mechanisms in colonic mucosal and muscular dysfunction in adult rats following neonatal colonic irritation.

PubMed

Chaloner, A; Rao, A; Al-Chaer, E D; Greenwood-Van Meerveld, B

2010-02-01

Previous studies have shown that early life trauma induced by maternal separation or colonic irritation leads to hypersensitivity to colorectal distension in adulthood. We tested the hypothesis that repetitive colorectal distension in neonates leads to abnormalities in colonic permeability and smooth muscle function in the adult rat. In neonatal rats, repetitive colorectal distension was performed on days 8, 10, and 12. As adults, stool consistency was graded from 0 (formed stool) to 3 (liquid stool). Colonic tissue was isolated for histology and myeloperoxidase levels. The colonic mucosa was placed in modified Ussing chambers for measurements of permeability and short-circuit current responses to forskolin, electrical field stimulation, and carbachol. Segments of colonic musculature were placed in organ baths and contractile response to potassium chloride, electrical field stimulation, and carbachol were determined. In adult rats that experienced neonatal colonic irritation, no significant changes in colonic histology or myeloperoxidase activity were observed; however, stool consistency scores were increased. Mucosal permeability, measured as an increase in basal conductance, was significantly increased but no changes in short-circuit current responses were observed. In adulthood, rats that underwent colorectal distension as neonates exhibited an elevated smooth muscle contractile response to potassium chloride, but no changes in response to electrical field stimulation or carbachol. In summary, neonatal colonic irritation, shown previously to produce colonic hypersensitivity, leads to significant alterations in colonic mucosal and smooth muscle function characterized by loose stools, increased mucosal permeability, and increased smooth muscle contractility in the absence of colon inflammation in adulthood. Published by Elsevier Ltd.

Sex differences in neonatal and young adult rat lower urinary tract function caused by bladder reduction.

PubMed

Chien, China; Chang, Huiyi Harriet; Wu, Hsi-Yang

2015-08-01

Pediatric urinary incontinence has been proposed as a cause for adult urinary incontinence, yet animal models mimic the findings of overactive bladder more closely than dysfunctional voiding. We used the bladder reduction (BR) model to study the effects of early external urethral sphincter (EUS) dysfunction on the maturation of lower urinary tract function in neonatal and young adult rats of both sexes. To determine long-term alterations in bladder and EUS function in young adult rats caused by neonatal BR. 46 Sprague-Dawley rats underwent BR and 52 underwent sham surgery at 1 week of age. At 3, 6, and 9 weeks of life, cystometry was carried out, 8-OH-DPAT (serotonergic receptor agonist) and WAY 100,635 (serotonergic receptor antagonist) were administered intravenously. Pressure threshold (PT), volume threshold (VT), storage tonic AUC, contraction area under the curve (AUC), EUS burst amplitude and burst duration were measured at baseline and after administration of serotonergic agents. PT increased in 3-week BR females compared with shams (31.1 vs. 22.7 cm H2O, p < 0.01), in conjunction with less efficient EUS emptying, as burst amplitude was suppressed (BR 0.04 vs. sham 0.07 mV, p < 0.05). VT subsequently increased in 9-week BR females compared with shams (0.81 vs. 0.36 mL, p < 0.05). Although 3-week BR males also experienced suppressed burst amplitude (BR 0.17 vs. sham 0.28 mV, p < 0.05), they showed no difference in PT at 3 weeks or VT at 9 weeks compared with sham males. The burst amplitude returned to normal in 6- and 9-week BR animals of both sexes, confirming a spontaneous recovery of EUS function over time. The thresholds for voiding in male rats are not as sensitive to early changes in EUS function compared with female rats. The response to serotonergic agents was identical between BR and sham animals. In the female animals, 8-OH-DPAT increased storage tonic AUC and burst duration, whereas in male animals, 8-OH-DPAT increased contraction AUC, burst

The brain renin‐angiotensin system plays a crucial role in regulating body weight in diet‐induced obesity in rats

PubMed Central

Winkler, Martina; Schuchard, Johanna; Stölting, Ines; Vogt, Florian M; Barkhausen, Jörg; Thorns, Christoph; Bader, Michael

2016-01-01

Background and Purpose Reduced weight gain after treatment with AT1 receptor antagonists may involve a brain‐related mechanism. Here, we investigated the role of the brain renin‐angiotensin system on weight regulation and food behaviour, with or without additional treatment with telmisartan. Methods Transgenic rats with a brain‐specific deficiency in angiotensinogen (TGR(ASrAOGEN)) and the corresponding wild‐type, Sprague Dawley (SD) rats were fed (3 months) with a high‐calorie cafeteria diet (CD) or standard chow. SD and TGR(ASrAOGEN) rats on the CD diet were also treated with telmisartan (8 mg·kg−1·d−1, 3 months). Results Compared with SD rats, TGR(ASrAOGEN) rats (i) had lower weights during chow feeding, (ii) did not become obese during CD feeding, (iii) had normal baseline leptin plasma concentrations independent of the feeding regimen, whereas plasma leptin of SD rats was increased due to CD, (iv) showed a reduced energy intake, (v) had a higher, strain‐dependent energy expenditure, which is additionally enhanced during CD feeding, (vi) had enhanced mRNA levels of pro‐opiomelanocortin and (vii) showed improved glucose control. Weight gain and energy intake in rats fed the CD diet were markedly reduced by telmisartan in SD rats but only to a minor extent in TGR(ASrAOGEN) rats. Conclusions The brain renin‐angiotensin system affects body weight regulation, feeding behaviour and metabolic disorders. When angiotensin II levels are low in brain, rats are protected from developing diet‐induced obesity and obesity‐related metabolic impairments. We further suggest that telmisartan at least partly lowers body weight via a CNS‐driven mechanism. PMID:26892671

Stress, κ manipulations, and aversive effects of ethanol in adolescent and adult male rats.

PubMed

Anderson, R I; Agoglia, A E; Morales, M; Varlinskaya, E I; Spear, L P

2013-09-26

Elevated ethanol use during adolescence, a potentially stressful developmental period, is accompanied by insensitivity to many aversive effects of ethanol relative to adults. Given evidence that supports a role for stress and the kappa opioid receptor (KOR) system in mediating aversive properties of ethanol and other drugs, the present study assessed the role of KOR antagonism by nor-binaltorphimine (nor-BNI) on ethanol-induced conditioned taste aversion (CTA) in stressed (exposed to repeated restraint) and non-stressed male rats (Experiment 1), with half of the rats pretreated with nor-BNI before stressor exposure. In Experiment 2, CTA induced by the kappa agonist U62,066 was also compared in stressed and non-stressed adolescents and adults. A highly palatable solution (chocolate Boost) was used as the conditioned stimulus (CS), thereby avoiding the need for water deprivation to motivate consumption of the CS during conditioning. No effects of stress on ethanol-induced CTA were found, with all doses eliciting aversions in adolescents and adults in both stress conditions. However, among stressed subjects, adults given nor-BNI before the repeated stressor displayed blunted ethanol aversion relative to adults given saline at that time. This effect of nor-BNI was not seen in adolescents, findings that support a differential role for the KOR involvement in ethanol CTA in stressed adolescents and adults. Results from Experiment 2 revealed that all doses of U62,066 elicited aversions in non-stressed animals of both ages that were attenuated in stressed animals, findings that support a modulatory role for stress in aversive effects of KOR activation. Collectively, these results suggest that although KOR sensitivity appears to be reduced in stressed subjects, this receptor system does not appear to contribute to age differences in ethanol-induced CTA under the present test circumstances. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Impact of experimental hypothyroidism on monoamines level in discrete brain regions and other peripheral tissues of young and adult male rats.

PubMed

Hassan, Wafaa A; Aly, Mona S; Rahman, Taghride Abdel; Shahat, Asmaa S

2013-06-01

The levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT) in different brain regions as well as in blood plasma, cardiac muscle and adrenal gland of young and adult male albino rats were measured following experimentally induced hypothyroidism. Hypothyroidism induced by daily oral administration of propylthiouracil (PTU, 5mg/kg body wt) caused a significant reduction in DA levels in most of the tissues examined of both young and adult rats after 21 and 28 days, in NE levels after all the time intervals studied in young rats, and after 21 and 28 days in adult rats. 5-HT exhibited a significant reduction in the selected brain regions and blood plasma after 21 and 28 days and in cardiac muscle after all the time intervals in the two age groups of animals. It may be suggested that the changes in monoamine levels induced by hypothyroidism may be due to disturbance in the synthesis and release of these amines through the neurons impairment or may be due to an alteration pattern of their synthesizing and/or degradative enzymes. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

EFFECTS OF PERFLUOROOCTANE SULFONATE (PFOS) ON THYROID HORMONE STATUS IN ADULT AND NEONATAL RATS

EPA Science Inventory

EFFECTS OF PERFLUOROOCTANE SULFONATE (PFOS) ON THYROID HORMONE STATUS IN ADULT AND NEONATAL RATS. M.N. Logan1, J.R. Thibodeaux2, R.G. Hanson2, C. Lau2. 1North Carolina Central University, Durham, NC, 2Reprod. Tox. Div. NHEERL, US EPA, Research Triangle Park, NC.

Perfluor...

Neonatal handling reduces renal function in adult rats.

PubMed

Donadio, Márcio Vinícius Fagundes; Jacobs, Silvana; Corezola, Kizzy Ludnila; Melo, Denizar Alberto da Silva; Dias, Henrique Bregolin; Reichel, Carlos Luiz; Franci, Celso Rodrigues; Jeckel-Neto, Emilio Antonio; Lulhier, Francisco; Lucion, Aldo Bolten; de Oliveira, Jarbas Rodrigues; Sanvitto, Gilberto Luiz

2009-01-01

To evaluate the effects of neonatal handling on hydroelectrolytic balance in adult rats. The litters were divided into two groups: nonhandled and handled. The procedure consisted of handling the pups for 1 min/day in the first 10 days postnatally. When adults, animals had their body weight verified and were housed in individual metabolic cages. After a 24-hour period, urine samples were collected and the urinary and water intake volumes measured. Blood samples to determine osmolality, aldosterone, corticosterone, angiotensin II, creatinine, urea, sodium and potassium levels were collected. The kidneys were removed for histological assessment. Urinary osmolality, sodium, urea and creatinine were also measured and the creatinine clearance (CC) calculated. No difference between groups was found in the body weight. Handled animals showed a reduction in the total kidney wet weight, water intake, urinary volume, CC, plasma angiotensin II, corticosterone and aldosterone when compared to the nonhandled and an increase in the urinary osmolality and sodium excretion fraction. No differences in serum potassium and no evidence of structural changes were demonstrated by histological analysis. Neonatal handling induced long-lasting effects decreasing renal function without evidence of kidney structural changes. (c) 2009 S. Karger AG, Basel.

The Effects of Early-Life Predator Stress on Anxiety- and Depression-Like Behaviors of Adult Rats

PubMed Central

Chen, Lu-jing; Shen, Bing-qing; Liu, Dan-dan; Li, Sheng-tian

2014-01-01

Childhood emotional trauma contributes significantly to certain psychopathologies, such as post-traumatic stress disorder. In experimental animals, however, whether or not early-life stress results in behavioral abnormalities in adult animals still remains controversial. Here, we investigated both short-term and long-term changes of anxiety- and depression-like behaviors of Wistar rats after being exposed to chronic feral cat stress in juvenile ages. The 2-week predator stress decreased spontaneous activities immediately following stress but did not increase depression- or anxiety-like behaviors 4 weeks after the stimulation in adulthood. Instead, juvenile predator stress had some protective effects, though not very obvious, in adulthood. We also exposed genetic depression model rats, Wistar Kyoto (WKY) rats, to the same predator stress. In WKY rats, the same early-life predator stress did not enhance anxiety- or depression-like behaviors in both the short-term and long-term. However, the stressed WKY rats showed slightly reduced depression-like behaviors in adulthood. These results indicate that in both normal Wistar rats and WKY rats, early-life predator stress led to protective, rather than negative, effects in adulthood. PMID:24839560

Prolonged exposure to a low-dose of bisphenol A increases spontaneous motor activity in adult male rats.

PubMed

Nojima, Kazuo; Takata, Tomoyo; Masuno, Hiroshi

2013-07-01

We investigated the effects of bisphenol A (BPA), an environmental endocrine-disrupting chemical, on spontaneous motor activity in adult male rats. The rats were implanted intraperitoneally with mini-osmotic pumps containing either BPA (50 μg/kg body weight per day) in sesame oil (BPA-treated group) or sesame oil only (vehicle-treated group). Spontaneous motor activity during a 24-h period was measured over 5 days from day 9 to day 13 after implantation using an animal movement analysis system. Spontaneous motor activity during the last 2 h of the dark phase and during the first 1-h of the light phase was increased in the BPA-treated group. Total spontaneous motor activity during the 12-h light phase, but not the 12-h dark phase, was higher in the BPA-treated group than in the vehicle-treated group. These findings suggest that BPA may induce hyperactivity in adult male rats during the 12-h light phase, especially during the 2 h immediately preceding sleep-onset and 1 h immediately following sleep-onset.

Neurochemical Changes after Acute Binge Toluene Inhalation in Adolescent and Adult Rats: A High-Resolution Magnetic Resonance Spectroscopy Study

PubMed Central

O'Leary-Moore, Shonagh K.; Galloway, Matthew P.; McMechan, Andrew P.; Irtenkauf, Susan; Hannigan, John H.; Bowen, Scott E.

2009-01-01

Inhalant abuse in young people is a growing public health concern. We reported previously that acute toluene intoxication in young rats, using a pattern of exposures that approximate abuse patterns of inhalant use in humans, significantly altered neurochemical measures in select brain regions. In this study, adolescent and young adult rats were exposed similarly to an acute (2 × 15 min), high dose (8000 − 12000 ppm) of toluene and high-resolution magic angle spinning proton magnetic resonance spectroscopy (HR-MAS 1H-MRS) was used to assess neurochemical profiles of tissue samples from a number of brain regions collected immediately following solvent exposure. The current investigation focused on N-acetyl-aspartate (NAA), choline-containing compounds, creatine, glutamate, GABA, and glutamine. Contrary to our predictions, no significant alterations were found in levels of NAA, choline, creatine, glutamate, or glutamine in adolescent animals. In contrast to these minimal effects in adolescents, binge toluene exposure altered several neurochemical parameters in young adult rats, including decreased levels of choline and GABA in the frontal cortex and striatum and lowered glutamine and NAA levels in the frontal cortex. One of the more robust findings was a wide-ranging increase in lactate after toluene exposure in adult animals, an effect not observed in adolescents. These age-dependent effects of toluene are distinct from those reported previously in juvenile rats and suggest a developmental difference in vulnerability to the effects of inhalants. Specifically, the results suggest that the neurochemical response to toluene in adolescents is attenuated compared to adults, and imply an association between these neurochemical differences and age-influenced differences in solvent abuse in humans. PMID:19628036

Product of the SNPP VIIRS SD Screen Transmittance and the SD BRDF (RSB) From Both Yaw Maneuver and Regular On-Orbit Data

NASA Technical Reports Server (NTRS)

Lei, Ning; Xiong, Xiaoxiong

2016-01-01

To assure data quality, the Earth-observing Visible Infrared Imaging Radiometer Suite (VIIRS) regularly performs on-orbit radiometric calibrations of its 22 spectral bands. The primary calibration radiance source for the reflective solar bands (RSBs) is a sunlit solar diffuser (SD). During the calibration process, sunlight goes through a perforated plate (the SD screen) and then strikes the SD. The SD scattered sunlight is used for the calibration, with the spectral radiance proportional to the product of the SD screen transmittance and the SD bidirectional reflectance distribution function (BRDF). The BRDF is decomposed to the product of its value at launch and a numerical factor quantifying its change since launch. Therefore, the RSB calibration requires accurate knowledge of the product of the SD screen transmittance and the BRDF (RSB; launch time). Previously, we calculated the product with yaw maneuver data and found that the product had improved accuracy over the prelaunch one. With both yaw maneuver and regular on orbit data, we were able to improve the accuracy of the SDSM screen transmittance and the product for the solar diffuser stability monitor SD view. In this study, we use both yaw maneuver and a small portion of regular on-orbit data to determine the product for the RSB SD view.

Comparison of bilateral whisker movement in freely exploring and head-fixed adult rats.

PubMed

Sellien, Heike; Eshenroder, Donna S; Ebner, Ford F

2005-09-01

Rats move their whiskers actively during tactile exploration of their environment. The whiskers emanate from densely innervated whisker follicles that are moved individually by intrinsic facial muscles and as a group by extrinsic muscles. Several descriptions of whisker movements in normal adult rats during unrestrained exploration indicate that rats move their whiskers in the 6-9 Hz range when exploring a new environment. The rate can be elevated to nearly 20 Hz for brief episodes just prior to making a behavioural decision. The present studies were undertaken to compare whisker dynamics in head-restrained and freely moving rats with symmetrical or asymmetrical numbers of whiskers on the two sides of their face and to provide a description of differences in whisker use in exploring rats after trimming all but two whiskers on one side of the face, a condition that has been shown to induce robust cortical plasticity. Head-fixed rats were trained to protract their whiskers against a contact detector with sufficient force to trigger a chocolate milk reward. Whisker movements were analyzed, and the results from head-fixed animals were compared with free-running animals using trials taken during their initial exploration of novel objects that blocked the rat's progress down an elevated runway. The results show that symmetrical whisker movements are modulated both by the nature of the task and the number of whiskers available for exploration. Rats can change their whisker movements when the sensitivity (threshold) of a contact detector is raised or lowered, or when the nature of the task requires bilateral input from the whiskers. We show that trimming some, but not all whiskers on one side of the face modifies the synchrony of whisker movement compared to untrimmed or symmetrically trimmed whiskers.

Elucidating the 16S rRNA 3' boundaries and defining optimal SD/aSD pairing in Escherichia coli and Bacillus subtilis using RNA-Seq data.

PubMed

Wei, Yulong; Silke, Jordan R; Xia, Xuhua

2017-12-15

Bacterial translation initiation is influenced by base pairing between the Shine-Dalgarno (SD) sequence in the 5' UTR of mRNA and the anti-SD (aSD) sequence at the free 3' end of the 16S rRNA (3' TAIL) due to: 1) the SD/aSD sequence binding location and 2) SD/aSD binding affinity. In order to understand what makes an SD/aSD interaction optimal, we must define: 1) terminus of the 3' TAIL and 2) extent of the core aSD sequence within the 3' TAIL. Our approach to characterize these components in Escherichia coli and Bacillus subtilis involves 1) mapping the 3' boundary of the mature 16S rRNA using high-throughput RNA sequencing (RNA-Seq), and 2) identifying the segment within the 3' TAIL that is strongly preferred in SD/aSD pairing. Using RNA-Seq data, we resolve previous discrepancies in the reported 3' TAIL in B. subtilis and recovered the established 3' TAIL in E. coli. Furthermore, we extend previous studies to suggest that both highly and lowly expressed genes favor SD sequences with intermediate binding affinity, but this trend is exclusive to SD sequences that complement the core aSD sequences defined herein.

Long-term Characterization of Retinal Degeneration in Royal College of Surgeons Rats Using Spectral-Domain Optical Coherence Tomography.

PubMed

Ryals, Renee C; Andrews, Michael D; Datta, Shreya; Coyner, Aaron S; Fischer, Cody M; Wen, Yuquan; Pennesi, Mark E; McGill, Trevor J

2017-03-01

Prospective treatments for age-related macular degeneration and inherited retinal degenerations are commonly evaluated in the Royal College of Surgeons (RCS) rat before translation into clinical application. Historically, retinal thickness obtained through postmortem anatomic assessments has been a key outcome measure; however, utility of this measurement is limited because it precludes the ability to perform longitudinal studies. To overcome this limitation, the present study was designed to provide a baseline longitudinal quantification of retinal thickness in the RCS rat by using spectral-domain optical coherence tomography (SD-OCT). Horizontal and vertical linear SD-OCT scans centered on the optic nerve were captured from Long-Evans control rats at P30, P60, P90 and from RCS rats between P17 and P90. Total retina (TR), outer nuclear layer+ (ONL+), inner nuclear layer (INL), and retinal pigment epithelium (RPE) thicknesses were quantified. Histologic sections of RCS retina obtained from P21 to P60 were compared to SD-OCT images. In RCS rats, TR and ONL+ thickness decreased significantly as compared to Long-Evans controls. Changes in INL and RPE thickness were not significantly different between control and RCS retinas. From P30 to P90 a subretinal hyperreflective layer (HRL) was observed and quantified in RCS rats. After correlation with histology, the HRL was identified as disorganized outer segments and the location of accumulated debris. Retinal layer thickness can be quantified longitudinally throughout the course of retinal degeneration in the RCS rat by using SD-OCT. Thickness measurements obtained with SD-OCT were consistent with previous anatomic thickness assessments. This study provides baseline data for future longitudinal assessment of therapeutic agents in the RCS rat.

Effects of chronic prenatal MK-801 treatment on object recognition, cognitive flexibility, and drug-induced locomotor activity in juvenile and adult rat offspring.

PubMed

Gallant, S; Welch, L; Martone, P; Shalev, U

2017-06-15

Patients with schizophrenia display impaired cognitive functioning and increased sensitivity to psychomimetic drugs. The neurodevelopmental hypothesis of schizophrenia posits that disruption of the developing brain predisposes neural networks to lasting structural and functional abnormalities resulting in the emergence of such symptoms in adulthood. Given the critical role of the glutamatergic system in early brain development, we investigated whether chronic prenatal exposure to the glutamate NMDA receptor antagonist, MK-801, induces schizophrenia-like behavioural and neurochemical changes in juvenile and adult rats. Pregnant Long-Evans rats were administered saline or MK-801 (0.1mg/kg; s.c.) at gestation day 7-19. Object recognition memory and cognitive flexibility were assessed in the male offspring using a novel object preference task and a maze-based set-shifting procedure, respectively. Locomotor-activating effects of acute amphetamine and MK-801 were also assessed. Adult, but not juvenile, prenatally MK-801-treated rats failed to show novel object preference after a 90min delay, suggesting that object recognition memory may have been impaired. In addition, the set-shifting task revealed impaired acquisition of a new rule in adult prenatally MK-801-treated rats compared to controls. This deficit appeared to be driven by regression to the previously learned behaviour. There were no significant differences in drug-induced locomotor activity in juvenile offspring or in adult offspring following acute amphetamine challenges. Unexpectedly, MK-801-induced locomotor activity in adult prenatally MK-801-treated rats was lower compared to controls. Glutamate transmission dysfunction during early development may modify behavioural parameters in adulthood, though these parameters do not appear to model deficits observed in schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

Products of the SNPP VIIRS SD Screen Transmittance and the SD BRDFs From Both Yaw Maneuver and Regular On-Orbit Data

NASA Technical Reports Server (NTRS)

Lei, Ning; Xiong, Xiaoxiong

2017-01-01

To ensure data quality, the Earth-observing Visible Infrared Imaging Radiometer Suite (VIIRS) on the Suomi National Polar-orbiting Partnership satellite regularly performs on-orbit radiometric calibration of its 22 spectral bands. The primary radiance source for the calibration of the VIIRS reflective solar bands (RSBs) is a sunlit onboard solar diffuser (SD).During the calibration process, sunlight goes through a perforated plate (the SD screen) and then strikes the SD. The sunlight, scattered off the SD of near-Lambertian property, is used for the calibration. Consequently, the spectral radiance of the scattered sunlight is proportional to the product of the SD screen transmittance and the SD bidirectional reflectance distribution function (BRDF) value at the observation direction. The BRDF value is decomposed to the product of its initial value at launch and a numerical degradation factor that quantifies the decrease from the initial value. The degradation factor is determined by an onboard SD stability monitor (SDSM). During the BRDF degradation factor determination process, the SDSM receives the SD scattered sunlight and the sunlight that goes through another perforated plate at almost the same time. The ratio of the signal strengths from the two observations is used to determine the BRDF degradation factor. Consequently, the RSB radiometric calibration requires the accurate knowledge of the product of the SD screen transmittance and the initial BRDF value as sensed by the RSB and the SDSM detectors. We use both yaw maneuver and a small portion of regular on-orbit data to determine the products.

Astrocytes from adult Wistar rats aged in vitro show changes in glial functions.

PubMed

Souza, Débora Guerini; Bellaver, Bruna; Raupp, Gustavo Santos; Souza, Diogo Onofre; Quincozes-Santos, André

2015-11-01

Astrocytes, the most versatile cells of the central nervous system, play an important role in the regulation of neurotransmitter homeostasis, energy metabolism, antioxidant defenses and the anti-inflammatory response. Recently, our group characterized cortical astrocyte cultures from adult Wistar rats. In line with that work, we studied glial function using an experimental in vitro model of aging astrocytes (30 days in vitro after reaching confluence) from newborn (NB), adult (AD) and aged (AG) Wistar rats. We evaluated metabolic parameters, such as the glucose uptake, glutamine synthetase (GS) activity, and glutathione (GSH) content, as well as the GFAP, GLUT-1 and xCT expression. AD and AG astrocytes take up less glucose than NB astrocytes and had decreased GLUT1 expression levels. Furthermore, AD and AG astrocytes exhibited decreased GS activity compared to NB cells. Simultaneously, AD and AG astrocytes showed an increase in GSH levels, along with an increase in xCT expression. NB, AD and AG astrocytes presented similar morphology; however, differences in GFAP levels were observed. Taken together, these results improve the knowledge of cerebral senescence and represent an innovative tool for brain studies of aging. Copyright © 2015 Elsevier Ltd. All rights reserved.

A new scale for assessing wisdom based on common domains and a neurobiological model: The San Diego Wisdom Scale (SD-WISE).

PubMed

Thomas, Michael L; Bangen, Katherine J; Palmer, Barton W; Sirkin Martin, Averria; Avanzino, Julie A; Depp, Colin A; Glorioso, Danielle; Daly, Rebecca E; Jeste, Dilip V

2017-09-08

Wisdom is an ancient concept that has gained new interest among clinical researchers as a complex trait relevant to well-being and healthy aging. As the empirical data regarding wisdom have grown, several measures have been used to assess an individual's level of wisdom. However, none of these measures has been based on a construct of wisdom with neurobiological underpinnings. We sought to develop a new scale, the San Diego Wisdom Scale (SD-WISE), which builds upon recent gains in the understanding of psychological and neurobiological models of the trait. Data were collected from 524 community-dwelling adults age 25-104 years as part of a structured multi-cohort study of adult lifespan. Participants were administered the SD-WISE along with two existing measures of wisdom that have been shown to have good psychometric properties. Factor analyses confirmed the hypothesized measurement model. SD-WISE total scores were reliable, demonstrated convergent and discriminant validity, and correlated, as hypothesized, negatively with emotional distress, but positively with well-being. However, the magnitudes of these associations were small, suggesting that the SD-WISE is not just a global measure of mental state. The results support the reliability and validity of SD-WISE scores. Study limitations are discussed. The SD-WISE, with good psychometric properties, a brief administration time, and a measurement model that is consistent with commonly cited content domains of wisdom based on a putative neurobiological model, may be useful in clinical practice as well as in bio-psycho-social research, especially investigations into the neurobiology of wisdom and experimental interventions to enhance wisdom. Copyright © 2017 Elsevier Ltd. All rights reserved.

Differences in Methylphenidate Dose Response between Periadolescent and Adult Rats in the Familiar Arena-Novel Alcove TaskS⃞

PubMed Central

Zarcone, Troy J.; Davis, Paul F.; Ozias, Marlies K.; Fowler, Stephen C.

2011-01-01

Methylphenidate is a psychostimulant widely used in the treatment of attention deficit hyperactivity disorder. In this study, the effects of two nonstereotypy-inducing doses of methylphenidate (2.5 and 5.0 mg/kg s.c.) were examined in periadolescent [postnatal days (P) 35 and 42] and young adult (P70), male Long-Evans rats using a three-period locomotor activity paradigm that affords inferences about exploration, habituation, and attention to a novel stimulus (an “alcove”) in a familiar environment in a single test session. In the first test period, P35 and P42 rats were more active than P70 rats, and methylphenidate increased locomotion in a dose-related manner. The introduction of a novel spatial stimulus in the third test period revealed a significant interaction of dose and age such that P70 rats exhibited dose-related increases in distance traveled, but P35 rats did not. Furthermore, methylphenidate dose-relatedly disrupted the rats' tendency to spend increasing amounts of time in the alcove across the test period at P70 but not at P35. Brain and serum methylphenidate concentrations were significantly lower at P35 than at P70, with intermediate levels at P42. Developmental differences in dopaminergic neurochemistry were also observed, including increased dopamine content in the caudate-putamen, nucleus accumbens, and frontal cortex and decreased densities of D1-like receptors in the frontal cortex in P70 than in P42 rats. These results raise the possibility that children and adults may respond differently when treated with this drug, particularly in situations involving response to novelty and that these effects involve developmental differences in pharmacokinetics and dopaminergic neurochemistry. PMID:21205916

Neonatal lipopolysaccharide exposure induces long-lasting learning impairment, less anxiety-like response and hippocampal injury in adult rats.

PubMed

Wang, K-C; Fan, L-W; Kaizaki, A; Pang, Y; Cai, Z; Tien, L-T

2013-03-27

Infection during early neonatal period has been shown to cause lasting neurological disabilities and is associated with the subsequent impairment in development of learning and memory ability and anxiety-related behavior in adults. We have previously reported that neonatal lipopolysaccharide (LPS) exposure resulted in cognitive deficits in juvenile rats (P21); thus, the goal of the present study was to determine whether neonatal LPS exposure has long-lasting effects in adult rats. After an LPS (1mg/kg) intracerebral (i.c.) injection in postnatal day 5 (P5) Sprague-Dawley female rat pups, neurobehavioral tests were carried out on P21 and P22, P49 and P50 or P70 and P71 and brain injury was examined at 66days after LPS injection (P71). Our data indicate that neonatal LPS exposure resulted in learning deficits in the passive avoidance task, less anxiety-like (anxiolytic-like) responses in the elevated plus-maze task, reductions in the hippocampal volume and the number of neuron-specific nuclear protein (NeuN)+ cells, as well as axonal injury in the CA1 region of the middle dorsal hippocampus in P71 rats. Neonatal LPS exposure also resulted in sustained inflammatory responses in the P71 rat hippocampus, as indicated by an increased number of activated microglia and elevation of interleukin-1β content in the rat hippocampus. This study reveals that neonatal LPS exposure causes persistent injuries to the hippocampus and results in long-lasting learning disabilities, and these effects are related to the chronic inflammation in the rat hippocampus. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Expression of estrogen, estrogen related and androgen receptors in adrenal cortex of intact adult male and female rats.

PubMed

Trejter, Marcin; Jopek, Karol; Celichowski, Piotr; Tyczewska, Marianna; Malendowicz, Ludwik K; Rucinski, Marcin

2015-01-01

Adrenocortical activity in various species is sensitive to androgens and estrogens. They may affect adrenal cortex growth and functioning either via central pathways (CRH and ACTH) or directly, via specific receptors expressed in the cortex and/or by interfering with adrenocortical enzymes, among them those involved in steroidogenesis. Only limited data on expression of androgen and estrogen receptors in adrenal glands are available. Therefore the present study aimed to characterize, at the level of mRNA, expression of these receptors in specific components of adrenal cortex of intact adult male and female rats. Studies were performed on adult male and female (estrus) Wistar rats. Total RNA was isolated from adrenal zona glomerulosa (ZG) and fasciculate/reticularis (ZF/R). Expression of genes were evaluated by means of Affymetrix® Rat Gene 1.1 ST Array Strip and QPCR. By means of Affymetrix® Rat Gene 1.1 ST Array we examined adrenocortical sex differences in the expression of nearly 30,000 genes. All data were analyzed in relation to the adrenals of the male rats. 32 genes were differentially expressed in ZG, and 233 genes in ZF/R. In the ZG expression levels of 24 genes were lower and 8 higher in female rats. The more distinct sex differences were observed in the ZF/R, in which expression levels of 146 genes were lower and 87 genes higher in female rats. Performed analyses did not reveal sex differences in the expression levels of both androgen (AR) and estrogen (ER) receptor genes in the adrenal cortex of male and female rats. Therefore matrix data were validated by QPCR. QPCR revealed higher expression levels of AR gene both in ZG and ZF/R of male than female rats. On the other hand, QPCR did not reveal sex-related differences in the expression levels of ERα, ERβ and non-genomic GPR30 (GPER-1) receptor. Of those genes expression levels of ERα genes were the highest. In studied adrenal samples the relative expression of ERα mRNA was higher than ERβ m

PREPUBERTAL EXPOSURES TO COMPOUNDS THAT INCREASE PROLACTIN SECRETION IN THE MALE RAT: EFFECTS ON ADULT PROSTATE

EPA Science Inventory

Prepubertal exposure to compounds that increase prolactin secretion in the male rat: effects on the adult prostate.

Stoker TE, Robinette CL, Britt BH, Laws SC, Cooper RL.

Endocrinology Branch, Reproductive Toxicology Division, National Health and Environmental Effec...

Neurological assessments after treatment with the antimalarial β-arteether in neonatal and adult rats.

PubMed

Erickson, R I; Defensor, E B; Fairchild, D G; Mirsalis, J C; Steinmetz, K L

2011-08-01

The World Health Organization currently recommends combinatorial treatment including artemisinins as first-line therapy against drug-resistant Plasmodium falciparum malaria. Although highly efficacious, artemisinin and its derivatives, including β-arteether (βAE), are associated with ototoxicity, tremors, and other autonomic and motor impairments in the clinic. Similar neurological symptoms, as well as brainstem lesions, have been observed in adult laboratory species (mice, rats, dogs, and non human primates) following acute treatment with βAE; however, few long-term, nonclinical studies have been conducted. Furthermore, the majority of deaths attributed to malarial infection occur in children under age five, yet no laboratory studies have been initiated in neonatal or juvenile animals. In the current study, neonatal 7-day-old rats were administered intramuscular doses of 1-90 mg/kg βAE in sesame oil for up to eight treatment cycles (one cycle=7 days treatment+7 days without treatment). Neonates were tested for changes in sensorimotor function, and the same animals were tested as adults in the Functional Observational Battery, for motor activity, and in the 8-arm radial maze. Pups receiving a single cycle of 60 or 90 mg/kg died within a week of treatment but had few behavioral changes and no brainstem pathology. In the long-term study, behavioral and motor changes and brainstem lesions were observed in a dose- and time-related manner. Rats given repeated cycles of 1 or 5mg/kg βAE showed subtle motor abnormalities (e.g., slight loss of righting reflex) while repeated cycles of 10mg/kg βAE treatment resulted in obvious motor and behavioral changes. Rats receiving 1mg/kg βAE had no brainstem lesions whereas some rats treated with 5mg/kg βAE and all rats treated with 10 mg/kg βAE had brainstem lesions. Brainstem lesions were observed after as few as five cycles and were characterized by gliosis, satellitosis and progressive necrosis in motor neurons of the

Effects of Maternal Behavior Induction and Pup Exposure on Neurogenesis in Adult, Virgin Female Rats

PubMed Central

Furuta, Miyako; Bridges, Robert S.

2009-01-01

The states of pregnancy and lactation bring about a range of physiological and behavioral changes in the adult mammal that prepare the mother to care for her young. Cell proliferation increases in the subventricular zone (SVZ) of the female rodent brain during both pregnancy and lactation when compared to that in cycling, diestrous females. In the present study, the effects of maternal behavior induction and pup exposure on neurogenesis in nulliparous rats were examined in order to determine whether maternal behavior itself, independent of pregnancy and lactation, might affect neurogenesis. Adult, nulliparous, Sprague-Dawley, female rats were exposed daily to foster young in order to induce maternal behavior. Following the induction of maternal behavior each maternal subject plus females that were exposed to pups for a comparable number of test days, but did not display maternal behavior, and subjects that had received no pup exposure were injected with bromodeoxyuridine (BrdU, 90 mg/kg, i.v.). Brain sections were double-labeled for BrdU and the neural marker, NeuN, to examine the proliferating cell population. Increases in the number of double-labeled cells were found in the maternal virgin brain when compared with the number of double-labeled cells present in non-maternal, pup-exposed nulliparous rats and in females not exposed to young. No changes were evident in the dentate gyrus of the hippocampus as a function of maternal behavior. These data indicate that in nulliparous female rats maternal behavior itself is associated with the stimulation of neurogenesis in the SVZ. PMID:19712726

Chronic Oral Capsaicin Exposure During Development Leads to Adult Rats with Reduced Taste Bud Volumes.

PubMed

Omelian, Jacquelyn M; Samson, Kaeli K; Sollars, Suzanne I

2016-09-01

Cross-sensory interaction between gustatory and trigeminal nerves occurs in the anterior tongue. Surgical manipulations have demonstrated that the strength of this relationship varies across development. Capsaicin is a neurotoxin that affects fibers of the somatosensory lingual nerve surrounding taste buds, but not fibers of the gustatory chorda tympani nerve which synapse with taste receptor cells. Since capsaicin is commonly consumed by many species, including humans, experimental use of this neurotoxin provides a naturalistic perturbation of the lingual trigeminal system. Neonatal or adults rats consumed oral capsaicin for 40 days and we examined the cross-sensory effect on the morphology of taste buds across development. Rats received moderate doses of oral capsaicin, with chronic treatments occurring either before or after taste system maturation. Tongue morphology was examined either 2 or 50 days after treatment cessation. Edema, which has been previously suggested as a cause of changes in capsaicin-related gustatory function, was also assessed. Reductions in taste bud volume occurred 50 days, but not 2 days post-treatment for rats treated as neonates. Adult rats at either time post-treatment were unaffected. Edema was not found to occur with the 5 ppm concentration of capsaicin we used. Results further elucidate the cooperative relationship between these discrete sensory systems and highlight the developmentally mediated aspect of this interaction. Chronic exposure to even moderate levels of noxious stimuli during development has the ability to impact the orosensory environment, and these changes may not be evident until long after exposure has ceased.

Oral methylphenidate alleviates the fine motor dysfunction caused by chronic postnatal manganese exposure in adult rats.

PubMed

Beaudin, Stéphane A; Strupp, Barbara J; Lasley, Stephen M; Fornal, Casimir A; Mandal, Shyamali; Smith, Donald R

2015-04-01

Developmental manganese (Mn) exposure is associated with motor dysfunction in children and animal models, but little is known about the underlying neurochemical mechanisms or the potential for amelioration by pharmacotherapy. We investigated whether methylphenidate (MPH) alleviates fine motor dysfunction due to chronic postnatal Mn exposure, and whether Mn exposure impairs brain extracellular dopamine (DA) and norepinephrine (NE) in the prefrontal cortex (PFC) and striatum in adult animals. Rats were orally exposed to 0 or 50 mg Mn/kg/day from postnatal day 1 until the end of the study (PND 145). The staircase test was used to assess skilled forelimb function. Oral MPH (2.5 mg/kg/day) was administered daily 1 h before staircase testing for 16 days. DA and NE levels were measured by dual probe microdialysis. Results show that Mn exposure impaired reaching and grasping skills and the evoked release of DA and NE in the PFC and striatum of adult rats. Importantly, oral MPH treatment fully alleviated the fine motor deficits in the Mn-exposed animals, but did not affect forelimb skills of control rats not exposed to Mn. These results suggest that catecholaminergic hypofunctioning in the PFC and striatum may underlie the Mn-induced fine motor dysfunction, and that oral MPH pharmacotherapy is an effective treatment approach for alleviating this dysfunction in adult animals. The therapeutic potential of MPH for the treatment of motor dysfunction in Mn-exposed children and adults appears promising pending further characterization of MPH efficacy in other functional areas (eg, attention) believed to be affected by developmental Mn exposure. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

"Despair" induced by extinction trials in the water maze: relationship with measures of anxiety in aged and adult rats.

PubMed

Schulz, Daniela; Huston, Joseph P; Buddenberg, Tim; Topic, Bianca

2007-03-01

We have previously reported that extinction of escape behavior in the water maze due to the removal of the platform coincided with the development of behavioral "despair" in aged and adult rats, as assessed by immobility. The present study examines further predictions derived from the hypothesis that the withholding of reinforcement induces behaviors akin to depression. We tested for correlations between extinction performance and immobility, as well as between immobility and measures of anxiety in aged and adult rats. Age comparisons were also performed on these variables. Forty aged and 29 adult male Wistar rats (24 and 3 months old, respectively) were examined in the open field, black/white box and elevated-plus maze followed by 6 days of training in the water maze hidden platform task and 8 days of extinction without the platform. Indices of immobility increased over trials of extinction, with the aged showing higher levels, earlier onsets and larger slope increases of immobility than the adults. A lower resistance-to-extinction was predictive of more "despair" in both age groups. Between-group differences in the open field, black/white box and elevated-plus maze indicated that the aged showed more anxiety-like behavior than the adults and/or explored these environments less. Within the aged group, indicators of fearfulness in the three tests were predictive of higher levels of "despair". The extinction-despair model is held to provide the promise of a conceptual and empirical model of human depression that is the consequence of withdrawal of reinforcement.

Purification, Characterization, and Optimum Conditions of Fermencin SD11, a Bacteriocin Produced by Human Orally Lactobacillus fermentum SD11.

PubMed

Wannun, Phirawat; Piwat, Supatcharin; Teanpaisan, Rawee

2016-06-01

Fermencin SD11, a bacteriocin produced by human orally Lactobacillus fermentum SD11, was purified, characterized, and optimized in conditions for bacterial growth and bacteriocin production. Fermencin SD11 was purified using three steps of ammonium sulfate precipitation, gel filtration chromatography, and reverse-phase high-performance liquid chromatography. The molecular weight was found to be 33,000 Da using SDS-PAGE and confirmed as 33,593.4 Da by liquid chromatography-mass spectrometry. Fermencin SD11 exhibited activity against a wide range of oral pathogens including cariogenic and periodontogenic pathogens and Candida. The active activity was stable between 60 - 80 °C in a pH range of 3.0 to 7.0. It was sensitive to proteolytic enzymes (proteinase K and trypsin), but it was not affected by α-amylase, catalase, lysozyme, and saliva. The optimum conditions for growth and bacteriocin production of L. fermentum SD11 were cultured at acidic with pH of 5.0-6.0 at 37 or 40 °C under aerobic or anaerobic conditions for 12 h. It is promising that L. fermentum SD11 and its bacteriocin may be an alternative approach for promoting oral health or prevention of oral diseases, e.g., dental caries and periodontitis, which would require further clinical trials.

Mechanically induced orientation of adult rat cardiac myocytes in vitro

NASA Technical Reports Server (NTRS)

Samuel, J.-L.; Vandenburgh, H. H.

1990-01-01

The present study describes the spatial orientation of a population of freshly isolated adult rat cardiac myocytes using a computerized mechanical cell stimulator device for tissue cultured cells. A continuous unidirectional stretch of the substratum at 60 to 400 microns/min for 120 to 30 min, respectively, during the cell attachment period in a serum-free medium was found to induce a significant threefold increase in the number of rod-shaped myocytes oriented parallel to the direction of movement. The myocytes orient less well with unidirectional substratum stretching after their adhesion to the substratum. Adult myocytes plated onto a substratum undergoing continuous 10-percent stretch-relaxation cycling show no significant change in the myocyte orientation or cytoskeletal organization. In addition to the type of mechanical activity, orientation of rod-shaped myocytes is dependent on the speed of the substratum, the final stretch amplitude, and the timing between initiation of substratum stretching and adhesion of myocytes to the substratum.

Cardiovascular and metabolic consequences of the association between chronic stress and high-fat diet in rats.

PubMed

Simas, Bruna B; Nunes, Everson A; Crestani, Carlos C; Speretta, Guilherme F

2018-05-01

Obesity and chronic stress are considered independent risk factors for the development of cardiovascular diseases and changes in autonomic system activity. However, the cardiovascular consequences induced by the association between high-fat diet (HFD) and chronic stress are not fully understood. We hypothesized that the association between HFD and exposure to a chronic variable stress (CVS) protocol for four weeks might exacerbate the cardiovascular and metabolic disturbances in rats when compared to these factors singly. To test this hypothesis, male Wistar rats were divided into four groups: control-standard chow diet (SD; n = 8); control-HFD (n = 8); CVS-SD (n = 8); and CVS-HFD (n = 8). The CVS consisted of repeated exposure of the rats to different inescapable and unpredictable stressors (restraint tress; damp sawdust, cold, swim stress and light cycle inversion). We evaluated cardiovascular function, autonomic activity, dietary intake, adiposity and metabolism. The HFD increased body weight, adiposity and blood glucose concentration (∼15%) in both control and CVS rats. The CVS-HFD rats showed decreased insulin sensitivity (25%) compared to CVS-SD rats. The control-HFD and CVS-HFD rats presented increased intrinsic heart rate (HR) values (∼8%). CVS increased cardiac sympathetic activity (∼65%) in both SD- and HFD-fed rats. The HFD increased basal HR (∼10%). Blood pressure and baroreflex analyzes showed no differences among the experimental groups. In conclusion, the present data indicate absence of interaction on autonomic imbalance evoked by either CVS or HFD. Additionally, HFD increased HR and evoked metabolic disruptions which are independent of stress exposure.

Partial sleep deprivation by environmental noise increases food intake and body weight in obesity resistant rats

PubMed Central

Mavanji, Vijayakumar; Teske, Jennifer A.; Billington, Charles J.; Kotz, Catherine M.

2012-01-01

Objective Sleep-restriction in humans increases risk for obesity, but previous rodent studies show weight loss following sleep deprivation, possibly due to stressful-methods used to prevent sleep. Obesity-resistant (OR) rats exhibit consolidated-sleep and resistance to weight-gain. We hypothesized that sleep disruption by a less-stressful method would increase body weight, and examined effect of partial sleep deprivation (PSD) on body weight in OR and Sprague-Dawley (SD) rats. Design and Methods OR and SD rats (n=12/group) were implanted with transmitters to record sleep/wake. After baseline recording, six SD and six OR rats underwent 8 h PSD during light-phase for 9 d. Sleep was reduced using recordings of random noise. Sleep/wake states were scored as wakefulness (W), slow-wave-sleep (SWS) and rapid-eye-movement-sleep (REMS). Total number of transitions between stages, SWS-delta-power, food intake and body weight were documented. Results Exposure to noise decreased SWS and REMS time, while increasing W time. Sleep-deprivation increased number of transitions between stages and SWS-delta-power. Further, PSD during the rest phase increased recovery-sleep during active phase. The PSD SD and OR rats had greater food intake and body weight compared to controls Conclusions PSD by less-stressful means increases body weight in rats. Also, PSD during rest phase increases active period sleep. PMID:23666828

Partial sleep deprivation by environmental noise increases food intake and body weight in obesity-resistant rats.

PubMed

Mavanji, Vijayakumar; Teske, Jennifer A; Billington, Charles J; Kotz, Catherine M

2013-07-01

Sleep restriction in humans increases risk for obesity, but previous rodent studies show weight loss following sleep deprivation, possibly due to stressful methods used to prevent sleep. Obesity-resistant (OR) rats exhibit consolidated-sleep and resistance to weight gain. It was hypothesized that sleep disruption by a less-stressful method would increase body weight, and the effect of partial sleep deprivation (PSD) on body weight in OR and Sprague-Dawley (SD) rats was examined. OR and SD rats (n = 12/group) were implanted with transmitters to record sleep/wake. After baseline recording, six SD and six OR rats underwent 8 h PSD during light phase for 9 days. Sleep was reduced using recordings of random noise. Sleep/wake states were scored as wakefulness (W), slow-wave-sleep (SWS), and rapid-eye-movement-sleep (REMS). Total number of transitions between stages, SWS-delta-power, food intake, and body weight were documented. Exposure to noise decreased SWS and REMS time, while increasing W time. Sleep-deprivation increased the number of transitions between stages and SWS-delta-power. Further, PSD during the rest phase increased recovery sleep during the active phase. The PSD SD and OR rats had greater food intake and body weight compared to controls PSD by less-stressful means increases body weight in rats. Also, PSD during the rest phase increases active period sleep. Copyright © 2012 The Obesity Society.

Intravenous gestational nicotine exposure results in increased motivation for sucrose reward in adult rat offspring.

PubMed

Lacy, Ryan T; Hord, Lauren L; Morgan, Amanda J; Harrod, Steven B

2012-08-01

Prenatal tobacco smoke exposure is associated with alterations in motivated behavior in offspring, such as increased consumption of highly palatable foods and abused drugs. Animal models show that gestational nicotine (GN) exposure mediates changes in responding for sucrose and drug reward. A novel, intermittent low-dose intravenous (IV) exposure model was used to administer nicotine (0.05 mg/kg/injection) or saline 3×/day to rats on gestational days 8-21. Two experiments investigated the effect of IV GN on (1) the habituation of spontaneous locomotor activity and on (2) sucrose reinforced responding in offspring. For the operant experiments, animals acquired fixed-ratio (FR-3) responding for sucrose, 26% (w/v), and were tested on varying concentrations (0, 3, 10, 30, and 56%; Latin-square) according to a FR-3, and then a progressive-ratio (PR) schedule. Male and female adult offspring were used. IV GN did not alter birth or growth weight, or the number of pups born. No between-group differences in habituation to spontaneous locomotor activity were observed. FR testing produced an inverted U-shaped response curve, and rats showed peak responding for 10% sucrose reinforcement. Neither gestation nor sex affected responding, suggesting equivalent sensitivity to varying sucrose concentrations. PR testing revealed that GN rats showed greater motivation for sucrose reinforcement relative to controls. A low-dose, IV GN exposure model resulted in increased motivation to respond for sucrose reinforcement in adult offspring. This suggests that using a low number of cigarettes throughout pregnancy will result in increased motivation for highly palatable foods in adult, and perhaps, adolescent offspring. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Quantitative evaluation of retinal degeneration in royal college of surgeons rats by contrast enhanced ultrahigh resolution optical coherence tomography

NASA Astrophysics Data System (ADS)

Syu, Jia-Pu; Su, Min-Jyun; Chen, Po-Wei; Ke, Chang-Chih; Chiou, Shih-Hwa; Kuo, Wen-Chuan

2018-02-01

This study presents a spectral domain optical coherence tomography (SD-OCT) using supercontinuum laser combined with a fundus photography for in vivo high-resolution imaging of retinal degeneration in Royal College of Surgeons (RCS-/- rat). These findings were compared with the Sprague-Dawley (SD) rats and the corresponding histology. Quantitative measurements show that changes in thickness were not significantly different between SD control and young RCS retinas (4 weeks). However, in old RCS rats (55 weeks), the thickness of photoreceptor layer decreased significantly as compared to young RCS rats (both 4 weeks and 5 weeks). After contrast enhancement method, this platform will be useful for the quantitative evaluation of the degree of retinal degeneration, treatment outcome after therapy, and drug screening development in the future.

Long-lasting effects of prenatal dietary choline availability on object recognition memory ability in adult rats.

PubMed

Moreno, Hayarelis C; de Brugada, Isabel; Carias, Diamela; Gallo, Milagros

2013-11-01

Choline is an essential nutrient required for early development. Previous studies have shown that prenatal choline availability influences adult memory abilities depending on the medial temporal lobe integrity. The relevance of prenatal choline availability on object recognition memory was assessed in adult Wistar rats. Three groups of pregnant Wistar rats were fed from E12 to E18 with choline-deficient (0 g/kg choline chloride), standard (1.1 g/kg choline chloride), or choline-supplemented (5 g/kg choline chloride) diets. The offspring was cross-fostered to rat dams fed a standard diet during pregnancy and tested at the age of 3 months in an object recognition memory task applying retention tests 24 and 48 hours after acquisition. Although no significant differences have been found in the performance of the three groups during the first retention test, the supplemented group exhibited improved memory compared with both the standard and the deficient group in the second retention test, 48 hours after acquisition. In addition, at the second retention test the deficient group did not differ from chance. Taken together, the results support the notion of a long-lasting beneficial effect of prenatal choline supplementation on object recognition memory which is evident when the rats reach adulthood. The results are discussed in terms of their relevance for improving the understanding of the cholinergic involvement in object recognition memory and the implications of the importance of maternal diet for lifelong cognitive abilities.

Prenatal ethanol exposure impairs temporal ordering behaviours in young adult rats.

PubMed

Patten, Anna R; Sawchuk, Scott; Wortman, Ryan C; Brocardo, Patricia S; Gil-Mohapel, Joana; Christie, Brian R

2016-02-15

Prenatal ethanol exposure (PNEE) causes significant deficits in functional (i.e., synaptic) plasticity in the dentate gyrus (DG) and cornu ammonis (CA) hippocampal sub-regions of young adult male rats. Previous research has shown that in the DG, these deficits are not apparent in age-matched PNEE females. This study aimed to expand these findings and determine if PNEE induces deficits in hippocampal-dependent behaviours in both male and female young adult rats (PND 60). The metric change behavioural test examines DG-dependent deficits by determining whether an animal can detect a metric change between two identical objects. The temporal order behavioural test is thought to rely in part on the CA sub-region of the hippocampus and determines whether an animal will spend more time exploring an object that it has not seen for a larger temporal window as compared to an object that it has seen more recently. Using the liquid diet model of FASD (where 6.6% (v/v) ethanol is provided through a liquid diet consumed ad libitum throughout the entire gestation), we found that PNEE causes a significant impairment in the temporal order task, while no deficits in the DG-dependent metric change task were observed. There were no significant differences between males and females for either task. These results indicate that behaviours relying partially on the CA-region may be more affected by PNEE than those that rely on the DG. Copyright © 2015 Elsevier B.V. All rights reserved.

Functional capacity and cryopreservation of fetal rat pancreas in streptozotocin-diabetes. [Effectiveness of transplantation of fetal pancreas for control of diabetes in adult rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, J.; Clark, W.; Molnar, I.G.

1976-01-01

The fetal rat pancreas has a marked capacity for growth and maturation in glucose responsivity after transplantation under the kidney capsules of adult rats. The optimal conditions for function of the organ are a 3-week period of growth in a normal rat before transfer to a diabetic animal. Under these conditions diabetes is completely reversed by one fetal pancreas, and glucose disappearance rate and plasma insulin response to glucose are normal. Shunting of the venous drainage into the liver from fetal pancreases placed beneath the kidney capsule results in a marked improvement in diabetes control, and this technique may provemore » useful in experimental or human applications. Cryopreservation of the fetal pancreas has been successfully accomplished and will serve as a useful adjuvant to this method of reversing experimental diabetes.« less

Nano-hydroxyapatite particles induce apoptosis on MC3T3-E1 cells and tissue cells in SD rats

NASA Astrophysics Data System (ADS)

Wang, Liting; Zhou, Gang; Liu, Haifeng; Niu, Xufeng; Han, Jingyun; Zheng, Lisha; Fan, Yubo

2012-04-01

While the advantages of nanomaterials are being increasingly recognized, their potential toxicity is drawing more and more attention and concern. In this study, we explore the toxicity mechanism of 20-30 nm rod-shaped hydroxyapatite (HA) nanoparticles in vitro and in vivo. The nanoparticles were prepared by precipitation and characterized by IR, XRD and TEM. Concentrations of 0 μg mL-1, 10 μg mL-1, 100 μg mL-1, 1 mg mL-1, and 10 mg mL-1 were applied to the MC3T3-E1 cells for viability (MTT-test). Based on the characteristic differences of the two methods of cell death, the morphological features of the MC3T3-E1 cell line co-cultured with nano-hydroxyapatite (n-HA) (10 mg mL-1) for 24 h were also observed by TEM. Furthermore, important serum biochemical markers and histopathological examinations were used to evaluate the potential toxicological effect of n-HA on the major organs of SD rats injected intraperitoneally with n-HA (33.3 mg kg-1 body weight). In the results, we found cell growth inhibition and apoptosis in MC3T3-E1 cells co-cultured with n-HA. Moreover, apoptosis but not necrosis was illustrated in liver and renal tissue by using histopathology slices and serum biochemical markers. It suggests that apoptosis may be the possible mechanism of n-HA toxicity and provides a better understanding of the biocompatibility of nanomaterials applied in human bone repair.

Site- and compartment-specific changes in bone with hindlimb unloading in mature adult rats

NASA Technical Reports Server (NTRS)

Bloomfield, S. A.; Allen, M. R.; Hogan, H. A.; Delp, M. D.

2002-01-01

The purpose of this study was to examine site- and compartment-specific changes in bone induced by hindlimb unloading (HU) in the mature adult male rat (6 months old). Tibiae, femora, and humeri were removed after 14, 21, and 28 days of HU for determination of bone mineral density (BMD) and geometry by peripheral quantitative computed tomography (pQCT), mechanical properties, and bone formation rate (BFR), and compared with baseline (0 day) and aging (28 day) controls. HU resulted in 20%-21% declines in cancellous BMD at the proximal tibia and femoral neck after 28 day HU vs. 0 day controls (CON). Cortical shell BMD at these sites was greater (by 4%-6%) in both 28 day HU and 28 day CON vs. 0 day CON animals, and nearly identical to that gain seen in the weight-bearing humerus. Mechanical properties at the proximal tibia exhibited a nonsignificant decline after HU vs. those of 0 day CON rats. At the femoral neck, a 10% decrement was noted in ultimate load in 28 day HU rats vs. 28 day CON animals. Middiaphyseal tibial bone increased slightly in density and area during HU; no differences in structural and material properties between 28 day HU and 28 day CON rats were noted. BFR at the tibial midshaft was significantly lower (by 90%) after 21 day HU vs. 0 day CON; this decline was maintained throughout 28 day HU. These results suggest there are compartment-specific differences in the mature adult skeletal response to hindlimb unloading, and that the major impact over 28 days of unloading is on cancellous bone sites. Given the sharp decline in BFR for midshaft cortical bone, it appears likely that deficits in BMD, area, or mechanical properties would develop with longer duration unloading.

Enduring deficits in contextual and auditory fear conditioning after adolescent, not adult, social instability stress in male rats.

PubMed

Morrissey, Mark D; Mathews, Iva Z; McCormick, Cheryl M

2011-01-01

Adolescence is a time of developmental changes and reorganization in the brain and stress systems, thus, adolescents may be more vulnerable than adults to the effects of chronic mild stressors. Most studies, however, have not directly compared stress experienced in adolescence to the same stress experience in adulthood. In the present study, adolescent (n=46) and adult (n=48) male rats underwent 16 days of social instability stress (daily 1h isolation and change of cage partners) or were non-stress controls. Rats were then tested on the strength of acquired contextual and cued fear conditioning, as well as extinction learning, beginning either the day after the stress procedure or 3 weeks later. No difference was found among the groups during the Training Phase of conditioning. Irrespective of the time between the social stress experience and fear conditioning, rats stressed in adolescence had decreased context and cue memory, and cue generalization compared to control rats, as measured by the percentage of time spent freezing in tests. Social instability stress in adulthood had no effect on any measure of fear conditioning. The results support the hypothesis that adolescence is a time of heightened vulnerability to stressors. Copyright © 2010 Elsevier Inc. All rights reserved.

Molecular weight dependent glucose lowering effect of low molecular weight Chitosan Oligosaccharide (GO2KA1) on postprandial blood glucose level in SD rats model.

PubMed

Jo, Sung-Hoon; Ha, Kyoung-Soo; Moon, Kyoung-Sik; Kim, Jong-Gwan; Oh, Chen-Gum; Kim, Young-Cheul; Apostolidis, Emmanouil; Kwon, Young-In

2013-07-09

This research investigated the effect of enzymatically digested low molecular weight (MW) chitosan oligosaccharide on type 2 diabetes prevention. Three different chitosan oligosaccharide samples with varying MW were evaluated in vitro for inhibition of rat small intestinal α-glucosidase and porcine pancreatic α-amylase (GO2KA1; <1000 Da, GO2KA2; 1000-10,000 Da, GO2KA3; MW > 10,000 Da). The in vitro results showed that all tested samples had similar rat α-glucosidase inhibitory and porcine α-amylase inhibitory activity. Based on these observations, we decided to further investigate the effect of all three samples at a dose of 0.1 g/kg, on reducing postprandial blood glucose levels in Sprague-Dawley (SD) rat model after sucrose loading test. In the animal trial, all tested samples had postprandial blood glucose reduction effect, when compared to control, however GO2KA1 supplementation had the strongest effect. The glucose peak (Cmax) for GO2KA1 and control was 152 mg/dL and 193 mg/dL, respectively. The area under the blood glucose-time curve (AUC) for GO2KA1 and control was 262 h mg/dL and 305 h mg/dL, respectively. Furthermore, the time of peak plasma concentration of blood glucose (Tmax) for GO2KA1 was significantly delayed (0.9 h) compared to control (0.5 h). These results suggest that GO2KA1 could have a beneficial effect for blood glucose management relevant to diabetes prevention in normal and pre-diabetic individuals. The suggested mechanism of action is via inhibition of the carbohydrate hydrolysis enzyme α-glucosidase and since GO2KA1 (MW < 1000 Da) had higher in vivo effect, we hypothesize that it is more readily absorbed and might exert further biological effect once it is absorbed in the blood stream, relevant to blood glucose management.

Toxicity assessment of molindone hydrochloride, a dopamine D2/D5 receptor antagonist in juvenile and adult rats.

PubMed

Krishna, Gopala; Gopalakrishnan, Gopa; Goel, Saryu

2017-06-01

Neuroleptic drug molindone hydrochloride is a dopamine D2/D5 receptor antagonist and it is in late stage development for the treatment of impulsive aggression in children and adolescents who have attention deficient/hyperactivity disorder (ADHD). This new indication for this drug would expand the target population to include younger patients, and therefore, toxicity assessments in juvenile animals were undertaken in order to determine susceptibility differences, if any, between this age group and the adult rats. Adult rats were administered molindone by oral gavage for 13 weeks at dose levels of 0, 5, 20, or 60 mg/kg-bw/day. Juvenile rats were dosed for 8 weeks by oral gavage at dose levels of 0, 5, 25, 50, or 75 mg/kg-bw/day. Standard toxicological assessments were made using relevant study designs in consultation with FDA. Treatment-related elevation in serum cholesterol and triglycerides and decreases in glucose levels were observed in both the age groups. Organ weight changes included increases in liver, adrenal gland and seminal vesicles/prostate weights. Decreases in uterine weights were also observed in adult females exposed to the top two doses with sufficient exposure. In juveniles, sexual maturity parameters secondary to decreased body weights were observed, but, were reversed. In conclusion, the adverse effects noted in reproductive tissues of adults were attributed to hyperprolactinemia and these changes were not considered to be relevant to humans due to species differences in hormonal regulation of reproduction. On the whole, there were no remarkable differences in the toxicity profile of the drug between the two age groups.

Peri-pubertal high caffeine exposure increases ovarian estradiol production in immature rats.

PubMed

Kwak, Yoojin; Choi, Hyeonhae; Bae, Jaeman; Choi, Yun-Young; Roh, Jaesook

2017-04-01

Chronic caffeine consumption exerts a negligible effect on the reproductive organs of normal adult females, but it is not known whether this is also true for children and adolescents. Here, we investigated the effects of high caffeine exposure on sexual maturation and ovarian estradiol production in immature female rats. Immature female SD rats were divided into controls and caffeine groups fed 120 and 180mg/kg/day for 4 or 8 weeks. There was a significant delay in vaginal opening in the caffeine-fed groups. In addition, serum estradiol levels were elevated in the caffeine-fed animals after 2 and 4 weeks of exposure. Estradiol secretion as well as aromatase expression also increased significantly in the ovarian cells in response to caffeine. These results demonstrate that peripubertal exposure to high caffeine increases estradiol production in the ovary; this may disturb the coordinated regulation of the hypothalamo-pituitary-ovarian axis, thereby interfering with sexual maturation. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-term Characterization of Retinal Degeneration in Royal College of Surgeons Rats Using Spectral-Domain Optical Coherence Tomography

PubMed Central

Ryals, Renee C.; Andrews, Michael D.; Datta, Shreya; Coyner, Aaron S.; Fischer, Cody M.; Wen, Yuquan; Pennesi, Mark E.; McGill, Trevor J.

2017-01-01

Purpose Prospective treatments for age-related macular degeneration and inherited retinal degenerations are commonly evaluated in the Royal College of Surgeons (RCS) rat before translation into clinical application. Historically, retinal thickness obtained through postmortem anatomic assessments has been a key outcome measure; however, utility of this measurement is limited because it precludes the ability to perform longitudinal studies. To overcome this limitation, the present study was designed to provide a baseline longitudinal quantification of retinal thickness in the RCS rat by using spectral-domain optical coherence tomography (SD-OCT). Methods Horizontal and vertical linear SD-OCT scans centered on the optic nerve were captured from Long-Evans control rats at P30, P60, P90 and from RCS rats between P17 and P90. Total retina (TR), outer nuclear layer+ (ONL+), inner nuclear layer (INL), and retinal pigment epithelium (RPE) thicknesses were quantified. Histologic sections of RCS retina obtained from P21 to P60 were compared to SD-OCT images. Results In RCS rats, TR and ONL+ thickness decreased significantly as compared to Long-Evans controls. Changes in INL and RPE thickness were not significantly different between control and RCS retinas. From P30 to P90 a subretinal hyperreflective layer (HRL) was observed and quantified in RCS rats. After correlation with histology, the HRL was identified as disorganized outer segments and the location of accumulated debris. Conclusions Retinal layer thickness can be quantified longitudinally throughout the course of retinal degeneration in the RCS rat by using SD-OCT. Thickness measurements obtained with SD-OCT were consistent with previous anatomic thickness assessments. This study provides baseline data for future longitudinal assessment of therapeutic agents in the RCS rat. PMID:28253400

Anti-dopamine beta-hydroxylase immunotoxin-induced sympathectomy in adult rats

NASA Technical Reports Server (NTRS)

Picklo, M. J.; Wiley, R. G.; Lonce, S.; Lappi, D. A.; Robertson, D.

1995-01-01

Anti-dopamine beta-hydroxylase immunotoxin (DHIT) is an antibody-targeted noradrenergic lesioning tool comprised of a monoclonal antibody against the noradrenergic enzyme, dopamine beta-hydroxylase, conjugated to saporin, a ribosome-inactivating protein. Noradrenergic-neuron specificity and completeness and functionality of sympathectomy were assessed. Adult, male Sprague-Dawley rats were given 28.5, 85.7, 142 or 285 micrograms/kg DHIT i.v. Three days after injection, a 6% to 73% decrease in the neurons was found in the superior cervical ganglia of the animals. No loss of sensory, nodose and dorsal root ganglia, neurons was observed at the highest dose of DHIT. In contrast, the immunotoxin, 192-saporin (142 micrograms/kg), lesioned all three ganglia. To assess the sympathectomy, 2 wk after treatment (285 micrograms/kg), rats were anesthetized with urethane (1 g/kg) and cannulated in the femoral artery and vein. DHIT-treated animals' basal systolic blood pressure and heart rate were significantly lower than controls. Basal plasma norepinephrine levels were 41% lower in DHIT-treated animals than controls. Tyramine-stimulated release of norepinephrine in DHIT-treated rats was 27% of controls. Plasma epinephrine levels of DHIT animals were not reduced. DHIT-treated animals exhibited a 2-fold hypersensitivity to the alpha-adrenergic agonist phenylephrine. We conclude that DHIT selectively delivered saporin to noradrenergic neurons resulting in destruction of these neurons. Anti-dopamine beta-hydroxylase immunotoxin administration produces a rapid, irreversible sympathectomy.

Lipoic acid attenuates Aroclor 1260-induced hepatotoxicity in adult rats.

PubMed

Aly, Hamdy A A; Mansour, Ahmed M; Hassan, Memy H; Abd-Ellah, Mohamed F

2016-08-01

The present study was aimed to investigate the mechanistic aspect of Aroclor 1260-induced hepatotoxicity and its protection by lipoic acid. The adult male Albino rats were divided into six groups. Group I served as control. Group II received lipoic acid (35 mg/kg/day). Aroclor 1260 was given to rats by oral gavage at doses 20, 40, or 60 mg/kg/day (Groups III, IV, and V, respectively). Group VI was pretreated with lipoic acid (35 mg/kg/day) 24 h before Aroclor 1260 (40 mg/kg/day). Treatment in all groups was continued for further 15 consecutive days. Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities and total bilirubin, total cholesterol, and triglycerides were significantly increased while total protein, total albumin, and high-density lipoprotein were significantly decreased. Hydrogen peroxide production and lipid peroxidation were significantly increased while superoxide dismutase and catalase activities and reduced glutathione (GSH) content was significantly decreased in liver. Caspase-3 & -9 activities were significantly increased in liver. Lipoic acid pretreatment significantly reverted all these abnormalities toward their normal levels. In conclusion, Aroclor 1260 induced liver dysfunction, at least in part, by induction of oxidative stress. Apoptotic effect of hepatic cells is involved in Aroclor 1260-induced liver injury. Lipoic acid could protect rats against Aroclor 1260-induced hepatotoxicity. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 913-922, 2016. © 2014 Wiley Periodicals, Inc.

Gestational Protein Restriction Increases Cardiac Connexin 43 mRNA levels in male adult rat offspring

PubMed Central

Rossini, Kamila Fernanda; de Oliveira, Camila Andrea; Rebelato, Hércules Jonas; Esquisatto, Marcelo Augusto Marreto; Catisti, Rosana

2017-01-01

Background The dietary limitation during pregnancy influences the growth and development of the fetus and offspring and their health into adult life. The mechanisms underlying the adverse effects of gestational protein restriction (GPR) in the development of the offspring hearts are not well understood. Objectives The aim of this study was to evaluate the effects of GPR on cardiac structure in male rat offspring at day 60 after birth (d60). Methods Pregnant Wistar rats were fed a normal-protein (NP, 17% casein) or low-protein (LP, 6% casein) diet. Blood pressure (BP) values from 60-day-old male offspring were measured by an indirect tail-cuff method using an electro sphygmomanometer. Hearts (d60) were collected for assessment of connexin 43 (Cx43) mRNA expression and morphological and morphometric analysis. Results LP offspring showed no difference in body weight, although they were born lighter than NP offspring. BP levels were significantly higher in the LP group. We observed a significant increase in the area occupied by collagen fibers, a decrease in the number of cardiomyocytes by 104 µm2, and an increase in cardiomyocyte area associated with an increased Cx43 expression. Conclusion GPR changes myocardial levels of Cx43 mRNA in male young adult rats, suggesting that this mechanism aims to compensate the fibrotic process by the accumulation of collagen fibers in the heart interstitium. PMID:28678925

Protective effect of DA-9401 in finasteride-induced apoptosis in rat testis: inositol requiring kinase 1 and c-Jun N-terminal kinase pathway.

PubMed

Soni, Kiran Kumar; Shin, Yu Seob; Choi, Bo Ram; Karna, Keshab Kumar; Kim, Hye Kyung; Lee, Sung Won; Kim, Chul Young; Park, Jong Kwan

2017-01-01

Finasteride is used to treat male pattern baldness and benign prostatic hyperplasia. This study investigated the toxicity of finasteride and recovery by DA-9401 using Sprague Dawley (SD) rats. Forty adult male SD rats were assigned to four groups: control (CTR), finasteride 1 mg/kg/day (F), finasteride 1 mg/kg + DA-9401 100 mg/kg/day (F + DA 100) and finasteride 1 mg/kg + DA-9401 200 mg/kg/day (F + DA 200). Treatments were by oral delivery once daily for 90 consecutive days. The gross anatomical parameters assessed included: genital organ weight; vas deferens sperm count and sperm motility; testosterone, dihydrotestosterone (DHT) and malondialdehyde levels; and histological and terminal deoxynucleotidyl transferase enzyme mediated dUTP nick-end labeling (TUNEL) staining of testis for spermatogenic cell density, Johnsen's score and apoptosis. Testicular tissue was also used for evaluating endoplasmic reticulum (ER) stress and apoptotic proteins. Epididymis weight, seminal vesicle weight, prostate weight, penile weight and vas deferens sperm motility showed significant differences between the F group and the CTR, F + DA 100 and F + DA 200 groups. There was no significant change in the testosterone level. DHT level decreased significantly in the F group compared with the CTR group. Testis tissue revealed significant changes in spermatogenic cell density, Johnsen's score and apoptotic index. Western blot showed significant changes in the ER stress and apoptotic markers. Finasteride resulted in reduced fertility and increased ER stress and apoptotic markers, which were recovered by administration of DA-9401 in the SD rats.

Role of inducible nitric oxide synthase in myocardial ischemia-reperfusion injury in sleep-deprived rats.

PubMed

Jeddi, Sajad; Ghasemi, Asghar; Asgari, Alireza; Nezami-Asl, Amir

2018-05-01

REM sleep deprivation (SD) decreases tolerance of the rat heart to ischemia-reperfusion (IR) injury; the underlying mechanisms, however, are unknown. This study aimed at determining whether changes in iNOS, Bax, and Bcl-2 gene expression are involved in this detrimental effect. SD was induced by flowerpot technique for a period of 4 days. This method is simple and able to induce sleep fragmentation which occurs as one of the sleep disorder symptoms in clinical conditions. The hearts of control and SD rats were perfused in Langendorff apparatus and subjected to 30 min ischemia, followed by 90 min reperfusion. The hemodynamic parameters (left ventricular developed pressure (LVDP), and ± dp/dt), NOx (nitrite + nitrate) level, infarct size, and mRNA expression of iNOS, Bax, and Bcl-2 were measured after IR. SD rats had lower recovery of post-ischemic LVDP (32.8 ± 2.5 vs. 51.5 ± 2.1 mmHg; P < 0.05), + dp/dt (1555 ± 66 vs. 1119.5 ± 87 mmHg/s; P < 0.05) and - dp/dt (1437 ± 65 vs. 888 ± 162 mmHg/s; P < 0.05). SD rats also had higher NOx levels (41.4 ± 3.1 vs. 22.4 ± 3.6 μmol/L; P < 0.05) and infarct size (64.3 ± 2.3 vs. 38.3 ± 1.6%; P < 0.05) after IR, which along with LVDP, ± dp/dt restored to near normal status in the presence of aminoguanidine, a selective iNOS inhibitor. Following IR, expression of iNOS and Bax increased and Bcl-2 decreased (502, 372, and 54%, respectively) in SD rats; whereas in the presence of aminoguanidine, expression of iNOS and Bax significantly decreased and Bcl-2 increased (165, 168, and 19%, respectively). Higher expression of iNOS and subsequent increase in apoptosis in the hearts after IR may contribute to less tolerance to myocardial IR injury in SD rats.

Development of a highly sensitive and specific ELISA method for the determination of l-corydalmine in SD rats with monoclonal antibody.

PubMed

Zhang, Hongwei; Gao, Lan; Shu, Menglin; Liu, Jihua; Yu, Boyang

2018-01-15

l-Corydalmine (l-CDL) is a potent analgesic constituent of the traditional Chinese medicine, Rhizoma Corydalis. However, the pharmacokinetic process and tissue distribution of l-CDL in vivo are still unknown. Therefore, it is necessary to establish a simple and sensitive method to detect l-CDL, which will be helpful to study its distribution and pharmacokinetic process. To determine this compound in biological samples, a monoclonal antibody (mAb) against l-CDL was produced and a fast and highly sensitive indirect competitive enzyme-linked immunosorbent assay (icELISA) was developed in this study. The icELISA was applied to determine l-CDL in biological samples. The limit of detection (LOD) of the method was 0.015 ng/mL with a liner range of 1-1000 ng/mL (R 2  = 0.9912). The intra- and inter-day precision were below 15% and the recoveries were within 80-117%. Finally, the developed immunoassay was successfully applied to the analysis of the distribution of l-CDL in SD rats. In conclusion, the icELISA based on the anti-l-CDL mAb could be considered as a highly sensitive and rapid method for the determination of l-CDL in biological samples. The ELISA approach may provide a valuable tool for the analysis of small molecules in biological samples. Copyright © 2017. Published by Elsevier B.V.

Adolescent cocaine exposure enhances goal-tracking behavior and impairs hippocampal cell genesis selectively in adult bred low-responder rats

PubMed Central

García-Fuster, M. Julia; Parsegian, Aram; Watson, Stanley J.; Akil, Huda; Flagel, Shelly B.

2018-01-01

Rationale Environmental challenges during adolescence, such as drug exposure, can cause enduring behavioral and molecular changes that contribute to life-long maladaptive behaviors, including addiction. Selectively bred high-responder (bHR) and low-responder (bLR) rats represent a unique model for assessing the long-term impact of adolescent environmental manipulations, as they inherently differ on a number of addiction-related traits. bHR rats are considered “addiction-prone”, whereas bLR rats are “addiction-resilient”, at least under baseline conditions. Moreover, relative to bLRs, bHR rats are more likely to attribute incentive motivational value to reward cues, or to “sign-track”. Objectives We utilized bHR and bLR rats to determine whether adolescent cocaine exposure can alter their inborn behavioral and neurobiological profiles, with a specific focus on Pavlovian conditioned approach behavior (i.e. sign- vs. goal-tracking) and hippocampal neurogenesis. Methods bHR and bLR rats were administered cocaine (15 mg/kg) or saline for 7 days during adolescence (postnatal day, PND 33–39) and subsequently tested for Pavlovian conditioned approach behavior in adulthood (PND 62–75), wherein an illuminated lever (conditioned stimulus) was followed by the response-independent delivery of a food pellet (unconditioned stimulus). Behaviors directed towards the lever and the food cup were recorded as sign- and goal-tracking, respectively. Hippocampal cell genesis was evaluated on PND 77 by immunohistochemistry. Results Adolescent cocaine exposure impaired hippocampal cell genesis (proliferation and survival) and enhanced the inherent propensity to goal-track in adult bLR, but not bHR, rats. Conclusions Adolescent cocaine exposure elicits long-lasting changes in stimulus-reward learning and enduring deficits in hippocampal neurogenesis selectively in adult bLR rats. PMID:28210781

User's Manual for Space Debris Surfaces (SD_SURF)

NASA Technical Reports Server (NTRS)

Elfer, N. C.

1996-01-01

A unique collection of computer codes, Space Debris Surfaces (SD_SURF), have been developed to assist in the design and analysis of space debris protection systems. SD_SURF calculates and summarizes a vehicle's vulnerability to space debris as a function of impact velocity and obliquity. An SD_SURF analysis will show which velocities and obliquities are the most probable to cause a penetration. This determination can help the analyst select a shield design which is best suited to the predominant penetration mechanism. The analysis also indicates the most suitable parameters for development or verification testing. The SD_SURF programs offer the option of either FORTRAN programs and Microsoft EXCEL spreadsheets and macros. The FORTRAN programs work with BUMPERII version 1.2a or 1.3 (Cosmic released). The EXCEL spreadsheets and macros can be used independently or with selected output from the SD_SURF FORTRAN programs.

Effect of Ruta graveolens and Cannabis sativa alcoholic extract on spermatogenesis in the adult wistar male rats.

PubMed

Sailani, M R; Moeini, H

2007-07-01

The present study was undertaken to evaluate the effects of alcohol extracts of Ruta graveolens and Cannabis sativa that were used traditionally in medieval Persian medicine as male contraceptive drugs, on spermatogenesis in the adult male rats. Ethanol extracts of these plants were obtained by the maceration method. The male rats were injected intraperitionaly with C. sativa and R. graveolens 5% ethanol extracts at dose of 20 mg/day for 20 consecutive days, respectively. Twenty-four hours after the last treatment, testicular function was assessed by epididymal sperm count. The statistical results showed that the ethanol extracts of these plants reduced the number of sperms significantly (P=0.00) in the treatment groups in comparison to the control group. The results also showed that the group, treated by extract of R. graveolens reduced spermatogenesis more than the group treated by extracts of C. sativa. The present study demonstrated the spermatogenesis reducing properties of the ethanol extracts of R. graveolens and C. sativa in the adult male wistar rats but more studies are necessary to reveal the mechanism of action that is involved in spermatogenesis.

Endogenous stem cell proliferation induced by intravenous hedgehog agonist administration after contusion in the adult rat spinal cord.

PubMed

Bambakidis, Nicholas C; Horn, Eric M; Nakaji, Peter; Theodore, Nicholas; Bless, Elizabeth; Dellovade, Tammy; Ma, Chiyuan; Wang, Xukui; Preul, Mark C; Coons, Stephen W; Spetzler, Robert F; Sonntag, Volker K H

2009-02-01

Sonic hedgehog (Shh) is a glycoprotein molecule that upregulates the transcription factor Gli1. The Shh protein plays a critical role in the proliferation of endogenous neural precursor cells when directly injected into the spinal cord after a spinal cord injury in adult rodents. Small-molecule agonists of the hedgehog (Hh) pathway were used in an attempt to reproduce these findings through intravenous administration. The expression of Gli1 was measured in rat spinal cord after the intravenous administration of an Hh agonist. Ten adult rats received a moderate contusion and were treated with either an Hh agonist (10 mg/kg, intravenously) or vehicle (5 rodents per group) 1 hour and 4 days after injury. The rats were killed 5 days postinjury. Tissue samples were immediately placed in fixative. Samples were immunohistochemically stained for neural precursor cells, and these cells were counted. Systemic dosing with an Hh agonist significantly upregulated Gli1 expression in the spinal cord (p < 0.005). After spinal contusion, animals treated with the Hh agonist had significantly more nestin-positive neural precursor cells around the rim of the lesion cavity than in vehicle-treated controls (means +/- SDs, 46.9 +/- 12.9 vs 20.9 +/- 8.3 cells/hpf, respectively, p < 0.005). There was no significant difference in the area of white matter injury between the groups. An intravenous Hh agonist at doses that upregulate spinal cord Gli1 transcription also increases the population of neural precursor cells after spinal cord injury in adult rats. These data support previous findings based on injections of Shh protein directly into the spinal cord.

SD DOT Customer Survey

DOT National Transportation Integrated Search

1997-06-30

Following a series of qualitative interviews with South Dakota Department of Transportation (SD DOT) as well as consumers during the week of March 24, 1997, a telephone survey of 800 interviews was conducted between April 17 and May 8, 1997 among two...

Transient gestational and neonatal hypothyroidism-induced specific changes in androgen receptor expression in skeletal and cardiac muscles of adult rat.

PubMed

Annapoorna, K; Anbalagan, J; Neelamohan, R; Vengatesh, G; Stanley, J; Amudha, G; Aruldhas, M M

2013-03-01

The present study aims to identify the association between androgen status and metabolic activity in skeletal and cardiac muscles of adult rats with transient gestational/neonatal-onset hypothyroidism. Pregnant and lactating rats were made hypothyroid by exposing to 0.05% methimazole in drinking water; gestational exposure was from embryonic day 9-14 (group II) or 21 (group III), lactational exposure was from postnatal day 1-14 (group IV) or 29 (group V). Serum was collected for hormone assay. Androgen receptor status, Glu-4 expression, and enzyme activities were assessed in the skeletal and cardiac muscles. Serum testosterone and estradiol levels decreased in adult rats of groups II and III, whereas testosterone remained normal but estradiol increased in group IV and V, when compared to coeval control. Androgen receptor ligand binding activity increased in both muscle phenotypes with a consistent increase in the expression level of its mRNA and protein expressions except in the forelimb of adult rats with transient hypothyroidism (group II-V). Glut-4 expression remained normal in skeletal and cardiac muscle of experimental rats. Specific activity of hexokinase and lactate dehydrogenase increased in both muscle phenotypes whereas, creatine kinase activity increased in skeletal muscles alone. It is concluded that transient gestational/lactational exposure to methimazole results in hypothyroidism during prepuberal life whereas it increases AR status and glycolytic activity in skeletal and cardiac muscles even at adulthood. Thus, the present study suggests that euthyroid status during prenatal and early postnatal life is essential to have optimal AR status and metabolic activity at adulthood. © Georg Thieme Verlag KG Stuttgart · New York.

Effect of Sleep Deprivation on the Male Reproductive System in Rats.

PubMed

Choi, Ji Ho; Lee, Seung Hoon; Bae, Jae Hyun; Shim, Ji Sung; Park, Hong Seok; Kim, Young Sik; Shin, Chol

2016-10-01

There has been no study reporting on the influence of sleep deprivation on the male reproductive system including sperm quality. In this study, we hypothesized that sleep deprivation could lead to adverse effect on the male reproductive system. The rats were divided into three groups: 1) control (home-cage, n = 10); 2) SD4 (sleep deprivation for 4 days, n = 10); and 3) SD7 (sleep deprivation for 7 days, n = 10). Sleep deprivation was performed by a modified multiple platform method. Sperm quality (sperm motion parameters and counts), hormone levels (corticosterone and testosterone), and the histopathology of testis were evaluated and compared between the three groups. A statistically significant reduction (P = 0.018) was observed in sperm motility in the SD7 group compared to those of the control group. However, there were no significant differences in other sperm motion parameters, or in sperm counts of the testis and cauda epididymis between three groups. Compared with the control group, the SD4 (P = 0.033) and SD7 (P = 0.002) groups exhibited significant increases of corticosterone levels, but significant decreases of testosterone levels were found in the SD4 (P = 0.001) and SD7 (P < 0.001) groups. Seminiferous tubular atrophy and/or spermatid retention was partially observed in the SD4 and SD7 groups, compared with the normal histopathology of the control group. Sleep deprivation may have an adverse effect on the male reproductive system in rats.

A comparison of the ability of a 4:1 ketogenic diet and a 6.3:1 ketogenic diet to elevate seizure thresholds in adult and young rats.

PubMed

Nylen, Kirk; Likhodii, Sergei; Abdelmalik, Peter A; Clarke, Jasper; Burnham, W McIntyre

2005-08-01

The pentylenetetrazol (PTZ) infusion test was used to compare seizure thresholds in adult and young rats fed either a 4:1 ketogenic diet (KD) or a 6.3:1 KD. We hypothesized that both KDs would significantly elevate seizure thresholds and that the 4:1 KD would serve as a better model of the KD used clinically. Ninety adult rats and 75 young rats were placed on one of five experimental diets: (a) a 4:1 KD, (b) a control diet balanced to the 4:1 KD, (c) a 6.3:1 KD, (d) a standard control diet, or (e) an ad libitum standard control diet. All subjects were seizure tested by using the PTZ infusion test. Blood glucose and beta-hydroxybutyrate (beta-OHB) levels were measured. Neither KD elevated absolute "latencies to seizure" in young or adult rats. Similarly, neither KD elevated "threshold doses" in adult rats. In young rats, the 6.3:1 KD, but not the 4:1 KD, significantly elevated threshold doses. The 6.3:1 KD group showed poorer weight gain than the 4:1 KD group when compared with respective controls. The most dramatic discrepancies were seen in young rats. "Threshold doses" and "latency to seizure" data provided conflicting measures of seizure threshold. This was likely due to the inflation of threshold doses calculated by using the much smaller body weights found in the 6.3:1 KD group. Ultimately, the PTZ infusion test in rats may not be a good preparation to model the anticonvulsant effects of the KD seen clinically, especially when dietary treatments lead to significantly mismatched body weights between the groups.

Ascorbic acid and sodium benzoate synergistically aggravates testicular dysfunction in adult Wistar rats.

PubMed

Kehinde, Olaniyi S; Christianah, Oyewopo I; Oyetunji, Oyewopo A

2018-01-01

The effect of the concomitant use of sodium benzoate (NaB) and ascorbic acid on human health remains controversial. Therefore, the current study is designed to investigate the effect of NaB and ascorbic acid on the testicular function of adult Wistar rats. Adult Wistar rats were randomly allotted into Control (vehicle; received 1 ml of distilled water), NaB-treated (SB-treated; received 100 mg/kg body weight; b.w ), ascorbic acid-treated (AA-treated; received 150 mg/kg b.w ) and NaB+ ascorbic acid-treated (SB+AA-treated) groups. The treatment lasted for 28 days and the administration was given orally. The body weight change was monitored. Semen analysis, biochemical assay and histological examination were performed. Treatment with NaB significantly altered the cytoarchitecture of testicular tissue, sperm quality, testicular endocrine function and oxidative stress status without any alteration in body weight gain compared to control. In addition, treatment with NaB+ ascorbic acid exacerbated testicular tissue disruption, impaired sperm quality and testicular endocrine impairment with significant reduction in oxidative stress and unaltered body weight gain when compared with NaB-treated group. This study suggests that ascorbic acid and NaB synergistically aggravates testicular dysfunction. This is independent of oxidative stress status.

Respiratory pattern in awake rats: effects of motor activity and of alerting stimuli.

PubMed

Kabir, Muammar M; Beig, Mirza I; Baumert, Mathias; Trombini, Mimosa; Mastorci, Francesca; Sgoifo, Andrea; Walker, Frederick R; Day, Trevor A; Nalivaiko, Eugene

2010-08-04

Our aim was to assess the impact of motor activity and of arousing stimuli on respiratory rate in the awake rats. The study was performed in male adult Sprague-Dawley (SD, n=5) and Hooded Wistar (HW, n=5) rats instrumented for ECG telemetry. Respiratory rate was recorded using whole-body plethysmograph, with a piezoelectric sensor attached for the simultaneous assessment of motor activity. All motor activity was found to be associated with an immediate increase in respiratory rate that remained elevated for the whole duration of movement; this was reflected by: i) bimodal distribution of respiratory intervals (modes for slow peak: 336+/-19 and 532+/-80 ms for HW and SD, p<0.05; modes for fast peak 128+/-6 and 132+/-7 ms for HW and SD, NS); and ii) a tight correlation between total movement time and total time of tachypnoea, with an R(2) ranging 0.96-0.99 (n=10, p<0001). The extent of motor-related tachypnoea was significantly correlated with the intensity of associated movement. Mild alerting stimuli produced stereotyped tachypnoeic responses, without affecting heart rate: tapping the chamber raised respiratory rate from 117+/-7 to 430+/-15 cpm; sudden side move--from 134+/-13 to 487+/-16 cpm, and turning on lights--from 136+/-12 to 507+/-14 cpm (n=10; p<0.01 for all; no inter-strain differences). We conclude that: i) sniffing is an integral part of the generalized arousal response and does not depend on the modality of sensory stimuli; ii) tachypnoea is a sensitive index of arousal; and iii) respiratory rate is tightly correlated with motor activity. Copyright 2010 Elsevier Inc. All rights reserved.

Protein Restriction During the Last Third of Pregnancy Malprograms the Neuroendocrine Axes to Induce Metabolic Syndrome in Adult Male Rat Offspring

PubMed Central

Gomes, Rodrigo Mello; Miranda, Rosiane Aparecida; Barella, Luiz Felipe; Malta, Ananda; Martins, Isabela Peixoto; Franco, Claudinéia Conationi da Silva; Pavanello, Audrei; Torrezan, Rosana; Natali, Maria Raquel Marçal; Lisboa, Patrícia Cristina; de Moura, Egberto Gaspar

2016-01-01

Metabolic malprogramming has been associated with low birth weight; however, the interplay between insulin secretion disruption and adrenal function upon lipid metabolism is unclear in adult offspring from protein-malnourished mothers during the last third of gestation. Thus, we aimed to study the effects of a maternal low-protein diet during the last third of pregnancy on adult offspring metabolism, including pancreatic islet function and morphophysiological aspects of the liver, adrenal gland, white adipose tissue, and pancreas. Virgin female Wistar rats (age 70 d) were mated and fed a protein-restricted diet (4%, intrauterine protein restricted [IUPR]) from day 14 of pregnancy until delivery, whereas control dams were fed a 20.5% protein diet. At age 91 d, their body composition, glucose-insulin homeostasis, ACTH, corticosterone, leptin, adiponectin, lipid profile, pancreatic islet function and liver, adrenal gland, and pancreas morphology were assessed. The birth weights of the IUPR rats were 20% lower than the control rats (P < .001). Adult IUPR rats were heavier, hyperphagic, hyperglycemic, hyperinsulinemic, hyperleptinemic, and hypercorticosteronemic (P < .05) with higher low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol, adiponectin, ACTH, and insulin sensitivity index levels (P < .01). The insulinotropic action of glucose and acetylcholine as well as muscarinic and adrenergic receptor function were impaired in the IUPR rats (P < .05). Maternal undernutrition during the last third of gestation disrupts the pancreatic islet insulinotropic response and induces obesity-associated complications. Such alterations lead to a high risk of metabolic syndrome, characterized by insulin resistance, visceral obesity, and lower high-density lipoprotein cholesterol. PMID:27007071

Alterations in monoamines level in discrete brain regions and other peripheral tissues in young and adult male rats during experimental hyperthyroidism.

PubMed

Hassan, Wafaa A; Rahman, Taghride Abdel; Aly, Mona S; Shahat, Asmaa S

2013-08-01

The present study was conducted to investigate the effect of experimentally-induced hyperthyroidism on dopamine (DA), norepinephrine (NE) and serotonin (5-HT) levels in different brain regions as well as in blood plasma, cardiac muscle and adrenal gland of young and adult male albino rats (60 rats of each age). Hyperthyroidism was induced by daily s.c. injection of L-thyroxine (L-T4, 500 μg/kg body wt.) for 21 consecutive days. Induction of hyperthyroidism caused a significant elevation in DA and 5-HT levels in most of the tissues studied of both young and adult animals after 7, 14, and 21 days. NE content significantly decreased after 21 days in most of the brain regions examined and after 14 and 21 days in blood plasma of young rats following hyperthyroidism. In adult rats, NE content decreased after 14 and 21 days in cardiac muscle and after 21 days only in adrenal gland. It may be suggested that the changes in monoamines level induced by hyperthyroidism may be due to disturbance in the synthesis, turnover and release of these amines through the neurons impairment or may attributed to an alteration pattern of their synthesis and/or degradative enzymes or changes in the sensitivity of their receptors. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

Expression of heat shock protein in the atrophic corneal epithelium of the Royal College of Surgeons dystrophic rat.

PubMed

Yamaguchi, K; Yamaguchi, K; Sheedlo, H J; Turner, J E

1991-03-01

We report atrophic changes in the corneal epithelium of Royal College of Surgeons (RCS) dystrophic rats. The thickness of the corneal epithelium of 180-day-old RCS dystrophic rats was significantly decreased compared to that of 26-day-old RCS dystrophic and age-matched Sprague-Dawley (SD) rats. Immunostaining for (Na+ + K+) ATPase in the corneal epithelium of 180-day-old RCS dystrophic rats was dramatically reduced when compared to that of 26-day-old RCS dystrophic and age-matched SD rats. In contrast, heat shock protein immunostaining in the corneal epithelium was dense in all of the basal cells, wing cells, and superficial cells of 180-day-old RCS dystrophic rats but was minimally observed in some of the basal cells and in fewer wing and superficial cells of the corneal epithelium of 26-day-old RCS dystrophic and age-matched SD rats. We speculate that toxic products from the degenerating rod outer segments in the course of retinal dystrophy may affect the corneal epithelium, resulting in its atrophy. It is also possible that heat shock proteins appear in the atrophic corneal epithelium due to its degenerative condition.

Amphetamine-induced incentive sensitization of sign-tracking behavior in adolescent and adult female rats

PubMed Central

Doremus-Fitzwater, Tamara L.; Spear, Linda P.

2010-01-01

Age-specific behavioral and neural characteristics may predispose adolescents to initiate and escalate use of alcohol and drugs. Adolescents may avidly seek novel experiences, including drugs of abuse, because of enhanced incentive motivation for drugs and natural rewards, perhaps especially when that incentive motivation is sensitized by prior drug exposure. Using a Pavlovian conditioned approach (PCA) procedure, sign-tracking (ST) and goal-tracking (GT) behavior was examined in amphetamine-sensitized and control adolescent and adult female Sprague-Dawley rats, with expression of elevated ST behavior used to index enhanced incentive motivation for reward-associated cues. Rats were first exposed to a sensitizing regimen of amphetamine injections (3.0 mg/kg/ml d-amphetamine per day) or given saline (0.9% w/v) once daily for 4 days. Expression of ST and GT was then examined over 8 days of PCA training consisting of 25 pairings of an 8-sec presentation of an illuminated lever immediately followed by response-independent delivery of a banana-flavored food pellet. Results showed that adults clearly displayed more ST behavior than adolescents, reflected via both more contacts with, and shorter latencies to approach, the lever. Prior amphetamine sensitization increased ST (but not GT) behaviors regardless of age. Thus, when indexed via ST, incentive motivation was found to be greater in adults than adolescents, with a prior history of amphetamine exposure generally sensitizing incentive motivation for cues predicting a food reward regardless of age. PMID:21534648

77 FR 4617 - Environmental Impact Statement: Pennington County, SD

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-30

...: Pennington County, SD AGENCY: Federal Highway Administration (FHWA), DOT. ACTION: Notice of Intent. SUMMARY..., Suite A, Pierre, SD 57501, (605) 226-7326; Mr. Terry Keller, Environmental Supervisor, Project Development, South Dakota Department of Transportation, 700 E. Broadway Avenue, Pierre, SD 57501, (605) 773...

Effect of housing rats in dim light or long nights on heart rate.

PubMed

Azar, Toni A; Sharp, Jody L; Lawson, David M

2008-07-01

Housing laboratory animals under lighting conditions that more closely mimic the natural environment may improve their wellbeing. This study examined the effects of dim light or a long-night photocycle on resting heart rate (HR) of rats and their HR responses to acute procedures. Male and female Sprague-Dawley (SD) and spontaneously hypertensive (SHR) rats, instrumented with radiotelemetry transmitters and housed individually under a 12:12-h light:dark photocycle with 10 lx illumination (dim light) or under an 8:16-h light:dark photocycle with 200 lx illumination (long nights), were compared with control rats individually housed under a 12:12-h light:dark photocycle with 200 lx illumination. Dim light and long nights significantly reduced the HR of undisturbed SD and SHR male and SHR female rats during the day and at night; however, the HR of undisturbed SD females was not affected. When rats were subjected acutely to husbandry, experimental, or stressful procedures, dim light or long nights (or both) reduced HR responses to some procedures, did not alter responses to others, and increased responses to yet other procedures. The pattern of effects varied between strains and between male and female rats. Because basal HR was reduced when rats were housed under 10 lx illumination or an 8:16-h light:dark photocycle, we concluded that housing rats under 12:12-h light:dark, 200 lx ambient light conditions was potentially stressful, We also concluded that dim light or long nights did not uniformly reduce the increased HR responses induced by acute procedures.

Absence of “Warm-Up” during Active Avoidance Learning in a Rat Model of Anxiety Vulnerability: Insights from Computational Modeling

PubMed Central

Myers, Catherine E.; Smith, Ian M.; Servatius, Richard J.; Beck, Kevin D.

2014-01-01

Avoidance behaviors, in which a learned response causes omission of an upcoming punisher, are a core feature of many psychiatric disorders. While reinforcement learning (RL) models have been widely used to study the development of appetitive behaviors, less attention has been paid to avoidance. Here, we present a RL model of lever-press avoidance learning in Sprague-Dawley (SD) rats and in the inbred Wistar Kyoto (WKY) rat, which has been proposed as a model of anxiety vulnerability. We focus on “warm-up,” transiently decreased avoidance responding at the start of a testing session, which is shown by SD but not WKY rats. We first show that a RL model can correctly simulate key aspects of acquisition, extinction, and warm-up in SD rats; we then show that WKY behavior can be simulated by altering three model parameters, which respectively govern the tendency to explore new behaviors vs. exploit previously reinforced ones, the tendency to repeat previous behaviors regardless of reinforcement, and the learning rate for predicting future outcomes. This suggests that several, dissociable mechanisms may contribute independently to strain differences in behavior. The model predicts that, if the “standard” inter-session interval is shortened from 48 to 24 h, SD rats (but not WKY) will continue to show warm-up; we confirm this prediction in an empirical study with SD and WKY rats. The model further predicts that SD rats will continue to show warm-up with inter-session intervals as short as a few minutes, while WKY rats will not show warm-up, even with inter-session intervals as long as a month. Together, the modeling and empirical data indicate that strain differences in warm-up are qualitative rather than just the result of differential sensitivity to task variables. Understanding the mechanisms that govern expression of warm-up behavior in avoidance may lead to better understanding of pathological avoidance, and potential pathways to modify these processes. PMID

Comparison of erythropoietin and sildenafil protective role against ischemia/reperfusion injury of the testis in adult rats.

PubMed

Zavras, Nick; Kostakis, Ioannis D; Sakellariou, Stratigoula; Damaskos, Christos; Roupakas, Evangelos; Tsagkari, Eleni; Spartalis, Eleftherios; Velaoras, Konstantinos; Dontas, Ismene A; Karatzas, Theodore

2014-04-01

Tissue damage in testicular torsion/detorsion is caused not only by the ischemia, but also by the ischemia/reperfusion injury after detorsion. Erythropoietin and sildenafil are considered to protect against ischemia/reperfusion injury. Here, we studied and compared their actions in testicular torsion/detorsion in adult rats. Twenty-two adult male Wistar Albino rats were divided into four groups. Rats in group A (n = 5) were sham operated. Rats in group B (n = 5), group C (n = 6) and group D (n = 6) underwent torsion of the right testis and detorsion after 90 min. No pharmaceutical intervention was performed in group B. Erythropoietin (1,000 IU/kg) and sildenafil (0.7 mg/kg) were injected intraperitoneally in groups C and D, respectively, after 60 min of torsion. All animals were killed 24 h after detorsion, and their right testis was extracted, placed into 10 % formalin solution and sent for histopathological examination. The histological changes in the testes were scored according to the four-point grading system proposed by Cosentino et al. All rats in group A had normal testicular architecture (grade 1). The untreated group B had a mean grade of 3.81 (range 3.65-4). The treated groups C (mean grade 3.24; range 3.05-3.45) and D (2.69, range 2.4-2.9) presented statistically significant better results (lower grades) compared with the untreated group B. Group D had significantly better results (lower grades) than group C. The intraperitoneal injection of erythropoietin and sildenafil protects against ischemia/reperfusion injury after testicular torsion and detorsion. Sildenafil may have a stronger action than erythropoietin at the doses used in this study.

Moderate perinatal thyroid hormone insufficiency alters visual system function in adult rats.

PubMed

Boyes, William K; Degn, Laura; George, Barbara Jane; Gilbert, Mary E

2018-04-21

Thyroid hormone (TH) is critical for many aspects of neurodevelopment and can be disrupted by a variety of environmental contaminants. Sensory systems, including audition and vision are vulnerable to TH insufficiencies, but little data are available on visual system development at less than severe levels of TH deprivation. The goal of the current experiments was to explore dose-response relations between graded levels of TH insufficiency during development and the visual function of adult offspring. Pregnant Long Evans rats received 0 or 3 ppm (Experiment 1), or 0, 1, 2, or 3 ppm (Experiment 2) of propylthiouracil (PTU), an inhibitor of thyroid hormone synthesis, in drinking water from gestation day (GD) 6 to postnatal day (PN) 21. Treatment with PTU caused dose-related reductions of serum T4, with recovery on termination of exposure, and euthyroidism by the time of visual function testing. Tests of retinal (electroretinograms; ERGs) and visual cortex (visual evoked potentials; VEPs) function were assessed in adult offspring. Dark-adapted ERG a-waves, reflecting rod photoreceptors, were increased in amplitude by PTU. Light-adapted green flicker ERGs, reflecting M-cone photoreceptors, were reduced by PTU exposure. UV-flicker ERGs, reflecting S-cones, were not altered. Pattern-elicited VEPs were significantly reduced by 2 and 3 ppm PTU across a range of stimulus contrast values. The slope of VEP amplitude-log contrast functions was reduced by PTU, suggesting impaired visual contrast gain. Visual contrast gain primarily reflects function of visual cortex, and is responsible for adjusting sensitivity of perceptual mechanisms in response to changing visual scenes. The results indicate that moderate levels of pre-and post-natal TH insufficiency led to alterations in visual function of adult rats, including both retinal and visual cortex sites of dysfunction. Copyright © 2018. Published by Elsevier B.V.

The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult rats.

PubMed

Andersen, N B; Malmlöf, K; Johansen, P B; Andreassen, T T; Ørtoft, G; Oxlund, H

2001-10-01

The ability of the growth hormone secretagogue (GHS) Ipamorelin to counteract the catabolic effects of glucocorticoid (GC) on skeletal muscles and bone was investigated in vivo in an adult rat model. Groups of 8-month-old female rats were injected subcutaneously for 3 months with GC (methylprednisolone) 9 mg/kg/day or GHS (Ipamorelin) 100 microg/kg three times daily, or both GC and GHS in combination. The maximum tetanic tension of the calf muscles was determined in vivo in a materials testing machine. The maximum tetanic tension was increased significantly, and the periosteal bone formation rate increased four-fold in animals injected with GC and GHS in combination, compared with the group injected with GC alone. In conclusion, the decrease in muscle strength and bone formation found in GC-injected rats was counteracted by simultaneous administration of the growth hormone secretagogue. Copyright 2001 Harcourt Publishers Ltd.

Preweaning modulation of intestinal microbiota by oligosaccharides or amoxicillin can contribute to programming of adult microbiota in rats.

PubMed

Morel, Fanny B; Oozeer, Raish; Piloquet, Hugues; Moyon, Thomas; Pagniez, Anthony; Knol, Jan; Darmaun, Dominique; Michel, Catherine

2015-03-01

Increasing evidence suggests that early nutrition has programming effects on adult health. Identifying mechanisms underlying nutritional programming would aid in the design of new disease prevention strategies. The intestinal microbiota could be a key player in this programming because it affects host metabolic homeostasis, postnatal gut colonization is sensitive to early nutrition, and initial microbial set-up is thought to shape microbiota composition for life. The aim of this study was to determine whether early manipulation of intestinal microbiota actually programs adult microbiota in rats. Suckling rats pups were supplemented with fructo-oligosaccharides, galacto-oligosaccharides/long-chain fructan mix (GOS/lcF, 9/1), acidic oligosaccharides, amoxicillin, or vehicle from the fifth to the fourteenth day of life, and weaned to standard chow at day 21. Ceco-colonic microbiota was characterized at 14 and 131 d by real-time polymerase chain reaction analysis. At day 14, all treatments affected microbiota. Amoxicillin had the most significant effect. All oligosaccharides decreased Firmicutes levels, whereas only fructo-oligosaccharides and GOS/lcF increased bifidobacteria. At day 131, most of these effects had faded away but a significant, albeit minor, adult microbiota programming was observed for rats that received GOS/lcF mix before weaning, regarding Roseburia intestinalis cluster, one subdivision of the Erysipelotrichaceae family as well as butyrate kinase gene. As revealed by a targeted quantitative polymerase chain reaction approach, programming of adult intestinal microbiota seems to vary according to the nature of the preweaning microbiotal modulator. This suggests that intestinal microbiota may, only under specific circumstances, serve as a relay of neonatal nutrition and thus potentially contribute to nutritional programming of host physiology. Copyright © 2015 Elsevier Inc. All rights reserved.

Maternal periodontal disease in rats decreases insulin sensitivity and insulin signaling in adult offspring.

PubMed

Shirakashi, Daisy J; Leal, Rosana P; Colombo, Natalia H; Chiba, Fernando Y; Garbin, Cléa A S; Jardim, Elerson G; Antoniali, Cristina; Sumida, Doris H

2013-03-01

Periodontal disease during pregnancy has been recognized as one of the causes of preterm and low-birth-weight (PLBW) babies. Several studies have demonstrated that PLBW babies are prone to developing insulin resistance as adults. Although there is controversy over the association between periodontal disease and PLBW, the phenomenon known as programming can translate any stimulus or aggression experienced during intrauterine growth into physiologic and metabolic alterations in adulthood. The purpose of the present study is to investigate whether the offspring of rats with periodontal disease develop insulin resistance in adulthood. Ten female Wistar rats were divided into periodontal disease (PED) and control (CN) groups. All rats were mated at 7 days after induction of periodontal disease. Male offspring were divided into two groups: 1) periodontal disease offspring (PEDO; n = 24); and 2) control offspring (CNO; n = 24). Offspring body weight was measured from birth until 75 days. When the offspring reached 75 days old, the following parameters were measured: 1) plasma concentrations of glucose, insulin, fructosamine, lipase, amylase, and tumor necrosis factor-α (TNF-α); 2) insulin sensitivity (IS); and 3) insulin signal transduction (IST) in insulin-sensitive tissues. Low birth weight was not detected in the PEDO group. However, plasma concentrations of glucose, insulin, fructosamine, lipase, amylase, and TNF-α were increased and IS and IST were reduced (P <0.05) in the PEDO group compared with the CNO group. Maternal periodontal disease may induce insulin resistance and reduce IST in adult offspring, but such alterations are not attributable to low birth weight.

9-Hydroxyprostaglandin dehydrogenase activity in the adult rat kidney. Regional distribution and sub-fractionation.

PubMed

Asciak, C P; Domazet, Z

1975-02-20

1. Catabolism of prostaglandin F2alpha in the adult rat kidney takes place by the following sequence of enzymatic steps: (1) 15-hydroxyprostaglandin dehydrogenase; (2) prostaglandin delta13-reductase; and (3) 9-hydroxyprostaglandin dehydrogenase. 2. 9-Hydroxyprostaglandin dehydrogenase activity was highest in the cortex with lesser amounts in the medulla and negligible activity detected in the papilla. A similar distribution was observed for 15-hydroxyprostaglandin dehydrogenase and prostaglandin delta13-reductase. 3. Most of the 9-hydroxyprostaglandin dehydrogenase activity in the homogenate was found in the high-speed supernatant as also observed for 15-hydroxyprostaglandin dehydrogenase and prostaglandin delta13-reductase. 4. These observations indicate that the rat kidney contains an abundance of prostaglandin-catabolising enzymes which favour formation of metabolites of the E-type.

Adolescent chronic restraint stress (aCRS) elicits robust depressive-like behavior in freely cycling, adult female rats without increasing anxiety-like behaviors.

PubMed

Hibicke, Meghan; Graham, Martha A; Hayslett, Renée L

2017-04-01

Stress during times of rapid development is a risk factor for Major Depressive Disorder, a mood disorder that disproportionately affects women. We developed an adolescent chronic restraint stress (aCRS) protocol using female rats to address the impact of adolescent stress on female adult depressive-like behavior. Animals were divided into 4 treatment groups: not restrained:saline (NRSAL), not restrained:desipramine (NRDES), restrained:saline (RSAL), and restrained:desipramine (RDES). NRSAL and NRDES rats were housed in a separate colony room from RSAL and RDES rats. All animals were weighed and handled daily. Beginning postnatal day (PND) 34(±1), RSAL and RDES rats were restrained for 1 hour daily for 14 consecutive days. Beginning PND 55(±1), NRDES and RDES rats were given subcutaneous desipramine (5 mg/kg), which served as a positive control, daily for 14 consecutive days. During that same time period, NRSAL and RSAL rats were given subcutaneous saline daily. aCRS (RSAL and RDES) rats showed significantly attenuated weight gain compared with nonrestrained (NRSAL and NRDES) rats during the restraint period. Weight gain normalized after the final restraint session. Behavioral testing took place PND 68-69(±1), and included open field testing, the elevated plus maze, locomotor activity, and the forced swim test (FST). RSAL rats showed significantly more immobility in the FST versus all other groups, indicating depressive-like behavior. No differences between groups were observed in the other behavioral measures. These results indicate that aCRS elicits depressive-like behavioral characteristics in adult female rats without increasing anxiety-like behaviors. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Effect of Hibiscus sabdariffa L. Dried Calyx Ethanol Extract on Fat Absorption-Excretion, and Body Weight Implication in Rats

PubMed Central

Carvajal-Zarrabal, O.; Hayward-Jones, P. M.; Orta-Flores, Z.; Nolasco-Hipólito, C.; Barradas-Dermitz, D. M.; Aguilar-Uscanga, M. G.; Pedroza-Hernández, M. F.

2009-01-01

The effect of Hibiscus sabdariffa L. (Hs) calyx extract on fat absorption-excretion and body weight in rats, was investigated. Rats were fed with either a basal diet (SDC = Control diet) or the same diet supplemented with Hs extracts at 5%, 10% and 15% (SD5, SD10 and SD15). Only SD5 did not show significant increases in weight, food consumption and efficiency compared to SDC. The opposite occurred in SD15 group which showed a significant decrease for these three parameters. The SD10 responses were similar to SD15, with the exception of food consumption. In both SDC and SD5 groups, no body weight loss was observed; however, only in the latter group was there a significantly greater amount of fatty acids found in feces. A collateral effect emerging from the study is that components of Hs extract at the intermediate and greater concentrations used in this experiment could be considered possible antiobesity agents. PMID:19756159

Stress hormones, sleep deprivation and cognition in older adults.

PubMed

Maggio, Marcello; Colizzi, Elena; Fisichella, Alberto; Valenti, Giorgio; Ceresini, Graziano; Dall'Aglio, Elisabetta; Ruffini, Livia; Lauretani, Fulvio; Parrino, Liborio; Ceda, Gian Paolo

2013-09-01

Cognition can be deteriorated in older persons because of several potential mechanisms including the hormonal changes occurring with age. Stress events cause modification in hormonal balance with acute and chronic changes such as increase in cortisol and thyroid hormones, and simultaneous alterations in dehydroepiandrosterone sulphate, testosterone and insulin like growth factor-1 levels. The ability to cope with stress and regain previous healthy status, also called resiliency, is particularly impaired in older persons Thus, stressful conditions and hormonal dysregulation might concur to the onset of cognitive impairment in this population. In this review we address the relationship between stress hormones and cognitive function in older persons focusing on the role of one of the main stress factors, such as sleep deprivation (SD). We extracted and cross-checked data from 2000 to 2013 March and selected 112 full-text articles assessed for eligibility. In particular we considered 68 studies regarding the contribution of hormonal pathway to cognition in older adults, and 44 regarding hormones and SD both in rats and humans. We investigated how the activation of a stress-pattern response, like the one evoked from SD, can influence cognitive development and worsen cognitive status in the elderly. We will show the limited number of studies targeting the effects of SD and the consequent changes in stress hormones on cognitive function in this age group. We conclude that the current literature is not strong enough to give definitive answers on the role of stress hormonal pathway to the development of cognitive impairment in older individuals. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Prolonged hypothyroidism severely reduces ovarian follicular reserve in adult rats.

PubMed

Meng, Li; Rijntjes, Eddy; Swarts, Hans J M; Keijer, Jaap; Teerds, Katja J

2017-03-16

There is substantial evidence both in humans and in animals that a prolonged reduction in plasma thyroid hormone concentration leads to reproductive problems, including disturbed folliculogenesis, impaired ovulation and fertilization rates, miscarriage and pregnancy complications. The objective of the present study is to examine the consequences of chronic hypothyroidism, induced in adulthood, for the size of the ovarian follicle pool. In order to investigate this, adult female rats were provided either a control or an iodide deficient diet in combination with perchlorate supplementation to inhibit iodide uptake by the thyroid. Sixteen weeks later animals were sacrificed. Blood was collected for hormone analyses and ovaries were evaluated histologically. At the time of sacrifice, plasma thyroid-stimulating hormone concentrations were 20- to 40-fold increased, thyroxine concentrations were negligible while tri-iothyronin concentrations were decreased by 40% in the hypothyroid group, confirming that the animals were hypothyroid. Primordial, primary and preantral follicle numbers were significantly lower in the hypothyroid ovaries compared to the euthyroid controls, while a downward trend in antral follicle and corpora lutea numbers was observed. Surprisingly the percentage of atretic follicles was not significantly different between the two groups, suggesting that the reduced preantral and antral follicle numbers were presumably not the consequence of increased degeneration of these follicle types in the hypothyroid group. Plasma anti-Müllerian hormone (AMH) levels showed a significant correlation with the growing follicle population represented by the total ovarian number of primary, preantral and antral follicles, suggesting that also under hypothyroid conditions AMH can serve as a surrogate marker to assess the growing ovarian follicle population. The induction of a chronic hypothyroid condition in adult female rats negatively affects the ovarian follicular

Profiling of the fetal and adult rat liver transcriptome and translatome reveals discordant regulation by the mechanistic target of rapamycin (mTOR).

PubMed

Boylan, Joan M; Sanders, Jennifer A; Neretti, Nicola; Gruppuso, Philip A

2015-07-01

The mechanistic target of rapamycin (mTOR) integrates growth factor signaling, nutrient abundance, cell growth, and proliferation. On the basis of our interest in somatic growth in the late gestation fetus, we characterized the role of mTOR in the regulation of hepatic gene expression and translation initiation in fetal and adult rats. Our strategy was to manipulate mTOR signaling in vivo and then characterize the transcriptome and translating mRNA in liver tissue. In adult rats, we used the nonproliferative growth model of refeeding after a period of fasting and the proliferative model of liver regeneration following partial hepatectomy. We also studied livers from preterm fetal rats (embryonic day 19) in which fetal hepatocytes are asynchronously proliferating. All three models employed rapamycin to inhibit mTOR signaling. Analysis of the transcriptome in fasted-refed animals showed rapamycin-mediated induction of genes associated with oxidative phosphorylation. Genes associated with RNA processing were downregulated. In liver regeneration, rapamycin induced genes associated with lysosomal metabolism, steroid metabolism, and the acute phase response. In fetal animals, rapamycin inhibited expression of genes in several functional categories that were unrelated to effects in the adult animals. Translation control showed marked fetal-adult differences. In both adult models, rapamycin inhibited the translation of genes with complex 5' untranslated regions, including those encoding ribosomal proteins. Fetal translation was resistant to the effects of rapamycin. We conclude that the mTOR pathway in liver serves distinct physiological roles in the adult and fetus, with the latter representing a condition of rapamycin resistance. Copyright © 2015 the American Physiological Society.

Avoiding escalation from play to aggression in adult male rats: The role of ultrasonic calls.

PubMed

Burke, Candace J; Kisko, Theresa M; Pellis, Sergio M; Euston, David R

2017-11-01

Play fighting is most commonly associated with juvenile animals, but in some species, including rats, it can continue into adulthood. Post-pubertal engagement in play fighting is often rougher and has an increased chance of escalation to aggression, making the use of play signals to regulate the encounter more critical. During play, both juvenile and adult rats emit many 50-kHz calls and some of these may function as play facilitating signals. In the present study, unfamiliar adult male rats were introduced in a neutral enclosure and their social interactions were recorded. While all pairs escalated their playful encounters to become rougher, only the pairs in which one member was devocalized escalated to serious biting. A Monte Carlo shuffling technique was used for the analysis of the correlations between the overt playful and aggressive actions performed and the types and frequencies of various 50-kHz calls that were emitted. The analysis revealed that lower frequency (20-30kHz) calls with a flat component maybe particularly critical for de-escalating encounters and so allowing play to continue. Moreover, coordinating calls reciprocally, with either the same call mimicked in close, temporal association or with complementary calls emitted by participants as they engage in complementary actions (e.g., attacking the nape, being attacked on the nape), appeared to be ways with which calls could be potentially used to avoid escalation to aggression and so sustain playful interactions. Copyright © 2017 Elsevier B.V. All rights reserved.

In utero protein restriction causes growth delay and alters sperm parameters in adult male rats

PubMed Central

2011-01-01

Background Recent studies have supported the concept of "fetal programming" which suggests that during the intrauterine development the fetus may be programmed to develop diseases in adulthood. The possible effects of in utero protein restriction on sexual development of rat male offspring were evaluated in the present study. Methods Pregnant Wistar rats were divided into two experimental groups: one group treated with standard chow (SC, n = 8, 17% protein) and the other group treated with hypoproteic chow (HC, n = 10, 6% protein) throughout gestation. After gestation the two experimental groups received standard chow. To evaluate the possible late reproductive effects of in utero protein restriction, the male offspring of both groups were assessed at different phases of sexual development: prepubertal (30 days old); peripubertal (60 days old); adult (90 days old). Student's t-test and Mann-Whitney test were utilized. Differences were considered significant when p < 0.05. Results We found that in utero protein restriction reduced the body weight of male pups on the first postnatal day and during the different sexual development phases (prepubertal, peripubertal and adult). During adulthood, Sertoli cell number, sperm motility and sperm counts in the testis and epididymal cauda were also reduced in HC. Furthermore, the numbers of sperm presenting morphological abnormalities and cytoplasmic drop retention were higher in HC. Conclusions In conclusion, in utero protein restriction, under these experimental conditions, causes growth delay and alters male reproductive-system programming in rats, suggesting impairment of sperm quality in adulthood. PMID:21702915

In utero protein restriction causes growth delay and alters sperm parameters in adult male rats.

PubMed

Toledo, Fabíola C; Perobelli, Juliana E; Pedrosa, Flávia P C; Anselmo-Franci, Janete A; Kempinas, Wilma D G

2011-06-24

Recent studies have supported the concept of "fetal programming" which suggests that during the intrauterine development the fetus may be programmed to develop diseases in adulthood. The possible effects of in utero protein restriction on sexual development of rat male offspring were evaluated in the present study. Pregnant Wistar rats were divided into two experimental groups: one group treated with standard chow (SC, n = 8, 17% protein) and the other group treated with hypoproteic chow (HC, n = 10, 6% protein) throughout gestation. After gestation the two experimental groups received standard chow. To evaluate the possible late reproductive effects of in utero protein restriction, the male offspring of both groups were assessed at different phases of sexual development: prepubertal (30 days old); peripubertal (60 days old); adult (90 days old). Student's t-test and Mann-Whitney test were utilized. Differences were considered significant when p < 0.05. We found that in utero protein restriction reduced the body weight of male pups on the first postnatal day and during the different sexual development phases (prepubertal, peripubertal and adult). During adulthood, Sertoli cell number, sperm motility and sperm counts in the testis and epididymal cauda were also reduced in HC. Furthermore, the numbers of sperm presenting morphological abnormalities and cytoplasmic drop retention were higher in HC. In conclusion, in utero protein restriction, under these experimental conditions, causes growth delay and alters male reproductive-system programming in rats, suggesting impairment of sperm quality in adulthood.

Cognitive deficits in adult rats by lead intoxication are related with regional specific inhibition of cNOS.

PubMed

García-Arenas, Guadalupe; Ramírez-Amaya, Victor; Balderas, Israela; Sandoval, Jimena; Escobar, Martha L; Ríos, Camilo; Bermúdez-Rattoni, Federico

2004-02-04

It is well known that lead can affect several cognitive abilities in developing animals. In this work, we investigate the effects of different sub-chronic lead doses (0, 65, 125, 250 and 500 ppm of lead acetate in their drinking water for 14 days) in the performance of male adult rats in a water maze, cue maze and inhibitory avoidance tasks. We found that the acquisition of these tasks was not affected by lead, however, the highest dosage of lead (500 ppm) impaired memory consolidation in spatial and inhibitory avoidance tasks, but not in cue maze task while the 250 ppm dose only affected retrieval of spatial memory. Additionally, hippocampal long-term potentiation (LTP) induction in the perforant path after exposing adult rats to different doses of lead was studied. LTP induction was affected in a dose-dependent manner, and treatments of 250 and 500 ppm completely blocked LTP. We investigated the effects of lead intoxication on the activity of constitutive nitric oxide synthase (cNOS) in different brain regions of adult animals. The activity of cNOS was significantly inhibited in the hippocampus and cerebellum but not in the frontal cortex and brain stem, although lead had accumulated in all brain regions. These results suggest that lead intoxication can impair memory in adult animals and this impairment might be related with region-specific effects on cNOS activity.

Galanin-like peptide stimulates feeding and sexual behavior via dopaminergic fibers within the medial preoptic area of adult male rats.

PubMed

Taylor, A; Madison, F N; Fraley, G S

2009-03-01

Galanin-like peptide (GALP) is located in the arcuate nucleus (Arc) of the hypothalamus and is known to regulate both food intake and sexual behaviors in adult male rats. We have previously demonstrated that ICV GALP administration elicits a significant fos response within the medial preoptic area (mPOA). GALP is known to stimulate both food intake and male-typical sex behavior, presumably by direct actions within the mPOA. Recent data from our and other labs have led us to suspect that GALP effects on sex behaviors are due to activation of incertohypothalamic dopaminergic neurons that terminate within the mPOA. To test the hypothesis that GALP activates mPOA dopaminergic systems, we utilized an immunolesion technique to eliminate dopaminergic fiber input to the mPOA via a dopamine transporter-specific toxin (DATSAP, n=8) and compared to control injections (SAP, n=8). All animals were sexually experienced adult male Long-Evans rats. DATSAP-treated male rats showed a significant (p<0.001) reduction in male sexual behaviors compared to SAP controls. We found that elimination of dopaminergic fibers within the mPOA significantly (p<0.001) eliminated all aspects of male sexual behavior under normal mating paradigms. Injections of GALP (5.0 nmol) significantly increased (p<0.01) male sex behavior and food intake in SAP control male rats but GALP did not stimulate the expression of these behaviors in DATSAP-treated rats. The orexigenic and anorexigenic effects of GALP were significantly (p<0.001) attenuated in DATSAP-treated male rats compared to SAP controls; however, ICV GALP was still able to significantly (p<0.05) reduce 24h body weight in both DATSAP and SAP rats. ICV GALP significantly (p<0.05) stimulated fos within the mPOA of SAP rats but not in DATSAP-treated male rats. These data suggest that GALP activates feeding and sexual behaviors in male rats by stimulating dopaminergic neurons that terminate within the mPOA.

Does cross-fostering modify the prenatal effect of methamphetamine on learning of adult male rats?

PubMed

Hrubá, L; Schutová, B; Pometlová, M; Slamberová, R

2009-01-01

Our previous studies demonstrated that methamphetamine administered during gestation and lactation periods impairs maternal behavior, alters the functional development of rat pups and affects behavior in adulthood. The aim of our study was to investigate the effect of prenatal methamphetamine exposure and cross-fostering on learning tested in Morris water maze (MWM) in adult male rats. Mothers were daily exposed to injection of methamphetamine (MA) (5 mg/kg) or saline (S): prior to impregnation and throughout gestation and lactation periods. On postnatal day 1, pups were cross-fostered so that each mother received some of her own and some of the pups of mother with the opposite treatment. Based on the prenatal and postnatal treatments 4 experimental groups (S/S, S/MA, MA/S, MA/MA) were tested in MWM. Two types of tests were used: (1) "Place navigation test" (Learning) and (2) "Probe test" (Probe). In the test of learning, all animals fostered by methamphetamine-treated dams had longer latencies and trajectories, and bigger search error than the animals fostered by saline-treated control mother, regardless of prenatal exposure. Further, the animals prenatally exposed to methamphetamine swam slower than the animals prenatally exposed to saline, regardless of postnatal exposure in the test of learning and in the Probe test. Our results showed that neither prenatal nor postnatal methamphetamine exposure affected the Probe test. Our results showed that prenatal exposure to methamphetamine at dose of 5 mg/kg does not impair learning in the MWM, while postnatal exposure to methamphetamine from mothers' breastmilk and maternal care of mother exposed to methamphetamine impairs learning of adult male rats. On the other hand, the maternal care of control mothers does not impair learning of rat pups prenatally exposed to methamphetamine. The present study demonstrates that cross-fostering may affect learning in adulthood.

Moderate prenatal alcohol exposure and quantification of social behavior in adult rats.

PubMed

Hamilton, Derek A; Magcalas, Christy M; Barto, Daniel; Bird, Clark W; Rodriguez, Carlos I; Fink, Brandi C; Pellis, Sergio M; Davies, Suzy; Savage, Daniel D

2014-12-14

Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several independent laboratories have demonstrated robust alterations in the social behavior of rodents exposed to alcohol during brain development across a wide range of exposure durations, timing, doses, and ages at the time of behavioral quantification. Prior work from this laboratory has identified reliable alterations in specific forms of social interaction following moderate prenatal alcohol exposure (PAE) in the rat that persist well into adulthood, including increased wrestling and decreased investigation. These behavioral alterations have been useful in identifying neural circuits altered by moderate PAE(1), and may hold importance for progressing toward a more complete understanding of the neural bases of PAE-related alterations in social behavior. This paper describes procedures for performing moderate PAE in which rat dams voluntarily consume ethanol or saccharin (control) throughout gestation, and measurement of social behaviors in adult offspring.

Comparison of CYP2D metabolism and hepatotoxicity of the myocardial metabolic agent perhexiline in Sprague-Dawley and Dark Agouti rats.

PubMed

Licari, Giovanni; Somogyi, Andrew A; Milne, Robert W; Sallustio, Benedetta C

2015-01-01

1. Perhexiline, a chiral anti-anginal agent, may be useful to develop new cardiovascular therapies, despite its potential hepatotoxicity. 2. This study compared Dark Agouti (DA) and Sprague-Dawley (SD) rats, as models of perhexiline's metabolism and hepatotoxicity in humans. Rats (n = 4/group) received vehicle or 200 mg/kg/d of racemic perhexiline maleate for 8 weeks. Plasma and liver samples were collected to determine concentrations of perhexiline and its metabolites, hepatic function and histology. 3. Median (range) plasma and liver perhexiline concentrations in SD rats were 0.09 (0.04-0.13) mg/L and 5.42 (0.92-8.22) ng/mg, respectively. In comparison, DA rats showed higher (p < 0.05) plasma 0.50 (0.16-1.13) mg/L and liver 24.5 (9.40-54.7) ng/mg perhexiline concentrations, respectively, 2.5- and 3.7-fold higher cis-OH-perhexiline concentrations, respectively (p < 0.05), and lower plasma metabolic ratio (0.89 versus 1.55, p < 0.05). In both strains, the (+):(-) enantiomer ratio was 2:1. Perhexiline increased plasma LDH concentrations in DA rats (p < 0.05), but had no effect on plasma biochemistry in SD rats. Liver histology revealed lower glycogen content in perhexiline-treated SD rats (p < 0.05), but no effects on lipid content in either strain. 4. DA rats appeared more similar to humans with respect to plasma perhexiline concentrations, metabolic ratio, enantioselective disposition and biochemical changes suggestive of perhexiline-induced toxicity.

The inhibitory effect of tongxieyaofang on rats with post infectious irritable bowel syndrome through regulating colonic par-2 receptor.

PubMed

Hu, Xuguang; Zhang, Xiaojun; Han, Bin; Bei, Weijian

2013-10-02

The aims of this study were to evaluate the effect and mechanism of a traditional Chinese medicine formula: Tongxieyaofang (TXYF) on Rats with Post Infectious Irritable Bowel Syndrome (PI-IBS). SD male rats in adult were used to model PI-IBS and treated with TXYF at three dosage for 14 consecutive days, and then visceral sensation and the frequency of stool in PI-IBS rats were investigated. In addition, the contents of SP, TNF- α and IL-6 in colonic mucosal were analyzed by ELISA. Moreover faecal serine protease activity and PAR-2 mRNA expression were measured by ultraviolet spectrophotometry and RT-PCR, respectively. Our study showed that TXYF attenuated visceral hyperalgesia and inhibited stool frequency in Campylobacter-stimulated Post Infectious Irritable Bowel Syndrome (PI-IBS) rats. Furthermore, TXYF decreased the colonic SP, TNF- α and IL-6 content in PI-IBS rats. In addition, the up-regulated colonic mucosa PAR-2 mRNA expression in PI-IBS rats was significantly suppressed by orally TXYF. TXYF attenuated PI-IBS symptom by attenuating behavioral hyperalgesia and anti-diarrhea, the underlying mechanism was mediated by inhibiting PAR-2 receptor expression, reducing the levels of SP, TNF- α and IL-6 in colonic mucosa and decreasing faecal serine protease activity.

Methylmercury chloride damage to the adult rat hippocampus cannot be detected by proton magnetic resonance spectroscopy

PubMed Central

Lu, Zhiyan; Wu, Jinwei; Cheng, Guangyuan; Tian, Jianying; Lu, Zeqing; Bi, Yongyi

2014-01-01

Previous studies have found that methylmercury can damage hippocampal neurons and accordingly cause cognitive dysfunction. However, a non-invasive, safe and accurate detection method for detecting hippocampal injury has yet to be developed. This study aimed to detect methylmercury-induced damage on hippocampal tissue using proton magnetic resonance spectroscopy. Rats were given a subcutaneous injection of 4 and 2 mg/kg methylmercury into the neck for 50 consecutive days. Water maze and pathology tests confirmed that cognitive function had been impaired and that the ultrastructure of hippocampal tissue was altered after injection. The results of proton magnetic resonance spectroscopy revealed that the nitrogen-acetyl aspartate/creatine, choline complex/creatine and myoinositol/creatine ratio in rat hippocampal tissue were unchanged. Therefore, proton magnetic resonance spectroscopy can not be used to determine structural damage in the adult rat hippocampus caused by methylmercury chloride. PMID:25368649

Isolation of the synchronized A spermatogonia from adult vitamin A-deficient rat testes.

PubMed

van Pelt, A M; Morena, A R; van Dissel-Emiliani, F M; Boitani, C; Gaemers, I C; de Rooij, D G; Stefanini, M

1996-08-01

A method for isolating A spermatogonia from the adult vitamin A-deficient (VAD) rat testis is described. After removal, the testes were decapsulated and tubules were dissected. An enzymatic digestion with collagenase, hyaluronidase, and trypsin was performed first to eliminate most of the interstitial cells. A second digestion with collagenase and hyaluronidase was performed to obtain a cell suspension with a high number of A spermatogonia. The cell suspension was further enriched with A spermatogonia by preplating on peanut agglutinin and separating on a discontinuous Percoll gradient. By this procedure, purification of the suspension to 70-90% A spermatogonia was obtained. In the seminiferous tubules of the VAD rats, only Sertoli cells, A spermatogonia, and some preleptotene spermatocytes are present. In our rats, the A spermatogonia are almost all arrested in the G1 phase of the cell cycle before the S phase of A1 spermatogonia, and presumably before their differentiation into A1 spermatogonia. After administration of vitamin A, spermatogenesis starts synchronously from these A spermatogonia. The isolation of these synchronized A spermatogonia opens ways to investigate the regulation of differentiation and proliferation of A spermatogonia and the biochemical characteristics of the subsequent types of A spermatogonia.

Intrauterine Growth Restriction Programs the Hypothalamus of Adult Male Rats: Integrated Analysis of Proteomic and Metabolomic Data.

PubMed

Pedroso, Amanda P; Souza, Adriana P; Dornellas, Ana P S; Oyama, Lila M; Nascimento, Cláudia M O; Santos, Gianni M S; Rosa, José C; Bertolla, Ricardo P; Klawitter, Jelena; Christians, Uwe; Tashima, Alexandre K; Ribeiro, Eliane B

2017-04-07

Programming of hypothalamic functions regulating energy homeostasis may play a role in intrauterine growth restriction (IUGR)-induced adulthood obesity. The present study investigated the effects of IUGR on the hypothalamus proteome and metabolome of adult rats submitted to 50% protein-energy restriction throughout pregnancy. Proteomic and metabolomic analyzes were performed by data independent acquisition mass spectrometry and multiple reaction monitoring, respectively. At age 4 months, the restricted rats showed elevated adiposity, increased leptin and signs of insulin resistance. 1356 proteins were identified and 348 quantified while 127 metabolites were quantified. The restricted hypothalamus showed down-regulation of 36 proteins and 5 metabolites and up-regulation of 21 proteins and 9 metabolites. Integrated pathway analysis of the proteomics and metabolomics data indicated impairment of hypothalamic glucose metabolism, increased flux through the hexosamine pathway, deregulation of TCA cycle and the respiratory chain, and alterations in glutathione metabolism. The data suggest IUGR modulation of energy metabolism and redox homeostasis in the hypothalamus of male adult rats. The present results indicated deleterious consequences of IUGR on hypothalamic pathways involved in pivotal physiological functions. These results provide guidance for future mechanistic studies assessing the role of intrauterine malnutrition in the development of metabolic diseases later in life.

Variations in the neonatal environment modulate adult behavioral and brain responses to palatable food withdrawal in adult female rats.

PubMed

Colman, Juliana Barcellos; Laureano, Daniela Pereira; Reis, Tatiane Madeira; Krolow, Rachel; Dalmaz, Carla; Benetti, Carla da Silva; Silveira, Patrícia Pelufo

2015-02-01

Early handling alters adult behavioral responses to palatable food and to its withdrawal following a period of chronic exposure. However, the central mechanisms involved in this phenomenon are not known. Since neonatal handling has persistent effects on stress and anxiety responses, we hypothesized that its involvement in the aforementioned association may be associated with differential neuroadaptations in the amygdala during withdrawal periods. Litters were randomized into two groups: handled (H, removed from their dam for 10min per day from the first to the tenth postnatal day and placed in an incubator at 32°C) and non-handled (NH). Experiment 1: on PNDs 80-100, females were assigned to receive palatable food+rat chow for 15 or 30 days, and these two groups were compared in terms of palatable food preference, body weight and abdominal fat deposition. In Experiment 2, H and NH rats were exposed to a chronic diet of palatable food+rat chow for 15 days, followed by (a) no withdrawal, (b) 24h withdrawal from palatable food (receiving only rat chow) or (c) 7-day withdrawal from palatable food (receiving only rat chow). Body weight, 10-min rebound palatable food intake, abdominal fat deposition, serum corticosterone as well as TH and pCREB levels in the amygdala were then compared between groups. Experiment 1-chronic exposure to palatable food induces comparable metabolic effects after 15 and 30 days. Experiment 2-neonatal handling is associated with a peculiar response to palatable food withdrawal following chronic exposure for 15 days. Rats exposed to early handling ingested less of this food after a 24h withdrawal period, and displayed increased amygdala TH and pCREB levels. Variations in the neonatal environment affect both behavioral responses and amygdala neuroadaptation to acute withdrawal from a palatable diet. These findings contribute to the comprehension of the mechanisms that link early life events and altered feeding behavior and related morbidities

SENSITIZATION TO SOCIAL ANXIOLYTIC EFFECTS OF ETHANOL IN ADOLESCENT AND ADULT SPRAGUE-DAWLEY RATS FOLLOWING REPEATED ETHANOL EXPOSURE

PubMed Central

Varlinskaya, Elena; Spear, Linda Patia

2009-01-01

Ontogenetic studies using a social interaction paradigm have shown that adolescent rats are less sensitive to anxiolytic properties of acute ethanol than their adult counterparts. It is not known, however, whether adaptations to these anxiolytic effects upon repeated experiences with ethanol would be similar in adolescents and adults. The present study investigated sensitivity to the anxiolytic effects of ethanol in adolescent and adult male and female Sprague-Dawley rats following 7 days of exposure [postnatal day (P) 27–33 for adolescents and P62–68 for adults] to 1 g/kg ethanol or saline (i.p.), as well as in animals left non-manipulated during this time. Anxiolytic effects of ethanol (0, 0.75, 1.0, 1.25, and 1.5 g/kg for adolescents and 0, 0.25, 0.5, 0.75, 1.0, and 1.25 g/kg for adults in Experiments 1 and 2, respectively) were examined 48 hours after the last exposure using a modified social interaction test under unfamiliar test circumstances. At both ages, repeated ethanol exposure resulted in the development of apparent sensitization to anxiolytic effects of ethanol indexed via enhancement of social investigation and transformation of social avoidance into social indifference or preference, as well as expression of tolerance to the socially inhibiting effects induced by higher ethanol doses. Evidence for the emergence of sensitization in adults and tolerance at both ages was seen not only following chronic ethanol, but also after chronic saline exposure, suggesting that chronic manipulation per se may be sufficient to alter the sensitivity of both adolescents and adults to socially-relevant effects of ethanol. PMID:20113878

The protective effect of omega-3 oil against the hepatotoxicity of cadmium chloride in adult and weanling rats

NASA Astrophysics Data System (ADS)

Ismail, Treefa F.; Aziz, Falah M.

2017-09-01

The purpose of the present study was to investigate the protective role of omega-3 oil against the toxic effect of cadmium as cadmium chloride (CdCl2) on the liver of male, dams and weanling rats from the histological, ultrastructural and immunohistochemical points of view. Thirty adult male and thirty adult female rats (dams) were used in the present work, divided randomly into five groups, six rats for each group and ten weanling male rats were chosen from each dam group. First group was considered as control group and given only standard diet and drinking water, second group was given (40 mg/ L) of CdCl2 in drinking water. The third group was given (60 mg/ L) of CdCl2 in drinking water. The fourth group was given (40 mg/L) of CdCl2 in drinking water plus omega-3 oil (4 gm/ kg diet) and the fifth group was given (60 mg/L) of CdCl2 in drinking water plus omega-3 oil (4 gm/ kg diet). All the above groups were left for 30 days for males and 42 days for the females) i.e. at the 21th day of the weanling rats birth). Both doses of CdCl2 have caused a lot of histological and ultrastructural alterations in the liver including high degeneration of hepatocytes. Electron microscope images showed thickening of mitochondrial membrane, variation in the size and shape of the mitochondria of the above cells and deposition of Cd particles in the lining of blood sinusoids. The hepatocytes of the weanling rats showed more ultrastructural changes especially the accumulation of lipid droplets. The immunohistochemical images of the mother liver showed a positive P53 reaction in the cells of the liver of CdCl2 treated rats especially those around the portal area. These reactions disappeared in the omega-3 plus CdCl2 groups. The present results suggested a protective role of omega-3 against the cadmium induced hepatotoxicity.

Cytokeratin 8 in Association with sdLDL and ELISA Development

PubMed Central

Ashmaig, Mohmed

2015-01-01

Background: Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide. Cytokeratins (CKs) which may also be expressed in vascular smooth muscle cells (SMCs) are generally considered to be markers for the differentiation of epithelial cells. Small, dense, low-density lipoprotein (sdLDL) particles, also termed LDL-IV, independently predict risk of CVD. Aims: The aims of this study were to develop an analytical method, apart from ultracentrifugation capable of isolating sdLDL in order to study any associated proteins. Materials and Methods: Using modified gradient gel electrophoresis (GGE), de-identified sdLDL-enriched plasma was used to physically elute and isolate sdLDL particles. To validate the finding, additional plasma from 77 normal and 48 higher risk subjects were used to measure sdLDL particles and CK8. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting method were used to identify the characteristics of proteins associated with sdLDL. An enzyme-linked immunosorbent assay (ELISA) method was developed and validated for the measurement of CK8 in plasma. Results: The validation of the CK8 ELISA method showed good analytical performance. The isolated sdLDL particles were verified with nondenaturing GGE with the apolipoprotein B component confirmed by Western immunoblotting. Confirmed by SDS-PAGE and Western immunoblotting, CK8 was associated with sdLDL. Two-tailed statistical analysis showed that CK8 and sdLDL particles were significantly higher in the high-risk CVD group compared to control group (P < 0.01 and P < 0.01, respectively). Conclusion: This study reports a novel association between CK8 and sdLDL in individuals with CVD who have a predominance of sdLDL. PMID:26713292

Mouse embryonic stem cell-derived cells reveal niches that support neuronal differentiation in the adult rat brain.

PubMed

Maya-Espinosa, Guadalupe; Collazo-Navarrete, Omar; Millán-Aldaco, Diana; Palomero-Rivero, Marcela; Guerrero-Flores, Gilda; Drucker-Colín, René; Covarrubias, Luis; Guerra-Crespo, Magdalena

2015-02-01

A neurogenic niche can be identified by the proliferation and differentiation of its naturally residing neural stem cells. However, it remains unclear whether "silent" neurogenic niches or regions suitable for neural differentiation, other than the areas of active neurogenesis, exist in the adult brain. Embryoid body (EB) cells derived from embryonic stem cells (ESCs) are endowed with a high potential to respond to specification and neuralization signals of the embryo. Hence, to identify microenvironments in the postnatal and adult rat brain with the capacity to support neuronal differentiation, we transplanted dissociated EB cells to conventional neurogenic and non-neurogenic regions. Our results show a neuronal differentiation pattern of EB cells that was dependent on the host region. Efficient neuronal differentiation of EB cells occurred within an adjacent region to the rostral migratory stream. EB cell differentiation was initially patchy and progressed toward an even distribution along the graft by 15-21 days post-transplantation, giving rise mostly to GABAergic neurons. EB cells in the striatum displayed a lower level of neuronal differentiation and derived into a significant number of astrocytes. Remarkably, when EB cells were transplanted to the striatum of adult rats after a local ischemic stroke, increased number of neuroblasts and neurons were observed. Unexpectedly, we determined that the adult substantia nigra pars compacta, considered a non-neurogenic area, harbors a robust neurogenic environment. Therefore, neurally uncommitted cells derived from ESCs can detect regions that support neuronal differentiation within the adult brain, a fundamental step for the development of stem cell-based replacement therapies. © 2014 AlphaMed Press.

Adolescent social isolation affects schizophrenia-like behavior and astrocyte biomarkers in the PFC of adult rats.

PubMed

Sun, Lan; Min, Li; Zhou, Hao; Li, Man; Shao, Feng; Wang, Weiwen

2017-08-30

Social isolation is regarded as a cause of schizophrenia spectrum disorders. Animal models of schizophrenia are constructed by repeated early environment deprivation as an important paradigm to reveal its pathological mechanism. Male Sprague Dawley rats were assigned to either social-rearing (SR) or isolated-rearing (IR) groups during postnatal days (PNDs) 21-34. On PND 56, all rats underwent behavioral testing including locomotor activity, anxiety-related behaviors in an open field and prepulse inhibition (PPI). Then, the rats were sacrificed and prefrontal cortex (PFC) tissues were separated for high-throughput proteomics analysis and Western blot validation. Rats of the IR group showed increased spontaneous locomotion, increased anxiety-like behavior and disrupted PPI compared with rats of the SR group. Based on proteomics analysis, a total of 124 PFC proteins were found to be significantly differentially expressed between the SR group and the IR group, the most remarkable of which were glial fibrillary acidic protein (GFAP), Annexin A2 (ANXA2) and vimentin (VIM), three astrocyte biomarkers. Further Western blot measurement confirmed that the levels of GFAP, ANXA2 and VIM were increased significantly in IR rats. Adolescent social isolation induced schizophrenia-like behaviors and significantly different expression of 124 PFC proteins in adult rats, especially GFAP, ANXA2 and VIM, which suggests that astrocyte development might be involved in the neural mechanism of schizophrenia. Copyright © 2017. Published by Elsevier B.V.

Fluoxetine Dose and Administration Method Differentially Affect Hippocampal Plasticity in Adult Female Rats

PubMed Central

Pawluski, Jodi L.; van Donkelaar, Eva; Abrams, Zipporah; Steinbusch, Harry W. M.; Charlier, Thierry D.

2014-01-01

Selective serotonin reuptake inhibitor medications are one of the most common treatments for mood disorders. In humans, these medications are taken orally, usually once per day. Unfortunately, administration of antidepressant medications in rodent models is often through injection, oral gavage, or minipump implant, all relatively stressful procedures. The aim of the present study was to investigate how administration of the commonly used SSRI, fluoxetine, via a wafer cookie, compares to fluoxetine administration using an osmotic minipump, with regards to serum drug levels and hippocampal plasticity. For this experiment, adult female Sprague-Dawley rats were divided over the two administration methods: (1) cookie and (2) osmotic minipump and three fluoxetine treatment doses: 0, 5, or 10 mg/kg/day. Results show that a fluoxetine dose of 5 mg/kg/day, but not 10 mg/kg/day, results in comparable serum levels of fluoxetine and its active metabolite norfluoxetine between the two administration methods. Furthermore, minipump administration of fluoxetine resulted in higher levels of cell proliferation in the granule cell layer (GCL) at a 5 mg dose compared to a 10 mg dose. Synaptophysin expression in the GCL, but not CA3, was significantly lower after fluoxetine treatment, regardless of administration method. These data suggest that the administration method and dose of fluoxetine can differentially affect hippocampal plasticity in the adult female rat. PMID:24757568

Neuropeptide S alters anxiety, but not depression-like behaviour in Flinders Sensitive Line rats: a genetic animal model of depression.

PubMed

Wegener, Gregers; Finger, Beate C; Elfving, Betina; Keller, Kirsten; Liebenberg, Nico; Fischer, Christina W; Singewald, Nicolas; Slattery, David A; Neumann, Inga D; Mathé, Aleksander A

2012-04-01

Neuropeptide S (NPS) and its receptor (NPSR) have been implicated in the mediation of anxiolytic-like behaviour in rodents. However, little knowledge is available regarding the NPS system in depression-related behaviours, and whether NPS also exerts anxiolytic effects in an animal model of psychopathology. Therefore, the aim of this work was to characterize the effects of NPS on depression- and anxiety-related parameters, using male and female rats in a well-validated animal model of depression: the Flinders Sensitive Line (FSL), their controls, the Flinders Resistant Line (FRL), and Sprague-Dawley (SD) rats. We found that FSL showed greater immobility in the forced swim test (FST) than FRL, confirming their phenotype. However, NPS did not affect depression-related behaviour in any rat line. No significant differences in baseline anxiety levels between the FSL and FRL strains were observed, but FSL and FRL rats displayed less anxiety-like behaviour compared to SD rats. NPS decreased anxiety-like behaviour on the elevated plus-maze in all strains. The expression of the NPSR in the amygdala, periventricular hypothalamic nucleus, and hippocampus was equal in all male strains, although a trend towards reduced expression within the amygdala was observed in FSL rats compared to SD rats. In conclusion, NPS had a marked anxiolytic effect in FSL, FRL and SD rats, but did not modify the depression-related behaviour in any strain, in spite of the significant differences in innate level between the strains. These findings suggest that NPS specifically modifies anxiety behaviour but cannot overcome/reverse a genetically mediated depression phenotype.

Amphetamine modulates brain signal variability and working memory in younger and older adults.

PubMed

Garrett, Douglas D; Nagel, Irene E; Preuschhof, Claudia; Burzynska, Agnieszka Z; Marchner, Janina; Wiegert, Steffen; Jungehülsing, Gerhard J; Nyberg, Lars; Villringer, Arno; Li, Shu-Chen; Heekeren, Hauke R; Bäckman, Lars; Lindenberger, Ulman

2015-06-16

Better-performing younger adults typically express greater brain signal variability relative to older, poorer performers. Mechanisms for age and performance-graded differences in brain dynamics have, however, not yet been uncovered. Given the age-related decline of the dopamine (DA) system in normal cognitive aging, DA neuromodulation is one plausible mechanism. Hence, agents that boost systemic DA [such as d-amphetamine (AMPH)] may help to restore deficient signal variability levels. Furthermore, despite the standard practice of counterbalancing drug session order (AMPH first vs. placebo first), it remains understudied how AMPH may interact with practice effects, possibly influencing whether DA up-regulation is functional. We examined the effects of AMPH on functional-MRI-based blood oxygen level-dependent (BOLD) signal variability (SD(BOLD)) in younger and older adults during a working memory task (letter n-back). Older adults expressed lower brain signal variability at placebo, but met or exceeded young adult SD(BOLD) levels in the presence of AMPH. Drug session order greatly moderated change-change relations between AMPH-driven SD(BOLD) and reaction time means (RT(mean)) and SDs (RT(SD)). Older adults who received AMPH in the first session tended to improve in RT(mean) and RT(SD) when SD(BOLD) was boosted on AMPH, whereas younger and older adults who received AMPH in the second session showed either a performance improvement when SD(BOLD) decreased (for RT(mean)) or no effect at all (for RT(SD)). The present findings support the hypothesis that age differences in brain signal variability reflect aging-induced changes in dopaminergic neuromodulation. The observed interactions among AMPH, age, and session order highlight the state- and practice-dependent neurochemical basis of human brain dynamics.

Early Ethanol and Water Consumption: Accumulating Experience Differentially Regulates Drinking Pattern and Bout Parameters in Male Alcohol Preferring (P) vs. Wistar and Sprague Dawley Rats

PubMed Central

Azarov, Alexey V.; Woodward, Donald J.

2013-01-01

Alcohol-preferring (P) rats develop high ethanol intake over several weeks of water/10% ethanol (10E) choice drinking. However, it is not yet clear precisely what components of drinking behavior undergo modification to achieve higher intake. Our concurrent report compared precisely measured daily intake in P vs. non-selected Wistar and Sprague Dawley (SD) rats. Here we analyze their drinking patterns and bouts to clarify microbehavioral components that are common to rats of different origin, vs. features that are unique to each. Under sole-fluid conditions P, Wistar and SD rats all consumed water at a high initial rate followed by a slow maintenance phase, but 10E - in a distinctly different step-like pattern of evenly distributed bouts. During choice period, 10E vs. water patterns for P rat appeared as an overlap of sole-fluid patterns. The SD rat choice patterns resembled sole-fluid patterns but were less regular. Choice patterns in Wistar differed from both P and SD rats, by consisting of intermixed small frequent episodes of drinking both 10E and water. Wistar and SD rats increased choice ethanol intake by elevating the number of bouts. A key finding was that P rat increased choice ethanol intake through a gradual increase of the bout size and duration, but kept bout number constant. This supports the hypothesis that genetic selection modifies microbehavioral machinery controlling drinking bout initiation, duration, and other pattern features. Precision analysis of drinking patterns and bouts allows differentiation between genetic lines, and provides a venue for study of localized circuit and transmitter influences mediating mesolimbic control over ethanol consumption. PMID:24095931

Effects of chronic overload on muscle hypertrophy and mTOR signaling in adult and aged rats

USDA-ARS?s Scientific Manuscript database

We examined the effect of 28 days of overload on mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) signaling in young adult (Y; 6 mo old) and aged (O; 30 mo old) Fischer 344 x Brown Norway rats subjected to bilateral synergist ablation (SA) of two-thirds of the gas...

Prolongation of GFP-expressed skin graft after intrathymic injection of GFP positive splenocytes in adult rat

NASA Astrophysics Data System (ADS)

Hakamata, Yoji; Igarashi, Yuka; Murakami, Takashi; Kobayashi, Eiji

2006-02-01

GFP is a fluorescent product of the jellyfish Aequorea victoria and has been used for a variety of biological experiments as a reporter molecule. While GFP possesses advantages for the non-invasive imaging of viable cells, GFP-positive cells are still considered potential xeno-antigens. It is difficult to observe the precise fate of transplanted cells/organs in recipients without immunological control. The aim of this study was to determine whether intrathymic injection of GFP to recipients and the depletion of peripheral lymphocytes could lead to donor-specific unresponsiveness to GFP-expressed cell. LEW rats were administered intraperitoneally with 0.2 ml of anti-rat lymphocyte serum (ALS) 1 day prior to intrathymic injection of donor splenocytes or adeno-GFP vector. Donor cells and vector were non-invasively inoculated into the thymus under high frequency ultrasound imaging using an echo-guide. All animals subsequently received a 7 days GFP-expressed skin graft from the same genetic background GFP LEW transgenic rat. Skin graft survival was greater in rats injected with donor splenocytes (23.6+/-9.1) compared with adeno-GFP (13.0+/-3.7) or untreated control rats (9.5+/-1.0). Intrathymic injection of donor antigen into adult rats can induce donor-specific unresponsiveness. Donor cells can be observed for a long-term in recipients with normal immunity using this strategy.

Can Anxiety Tested in the Elevated Plus-maze Be Related to Nociception Sensitivity in Adult Male Rats?

PubMed

Pometlová, Marie; Yamamotová, Anna; Nohejlová, Kateryna; Šlamberová, Romana

Methamphetamine (MA) is one of the most addictive psychostimulant drugs with a high potential for abuse. Our previous studies demonstrated that MA administered to pregnant rats increases pain sensitivity and anxiety in their adult offspring and makes them more sensitive to acute administration of the same drug in adulthood. Because individuals can differ considerably in terms of behaviour and physiology, such as rats that do not belong in some characteristics (e.g. anxiety) to average, can be described as low-responders or high-responders, are then more or less sensitive to pain. Therefore, prenatally MA-exposed adult male rats treated in adulthood with a single dose of MA (1 mg/ml/kg) or saline (1 ml/kg) were tested in the present study. We examined the effect of acute MA treatment on: (1) the anxiety in the Elevated plus-maze (EPM) test and memory in EPM re-test; (2) nociception sensitivity in the Plantar test; (3) the correlation between the anxiety, memory and the nociception. Our results demonstrate that: (1) MA has an anxiogenic effect on animals prenatally exposed to the same drug in the EPM; (2) all the differences induced by acute MA treatment disappeared within the time of 48 hours; (3) there was no effect of MA on nociception per se, but MA induced higher anxiety in individuals less sensitive to pain than in animals more sensitive to pain. In conclusion, the present study demonstrates unique data showing association between anxiety and nociceptive sensitivity of prenatally MA-exposed rats that is induced by acute drug administration.

Cocaine enhances resistance to extinction of responding for brain-stimulation reward in adult prenatally stressed rats.

PubMed

Gao, Shuibo; Suenaga, Toshiko; Oki, Yutaka; Yukie, Masao; Nakahara, Daiichiro

2011-10-01

The present experiment assessed whether prenatal stress (PS) can alter the ability of acute and chronic cocaine administration to increase and decrease the rewarding effectiveness of the medial forebrain bundle (MFB) using intracranial self-stimulation (ICSS), and also whether PS can affect the extinction of the MFB stimulation response. Adult male offspring of female rats that received PS or no PS (nPS) were implanted with MFB stimulating electrodes, and were then tested in ICSS paradigms. In both nPS and PS offspring, acute cocaine injection decreased ICSS thresholds dose-dependently. However, the threshold-lowering effects at any dose were not significantly different between groups. There was also no group-difference in the threshold-elevating effects of chronic cocaine administration. Nevertheless, chronically drug-administered PS rats exhibited a resistance to the extinguishing of the response for brain-stimulation reward when acutely treated with cocaine, as compared to extinction without cocaine treatment. The results suggest that PS may weaken the ability for response inhibition under cocaine loading in male adult offspring. Copyright © 2011 Elsevier B.V. All rights reserved.

Effect of methamphetamine exposure and cross-fostering on cognitive function in adult male rats.

PubMed

Hrubá, Lenka; Schutová, Barbora; Pometlová, Marie; Rokyta, Richard; Slamberová, Romana

2010-03-17

The aim of our study was to examine the effect of prenatal methamphetamine (MA) exposure and cross-fostering on cognitive functions of adult male rats tested in Morris water maze (MWM). Rat mothers were exposed daily to injection of MA (5mg/kg) or saline for 9 weeks: prior to impregnation, throughout gestation and lactation periods. Females without any injections were used as an absolute control. On postnatal day 1, pups were cross-fostered so that each mother raised 4 pups of her own and 8 pups from the mothers with the other two treatments. Four types of tests were used: (1) Place navigation test (Learning), (2) Probe test (Probe), (3) Retention memory test (Memory) and (4) Visible platform task. Our results demonstrate that the prenatal exposure to MA does not impact learning and memory, while postnatal exposure to MA shows impairments in cognition. In the test of learning, all animals fostered to MA-treated dams had longer latencies, bigger search error and used lower spatial strategies than the animals fostered to control or saline-treated mother, regardless of prenatal exposure. Regardless of postnatal exposure, the animals prenatally exposed to saline swam faster in all the tests than the animals prenatally exposed to MA and controls, respectively. This study indicates that postnatal but not prenatal exposure to MA affects learning in adult male rats. However, it is still not clear whether these impairments are due to a direct effect of MA on neuronal structure or due to an indirect effect of MA mediated by impaired maternal care. Copyright 2009 Elsevier B.V. All rights reserved.

Role of Oxytocin in deceleration of early atherosclerotic inflammatory processes in adult male rats

PubMed Central

Ahmed, Marwa A; ELosaily, Gehan M

2011-01-01

Objective: The study aimed to examine the effect of exogenous OT administration on the inflammation and atherosclerosis in adult male rats and its possible mechanisms. Thirty adult male rats equally divided into three groups. Control group fed regular diet; group II fed control diet supplemented with L-methionine for 10 weeks. Group III received L-methionine and oxytocin treatment for 10 weeks. RT-PCR analysis showed that OT administration increased oxytocin receptor mRNA (2 fold, P, 0.05). Blood samples were evaluated for total homocysteine, interlukin-6 (IL-6), monocyte chemoatrratant protein-1 (MCP-1) and C-reactive protein (CRP) by ELIZA, lipid profile, nitric oxide (NO), malondialdehyde (MDA) and reduced glutathione (GSH) were determined. Specimens from aorta were processed for immunohistochemical staining for Aorta nuclear factor _B (NF-κB) p65 protein. Result showed that OT administration to group III decreased the plasma levels IL-6, MCP-1 and CRP levels which were elevated in group II. Moreover, there was decrease of the oxidative stress of group III in terms of increased plasma levels of NO and GSH and decreased plasma levels of MDA in blood. In addition, rats of group II showed histological abnormalities manifested by thickening and ulceration of the aortic wall. Marked increased expression of NF-κB in aorta of in group II was detected. However, OT administration restores the histological structure of the aorta and decreased the expression of NF-κB in aorta of group III similar to the control group. Conclusion: OT has anti inflammatory pathway in atherosclerosis as it decelerates atherosclerosis by decreasing the proinflammatory responses through many mechanisms, mainly the up regulation of its receptors. PMID:21977229

A comparison of the apoptotic effect of Delta(9)-tetrahydrocannabinol in the neonatal and adult rat cerebral cortex.

PubMed

Downer, Eric J; Gowran, Aoife; Campbell, Veronica A

2007-10-17

The maternal use of cannabis during pregnancy results in a number of cognitive deficits in the offspring that persist into adulthood. The endocannabinoid system has a role to play in neurodevelopmental processes such as neurogenesis, migration and synaptogenesis. However, exposure to phytocannabinoids, such as Delta(9)-tetrahydrocannabinol, during gestation may interfere with these events to cause abnormal patterns of neuronal wiring and subsequent cognitive impairments. Aberrant cell death evoked by Delta(9)-tetrahydrocannabinol may also contribute to cognitive deficits and in cultured neurones Delta(9)-tetrahydrocannabinol induces apoptosis via the CB(1) cannabinoid receptor. In this study we report that Delta(9)-tetrahydrocannabinol (5-50 microM) activates the stress-activated protein kinase, c-jun N-terminal kinase, and the pro-apoptotic protease, caspase-3, in in vitro cerebral cortical slices obtained from the neonatal rat brain. The proclivity of Delta(9)-tetrahydrocannabinol to impact on these pro-apoptotic signalling molecules was not observed in in vitro cortical slices obtained from the adult rat brain. In vivo, subcutaneous administration of Delta(9)-tetrahydrocannabinol (1-30 mg/kg) activated c-jun N-terminal kinase, caspase-3 and cathepsin-D, and induced DNA fragmentation in the cerebral cortex of neonatal rats. In contrast, in vivo administration of Delta(9)-tetrahydrocannabinol to adult rats was not associated with the apoptotic pathway in the cerebral cortex. The data provide evidence which supports the hypothesis that the neonatal rat brain is more vulnerable to the neurotoxic influence of Delta(9)-tetrahydrocannabinol, suggesting that the cognitive deficits that are observed in humans exposed to marijuana during gestation may be due, in part, to abnormal engagement of the apoptotic cascade during brain development.

[Cellphone electromagnetic radiation damages the testicular ultrastructure of male rats].

PubMed

Gao, Xiao-Hui; Hu, Hui-Rong; Ma, Xue-Lian; Chen, Jie; Zhang, Guo-Hong

2016-06-01

To investigate the influence of cellphone electromagnetic radiation (CER) on the testicular ultrastructure and the apoptosis of spermatogenic cells in male rats.atability, feasibility, applicability, and controllability in the construction of experimental animal models, we compared the major anatomic features of the penis of 20 adult beagle dogs with those of 10 adult men. Using microsurgical techniques, we performed cross-transplantation of the penis in the 20 (10 pairs) beagle dogs and observed the survival rate of the transplanted penises by FK506+MMF+MP immune induction. We compared the relevant indexes with those of the 10 cases of microsurgical replantation of the amputated penis. Thirty adult male SD rats were equally randomized into a 2 h CER, a 4 h CER, and a normal control group, the former two groups exposed to 30 days of 900 MHz CER for 2 and 4 hours a day, respectively, while the latter left untreated. Then the changes in the ultrastructure of the testis tissue were observed under the transmission electron microscope and the apoptosis of the spermatogenic cells was determined by TUNEL. Compared with the normal controls, the rats of the 2 h CER group showed swollen basement membrane of seminiferous tubules, separated tight junction of Sertoli cells, increased cell intervals, apparent vacuoles and medullization in some mitochondria, and increased apoptosis of spermatogenic cells, mainly the apoptosis of primary spermatocytes (P<0.05 ). In comparison with the 2 h CER group, the animals of the 4 h CER group exhibited swollen basement membrane of seminiferous tubules, more separated tight junction of Sertoli cells, wider cell intervals, incomplete membrane of spermatogonial cells, fragments of cytoplasm, nuclear pyknosis and notch, slight dilation of perinuclear space, abnormalities of intracellular mitochondria with vacuoles, fuzzy structure, and fusion or disappearance of some cristae, and increased damage of mitochondria and apoptosis of spermatogenic

Fertility of male adult rats submitted to forced swimming stress.

PubMed

Mingoti, G Z; Pereira, R N; Monteiro, C M R

2003-05-01

We investigated whether stress interferes with fertility during adulthood. Male Wistar rats (weighing 220 g in the beginning of the experiment) were forced to swim for 3 min in water at 32 degrees C daily for 15 days. Stress was assessed by the hot-plate test after the last stressing session. To assess fertility, control and stressed males (N = 15 per group) were mated with sexually mature normal females. Males were sacrificed after copulation. Stress caused by forced swimming was demonstrated by a significant increase in the latency of the pain response in the hot-plate test (14.6 +/- 1.25 s for control males vs 26.0 +/- 1.53 s for stressed males, P = 0.0004). No changes were observed in body weight, testicular weight, seminal vesicle weight, ventral prostate weight or gross histological features of the testes of stressed males. Similarly, no changes were observed in fertility rate, measured by counting live fetuses in the uterus of normal females mated with control and stressed males; no dead or incompletely developed fetuses were observed in the uterus of either group. In contrast, there was a statistically significant decrease in spermatid production demonstrated by histometric evaluation (154.96 +/- 5.41 vs 127.02 +/- 3.95 spermatids per tubular section for control and stressed rats, respectively, P = 0.001). These data demonstrate that 15 days of forced swimming stress applied to adult male rats did not impair fertility, but significantly decreased spermatid production. This suggests that the effect of stress on fertility should not be assessed before at least the time required for one cycle of spermatogenesis.

The effect of phloretin on synaptic proteins and adult hippocampal neurogenesis in Aβ (1-42)-injected male Wistar rats.

PubMed

Ghumatkar, Priya; Peshattiwar, Vaibhavi; Patil, Sachin; Muke, Suraj; Whitfield, David; Howlett, David; Francis, Paul; Sathaye, Sadhana

2018-04-23

Considering the deleterious effect of Aβ1-42, a study was designed to evaluate the effect of phloretin on altered synaptic proteins and adult hippocampal neurogenesis in Aβ1-42-injected Wistar rats. The rats were pretreated with 5 mg/kg p.o dose of phloretin and donepezil (positive control) for 28 days, followed by intrahippocampal injections of aggregated Aβ1-42. After termination, perfused brains were isolated and subjected to Western blot and immunohistochemistry (IHC) analysis. The Western blot revealed that Aβ1-42-injected rats had significantly low levels of synaptophysin as compared to sham control. Phloretin pretreatment significantly protected the presynaptic protein synaptophysin against the effects of Aβ1-42. There were no significant changes in the levels of PSD95 between different groups. The IHC findings showed that Aβ1-42 significantly reduced the Ki67 and DCX in the dentate gyrus as compared to sham control. However, phloretin significantly improved the number of Ki67- and DCX-positive neurons in the dentate gyrus region as compared to Aβ1-42 group. This study demonstrated the protective effect of phloretin on synaptophysin and adult neuronal proliferating cells in Aβ1-42-injected rats. The encouraging findings highlight the potential of phloretin as a dietary supplement targeting key therapeutic mechanisms in neurodegenerative disorders such as AD. © 2018 Royal Pharmaceutical Society.

Behavioral effects of subchronic inhalation of toluene in adult rats.

PubMed

Beasley, Tracey E; Evansky, Paul A; Gilbert, Mary E; Bushnell, Philip J

2010-01-01

Whereas the acute neurobehavioral effects of toluene are robust and well characterized, evidence for persistent effects of repeated exposure to this industrial solvent is less compelling. The present experiment sought to determine whether subchronic inhalation of toluene caused persistent behavioral changes in rats. Adult male Long-Evans rats inhaled toluene vapor (0, 10, 100, or 1000 ppm) for 6h/day, 5 days/week for 13 weeks and were evaluated on a series of behavioral tests beginning 3 days after the end of exposure. Toluene delayed appetitively-motivated acquisition of a lever-press response, but did not affect motor activity, anxiety-related behavior in the elevated plus maze, trace fear conditioning, acquisition of an appetitively-motivated visual discrimination, or performance of a visual signal detection task. Challenges with acute inhalation of toluene vapor (1200-2400 ppm for 1 h) and injections of quinpirole (0.01-0.03 mg/kg) and raclopride (0.03-0.10 mg/kg) revealed no toluene-induced latent impairments in visual signal detection. These results are consistent with a pattern of subtle and inconsistent long-term effects of daily exposure to toluene vapor, in contrast to robust and reliable effects of acute inhalation of the solvent. Published by Elsevier Inc.

Salicylate-induced changes in auditory thresholds of adolescent and adult rats.

PubMed

Brennan, J F; Brown, C A; Jastreboff, P J

1996-01-01

Shifts in auditory intensity thresholds after salicylate administration were examined in postweanling and adult pigmented rats at frequencies ranging from 1 to 35 kHz. A total of 132 subjects from both age levels were tested under two-way active avoidance or one-way active avoidance paradigms. Estimated thresholds were inferred from behavioral responses to presentations of descending and ascending series of intensities for each test frequency value. Reliable threshold estimates were found under both avoidance conditioning methods, and compared to controls, subjects at both age levels showed threshold shifts at selective higher frequency values after salicylate injection, and the extent of shifts was related to salicylate dose level.

Intravenous Single Dose Toxicity of Sweet Bee Venom in Sprague-Dawley Rats

PubMed Central

Lee, Kwang-Ho; Yu, JunSang; Sun, Seungho; Kwon, KiRok

2015-01-01

Objectives: Anaphylactic shock can be fatal to people who become hypersensitive when bee venom pharmacopuncture (BVP) is used. Thus, sweet bee venom (SBV) was developed to reduce these allergic responses. SBV is almost pure melittin, and SBV has been reported to have fewer allergic responses than BVP. BVP has been administered only into acupoints or intramuscularly, but we thought that intravenous injection might be possible if SBV were shown to be a safe medium. The aim of this study is to evaluate the intravenous injection toxicity of SBV through a single-dose test in Sprague-Dawley (SD) rats. Methods: Male and female 6-week-old SD rats were injected intravenously with SBV (high dosage: 1.0 mL/animal; medium dosage: 0.5 mL/animal; low dosage: 0.1 mL/animal). Normal saline was injected into the control group in a similar method. We conducted clinical observations, body weight measurements, and hematology, biochemistry, and histological observations. Results: No death was observed in any of the experimental groups. Hyperemia was observed in the high and the medium dosage groups on the injection day, but from next day, no general symptoms were observed in any of the experimental groups. No significant changes due to intravenous SBV injection were observed in the weights, in the hematology, biochemistry, and histological observations, and in the local tolerance tests. Conclusion: The results of this study confirm that the lethal dose of SBV is over 1.0 mL/animal in SD rats and that the intravenous injection of SBV is safe in SD rats. PMID:26389001

Effects of thyroid hormone on Leydig cell regeneration in the adult rat following ethane dimethane sulphonate treatment.

PubMed

Ariyaratne, H B; Mills, N; Mason, J I; Mendis-Handagama, S M

2000-10-01

We tested the effects of thyroid hormone on Leydig cell (LC) regeneration in the adult rat testis after ethane dimethyl sulphonate (EDS) treatment. Ninety-day-old, thyroid-intact (n = 96) and thyroidectomized (n = 5) male Sprague-Dawley rats were injected intraperitoneally (single injection) with EDS (75 mg/kg) to destroy LC. Thyroid-intact, EDS-treated rats were equally divided into three groups (n = 32 per group) and treated as follows: control (saline-injected), hypothyroid (provided 0.1% propyl thiouracil in drinking water), and hyperthyroid (received daily subcutaneous injections of tri-iodothyronine, 100 microg/kg). Testing was done at Days 2, 7, 14, and 21 for thyroid-intact rats and at Day 21 for thyroidectomized rats after the EDS treatment. Leydig cells were absent in control and hyperthyroid rats at Days 2, 7, and 14; in hypothyroid rats at all ages; and in thyroidectomized rats at Day 21. The LC number per testis in hyperthyroid rats was twice as those of controls at Day 21. 3beta-Hydroxysteroid dehydrogenase (LC marker) immunocytochemistry results agreed with these findings. Mesenchymal cell number per testis was similar in the three treatment groups of thyroid-intact rats on Days 2 and 7, but it was different on Days 14 and 21. The highest number was in the hypothyroid rats, and the lowest was in the hyperthyroid rats. Serum testosterone levels could be measured in control rats only on Day 21, were undetectable in hypothyroid rats at all stages, and were detected in hyperthyroid rats on Days 14 and 21. These levels in hyperthyroid rats were twofold greater than those of controls on Day 21. Serum androstenedione levels could be measured only in the hyperthyroid rats on Day 21. Testosterone and androstenedione levels in the incubation media showed similar patterns to those in serum, but with larger values. These findings indicate that hypothyroidism inhibits LC regeneration and hyperthyroidism results in accelerated differentiation of more mesenchymal

Experimentally induced hyperthyroidism influences oxidant and antioxidant status and impairs male gonadal functions in adult rats.

PubMed

Asker, M E; Hassan, W A; El-Kashlan, A M

2015-08-01

The objective of the present experiment was to study the effect of hyperthyroidism on male gonadal functions and oxidant/antioxidant biomarkers in testis of adult rats. Induction of hyperthyroidism by L-thyroxine (L-T4, 300 μg kg(-1) body weight) treatment once daily for 3 or 8 weeks caused a decrease in body weight gain as well as in absolute genital sex organs weight. The epididymal sperm counts and their motility were significantly decreased in a time-dependent manner following L-T4 treatment. Significant decline in serum levels of luteinising hormone, follicle stimulating hormone and testosterone along with significant increase in serum estradiol level was observed in hyperthyroid rats compared with euthyroid ones. Significant increase in malondialdehyde and nitric oxide concentration associated with significant decrease in superoxide dismutase and catalase activity was also noticed following hyperthyroidism induction. Both reduced glutathione content and glutathione peroxidase activity were increased in hyperthyroid rats compared with control rats. Marked histopathological alterations were observed in testicular section of hyperthyroid rats. These results provide evidence that hypermetabolic state induced by excess level of thyroid hormones may be a causative factor for the impairment of testicular physiology as a consequence of oxidative stress. © 2014 Blackwell Verlag GmbH.

Extinction-induced "despair" in aged and adult rats: links to neurotrophins in frontal cortex and hippocampus.

PubMed

Topic, Bianca; Huston, Joseph P; Namestkova, Katerina; Zhu, Shun-Wei; Mohammed, Abdul H; Schulz, Daniela

2008-10-01

In the search for animal models of human geriatric depression, we found that operant extinction of escape from water results in the expression of immobility in different age groups, indicative of behavioral "despair", which was also associated with the resistance-to-extinction (RTE) expressed by these animals. With respect to the neurotrophin hypothesis of depression, nerve-growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) protein levels in frontal cortex (FC) and hippocampus (HP) were examined and related to behavioral immobility and RTE in the water maze in aged and adult Wistar rats. Age-related increases in levels of NGF were found in HP and of NT-3 in FC. Indices of immobility showed relationships in the aged with NGF and, in adults, with BDNF, pointing to a dissociation of neurotrophic involvement in extinction trial-induced "despair" in aged and adult rats. The present results support the hypothesis, that extinction-induced immobility in the water maze reflects a state akin to behavioral despair and point to age-related differences of neurotrophic involvement in depressive-like symptoms. The concept of extinction-induced behavioral "despair" in the aged subsumes several aspects of human geriatric depression, such as co-morbidity of learning impairment and anxiety, and, thus could represent a useful paradigm to examine the neuronal mechanisms underlying depression, especially in aged rodents.

Anti-NGF monoclonal antibody muMab 911 does not deplete neurons in the superior cervical ganglia of young or old adult rats.

PubMed

Marcek, John; Okerberg, Carlin; Liu, Chang-Ning; Potter, David; Butler, Paul; Boucher, Magalie; Zorbas, Mark; Mouton, Peter; Nyengaard, Jens R; Somps, Chris

2016-10-01

Nerve growth factor (NGF) blocking therapies are an emerging and effective approach to pain management. However, concerns about the potential for adverse effects on the structure and function of the peripheral nervous system have slowed their development. Early studies using NGF antisera in adult rats reported effects on the size and number of neurons in the sympathetic chain ganglia. In the work described here, both young adult (6-8 week) and fully mature (7-8 month) rats were treated with muMab 911, a selective, murine, anti-NGF monoclonal antibody, to determine if systemic exposures to pharmacologically active levels of antibody for 1 month cause loss of neurons in the sympathetic superior cervical ganglia (SCG). State-of-the-art, unbiased stereology performed by two independent laboratories was used to determine the effects of muMab 911 on SCG neuronal number and size, as well as ganglion size. Following muMab 911 treatment, non-statistically significant trends toward smaller ganglia, and smaller and fewer neurons, were seen when routine, nonspecific stains were used in stereologic assessments. However, when noradrenergic neurons were identified using tyrosine hydroxylase (TH) immunoreactivity, trends toward fewer neurons observed with routine stains were not apparent. The only statistically significant effects detected were lower SCG weights in muMab 911-treated rats, and a smaller volume of TH immunoreactivity in neurons from younger rats treated with muMab 911. These results indicate that therapeutically relevant exposures to the anti-NGF monoclonal antibody muMab 911 for 1 month have no effect on neuron numbers within the SCG from young or old adult rats. Copyright © 2016 Elsevier B.V. All rights reserved.

Offspring predisposition to obesity due to maternal-diet-induced obesity in rats is preventable by dietary normalization before mating.

PubMed

Castro, Heriberto; Pomar, Catalina Amadora; Palou, Andreu; Picó, Catalina; Sánchez, Juana

2017-03-01

We studied in rats whether the expected detrimental effects in offspring associated to maternal dietary obesity may be reverted by obesogenic diet removal 1 month before mating. Female rats were fed a cafeteria diet (CD) from days 10 to 100 and then a standard diet (SD) (postcafeteria rats). One month after CD removal, postcafeteria rats and a group of SD-fed female rats (controls) were mated with males. At weaning, offspring were fed SD and followed until 4 months old. CD was effective at inducing obesity in dams. Its removal led to a reduction in body weight, although, after 30 days, rats retained excess body weight and fat than controls. During lactation, postcafeteria dams showed greater body fat, and higher leptin and adiponectin levels in milk than controls. From 2 months of life, offspring of postcafeteria dams displayed lower body weight than controls, with no differences in the percentage of fat, homeostatic model assessment for insulin resistance, or circulating parameters. Removal of CD in obese rats before gestation, although without complete reversion of body weight excess, may prevent the expected detrimental effects in offspring associated to an excess fat accumulation in adulthood and the related metabolic disturbances. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The sdA problem - I. Physical properties

NASA Astrophysics Data System (ADS)

Pelisoli, Ingrid; Kepler, S. O.; Koester, D.

2018-04-01

The so-called sdA stars are defined by having H-rich spectra and surface gravities similar to hot subdwarf stars, but effective temperature below the zero-age horizontal branch. Their evolutionary history is an enigma: their surface gravity is too high for main-sequence stars, but too low for single evolution white dwarfs. They are most likely byproducts of binary evolution, including blue-stragglers, extremely-low mass white dwarf stars (ELMs) and their precursors (pre-ELMs). A small number of ELMs with similar properties to sdAs is known. Other possibilities include metal-poor A/F dwarfs, second generation stars, or even stars accreted from dwarf galaxies. In this work, we analyse colours, proper motions, and spacial velocities of a sample of sdAs from the Sloan Digital Sky Survey to assess their nature and evolutionary origin. We define a probability of belonging to the main sequence and a probability of being a (pre-)ELM based on these properties. We find that 7 per cent of the sdAs are more likely to be (pre-)ELMs than main-sequence stars. However, the spacial velocity distribution suggests that over 35 per cent of them cannot be explained as single metal-poor A/F stars.

An augmented CO2 chemoreflex and overactive orexin system are linked with hypertension in young and adult spontaneously hypertensive rats.

PubMed

Li, Aihua; Roy, Sarah H; Nattie, Eugene E

2016-09-01

Activation of central chemoreceptors by CO2 increases sympathetic nerve activity (SNA), arterial blood pressure (ABP) and breathing. These effects are exaggerated in spontaneously hypertensive rats (SHRs), resulting in an augmented CO2 chemoreflex that affects both breathing and ABP. The augmented CO2 chemoreflex and the high ABP are measureable in young SHRs (postnatal day 30-58) and become greater in adult SHRs. Blockade of orexin receptors can normalize the augmented CO2 chemoreflex and the high ABP in young SHRs and normalize the augmented CO2 chemoreflex and significantly lower the high ABP in adult SHRs. In the hypothalamus, SHRs have more orexin neurons, and a greater proportion of them increase their activity with CO2 . The orexin system is overactive in SHRs and contributes to the augmented CO2 chemoreflex and hypertension. Modulation of the orexin system may be beneficial in the treatment of neurogenic hypertension. Activation of central chemoreceptors by CO2 increases arterial blood pressure (ABP), sympathetic nerve activity and breathing. In spontaneously hypertensive rats (SHRs), high ABP is associated with enhanced sympathetic nerve activity and peripheral chemoreflexes. We hypothesized that an augmented CO2 chemoreflex and overactive orexin system are linked with high ABP in both young (postnatal day 30-58) and adult SHRs (4-6 months). Our main findings are as follows. (i) An augmented CO2 chemoreflex and higher ABP in SHRs are measureable at a young age and increase in adulthood. In wakefulness, the ventilatory response to normoxic hypercapnia is higher in young SHRs (mean ± SEM: 179 ± 11% increase) than in age-matched normotensive Wistar-Kyoto rats (114 ± 9% increase), but lower than in adult SHRs (226 ± 10% increase; P < 0.05). The resting ABP is higher in young SHRs (122 ± 5 mmHg) than in age-matched Wistar-Kyoto rats (99 ± 5 mmHg), but lower than in adult SHRs (152 ± 4 mmHg; P < 0.05). (ii

Lens epithelium-derived growth factor promotes photoreceptor survival in light-damaged and RCS rats.

PubMed

Machida, S; Chaudhry, P; Shinohara, T; Singh, D P; Reddy, V N; Chylack, L T; Sieving, P A; Bush, R A

2001-04-01

To investigate possible protective effects of lens epithelium-derived growth factor (LEDGF) against photoreceptor death in light-damaged, Royal College of Surgeons (RCS) and P23H rhodopsin transgenic rats. Twelve-week-old Sprague-Dawley (SD), 6-week-old RCS, and 10-day-old P23H (line 1, heterozygote) rats received an intravitreal injection of LEDGF fused with glutathione-S-transferase (GST-LEDGF). Fellow eyes received vehicle and served as control specimens. Two days after the injections, the SD rats were exposed to light of 2000 lux for 48 hours. Corneal Ganzfeld ERGs were recorded 10 days after light damage, at 10 weeks of age in RCS rats, and at 4 weeks of age in P23H rats. The eyes were then processed for histologic analysis. Heat shock protein (hsp) content in the sensory retina was analyzed quantitatively by protein immunoblot. In light-damaged rats, the ERG indicated retinal protection in GST-LEDGF-injected eyes, with b-wave and STR thresholds being 1.14 +/- 0.50 (mean +/- SD) and 0.60 +/- 0.26 log candela (cd)/m2 lower, respectively, than in vehicle-injected eyes (P < 0.01). The GST-LEDGF-treated eyes had maximum b-wave amplitudes that were significantly larger (P < 0.0005), had more than twice as many remaining photoreceptors, and had better organized outer segments than the control eyes. In RCS rats, the treated eyes had 2.76 +/- 0.73 and 0.83 +/- 0.09 log cd/m(2) lower thresholds for the b-wave and STR, respectively (P < 0.005), and had significantly larger maximum b-wave amplitude (P < 0.0005). GST-LEDGF-treated eyes of RCS rats also had more photoreceptors remaining (P < 0.005) and a thinner debris layer than control eyes. In P23H rats, GST-LEDGF treatment did not protect either retinal function or structure. The retinas from GST-LEDGF-treated eyes of SD and RCS rats had higher levels of hsp25 and alphaB-crystallin than vehicle-injected eyes. GST-LEDGF protects photoreceptor structure and function in both light-damaged and RCS rats. The increased