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Sample records for stimulus-induced fos expression

  1. c-Fos expression during temporal order judgment in mice.

    PubMed

    Wada, Makoto; Higo, Noriyuki; Moizumi, Shunjiro; Kitazawa, Shigeru

    2010-05-05

    The neuronal mechanisms for ordering sensory signals in time still need to be clarified despite a long history of research. To address this issue, we recently developed a behavioral task of temporal order judgment in mice. In the present study, we examined the expression of c-Fos, a marker of neural activation, in mice just after they carried out the temporal order judgment task. The expression of c-Fos was examined in C57BL/6N mice (male, n = 5) that were trained to judge the order of two air-puff stimuli delivered bilaterally to the right and left whiskers with stimulation intervals of 50-750 ms. The mice were rewarded with a food pellet when they responded by orienting their head toward the first stimulus (n = 2) or toward the second stimulus (n = 3) after a visual "go" signal. c-Fos-stained cell densities of these mice (test group) were compared with those of two control groups in coronal brain sections prepared at bregma -2, -1, 0, +1, and +2 mm by applying statistical parametric mapping to the c-Fos immuno-stained sections. The expression of c-Fos was significantly higher in the test group than in the other groups in the bilateral barrel fields of the primary somatosensory cortex, the left secondary somatosensory cortex, the dorsal part of the right secondary auditory cortex. Laminar analyses in the primary somatosensory cortex revealed that c-Fos expression in the test group was most evident in layers II and III, where callosal fibers project. The results suggest that temporal order judgment involves processing bilateral somatosensory signals through the supragranular layers of the primary sensory cortex and in the multimodal sensory areas, including marginal zone between the primary somatosensory cortex and the secondary sensory cortex.

  2. Regional c-Fos and FosB/ΔFosB expression associated with chronic methamphetamine self-administration and methamphetamine-seeking behavior in rats.

    PubMed

    Cornish, J L; Hunt, G E; Robins, L; McGregor, I S

    2012-03-29

    The regional expression of the transcription factors c-Fos and FosB/ΔFosB was examined in rats given acute exposure to intravenous methamphetamine (METH) or repeated intravenous METH self-administration. One group of rats self-administered METH via lever pressing in 2 h sessions every day for 3 weeks and on a final test day received self-administered METH as usual. A second group with the same METH self-administration history received saline infusions on the test day, to induce drug-seeking behavior. Other rats were trained with infusions of intravenous saline that were yoked to the passive delivery of METH in the other two groups. On test day, half of these yoked rats received passive METH infusions for the first time, whereas the others received saline as usual. The results showed that acute METH produced a characteristic signature of Fos expression with elevations in striatal, cortical, and extended amygdala regions. Importantly, rats with a 3-week history of METH self-administration displayed similar regional Fos expression to rats receiving METH for the first time. Rats seeking, but not receiving, METH on the test day had augmented Fos in the lateral hypothalamus, septum, and vertical limb of the diagonal band of Broca, suggesting a primary role for these regions in METH-seeking behavior. Both acute and chronic METH activated orexin-positive cells in the perifornical area of the hypothalamus. FosB/ΔFosB was elevated in the lateral hypothalamus, posterior ventral tegmental area, central amygdala, and dorsal raphe of all the rats with a history of METH self-administration. This occurred regardless of whether they received METH on test day, suggesting presence of the long-lived FosB isoform, ΔFosB. Overall, these results show persistent upregulated regional brain Fos and FosB/ΔFosB expression with chronic METH self-administration and indicate a role for the lateral hypothalamus and lateral septum in METH-seeking behavior.

  3. Correlation of Fos expression and circling asymmetry during gerbil vestibular compensation

    NASA Technical Reports Server (NTRS)

    Kaufman, G. D.; Shinder, M. E.; Perachio, A. A.

    1999-01-01

    Vestibular compensation is a central nervous system process resulting in recovery of functional movement and control following a unilateral vestibular lesion. Small pressure injections of phosphorothioate 20mer oligonucleotides were used to probe the role of the Fos transcription protein during vestibular compensation in the gerbil brainstem. During isoflurane gas anesthesia, antisense probes against the c-fos mRNA sequence were injected into the medial vestibular and prepositus nuclei unilaterally prior to a unilateral surgical labyrinthectomy. Anionic dyes, which did not interact with the oligonucleotides, were used to mark the injection site and help determine the extent of diffusion. The antiFos oligonucleotide injections reduced Fos expression at the injection site in neurons which normally express Fos after the lesion, and also affected circling behavior induced by hemilabyrinthectomy. With both ipsilateral and contralateral medial vestibular and prepositus nuclei injections, less ipsilateral and more contralateral circling was noted in animals injected with antiFos injections as compared to non-injected controls. The degree of change in these behaviors was dependent upon the side of the injection. Histologically, antiFos injections reduced the number of Fos immunolabeled neurons around the injection site, and increased Fos expression contralaterally. The correlation of the number of neurons with Fos expression to turning behavior was stronger for contralateral versus ipsilateral turns, and for neurons in the caudal and ipsilateral sub-regions of the medial vestibular and prepositus nuclei. The results are discussed in terms of neuronal firing activity versus translational activity based on the asymmetrical expression of the Fos inducible transcription factor in the medial vestibular and prepositus nuclei. Although ubiquitous in the brain, transcription factors like Fos can serve localized and specific roles in sensory-specific adaptive stimuli. Antisense

  4. Correlation of Fos expression and circling asymmetry during gerbil vestibular compensation

    NASA Technical Reports Server (NTRS)

    Kaufman, G. D.; Shinder, M. E.; Perachio, A. A.

    1999-01-01

    Vestibular compensation is a central nervous system process resulting in recovery of functional movement and control following a unilateral vestibular lesion. Small pressure injections of phosphorothioate 20mer oligonucleotides were used to probe the role of the Fos transcription protein during vestibular compensation in the gerbil brainstem. During isoflurane gas anesthesia, antisense probes against the c-fos mRNA sequence were injected into the medial vestibular and prepositus nuclei unilaterally prior to a unilateral surgical labyrinthectomy. Anionic dyes, which did not interact with the oligonucleotides, were used to mark the injection site and help determine the extent of diffusion. The antiFos oligonucleotide injections reduced Fos expression at the injection site in neurons which normally express Fos after the lesion, and also affected circling behavior induced by hemilabyrinthectomy. With both ipsilateral and contralateral medial vestibular and prepositus nuclei injections, less ipsilateral and more contralateral circling was noted in animals injected with antiFos injections as compared to non-injected controls. The degree of change in these behaviors was dependent upon the side of the injection. Histologically, antiFos injections reduced the number of Fos immunolabeled neurons around the injection site, and increased Fos expression contralaterally. The correlation of the number of neurons with Fos expression to turning behavior was stronger for contralateral versus ipsilateral turns, and for neurons in the caudal and ipsilateral sub-regions of the medial vestibular and prepositus nuclei. The results are discussed in terms of neuronal firing activity versus translational activity based on the asymmetrical expression of the Fos inducible transcription factor in the medial vestibular and prepositus nuclei. Although ubiquitous in the brain, transcription factors like Fos can serve localized and specific roles in sensory-specific adaptive stimuli. Antisense

  5. FOS Expression in Blood as a LDL-Independent Marker of Statin Treatment

    PubMed Central

    Kang, Ju-Gyeong; Sung, Ho Joong; Jawed, Sarah I.; Brenneman, Cynthia L.; Rao, Yesoda N.; Sher, Salman; Facio, Flavia M.; Biesecker, Leslie G.; Quyyumi, Arshed A.; Sachdev, Vandana; Hwang, Paul M.

    2010-01-01

    Objectives The expression of FOS, a gene critical for monocyte and macrophage function, can be inhibited by statins through the disruption of a cholesterol independent signaling pathway. In this pilot study, we hypothesized that blood FOS mRNA levels will be sensitive to statin treatment independent of LDL cholesterol levels. Methods Three cohorts at increased risk of or with cardiovascular disease (CVD) were studied. Blood FOS mRNA levels were measured before and after statin treatment or in patients under stable treatment. Results Statin treatment for three months significantly reduced blood FOS mRNA and LDL cholesterol levels. However, in subjects with similar LDL levels achieved by different doses of long term statin treatment, there was an inverse relationship between statin dose and FOS expression. Conclusions FOS mRNA levels appear to be a sensitive marker of statin treatment that is dissociated from cholesterol levels. PMID:20619839

  6. Nitric oxide mediates Fos expression in the spinal cord induced by mechanical noxious stimulation.

    PubMed

    Lee, J H; Wilcox, G L; Beitz, A J

    1992-10-01

    Immunocytochemical localization of Fos protein was used to analyze the involvement of nitric oxide (NO) in the expression of Fos in the spinal cord, induced by mechanical noxious stimulation (NS). Mechanical NS was applied to the left hindpaw 30 minutes after intrathecal administration of the NO synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME) and the resulting Fos expression in the spinal cord dorsal horn was compared with that obtained in rats exposed only to the mechanical NS. Pretreatment with L-NAME but not its stereoisomer N omega-nitro-D-arginine methyl ester (D-NAME), produced a dose-dependent suppression of Fos expression induced by mechanical noxious stimulation. These results indicate that NO modulates the expression of Fos in the dorsal horn induced by mechanical noxious stimulation and further support the hypothesis that NO is involved in nociceptive events occurring in the spinal cord in response to a peripheral noxious stimulus.

  7. Effects of acute or chronic environmental enrichment on regional Fos protein expression following sucrose cue-reactivity testing in rats.

    PubMed

    Grimm, Jeffrey W; Barnes, Jesse L; Koerber, Jonathon; Glueck, Edwin; Ginder, Darren; Hyde, Jeff; Eaton, Laura

    2016-06-01

    Exposure to environmental enrichment (EE) reduces sucrose seeking by rats with a history of sucrose self-administration. The present experiment examined whether acute or chronic EE also reduces brain Fos levels, a protein marker indicative of neuronal activation. Fos levels were also examined after either 1 or 30 days of forced abstinence to examine whether Fos levels vary with the incubation of sucrose craving. Fos expression was examined in 18 regions and was identified in brain slices using immunohistochemistry. Fos levels were higher in most regions after 30 days of forced abstinence and were decreased in most regions by either acute or chronic EE. Eleven regions had some statistically significant effect and/or interaction of EE or incubation on Fos; the most salient of these are listed here. In the prelimbic cortex, there was an incubation of Fos and EE reduced Fos at both forced abstinence time points. In contrast, in the orbitofrontal cortex, there was no Fos incubation but EE reduced Fos at both forced abstinence time points. An interaction of EE and incubation was observed in the anterior cingulate cortex and nucleus accumbens core and shell where Fos incubated but EE only decreased Fos at the day 30 forced abstinence time point. In contrast, in the dorsolateral striatum Fos incubated, but EE robustly decreased Fos expression at both forced abstinence time points. These differential expression patterns provide rationale for more detailed, site-specific molecular functional studies in how they relate to the ability of EE to reduce sucrose seeking.

  8. Activation of c-fos expression in the rat inferior olivary nucleus by ghrelin.

    PubMed

    Zhang, Weizhen; Lin, Theodore R; Hu, Yuexian; Fan, Yongyi; Zhao, Lili; Mulholland, Michael W

    2003-12-26

    Ghrelin, a novel 28-amino-acid hormone secreted by gastric oxyntic glands, stimulates food intake and induces adiposity. We examined whether ghrelin activates the inferior olivary nucleus. Systemic administration of ghrelin (37 nmol/kg) induced the expression of c-fos immunoreactivity in inferior olive neurons (n=6 rats). The number of neurons containing c-fos staining was significantly increased in the ghrelin-treated rats (65+/-14 vs.11+/-6 positive neurons, n=5). No significant difference in c-fos-positive neurons was observed between left (32+/-5) and right (33+/-6) inferior olivary nuclei. The number of c-fos-positive neurons in rats with bilateral vagotomy was not significantly different from those with intact vagal nerves. The present study demonstrates that ghrelin induces c-fos expression in inferior olivary nucleus via a central mechanism.

  9. Expression of the proto-oncogene Fos after exposure to radiofrequency radiation relevant to wireless communications.

    PubMed

    Whitehead, Timothy D; Brownstein, Bernard H; Parry, Jesse J; Thompson, Dominic; Cha, Bibianna A; Moros, Eduardo G; Rogers, Buck E; Roti Roti, Joseph L

    2005-10-01

    In this study the expression levels of the proto-oncogene Fos were measured after exposure to radiofrequency (RF) radiation at two relatively high specific absorption rates (SARs) of 5 and 10 W/kg for three types of modulated signals: 847.74 MHz code division multiple access (CDMA), 835.62 MHz frequency division multiple access (FDMA), and 836.55 MHz time division multiple access (TDMA). This work was undertaken to confirm a previous report by Goswami et al. (Radiat. Res. 151, 300-309, 1999) that CDMA and FDMA radiation caused small but statistically significant increases in Fos levels as cells entered plateau phase during exposure. No effects on Myc or Jun levels were observed in that study. Therefore, in the present study, analyses were restricted to Fos expression during the transition from exponential growth to plateau phase. Fos expression was measured using the real-time polymerase chain reaction (RT-PCR) technique. Serum-stimulated C3H 10T(1/2) cells were used as a positive control for Fos expression. Possible influences of final cell number or pH variability on Fos expression were evaluated. Expression of Fos mRNA in C3H 10T(1/2) cells was not significantly different from that found after sham exposure at either SAR level for any signal modulation. Therefore, the results of Goswami et al. could not be confirmed.

  10. SETDB1 mediated FosB expression increases the cell proliferation rate during anticancer drug therapy.

    PubMed

    Na, Han-Heom; Noh, Hee-Jung; Cheong, Hyang-Min; Kang, Yoonsung; Kim, Keun-Cheol

    2016-04-01

    The efficacy of anticancer drugs depends on a variety of signaling pathways, which can be positively or negatively regulated. In this study, we show that SETDB1 HMTase is down-regulated at the transcriptional level by several anticancer drugs, due to its inherent instability. Using RNA sequence analysis, we identified FosB as being regulated by SETDB1 during anticancer drug therapy. FosB expression was increased by treatment with doxorubicin, taxol and siSETDB1. Moreover, FosB was associated with an increased rate of proliferation. Combinatory transfection of siFosB and siSETDB1 was slightly increased compared to transfection of siFosB. Furthermore, FosB was regulated by multiple kinase pathways. ChIP analysis showed that SETDB1 and H3K9me3 interact with a specific region of the FosB promoter. These results suggest that SETDB1- mediated FosB expression is a common molecular phenomenon, and might be a novel pathway responsible for the increase in cell proliferation that frequently occurs during anticancer drug therapy. [BMB Reports 2016; 49(4): 238-243].

  11. In vivo correlation between c-Fos expression and corticotroph stimulation by adrenocorticotrophic hormone secretagogues in rat anterior pituitary gland.

    PubMed

    Takigami, Shu; Fujiwara, Ken; Kikuchi, Motoshi; Yashiro, Takashi

    2008-03-01

    In the anterior pituitary gland, c-Fos expression is evoked by various stimuli. However, whether c-Fos expression is directly related to the stimulation of anterior pituitary cells by hypothalamic secretagogues is unclear. To confirm whether the reception of hormone-releasing stimuli evokes c-Fos expression in anterior pituitary cells, we have examined c-Fos expression of anterior pituitary glands in rats administered with synthetic corticotrophin-releasing hormone (CRH) intravenously or subjected to restraint stress. Single intravenous administration of CRH increases the number of c-Fos-expressing cells, and this number does not change even if the dose is increased. Double-immunostaining has revealed that most of the c-Fos-expressing cells contain adrenocorticotrophic hormone (ACTH); corticotrophs that do not express c-Fos in response to CRH have also been found. However, restraint stress evokes c-Fos expression in most of the corticotrophs and in a partial population of lactotrophs. These results suggest that c-Fos expression increases in corticotrophs stimulated by ACTH secretagogues, including CRH. Furthermore, we have found restricted numbers of corticotrophs expressing c-Fos in response to CRH. Although the mechanism underlying the different responses to CRH is not apparent, c-Fos is probably a useful immunohistochemical marker for corticotrophs stimulated by ACTH secretagogues.

  12. A Simple Method for Immunohistochemical Staining of Zebrafish Brain Sections for c-fos Protein Expression.

    PubMed

    Chatterjee, Diptendu; Tran, Steven; Shams, Soaleha; Gerlai, Robert

    2015-12-01

    Immediate early genes (IEGs) are transcription factors whose own transcription is initiated rapidly, for example, in the brain in response to environmental stimuli. c-fos is an IEG often used as a marker of neuronal activation. c-fos mRNA expression has started to be quantified and localized in the zebrafish brain following environmental manipulations but analysis of the expression of c-fos protein in the zebrafish brain has rarely been attempted. Here, we describe an immunofluorescence staining method for quantifying c-fos protein expression in different regions of the zebrafish brain. In addition, we expose zebrafish to caffeine, a positive control for c-fos activation in the brain. To confirm cell nucleus specific binding of the c-fos antibody, we counterstained brain sections with the nuclear fluorescent stain DAPI. Furthermore, we describe a method for reducing background autofluorescence often observed in zebrafish brain tissue. Our analysis showed that exposure to caffeine increased the number of c-fos protein-positive cells in specific zebrafish brain regions detected by the immunofluorescence method. Our results demonstrate the feasibility of immunofluorescence-based methods in the analysis of neuronal activation in the zebrafish brain, and reinforce the utility of the zebrafish in behavioral neuroscience research.

  13. Fos expression induced by cocaine-conditioned cues in male and female rats

    PubMed Central

    Zhou, Luyi; Pruitt, Carla; Shin, Christina B.; Garcia, Arturo D.; Zavala, Arturo R.; See, Ronald E.

    2013-01-01

    Previous studies have shown that female rats exhibit different patterns of drug seeking during multiple phases of cocaine addiction when compared with males. However, the underlying mechanisms for these sex differences remain largely unknown. Here, we used a cocaine self-administration/reinstatement model to examine neuronal activation, as determined by Fos expression, following cue-induced reinstatement of cocaine seeking in male and female rats. Fos expression revealed both similarities between sexes in some brain regions, as well as selective sexually dimorphic patterns. As compared to no cue control subjects, conditioned cues induced higher Fos expression in the Cg1 region of the anterior cingulate cortex, but lower expression in the nucleus accumbens in both males and females. Females exhibited higher Fos expression than males in multiple brain regions, including the agranular insular cortex, dorsal medial caudate-putamen, nucleus accumbens shell, ventral tegmental area, dorsal subiculum, and ventral CA1 and CA3 regions of the hippocampus. Notably, only Fos expression in the prelimbic cortex, nucleus accumbens shell, basolateral amygdala, and ventral subiculum correlated positively with lever responding in response to conditioned cues across males and females. These findings indicate that while sexually dimorphic Fos activation does occur, the relationship between cue-induced cocaine seeking and neuronal activation may be similar for males and females in key brain regions of the relapse circuit. PMID:23832598

  14. Fos expression induced by cocaine-conditioned cues in male and female rats.

    PubMed

    Zhou, Luyi; Pruitt, Carla; Shin, Christina B; Garcia, Arturo D; Zavala, Arturo R; See, Ronald E

    2014-09-01

    Previous studies have shown that female rats exhibit different patterns of drug seeking during multiple phases of cocaine addiction when compared with males. However, the underlying mechanisms for these sex differences remain largely unknown. Here, we used a cocaine self-administration/reinstatement model to examine neuronal activation, as determined by Fos expression, following cue-induced reinstatement of cocaine seeking in male and female rats. Fos expression revealed both similarities between sexes in some brain regions, as well as selective sexually dimorphic patterns. As compared to no cue control subjects, conditioned cues induced higher Fos expression in the Cg1 region of the anterior cingulate cortex, but lower expression in the nucleus accumbens in both males and females. Females exhibited higher Fos expression than males in multiple brain regions, including the agranular insular cortex, dorsal medial caudate-putamen, nucleus accumbens shell, ventral tegmental area, dorsal subiculum, and ventral CA1 and CA3 regions of the hippocampus. Notably, only Fos expression in the prelimbic cortex, nucleus accumbens shell, basolateral amygdala, and ventral subiculum correlated positively with lever responding in response to conditioned cues across males and females. These findings indicate that while sexually dimorphic Fos activation does occur, the relationship between cue-induced cocaine seeking and neuronal activation may be similar for males and females in key brain regions of the relapse circuit.

  15. Sustained Fos expression is observed in the developing brainstem auditory circuits of kanamycin-treated rats.

    PubMed

    Lee, Jae Ho; Kim, Hee Jung; Suh, Myung-Whan; Ahn, Seung Cheol

    2011-11-14

    It has been demonstrated that kanamycin treatment during early developmental period induces partial cochlear destruction and enhanced glutamatergic transmission at the medial nucleus of the trapezoid body (MNTB) - the lateral superior olive (LSO) synapses in the superior olivary complex (SOC). As c-fos was expected to be expressed in the SOC by kanamycin-induced cochlear damage, the expression of c-fos protein (Fos) was investigated using immunohistochemistry in kanamycin-treated rat pups. In the control rat pups less than postnatal (P) day 9 in age, Fos-like immunoreactivity (Fos-IR) was transiently observed in the MNTB and LSO on P6, but disappeared on P9, which reflects a physiologic process. In contrast, in kanamycin-treated rats, Fos-IR was consistently observed through P9. Because a significant increase in terminal uridine deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick-end labeling (TUNEL) and glial fibrillary acidic protein (GFAP) IR was not demonstrated in the MNTB and LSO of kanamycin-treated rats, the increased Fos-IR does not appear to indicate an ongoing pathologic process, but may be related to the increased activity caused by the disturbance in excitatory and inhibitory balance between brainstem auditory circuits.

  16. Persistent induction of c-fos and c-jun expression by asbestos

    SciTech Connect

    Heintz, N.H.; Mossman, B.T. ); Janssen, Y.M. Univ. of Limburg, Maastricht )

    1993-04-15

    To investigate the mechanisms of asbestos-induced carcinogenesis, expression of c-fos and c-jun protooncogenes was examined in rat pleural mesothelial cells and hamster tracheal epithelial cells after exposure to crocidolite or chrysotile asbestos. In contrast to phorbol 12-myristate 13-acetate, which induces rapid and transient increases in c-fos and c-jun mRNA, asbestos causes 2- to 5-fold increases in c-fos and c-jun mRNA that persist for at least 24 hr in mesothelial cells. The induction of c-fos and c-jun mRNA by asbestos in mesothelial cells is dose-dependent and is most pronounced with crocidolite, the type of asbestos most pathogenic in the causation of pleural mesothelioma. Induction of c-jun gene expression by asbestos occurs in tracheal epithelial cells but is not accompanied by a corresponding induction of c-fos gene expression. In both cell types, asbestos induces increases in protein factors that bind specifically to the DNA sites that mediate gene expression by the AP-1 family of transcription factors. The persistent induction of AP-1 transcription factors by asbestos suggests a model of asbestos-induced carcinogenesis involving chronic stimulation of cell proliferation through activation of the early response gene pathway that includes c-jun and/or c-fos. 30 refs., 5 figs.

  17. Fos Expression in Rat Brain During Depletion-Induced Thirst and Salt Appetite

    NASA Technical Reports Server (NTRS)

    Thunhorst, R. L.; Xu, Z.; Cicha, M. Z.; Zardetto-Smith, A. M.; Johnson, A. K.

    1998-01-01

    The expression of Fos protein (Fos immunoreactivity, Fos-ir) was mapped in the brain of rats subjected to an angiotensin-dependent model of thirst and salt appetite. The physiological state associated with water and sodium ingestion was produced by the concurrent subcutaneous administration of the diuretic furosemide (10 mg/kg) and a low dose of the angiotensin-converting enzyme (ACE) inhibitor captopril (5 mg/kg; Furo/Cap treatment). The animals were killed 2 h posttreatment, and the brains were processed for Fos-ir to assess neural activation. Furo/Cap treatment significantly increased Fos-ir density above baseline levels both in structures of the lamina terminalis and hypothalamus known to mediate the actions of ANG 2 and in hindbrain regions associated with blood volume and pressure regulation. Furo/Cap treatment also typically increased Fos-ir density in these structures above levels observed after administration of furosemide or captopril separately. Fos-ir was reduced to a greater extent in forebrain than in hindbrain areas by a dose of captopril (100 mg/kg sc) known to block the actions of ACE in the brain. The present work provides further evidence that areas of lamina terminalis subserve angiotensin-dependent thirst and salt appetite.

  18. Delta-9-tetrahydrocannabinol differently affects striatal c-Fos expression following haloperidol or clozapine administration.

    PubMed

    Marchese, Giorgio; Sanna, Angela; Casu, Gianluca; Casti, Paola; Spada, Gabriele Pinna; Ruiu, Stefania; Pani, Luca

    2008-11-19

    It was previously shown that haloperidol, but not clozapine, induced intense rat catalepsy when co-administered with delta-9-tetrahydrocannabinol. The present study investigated whether similar alterations could be observed on striatal c-Fos immunoreactivity after administration of the same drug combinations. Western Blot and immunocytochemistry stereological analyses indicated that delta-9-tetrahydrocannabinol (0.5 mg/kg) increased striatal c-Fos immunoreactivity induced by haloperidol (0.1 mg/kg). Conversely, no significant alterations of striatal c-Fos immunoreactivity were observed after injections of clozapine (10 mg/kg)+vehicle, clozapine+delta-9-tetrahydrocannabinol or vehicle+delta-9-tetrahydrocannabinol. The present results indicate that the behavioral effects induced by delta-9-tetrahydrocannabinol in haloperidol- and clozapine-treated rats are associated with different striatal c-Fos expressions.

  19. c-Fos expression correlates with performance on novel object and novel place recognition tests.

    PubMed

    Mendez, Marta; Arias, Natalia; Uceda, Sara; Arias, Jorge L

    2015-08-01

    In rodents, many studies have been carried out using novelty-preference paradigms. The results show that the perirhinal cortex and the hippocampus are involved in the recognition of a novel object, "what", and its new position, "where", respectively. We employed these two variants of a novelty-preference paradigm to assess whether the expression of the immediate-early gene c-fos in the dorsal hippocampus and perirhinal cortex correlates with the performance discrimination ratio (d2), on the respective versions of the novelty preference tests. A control group (CO) was added to explore c-fos activation not specific to recognition. The results showed different patterns of c-Fos protein expression in the hippocampus and perirhinal cortex. The Where Group presented more c-Fos positive nuclei than the What and CO groups in the CA1 and CA3 regions, whereas in the perirhinal cortex, the What Group showed more c-Fos positive nuclei than the Where and CO groups. The correlation results indicate that levels of c-Fos in the CA1 area and perirhinal cortex correlate with effective exploration, d2, on the respective versions of the novelty preference tests, novel place and novel object recognition. These data suggest that the hippocampal CA1 and perirhinal cortex are specifically related to the level of recognition of place and objects, respectively.

  20. Propofol inhibits ketamine-induced c-fos expression in the rat posterior cingulate cortex.

    PubMed

    Nagata, A; Nakao, S; Miyamoto, E; Inada, T; Tooyama, I; Kimura, H; Shingu, K

    1998-12-01

    Ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, has psychotomimetic activity. NMDA receptor antagonists cause morphological damage in the posterior cingulate cortex, which may be the brain region responsible for their psychotomimetic effects. Benzodiazepines are effective in preventing these effects through gamma-aminobutyric acid A (GABA(A)) receptor activation. We investigated the effect of propofol, which has both GABAA receptor-activating and NMDA receptor-suppressing activity, on ketamine-induced c-fos expression in the rat posterior cingulate cortex. Propofol or vehicle was continuously infused IV. Fifteen minutes later, 100 mg/kg ketamine or isotonic sodium chloride solution was injected intraperitoneally. Two hours later, brain sections were prepared, and c-fos expression was detected using immunohistochemical methods. Propofol significantly inhibited ketamine-induced c-fos expression in the posterior cingulate cortex. Propofol itself did not induce c-fos expression in this brain region. We conclude that propofol may be able to inhibit ketamine-induced psychotomimetic activity and neuronal damage. In the present study, we demonstrated that the clinically relevant dose of propofol significantly inhibited ketamine-induced c-fos expression in the rat posterior cingulate cortex. This finding implies that propofol may inhibit ketamine-induced psychotomimetic activity and neuronal damage.

  1. Pivotal role of c-Fos in nitric oxide synthase 2 expression in airway epithelial cells

    PubMed Central

    Chambellan, Arnaud; Leahy, Rachel; Xu, Weiling; Cruickshank, Paul J.; Janocha, Allison; Szabo, Katalin; Cannady, Steven B.; Comhair, Suzy A.A.; Erzurum, Serpil C.

    2010-01-01

    The regulation of nitric oxide synthase 2 (NOS2) in airway epithelial cells plays a key role in the innate host response to a wide variety of microbial agents and also participates in the generation of pathologic airway inflammation. Among the important signalling cascades that direct NOS2 gene expression are nuclear factor κB (NFκB) and interferon-γ (IFNγ)/signal transducer and activator of transcription 1 (STAT-1). Previous studies suggest activator protein-1 (AP-1), in particular c-Fos component of AP-1, influences NOS2 expression. We investigated the effect of c-Fos modulation using RNA interference siRNA on NOS2 gene expression. A549 cells stably transfected with a plasmid overexpressing a c-Fos siRNA construct (FOSi) resulted in a decrease of NOS2 protein inducibility by IFN γ. In contrast, classical IFN γ inducible signal transduction pathways interferon regulated factor-1 (IRF-1) and pSTAT-1 were activated at a similar magnitude in FOSi and control cells. DNA–protein binding assays showed that c-Fos binding was present in wild type cells, but reduced in FOSi clones. FOSi clones had activation of NFκB detectable by DNA–protein binding assays, which may have contributed to a decrease of NOS2 expression. Overall, these studies indicate that c-Fos is a requisite and specific component for inducible NOS2 expression. PMID:19135542

  2. c-Fos over-expression promotes radioresistance and predicts poor prognosis in malignant glioma

    PubMed Central

    Feng, Guokai; Chen, Furong; Tu, Ziwei; Liu, Guiyun; Zhao, Yu; Peng, Ming-Jing; He, Zheng-Wen; Chen, Xiao-Yan; Lindsay, Holly; Xia, Yun-Fei; Li, Xiao-Nan

    2016-01-01

    c-Fos is a major component of activator protein (AP)-1 complex. It has been implicated in cell differentiation, proliferation, angiogenesis, invasion, and metastasis. To investigate the role of c-Fos in glioma radiosensitivity and to understand the underlying molecular mechanisms, we downregulated c-Fos gene expression by lentivirus-mediated shRNA in glioma cell lines and subsequently analyzed the radiosensitivity, DNA damage repair capacity, and cell cycle distribution. Finally, we explored its prognostic value in 41 malignant glioma patients by immunohistochemistry. Our results showed that silencing c-Fos sensitized glioma cells to radiation by increasing radiation-induced DNA double strand breaks (DSBs), disturbing the DNA damage repair process, promoting G2/M cell cycle arrest, and enhancing apoptosis. c-Fos protein overexpression correlated with poor prognosis in malignant glioma patients treated with standard therapy. Our findings provide new insights into the mechanism of radioresistance in malignant glioma and identify c-Fos as a potentially novel therapeutic target for malignant glioma patients. PMID:27602752

  3. Increased dietary sodium alters Fos expression in the lamina terminalis during intravenous angiotensin II infusion.

    PubMed

    Bealer, Steven L; Metcalf, Cameron S; Heyborne, Ryan

    2007-03-01

    These studies examined the effects of increased dietary sodium on expression of Fos, the protein product of c-fos, in forebrain structures in the rat following intravenous infusion with angiotensin II (AngII). Animals were provided with either tap water (Tap) or isotonic saline solution (Iso) as their sole drinking fluid for 3-5 weeks prior to testing. Rats were then implanted with catheters in a femoral artery and vein. The following day, the conscious, unrestrained animals received iv infusion of either isotonic saline (Veh), AngII, or phenylephrine (Phen) for 2 h. Blood pressure and heart rate were monitored continuously throughout the procedure. Brains were subsequently processed for evaluation of Fos-like immunoreactivity (Fos-Li IR) in the organum vasculosum of the lamina terminalis (OVLT), the subfornical organ (SFO), and the median preoptic nucleus (MnPO). Fos-Li IR was significantly increased in the SFO and OVLT of animals consuming both Tap and Iso following AngII, but not Phen, compared to Veh infusions. Furthermore, Fos-Li IR in the MnPO was increased following AngII infusion in rats consuming a high sodium diet, but not in animals drinking Tap. These data suggest that increased dietary sodium sensitizes the MnPO neurons to excitatory input from brain areas responding to circulating AngII.

  4. The atypical dopamine D1 receptor agonist SKF 83959 induces striatal Fos expression in rats.

    PubMed

    Wirtshafter, David; Osborn, Catherine V

    2005-12-28

    The effects of dopamine D1 receptor agonists are often presumed to result from an activation of adenylyl cyclase, but dopamine D1 receptors may also be linked to other signal transduction cascades and the relative importance of these various pathways is currently unclear. SKF 83959 is an agonist at dopamine D1 receptors linked to phospholipase C, but has been reported to be an antagonist at receptors linked to adenylyl cyclase. The current report demonstrates that SKF 83959 induces pronounced, nonpatchy, expression of the immediate-early gene product Fos in the striatum of intact rats which can be converted to a patchy pattern by pretreatment with the dopamine D2-like receptor agonist quinpirole. In rats with unilateral 6-hydroxydopamine lesions SKF 83959 induces strong behavioral rotation and a greatly potentiated Fos response. All of the responses to SKF 83959, in both intact and dopamine-depleted animals, can be blocked by pretreatment with the dopamine D1 receptor antagonist SCH-23390. In intact subjects, SKF 83959 induced Fos expression less potently than the standard dopamine D1 receptor agonist SKF 82958, but the two drugs were approximately equipotent in deinnervated animals. These results demonstrate for the first time that possession of full efficacy at dopamine D1 receptors linked to adenylyl cyclase is not a necessary requirement for the induction of striatal Fos expression in intact animals and suggest that alternative signal transduction pathways may play a role in dopamine agonist induced Fos expression, especially in dopamine-depleted subjects.

  5. Peripheral injection of ghrelin induces Fos expression in the dorsomedial hypothalamic nucleus in rats

    PubMed Central

    Kobelt, Peter; Wisser, Anna-Sophia; Stengel, Andreas; Goebel, Miriam; Inhoff, Tobias; Noetzel, Steffen; Veh, Rüdiger W.; Bannert, Norbert; van der Voort, Ivo; Wiedenmann, Bertram; Klapp, Burghard F.; Taché, Yvette; Mönnikes, Hubert

    2009-01-01

    Peripheral ghrelin has been shown to act as a gut–brain peptide exerting a potent orexigenic effect on food intake. The dorsomedial nucleus of the hypothalamus (DMH) is innervated by projections from other brain areas being part of the network of nuclei controlling energy homeostasis, among others NPY/AgRP-positive fibers arising from the arcuate nucleus (ARC). The aim of the study was to determine if peripherally administered ghrelin affects neuronal activity in the DMH, as assessed by Fos expression. The number of Fos positive neurons was determined in the DMH, paraventricular nucleus of the hypothalamus (PVN), ARC, ventromedial hypothalamic nucleus (VMH), nucleus of the solitary tract (NTS) and in the area postrema(AP) in non-fasted Sprague–Dawley rats in response to intraperitoneally (ip) injected ghrelin (3 nmol/rat) or vehicle (0.15 M NaCl). Peripheral ghrelin induced a significant increase in the number of Fos-ir positive neurons/section compared with vehicle in the ARC (mean±SEM: 49±2 vs. 23±2 neurons/section, p=0.001), PVN (69±5 vs. 34±3, p=0.001), and DMH (142±5 vs. 83±5, p<0.001). Fos-ir positive neurons were mainly localized within the ventral part of the DMH. No change in Fos expression was observed in the VMH (53±8 vs. 48±6, p=0.581), NTS (42±2 vs.40±3, p=0.603), and in the AP (7±1 vs. 5±1, p=0.096). Additional double-labelling with anti-Fos and anti-AgRP revealed that Fos positive neurons in the DMH were encircled by a network of AgRP-ir positive fibers. These data indicate that peripheral ghrelin activates DMH neurons and that NPY-/AgRP-positive fibers may be involved in the response. PMID:18329635

  6. Acute estrogen surge enhances inflammatory nociception without altering spinal Fos expression.

    PubMed

    Ralya, Andrew; McCarson, Kenneth E

    2014-07-11

    Chronic pain is a major neurological disorder that can manifest differently between genders or sexes. The complex actions of sex hormones may underlie these differences; previous studies have suggested that elevated estrogen levels can enhance pain perception. The purpose of this study was to investigate the hypothesis that acute, activational effects of estradiol (E2) increase persistent inflammatory nociception, and anatomically where this modulation occurs. Spinal expression of Fos is widely used as a marker of nociceptive activation. This study used formalin-evoked nociception in ovariectomized (OVX) adult female rats and measured late-phase hindlimb flinching and Fos expression in the spinal cord, and their modification by acute estrogen supplementation similar to a proestrus surge. Six days after ovariectomy, female rats were injected subcutaneously (s.c.) with 10μg/kg E2 or vehicle. Twenty-four hours later, 50μL of 1.25% or 100μL of 5% formalin was injected into the right hindpaw; hindlimb flinches were counted, and spinal cords removed 2h after formalin injection. The numbers of Fos-expressing neurons in sections of the lumbar spinal cord were analyzed using immunohistochemistry. Formalin-induced inflammation produced a dose-dependent increase in late-phase hindlimb flinching, and E2 pretreatment increased flinching following 5%, but not 1.25% formalin injection. Despite the modification of behavior by E2, the number of spinal Fos-positive neurons was not altered by E2 pretreatment. These findings demonstrate that an acute proestrus-like surge in serum estrogen can produce a stimulus-intensity-dependent increase in inflammation-evoked nociceptive behavior. However, the lack of effect on spinal Fos expression suggests that this enhancement of nociceptive signaling by estrogen is independent of changes in peripheral activation of, expression of the immediate early gene Fos by, or signal throughput of spinal nociceptive neurons.

  7. Mechanically induced c-fos expression is mediated by cAMP in MC3T3-E1 osteoblasts

    NASA Technical Reports Server (NTRS)

    Fitzgerald, J.; Hughes-Fulford, M.

    1999-01-01

    In serum-deprived MC3T3-E1 osteoblasts, mechanical stimulation caused by mild (287 x g) centrifugation induced a 10-fold increase in mRNA levels of the proto-oncogene, c-fos. Induction of c-fos was abolished by the cAMP-dependent protein kinase inhibitor H-89, suggesting that the transient c-fos mRNA increase is mediated by cAMP. Down-regulation of protein kinase C (PKC) activity by chronic TPA treatment failed to significantly reduce c-fos induction, suggesting that TPA-sensitive isoforms of PKC are not responsible for c-fos up-regulation. In addition, 287 x g centrifugation increased intracellular prostaglandin E2 (PGE2) levels 2.8-fold (P<0. 005). Since we have previously shown that prostaglandin E2 (PGE2) can induce c-fos expression via a cAMP-mediated mechanism, we asked whether the increase in c-fos mRNA was due to centrifugation-induced PGE2 release. Pretreatment with the cyclooxygenase inhibitors indomethacin and flurbiprofen did not hinder the early induction of c-fos by mechanical stimulation. We conclude that c-fos expression induced by mild mechanical loading is dependent primarily on cAMP, not PKC, and initial induction of c-fos is not necessarily dependent on the action of newly synthesized PGE2.

  8. Mechanically induced c-fos expression is mediated by cAMP in MC3T3-E1 osteoblasts

    NASA Technical Reports Server (NTRS)

    Fitzgerald, J.; Hughes-Fulford, M.

    1999-01-01

    In serum-deprived MC3T3-E1 osteoblasts, mechanical stimulation caused by mild (287 x g) centrifugation induced a 10-fold increase in mRNA levels of the proto-oncogene, c-fos. Induction of c-fos was abolished by the cAMP-dependent protein kinase inhibitor H-89, suggesting that the transient c-fos mRNA increase is mediated by cAMP. Down-regulation of protein kinase C (PKC) activity by chronic TPA treatment failed to significantly reduce c-fos induction, suggesting that TPA-sensitive isoforms of PKC are not responsible for c-fos up-regulation. In addition, 287 x g centrifugation increased intracellular prostaglandin E2 (PGE2) levels 2.8-fold (P<0. 005). Since we have previously shown that prostaglandin E2 (PGE2) can induce c-fos expression via a cAMP-mediated mechanism, we asked whether the increase in c-fos mRNA was due to centrifugation-induced PGE2 release. Pretreatment with the cyclooxygenase inhibitors indomethacin and flurbiprofen did not hinder the early induction of c-fos by mechanical stimulation. We conclude that c-fos expression induced by mild mechanical loading is dependent primarily on cAMP, not PKC, and initial induction of c-fos is not necessarily dependent on the action of newly synthesized PGE2.

  9. Enhanced fos expression in the zebra finch (Taeniopygia guttata) brain following first courtship.

    PubMed

    Sadananda, Monika; Bischof, Hans-Joachim

    2002-06-24

    Young zebra finch males that court a female for the first time develop a stable preference for the females of that species. On the neuronal level, consolidation of the imprinted information takes place. Here we demonstrate that first courtship or being chased around in the cage leads to enhanced fos expression in forebrain areas implicated in learning and imprinting in zebra finch males compared with birds reared in isolation or in the aviary. Two of the forebrain areas highly active during first courtship (as demonstrated by the 14C-2-deoxyglucose technique), the imprinting locus latral neo/hyperstriatum ventrale (LNH) and the secondary visual area hyperstriatum accessorium/dorsale (HAD), demonstrate enhanced fos expression. Two other imprinting-related areas, the medial neo/hyperstriatum ventrale (MNH) and archistriatum/neostriatum caudale (ANC), do show c-fos induction; however, the areas are not congruous with those demarcated by the 2-DG autoradiographic studies. Additional telencephalic areas include the olfactory lobe, the information storage site lobus parolfactorius (LPO), the memory site hippocampus, the auditory caudomedial neostriatum implicated in the strength of song learning, and the caudolateral neostriatum, which is comparable to the mammalian prefrontal cortex. In addition, c-fos is induced by first courtship and chasing in neurosecretory cell groups of the preoptic area and hypothalamus associated with the repertoire of sexual behavior and stress or enhanced arousal. Enhanced fos expression is also observed in brainstem sources of specific (noradrenergic, catecholaminergic) and nonspecific (reticular formation) activating pathways with inputs to higher brain areas implicated in the imprinting process. Birds reared in isolation or alternatively in the aviary with social and sexual contact to conspecifics showed attenuated or no fos expression in most of the above-mentioned areas. First courtship and chasing both lead to enhanced uptake of 2-DG in

  10. 'Fluorescent Cell Chip' for immunotoxicity testing: Development of the c-fos expression reporter cell lines

    SciTech Connect

    Trzaska, Dominika; Zembek, Patrycja; Olszewski, Maciej; Adamczewska, Violetta; Ulleras, Erik; Dastych, JarosIaw . E-mail: jdastych@cbm.pan.pl

    2005-09-01

    The Fluorescent Cell Chip for in vitro immunotoxicity testing employs cell lines derived from lymphocytes, mast cells, and monocytes-macrophages transfected with various EGFP cytokine reporter gene constructs. While cytokine expression is a valid endpoint for in vitro immunotoxicity screening, additional marker for the immediate-early response gene expression level could be of interest for further development and refinement of the Fluorescent Cell Chip. We have used BW.5147.3 murine thymoma transfected with c-fos reporter constructs to obtain reporter cell lines expressing ECFP under the control of murine c-fos promoter. These cells upon serum withdrawal and readdition and incubation with heavy metal compounds showed paralleled induction of c-Fos expression as evidenced by Real-Time PCR and ECFP fluorescence as evidenced by computer-supported fluorescence microscopy. In conclusion, we developed fluorescent reporter cell lines that could be employed in a simple and time-efficient screening assay for possible action of chemicals on c-Fos expression in lymphocytes. The evaluation of usefulness of these cells for the Fluorescent Cell Chip-based detection of immunotoxicity will require additional testing with a larger number of chemicals.

  11. Decreased food anticipatory activity of obese mice relates to hypothalamic c-Fos expression.

    PubMed

    Luna-Illades, C; Morales, T; Miranda-Anaya, M

    2017-10-01

    During daily Food Restriction (FR), obese Neotomodon alstoni mice present decreased Food Anticipatory Activity (FAA) compared to lean mice. Here, we investigated whether FOS expression in hypothalamic nuclei involved in food synchronization and anticipation parallels decreased FAA during daily FR of obese N. alstoni. Locomotor activity of lean and obese mice in ad libitum feeding conditions was monitored for at least two weeks. Then, a gradual restriction of food access was followed to establish a 5h period of daily food access. FR was maintained during at least two weeks before sacrifice of mice at the starting point of the feeding period. Obese mice subjected to FR displayed an overall reduction of FOS-positive (FOS+) hypothalamic neurons, while lean mice in a similar protocol exhibited an increase in FOS+ neurons within the arcuate and dorsomedial hypothalamic nuclei. These results are consistent with decreased FAA displayed by obese mice in comparison to lean mice. Furthermore, limbic system areas of lean mice, such as the cingulate cortex and the hippocampus, showed an increase in FOS during FR, while no responses were observed in obese mice. The daily food intake of obese mice was severely reduced during FR, compared to the ad libitum condition, whereas food intake in lean mice was not affected by FR. Current data suggests that decreased hypothalamic and limbic neuronal activation may contribute to the reduction of FAA in obese N. alstoni mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. ΔFosB Regulates Gene Expression and Cognitive Dysfunction in a Mouse Model of Alzheimer's Disease.

    PubMed

    Corbett, Brian F; You, Jason C; Zhang, Xiaohong; Pyfer, Mark S; Tosi, Umberto; Iascone, Daniel M; Petrof, Iraklis; Hazra, Anupam; Fu, Chia-Hsuan; Stephens, Gabriel S; Ashok, Annie A; Aschmies, Suzan; Zhao, Lijuan; Nestler, Eric J; Chin, Jeannie

    2017-07-11

    Alzheimer's disease (AD) is characterized by cognitive decline and 5- to 10-fold increased seizure incidence. How seizures contribute to cognitive decline in AD or other disorders is unclear. We show that spontaneous seizures increase expression of ΔFosB, a highly stable Fos-family transcription factor, in the hippocampus of an AD mouse model. ΔFosB suppressed expression of the immediate early gene c-Fos, which is critical for plasticity and cognition, by binding its promoter and triggering histone deacetylation. Acute histone deacetylase (HDAC) inhibition or inhibition of ΔFosB activity restored c-Fos induction and improved cognition in AD mice. Administration of seizure-inducing agents to nontransgenic mice also resulted in ΔFosB-mediated suppression of c-Fos, suggesting that this mechanism is not confined to AD mice. These results explain observations that c-Fos expression increases after acute neuronal activity but decreases with chronic activity. Moreover, these results indicate a general mechanism by which seizures contribute to persistent cognitive deficits, even during seizure-free periods. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. d-LSD-induced c-Fos expression occurs in a population of oligodendrocytes in rat prefrontal cortex.

    PubMed

    Reissig, Chad J; Rabin, Richard A; Winter, Jerrold C; Dlugos, Cynthia A

    2008-03-31

    Induction of mRNA or protein for immediate-early genes, such as c-fos, is used to identify brain areas, specific cell types, and neuronal circuits that become activated in response to various stimuli including psychoactive drugs. The objective of the present study was to identify the cell types in the prefrontal cortex in which lysergic acid diethylamide (d-LSD) induces c-Fos expression. Systemic administration of d-LSD resulted in a dose-dependent increase in c-Fos immunoreactivity. Although c-Fos-positive cells were found in all cortical layers, they were most numerous in layers III, IV, and V. d-LSD-induced c-Fos immunoreactivity was found in cells co-labeled with anti-neuron-specific enolase or anti-oligodendrocyte Oligo1. The Oligo1-labeled cells had small, round bodies and nuclear diameters characteristic of oligodendrocytes. Studies using confocal microscopy confirmed colocalization of c-Fos-labeled nuclei in NeuN-labeled neurons. Astrocytes and microglia labeled with glial fibrillary acidic protein antibody and OX-42 antibody, respectively, did not display LSD-induced c-Fos expression. Pyramidal neurons labeled with anti-neurofilament antibody also did not show induction of c-Fos immunoreactivity after systemic d-LSD administration. The present study demonstrates that d-LSD induced expression of c-Fos in the prefrontal cortex occurs in subpopulations of neurons and in oligodendrocytes, but not in pyramidal neurons, astrocytes, and microglia.

  14. Stressor Controllability and Fos Expression in Stress Regulatory Regions in Mice

    PubMed Central

    Liu, X.; Tang, X.; Sanford, LD

    2009-01-01

    Controllability is an important determinant of the effects of stress on behavior. We trained mice with escapable (ES) and inescapable (IS) shock and examined behavioral freezing and Fos expression in brain regions involved in stress to determine whether stressor controllability produced differential activation of these regions. Mice (C57BL/6J) were trained to escape footshock by moving to a safe chamber in a shuttlebox. This terminated shock for both ES mice (n=5) and yoked-control mice receiving IS (n=5). Handling control (HC) mice (n=5) experienced the shuttlebox, but never received footshock. Training took place on three days (20 trials per day, 0.2 mA, 5.0 sec maximum duration, 1.0 min interstimulus interval). On day 3, the animals were killed two h after training and the brains were processed for Fos expression in the amygdala, hypothalamic paraventricular nucleus (PVN), laterodorsal tegmental nucleus, locus coeruleus and dorsal raphe nucleus. Fos expression after IS was greater than after ES and HC in all regions (p < .05). Fos expression after ES was greater than HC only in PVN (p < .05). Freezing in ES mice was equal to or greater than in IS mice whereas HC mice showed minimal freezing. Differential activation of brain regions implicated in stress may, in part, account for differences in behavior in the aftermath of uncontrollable and controllable stress. PMID:19275908

  15. Harmful algal bloom toxins alter c-Fos protein expression in the brain of killifish, Fundulus heteroclitus

    PubMed Central

    Salierno, J.D.; Snyder, N.S.; Murphy, A.Z.; Poli, M.; Hall, S.; Baden, D.; Kane, A.S.

    2009-01-01

    The immediate early gene c-fos, and its protein product c-Fos, are known to be induced in neurons of mammals and fish as a result of neuronal stimulation. The purpose of this study was to quantitatively examine CNS alterations in killifish, Fundulus heteroclitus, in relation to harmful algal bloom (HAB) toxin exposure. c-Fos expression was visualized using immunocytochemistry in the brains of killifish exposed to the excitatory neurotoxins domoic acid (DA) and brevetoxin (PbTx-2), and a paralytic neurotoxin, saxitoxin (STX), released from HABs. In addition, a simulated transport stress experiment was conducted to investigate effects of physical stress on c-Fos induction. Groups of fish were exposed to the different stress agents, brain sections were processed for c-Fos staining, and expression was quantified by brain region. Fish exposed to DA, STX, and transport stress displayed significant alterations in neuronal c-Fos expression when compared to control fish (p ≤ 0.05). DA, PbTx-2, and transport stress increased c-Fos expression in the optic tecta regions of the brain, whereas STX significantly decreased expression. This is the first study to quantify c-Fos protein expression in fish exposed to HAB toxins. General alterations in brain activity, as well as knowledge of specific regions within the brain activated in association with HABs or other stressors, provides valuable insights into the neural control of fish behavior as well as sublethal effects of specific stressors in the CNS. PMID:16750577

  16. Lysergic acid diethylamide-induced Fos expression in rat brain: role of serotonin-2A receptors.

    PubMed

    Gresch, P J; Strickland, L V; Sanders-Bush, E

    2002-01-01

    Lysergic acid diethylamide (LSD) produces altered mood and hallucinations in humans and binds with high affinity to serotonin-2A (5-HT(2A)) receptors. Although LSD interacts with other receptors, the activation of 5-HT(2A) receptors is thought to mediate the hallucinogenic properties of LSD. The goal of this study was to identify the brain sites activated by LSD and to determine the influence of 5-HT(2A) receptors in this activation. Rats were pretreated with the 5-HT(2A) receptor antagonist MDL 100907 (0.3 mg/kg, i.p.) or vehicle 30 min prior to LSD (500 microg/kg, i.p.) administration and killed 3 h later. Brain tissue was examined for Fos protein expression by immunohistochemistry. LSD administration produced a five- to eight-fold increase in Fos-like immunoreactivity in medial prefrontal cortex, anterior cingulate cortex, and central nucleus of amygdala. However, in dorsal striatum and nucleus accumbens no increase in Fos-like immunoreactivity was observed. Pretreatment with MDL 100907 completely blocked LSD-induced Fos-like immunoreactivity in medial prefrontal cortex and anterior cingulate cortex, but only partially blocked LSD-induced Fos-like immunoreactivity in amygdala. Double-labeled immunohistochemistry revealed that LSD did not induce Fos-like immunoreactivity in cortical cells expressing 5-HT(2A) receptors, suggesting an indirect activation of cortical neurons. These results indicate that the LSD activation of medial prefrontal cortex and anterior cingulate cortex is mediated by 5-HT(2A) receptors, whereas in amygdala 5-HT(2A) receptor activation is a component of the response. These findings support the hypothesis that the medial prefrontal cortex, anterior cingulate cortex, and perhaps the amygdala, are important regions involved in the production of hallucinations. Copyright 2002 IBRO

  17. Imaging C-Fos Gene Expression in Burns Using Lipid Coated Spion Nanoparticles.

    PubMed

    Papagiannaros, Aristarchos; Righi, Valeria; Day, George G; Rahme, Laurence G; Liu, Philip K; Fischman, Alan J; Tompkins, Ronald G; Tzika, A Aria

    2012-10-01

    MR imaging of gene transcription is important as it should enable the non-invasive detection of mRNA alterations in disease. A range of MRI methods have been proposed for in vivo molecular imaging of cells based on the use of ultra-small super-paramagnetic iron oxide (USPIO) nanoparticles and related susceptibility weighted imaging methods. Although immunohistochemistry can robustly differentiate the expression of protein variants, there is currently no direct gene assay technique that is capable of differentiating established to differentiate the induction profiles of c-Fos mRNA in vivo. To visualize the differential FosB gene expression profile in vivo after burn trauma, we developed MR probes that link the T2* contrast agent [superparamagnetic iron oxide nanoparticles (SPION)] with an oligodeoxynucleotide (ODN) sequence complementary to FosB mRNA to visualize endogenous mRNA targets via in vivo hybridization. The presence of this SPION-ODN probe in cells results in localized signal reduction in T2*-weighted MR images, in which the rate of signal reduction (R2*) reflects the regional iron concentration at different stages of amphetamine (AMPH) exposure in living mouse tissue. Our aim was to produce a superior contrast agent that can be administered using systemic as opposed to local administration and which will target and accumulate at sites of burn injury. Specifically, we developed and evaluated a PEGylated lipid coated MR probe with ultra-small super-paramagnetic iron oxide nanoparticles (USPION, a T2 susceptibility agent) coated with cationic fusogenic lipids, used for cell transfection and gene delivery and covalently linked to a phosphorothioate modified oligodeoxynucleotide (sODN) complementary to c-Fos mRNA (SPION-cFos) and used the agent to image mice with leg burns. Our study demonstrated the feasibility of monitoring burn injury using MR imaging of c-Fos transcription in vivo, in a clinically relevant mouse model of burn injury for the first time.

  18. Baclofen did not modify sexually dimorphic c-Fos expression during morphine withdrawal syndrome.

    PubMed

    Pedrón, Valeria T; Taravini, Irene R E; Induni, Andrea S; Balerio, Graciela N

    2013-03-01

    In previous studies, we have reported sex-related differences during morphine withdrawal. We have also shown that the GABA(B) agonist baclofen (BAC) was able to prevent the morphine withdrawal syndrome in male as well as in female mice. Considering that early gene expression is induced by drugs of abuse, we evaluated the expression of c-Fos in several brain areas, in mice of either sex during naloxone (NAL)-precipitated withdrawal, and after pretreatment with BAC. Swiss-Webster prepubertal mice were rendered dependent by i.p. injection of morphine (2 mg/kg), twice daily for 9 days. On the 10th day, dependent mice were divided into two groups: the withdrawal group received NAL (6 mg/kg, i.p.) after the last dose of morphine, while the prevention group received BAC (2 mg/kg, i.p.) before NAL. Thirty minutes after NAL, animals were sacrificed by transcardial perfusion. Brains were removed and slices were obtained to perform immunohistochemical studies. Our results show a significant decrease in c-Fos expression in hippocampal dentate gyrus, CA3, and CA1 areas of morphine withdrawn males, vs. their control group. Conversely, in females, the number of c-Fos positive nuclei was not modified in any of the areas studied. BAC pretreatment had no effect on the decreased c-Fos expression in morphine withdrawn males. The sexual dimorphism observed here confirms the greater sensitivity of males over females in their response to morphine. The preventive action of BAC on the expression of morphine withdrawal would not be related to an effect on c-Fos expression.

  19. The neurotensin agonist PD149163 increases Fos expression in the prefrontal cortex of the rat.

    PubMed

    Petrie, Kimberly A; Bubser, Michael; Casey, Cheryl D; Davis, M Duff; Roth, Bryan L; Deutch, Ariel Y

    2004-10-01

    Dopaminergic axons innervating the prefrontal cortex (PFC) target both pyramidal cells and GABAergic interneurons. Many of these dopamine (DA) axons in the rat coexpress the peptide neurotransmitter neurotensin. Previous electrophysiological data have suggested that neurotensin activates GABAergic interneurons in the PFC. Activation of D2-like DA receptors increases extracellular GABA levels in the PFC, as opposed to the striatum, where D2 receptor activation inhibits GABAergic neurons. Because activation of presynaptic D2 release-modulating autoreceptors in the PFC suppresses DA release but increases release of the cotransmitter neurotensin, D2 agonists may enhance the activity of GABAergic interneurons via release of neurotensin. In order to determine if neurotensin can activate GABAergic interneurons, we treated rats with the peptide neurotensin agonist, PD149163, and examined Fos expression in PFC neurons. Systemic administration of PD149163 increased overall Fos expression in the PFC, but not in the dorsal striatum. PD149163 induced Fos in PFC interneurons, as defined by the presence of calcium-binding proteins, and in pyramidal cells. Pretreatment with the high-affinity neurotensin antagonist, SR48692, blocked neurotensin agonist-induced Fos expression. These data suggest that neurotensin activates interneurons in the PFC of the rat.

  20. C-FOS expression in the rat brain in response to substance P and neurokinin B.

    PubMed

    Spitznagel, H; Baulmann, J; Blume, A; Unger, T; Culman, J

    2001-10-19

    Substance P, the principal neurokinin peptide in the mammalian brain and the natural ligand for the NK(1) tachykinin receptor, plays an integrative role in the regulation of cardiovascular, neuroendocrine and behavioural responses to stress. In rats, stimulation of periventricular NK(1) receptors in the forebrain induces a distinct pattern of cardiovascular responses which is accompanied by intense grooming behaviour. Ligands for NK(3) receptors induce a different pattern of cardiovascular and behavioural responses which comprises an increased release of vasopressin from the posterior pituitary and wet-dog shakes behaviour. To define the brain areas in the rat which respond to stimulation of forebrain NK(1) and NK(3) receptors and participate in the generation of these responses, the induction of c-Fos immunoreactivity was examined in brains following intracerebroventricular injections of substance P and neurokinin B in conscious rats. Stimulation of central NK(1) receptors by substance P (25, 100 and 500 pmol) injected into the lateral ventricle elicited grooming behaviour (face washing and hind limb grooming) and resulted in a marked c-Fos expression in the paraventricular, dorsomedial and parabrachial nuclei and in the medial thalamus. At 25 pmol, substance P did not significantly increase c-Fos expression, at 100 pmol, maximal c-Fos activation was induced in all four brain regions which responded to the peptide. Intracerebroventricular pretreatment of rats with the selective and high-affinity, non-peptide NK(1) receptor antagonist, RP 67580 (500 pmol), but not with its inactive enantiomer, RP 68651, completely abolished the behavioural response to substance P and reduced the substance P-induced c-Fos expression in all brain areas to nearly control levels. Intracerebroventricular injection of the natural ligand for NK(3) receptors, neurokinin B (500 pmol), elicited wet-dog shakes behaviour and activated c-Fos expression in localized regions of the forebrain

  1. The Changes of c-Fos Expression by Motor Cortex Stimulation in the Deafferentation Pain Model

    PubMed Central

    KUDO, Kanae; TAKAHASHI, Toshio; SUZUKI, Shigeharu

    2014-01-01

    The effect of motor cortex stimulation (MCS) therapy for deafferentation pain was evaluated based on c-Fos, a known pain marker. Nineteen mature cats weighing 1.5–3.5 kg were used. Cats were divided into three groups: a deafferentation pain group in which the left trigeminal ganglion was destroyed, an MCS group in which MCS was used following destruction of the trigeminal ganglion, and a control group. Sites and levels of c-Fos expression were examined immunohistochemically. The percentage of c-Fos-positive cells in the left spinal nucleus of the trigeminus, the bilateral insula, and the bilateral operculum increased in both the deafferentation pain and the MCS groups. There were no statistically significant differences between these groups. In the cingulate gyrus, the percentage of c-Fos-positive cells increased bilaterally in the deafferentation pain group and the MCS group, but the increase was greater in the MCS group. The increase in c-Fos-positive cells in the left spinal nucleus of the trigeminus in the deafferentation group may reflect reported electrical hyperactivity. The cingulate gyrus, insula, and parietal operculum were activated after deafferentation. This change (increase in c-Fos positive cells) is related to the development of deafferentation pain. Pain relief due to MCS is not dependent on the suppression of the activated left spinal nucleus of the trigeminus or the descending analgesic mechanism of the brain stem. Activation of the cingulate gyrus appears to be a factor in the analgesic mechanism of MCS. PMID:24965534

  2. Context-induced reinstatement of methamphetamine seeking is associated with unique molecular alterations in Fos-expressing dorsolateral striatum neurons.

    PubMed

    Rubio, F Javier; Liu, Qing-Rong; Li, Xuan; Cruz, Fabio C; Leão, Rodrigo M; Warren, Brandon L; Kambhampati, Sarita; Babin, Klil R; McPherson, Kylie B; Cimbro, Raffaello; Bossert, Jennifer M; Shaham, Yavin; Hope, Bruce T

    2015-04-08

    Context-induced reinstatement of drug seeking is a well established animal model for assessing the neural mechanisms underlying context-induced drug relapse, a major factor in human drug addiction. Neural activity in striatum has previously been shown to contribute to context-induced reinstatement of heroin, cocaine, and alcohol seeking, but not yet for methamphetamine seeking. In this study, we found that context-induced reinstatement of methamphetamine seeking increased expression of the neural activity marker Fos in dorsal but not ventral striatum. Reversible inactivation of neural activity in dorsolateral but not dorsomedial striatum using the GABA agonists muscimol and baclofen decreased context-induced reinstatement. Based on our previous findings that Fos-expressing neurons play a critical role in conditioned drug effects, we assessed whether context-induced reinstatement was associated with molecular alterations selectively induced within context-activated Fos-expressing neurons. We used fluorescence-activated cell sorting to isolate reinstatement-activated Fos-positive neurons from Fos-negative neurons in dorsal striatum and used quantitative PCR to assess gene expression within these two populations of neurons. Context-induced reinstatement was associated with increased expression of the immediate early genes Fos and FosB and the NMDA receptor subunit gene Grin2a in only Fos-positive neurons. RNAscope in situ hybridization confirmed that Grin2a, as well as Grin2b, expression were increased in only Fos-positive neurons from dorsolateral, but not dorsomedial, striatum. Our results demonstrate an important role of dorsolateral striatum in context-induced reinstatement of methamphetamine seeking and that this reinstatement is associated with unique gene alterations in Fos-expressing neurons.

  3. Quercetin potentiates UVB-induced c-Fos expression: Implications for its use as a chemopreventive agent

    PubMed Central

    Olson, Erik R.; Melton, Tania; Dickinson, Sally E.; Dong, Zigang; Alberts, David S.; Bowden, G. Tim

    2010-01-01

    Quercetin (Qu) is currently being investigated as a chemopreventive agent for a number of cancers including non-melanoma skin cancer induced by ultraviolet (UV) light. We previously reported that Qu degradation has important consequences on signaling and cell biology. In the current study, we report that Qu induces c-Fos mRNA and protein expression through activation of p38 and CREB, and Qu potentiates UVB-induced c-Fos expression. Inclusion of ascorbic acid (AA) in cell culture medium stabilizes Qu and completely prevents both Qu- and UVB- induced p38 and CREB activation, leading to a blockade of c-fos gene expression through reduced CREB/CRE binding. AA stabilizes c-Fos mRNA, increasing steady state levels even when c-fos gene expression is suppressed, but this has no effect on c-Fos protein levels in either mock- or UVB-irradiated cells. We report that Qu blocks mTOR signaling and inhibits c-Fos protein expression directly through this mechanism, since co-treatment with Qu and AA resulted in complete suppression of UVB-induced c-Fos protein expression even in the presence of significantly increased mRNA levels. We further confirmed that this was not due to increased protein turnover since inhibition of proteasome activity with MG-132 did not raise c-Fos protein levels in Qu+AA treated cells. Together, these data indicate that while Qu has been reported to have some beneficial properties as a chemopreventive agent, it is also capable of inducing c-fos expression, a cellular event important for the promotion phase of tumor development, if it is not stabilized. PMID:20551291

  4. Context-Induced Reinstatement of Methamphetamine Seeking Is Associated with Unique Molecular Alterations in Fos-Expressing Dorsolateral Striatum Neurons

    PubMed Central

    Rubio, F. Javier; Liu, Qing-Rong; Li, Xuan; Cruz, Fabio C.; Leão, Rodrigo M.; Warren, Brandon L.; Kambhampati, Sarita; Babin, Klil R.; McPherson, Kylie B.; Cimbro, Raffaello; Bossert, Jennifer M.; Shaham, Yavin

    2015-01-01

    Context-induced reinstatement of drug seeking is a well established animal model for assessing the neural mechanisms underlying context-induced drug relapse, a major factor in human drug addiction. Neural activity in striatum has previously been shown to contribute to context-induced reinstatement of heroin, cocaine, and alcohol seeking, but not yet for methamphetamine seeking. In this study, we found that context-induced reinstatement of methamphetamine seeking increased expression of the neural activity marker Fos in dorsal but not ventral striatum. Reversible inactivation of neural activity in dorsolateral but not dorsomedial striatum using the GABA agonists muscimol and baclofen decreased context-induced reinstatement. Based on our previous findings that Fos-expressing neurons play a critical role in conditioned drug effects, we assessed whether context-induced reinstatement was associated with molecular alterations selectively induced within context-activated Fos-expressing neurons. We used fluorescence-activated cell sorting to isolate reinstatement-activated Fos-positive neurons from Fos-negative neurons in dorsal striatum and used quantitative PCR to assess gene expression within these two populations of neurons. Context-induced reinstatement was associated with increased expression of the immediate early genes Fos and FosB and the NMDA receptor subunit gene Grin2a in only Fos-positive neurons. RNAscope in situ hybridization confirmed that Grin2a, as well as Grin2b, expression were increased in only Fos-positive neurons from dorsolateral, but not dorsomedial, striatum. Our results demonstrate an important role of dorsolateral striatum in context-induced reinstatement of methamphetamine seeking and that this reinstatement is associated with unique gene alterations in Fos-expressing neurons. PMID:25855177

  5. Role of the c-fos gene expression on the mitogenic response in EL2 rat fibroblasts.

    PubMed

    Di Francesco, P; Liboi, E

    1988-01-01

    Stimulation of the growth of quiescent fibroblasts by polypeptide growth factors is accompanied by the rapid induction of the c-fos proto-oncogene. To investigate whether there exists a relationship between mitogenic activity and c-fos expression, we analysed cellular responses (DNA synthesis and cell growth) and c-fos gene induction (mRNA and proteins) in a rat embryo fibroblast line (EL2) stimulated with epidermal growth factor (EGF), fibroblast growth factor (FGF), 12-O-tetradodecanoyl phorbol-13-acetate (TPA) and transforming growth factor beta (TGF beta). Our results suggest that the susceptibility of EL2 cells to a growth factor could be predicted as a function of the c-fos expression caused by the same growth factor. These also indicate that the c-fos gene expression may have contributed to moving our cells out of the quiescent state, but it is not the only essential event required to effect EL2 cell growth.

  6. Problem-Solving Test: The Role of a Micro-RNA in the Regulation of "fos" Gene Expression

    ERIC Educational Resources Information Center

    Szeberenyi, Jozsef

    2009-01-01

    The "fos" proto-oncogene codes for a component of the AP1 transcription factor, an important regulator of gene expression and cell proliferation. Dysregulation of AP1 function may lead to the malignant transformation of the cell. The present test describes an experiment in which the role of a micro-RNA (miR-7b) in the regulation of "fos" gene…

  7. Problem-Solving Test: The Role of a Micro-RNA in the Regulation of "fos" Gene Expression

    ERIC Educational Resources Information Center

    Szeberenyi, Jozsef

    2009-01-01

    The "fos" proto-oncogene codes for a component of the AP1 transcription factor, an important regulator of gene expression and cell proliferation. Dysregulation of AP1 function may lead to the malignant transformation of the cell. The present test describes an experiment in which the role of a micro-RNA (miR-7b) in the regulation of "fos" gene…

  8. Morphine-conditioned cue alters c-Fos protein expression in the brain of crayfish.

    PubMed

    Dziopa, Leah; Imeh-Nathaniel, Adebobola; Baier, Dana; Kiel, Michael; Sameera, Sayeed; Brager, Adam; Beatriz, Vega; Nathaniel, Thomas I

    2011-07-15

    With a highly organized stereotypic behavior and a simplified neuronal system that is characterized by cellular modularity, crayfish (Orconectes rusticus) represents an excellent model that we used in this study to explore how a drug-conditioned-cue alters c-Fos protein expression in the brain of an invertebrate species. The first set of experiments revealed that a single injection of different doses of morphine (3.0 μg/g, 6.0 μg/g and 12.0 μg/g) into the circulatory system of crayfish significantly increased locomotor activity. Repeated injections of morphine increased locomotion at lower doses (3.0 μg/g and 6.0 μg/g), and decreased locomotion at a higher dose of 12.0 μg/g. The second experiment revealed that a repeated or single injection of morphine serves as reward when paired with a distinct visual environment. In the third experiment, we found that the c-Fos profile of morphine treated crayfish in an unconditioned environment did not show a significant increase from the basal level comparable to saline treated crayfish. The brains of crayfish were more active during exposure to the cue-elicited drug conditioned environment than the unconditioned environment. These results indicate that chronic morphine treatment alone is not sufficient to induce changes in the expression of c-Fos; instead, morphine-environment pairing in a specific context contributes to the expression of alterations in c-Fos regulation. The enhancement of c-Fos expression in the brain of crayfish seems to reflect the sensory or anticipatory facets of conditioning that suggests that potential and even unanticipated hypotheses in drug addiction can emerge from studies of addiction in crayfish. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Identification of temperature-sensitive neural circuits in mice using c-Fos expression mapping.

    PubMed

    Bachtell, Ryan K; Tsivkovskaia, Natalia O; Ryabinin, Andrey E

    2003-01-17

    Expression of the inducible transcription factor c-Fos was mapped in mouse brain to identify neural circuits selectively involved in response to cold and hot external temperatures. Male C57BL/6J mice were exposed acutely or repeatedly (seven sessions) to 10 or 34 degrees C in sound-attenuated chambers. Control mice were acclimated to exposure to the experimental room at 20 degrees C. All animals were sacrificed at 90 min for immunohistochemical analysis. A statistically significant induction of c-Fos was observed in the shell of nucleus accumbens and posterior medial cortical amygdala only following the acute thermal exposure, showing a significant habituation of the response to repeated treatments, a finding arguing against specificity of responses in these nuclei to thermal exposures. In contrast, expression of c-Fos was significantly increased following both acute and repeated thermal exposures in subregions of hypothalamus (the median and medial preoptic nuclei, the paraventricular nucleus of hypothalamus and the posterior hypothalamic area), septum (the ventral and dorsal portions of the lateral septum), midbrain (the periaqueductal gray and the intermediate layers of superior colliculus), as well as in the dentate gyrus and the paraventricular nucleus of thalamus, suggesting specificity of their responses to external temperatures. Expression of c-Fos was also significantly increased in the Edinger-Westphal nucleus following acute thermal exposures versus control mice, but not versus mice repeatedly exposed to cold and hot temperatures, providing modest support for thermal specificity of c-Fos response in this nucleus. While thermal sensitivity of hypothalamic structures has been previously confirmed by many authors, the present study identifies a number of structures previously not found to be responsive to changes in external temperature, and lays ground for future work important for identification of neural circuits involved in thermoregulation.

  10. Treatment with neuropeptides attenuates c-fos expression in a mouse model of fetal alcohol syndrome.

    PubMed

    Incerti, Maddalena; Vink, Joy; Roberson, Robin; Abebe, Daniel; Spong, Catherine Y

    2010-10-01

    Fetal alcohol syndrome (FAS) is the most common nongenetic cause of mental retardation and is characterized by neurodevelopmental anomalies. C-FOS is a cellular marker of transcriptional activity in the stress-signal pathway. Previously, we showed the treatment with NAP (NAPVSIPQ) + SAL (SALLRSIPA) reversed the learning deficit after prenatal alcohol exposure in FAS. Our objective was to evaluate if the mechanism of actions of NAP + SAL involves the stress-signal pathway differentiating C-FOS expression in mouse brains after prenatal alcohol exposure. C57Bl6/J mice were treated with alcohol (0.03 mL/g) or placebo on gestational day 8. On postnatal day 40, in utero alcohol-exposed males were treated via gavage with 40 μg D-NAP and 40 μg D-SAL ( N = 6) or placebo ( N = 4); controls were gavaged with placebo daily ( N = 12). After learning evaluation, hippocampus, cerebellum, and cortex were isolated. Calibrator-normalized relative real-time polymerase chain reaction and Western blot analysis were performed. Statistics included analysis of variance and post hoc Fisher analysis. Adult treatment with NAP + SAL restored the down-regulation of C-FOS in the hippocampus after prenatal alcohol exposure ( P < 0.05), but not in the cerebellum. There was no difference in C-FOS expression in the cortex. Adult treatment with NAP + SAL restored the down-regulation of C-FOS expression in hippocampus attenuating the alcohol-induced alteration of the stress-signal pathway.

  11. Lipopolysaccharide induces delayed FosB/DeltaFosB immunostaining within the mouse extended amygdala, hippocampus and hypothalamus, that parallel the expression of depressive-like behavior

    PubMed Central

    Frenois, François; Moreau, Maïté; Connor, Jason O’; Lawson, Marc; Micon, Charlotte; Lestage, Jacques; Kelley, Keith W.; Dantzer, Robert; Castanon, Nathalie

    2007-01-01

    Proinflammatory cytokines induce both sickness behavior and depression, but their respective neurobiological correlates are still poorly understood. The aim of the present study was therefore to identify in mice the neural substrates of sickness and depressive-like behavior induced by lipopolysaccharide (LPS, 830 μg/kg, intraperitoneal). LPS-induced depressive-like behavior was dissociated from LPS-induced sickness by testing mice either at 6 h (at which time sickness was expected to be maximal) or at 24 h post-LPS (at which time sickness was expected to be minimal and not to bias the measurement of depressive-like behavior). Concurrently, the expression of acute and chronic cellular reactivity markers (c-Fos and FosB/ΔFosB respectively) was mapped by immunohistochemistry at these two time points. In comparison to saline, LPS decreased motor activity in a new cage at 6 but not at 24 h. In contrast, the duration of immobility in the tail suspension test was increased at both 6 and 24 h. This dissociation between decreased motor activity and depressive-like behavior was confirmed at 24 h post-LPS in the forced swim test. LPS also decreased sucrose consumption at 24 and 48 h, despite normal food and water consumption by that time. At 24 h post-LPS, LPS-induced depressive-like behavior was associated with a delayed cellular activity (as assessed by FosB/ΔFosB immunostaining) in specific brain structures, particularly within the extended amygdala, hippocampus and hypothalamus, whereas c-Fos labeling was markedly decreased by that time in all the brain areas at 6 h post-LPS. These results provide the first evidence in favor of a functional dissociation between the brain structures that underlie cytokine-induced sickness behavior and cytokine-induced depressive-like behavior, and provide important cues about the neuroanatomical brain circuits through which cytokines could have an impact on affect. PMID:17482371

  12. Regulation of fos-lacZ fusion gene expression in primary mouse epidermal keratinocytes isolated from transgenic mice.

    PubMed Central

    Bollag, W B; Xiong, Y; Ducote, J; Harmon, C S

    1994-01-01

    The expression of a fos-lacZ fusion gene was studied in primary mouse epidermal keratinocytes obtained from transgenic mice. This gene construct contains the entire upstream regulatory sequence of c-fos, and expression of the endogenous and fusion gene was shown by Northern analysis to correlate upon induction with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA). Using a chromogenic substrate of beta-galactosidase, we also demonstrated that expression of the fusion gene product, like that of Fos, was localized to the cell nucleus. In addition, we showed that epidermal keratinocytes responded to dialysed fetal bovine serum (FBS), TPA and high-calcium medium with enhanced Fos-lacZ expression and an inhibition of proliferation. The time course of induction of Fos-lacZ expression was similar for dialysed FBS and TPA, with a peak approximately 2 h after exposure. Exposure for approximately 24 h to an elevated extracellular calcium concentration was required to elicit an increase in Fos-lacZ expression. The lack of an immediate effect of raising medium calcium levels on Fos-lacZ expression contrasted with the rapidity of its effect on DNA synthesis, which was significantly inhibited within 6-8 h. In addition, we found that the protein kinase C inhibitor Ro 31-7549 blocked Fos-lacZ expression induced by TPA but had little or no effect on that elicited by high calcium levels. Thus, although our results indicate that the fos gene product may be involved in mediating epidermal keratinocyte growth arrest in response to differentiative agents such as FBS, TPA and high medium calcium levels, the exact role of this gene product remains unclear. Images Figure 1 Figure 2 PMID:8198544

  13. Regulation of fos-lacZ fusion gene expression in primary mouse epidermal keratinocytes isolated from transgenic mice.

    PubMed

    Bollag, W B; Xiong, Y; Ducote, J; Harmon, C S

    1994-05-15

    The expression of a fos-lacZ fusion gene was studied in primary mouse epidermal keratinocytes obtained from transgenic mice. This gene construct contains the entire upstream regulatory sequence of c-fos, and expression of the endogenous and fusion gene was shown by Northern analysis to correlate upon induction with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA). Using a chromogenic substrate of beta-galactosidase, we also demonstrated that expression of the fusion gene product, like that of Fos, was localized to the cell nucleus. In addition, we showed that epidermal keratinocytes responded to dialysed fetal bovine serum (FBS), TPA and high-calcium medium with enhanced Fos-lacZ expression and an inhibition of proliferation. The time course of induction of Fos-lacZ expression was similar for dialysed FBS and TPA, with a peak approximately 2 h after exposure. Exposure for approximately 24 h to an elevated extracellular calcium concentration was required to elicit an increase in Fos-lacZ expression. The lack of an immediate effect of raising medium calcium levels on Fos-lacZ expression contrasted with the rapidity of its effect on DNA synthesis, which was significantly inhibited within 6-8 h. In addition, we found that the protein kinase C inhibitor Ro 31-7549 blocked Fos-lacZ expression induced by TPA but had little or no effect on that elicited by high calcium levels. Thus, although our results indicate that the fos gene product may be involved in mediating epidermal keratinocyte growth arrest in response to differentiative agents such as FBS, TPA and high medium calcium levels, the exact role of this gene product remains unclear.

  14. Peripheral obestatin has no effect on feeding behavior and brain Fos expression in rodents

    PubMed Central

    Kobelt, Peter; Wisser, Anna-Sophia; Stengel, Andreas; Goebel, Miriam; Bannert, Norbert; Gourcerol, Guillaume; Inhoff, Tobias; Noetzel, Steffen; Wiedenmann, Bertram; Klapp, Burghard F.; Taché, Yvette; Mönnikes, Hubert

    2009-01-01

    Obestatin is produced in the stomach from proghrelin by post-translational cleavage. The initial report claimed anorexigenic effects of obestatin in mice. Contrasting studies indicated no effect of obestatin on food intake (FI). We investigated influences of metabolic state (fed/fasted), environmental factors (dark/light phase) and brain Fos response to intraperitoneal (ip) obestatin in rats, and used the protocol from the original study assessing obestatin effects in mice. FI was determined in male rats injected ip before onset of dark or light phase, with obestatin (1 or 5 μmol/kg), CCK8S (3.5 nmol/kg) or 0.15 M NaCl, after fasting (16 h, n = 8/group) or ad libitum (n = 10-14/group) food intake. Fos expression in hypothalamic and brainstem nuclei was examined in freely fed rats 90 min after obestatin (5 μmol/kg), CCK8S (1.75 nmol/kg) or 0.15 M NaCl (n = 4/group). Additionally, fasted mice were injected ip with obestatin (1 μmol/kg) or urocortin 1 (2 nmol/kg) 15 min before food presentation. No effect on FI was observed after obestatin administration during the light and dark phase under both metabolic conditions while CCK8S reduced FI irrespectively of the conditions. The number of Fos positive neurons was not modified by obestatin while CCK8S increased Fos expression in selective brain nuclei. Obestatin did not influence the refeeding response to a fast in mice, while urocortin was effective. Therefore, peripheral obestatin has no effect on FI under various experimental conditions and did not induce Fos in relevant central neuronal circuitries modulating feeding in rodents. PMID:18342400

  15. Conditioned Fear Inhibits c-fos mRNA Expression in the Central Extended Amygdala

    PubMed Central

    Day, Heidi E.W.; Kryskow, Elisa M.; Nyhuis, Tara J.; Herlihy, Lauren; Campeau, Serge

    2008-01-01

    We have shown previously that unconditioned stressors inhibit neurons of the lateral/capsular division of the central nucleus of the amygdala (CEAl/c) and oval division of the bed nucleus of the stria terminalis (BSTov), which form part of the central extended amygdala. The current study investigated whether conditioned fear inhibits c-fos mRNA expression in these regions. Male rats were trained either to associate a visual stimulus (light) with footshock or were exposed to the light alone. After training, animals were replaced in the apparatus, and 2 hours later injected remotely, via a catheter, with amphetamine (2 mg/kg i.p.), to induce c-fos mRNA and allow inhibition of expression to be measured. The rats were then presented with 15 visual stimuli over a 30 minute period. As expected, fear conditioned animals that were not injected with amphetamine, had extremely low levels of c-fos mRNA in the central extended amygdala. In contrast, animals that were trained with the light alone (no fear conditioning) and were injected with amphetamine had high levels of c-fos mRNA in the CEAl/c and BSTov. Animals that underwent fear-conditioning, and were re-exposed to the conditioned stimulus after amphetamine injection had significantly reduced levels of c-fos mRNA in both the BSTov and CEAl/c, compared to the non-conditioned animals. These data suggest that conditioned fear can inhibit neurons of the central extended amygdala. Because these neurons are GABAergic, and project to the medial CEA (an amygdaloid output region), this may be a novel mechanism whereby conditioned fear potentiates amygdaloid output. PMID:18634767

  16. Fos and FRA protein expression in rat precerebellar structures during the Neurolab Space Mission.

    PubMed

    d'Ascanio, Paola; Balaban, Evan; Pompeiano, Maria; Centini, Claudia; Pompeiano, Ottavio

    2003-12-30

    Changes in gene expression were examined in precerebellar structures during and after space flight. These structures included the inferior olive (IO), the source of climbing fibers, and the lateral reticular nucleus (LRt) and basilar pontine nuclei (PN), sources of mossy fibers. We examined two immediate early gene products with two different time courses of expression: Fos, which persists only for a few (6-8)h after activation and FRA expression, which lasts for longer periods of time, i.e. hours and/or days after activation. Gravity effects on Fos and FRA gene expression were evident in vestibular and visual areas of the IO, including the dorsomedial cell column, the beta subnucleus and the dorsal cap of Kooy of the medial nucleus (which projects to the flocculonodular lobe, i.e. to the vestibular area of the IO involved in the olivary control of the vestibulo-ocular reflex (VOR)). Gene expression also affected the subnuclei A, B, and C and the caudal part of the medial IO. These olivary regions do not receive vestibular afferents, but rather spinal afferents, and are particularly involved in the olivary control of the vestibulospinal reflex (VSR). Changes in Fos expression were also observed in the LRt and the PN. We suggest that sensory substitution, in which signals produced by a subject's own activity replace activity normally provided by macular stimulation, contributes to the recovery of microgravity-related postural and motor deficits. While no consistent increases in FRA expression occurred in vestibular IO regions 24h after launch, consistent increases in FRA expression occurred 24h after landing. We hypothesize that this asymmetrical pattern of gene expression resulted from (i). tonic microgravity experienced after launch counteracting the effects of increased phasic gravitational forces experienced during launch, and (ii). the tonic gravitational field experienced after landing potentiating the effects of increased phasic gravitational forces

  17. Suckling and genital stroking induces Fos expression in hypothalamic oxytocinergic neurons of rabbit pups.

    PubMed

    Caba, Mario; Rovirosa, Maria J; Silver, Rae

    2003-07-12

    Maternal behaviour in the rabbit is unusual among mammals because the doe visits her litter to nurse once every 24 h. In the present study we examined the consequences of milk intake on oxytocinergic (OT) and vasopressinergic (AVP) neurons of the supraoptic (SON) and paraventricular (PVN) nuclei of 7-day-old pups before suckling, after suckling and following anogenital stroking in un-nursed pups. To determine neuronal activation we assessed the expression of the Fos protein combined with antibodies against OT and AVP at two levels in the SON (supraoptic rostral, SOr, and supraoptic retrochiasmatic, SOrch), and three levels in the PVN (anterior, PVab; medial PVm and caudal, PVc). Daily nursing bouts lasted only 228+/-6 s throughout the observed 7 days, and pups ingested up to 34.95+/-9.0% of their body weight in milk on day 7, the day of perfusion. Suckling induced a significant increase in the number of double-labeled Fos/OT cells in both subdivisions of the SON (P<0.01) and in PVab and PVm (P<0.01). The effect in the SON was related to suckling, as it was not seen in stroked, un-nursed pups, which showed Fos increases only in PVab and PVm. All regions in the SON and PVN showed significant increases in the number of Fos/AVP neurons after suckling or stroking but, contrary to OT, the number of double-labeled Fos/AVP cells was very low. In conclusion, our results show that the oxytocinergic system of the SON and PVN is differentially activated by suckling of milk and anogenital stroking, and that the vagal-hypothalamic axis is mature in 7-day-old rabbits.

  18. Rapid-onset hypoglycemia suppresses Fos expression in discrete parts of the ventromedial nucleus of the hypothalamus

    PubMed Central

    Foster, Nicholas N.; Azam, Sana

    2016-01-01

    The consensus view of the ventromedial nucleus of the hypothalamus (VMH) is that it is a key node in the rodent brain network controlling sympathoadrenal counterregulatory responses to hypoglycemia. To identify the location of hypoglycemia-responsive neurons in the VMH, we performed a high spatial resolution Fos analysis in the VMH of rats made hypoglycemic with intraperitoneal injections of insulin. We examined Fos expression in the four constituent parts of VMH throughout its rostrocaudal extent and determined their relationship to blood glucose concentrations. Hypoglycemia significantly decreased Fos expression only in the dorsomedial and central parts of the VMH, but not its anterior or ventrolateral parts. Moreover, the number of Fos-expressing neurons was significantly and positively correlated in the two responsive regions with terminal blood glucose concentrations. We also measured Fos responses in the paraventricular nucleus of the hypothalamus (PVH) and in several levels of the periaqueductal gray (PAG), which receives strong projections from the VMH. We found the expected and highly significant increase in Fos in the neuroendocrine PVH, which was negatively correlated to terminal blood glucose concentrations, but no significant differences were seen in any part of the PAG. Our results show that there are distinct populations of VMH neurons whose Fos expression is suppressed by hypoglycemia, and their numbers correlate with blood glucose. These findings support a clear division of glycemic control functions within the different parts of the VMH. PMID:27030665

  19. Gonadotropin and kisspeptin gene expression, but not GnRH, are impaired in cFOS deficient mice

    PubMed Central

    Xie, Changchuan; Jonak, Carrie R.; Kauffman, Alexander S.; Coss, Djurdjica

    2015-01-01

    cFOS is a pleiotropic transcription factor, which binds to the AP1 site in the promoter of target genes. In the pituitary gonadotropes, cFOS mediates induction of FSHβ and GnRH receptor genes. Herein, we analyzed reproductive function in the cFOS-deficient mice to determine its role in vivo. In the pituitary cFOS is necessary for gonadotropin subunit expression, while TSHβ is unaffected. Additionally, cFOS null animals have the same sex-steroid levels, although gametogenesis is impeded. In the brain, cFOS is not necessary for GnRH neuronal migration, axon targeting, cell number, or mRNA levels. Conversely, cFOS nulls, particularly females, have decreased Kiss1 neuron numbers and lower Kiss1 mRNA levels. Collectively, our novel findings suggest that cFOS plays a cell-specific role at multiple levels of the hypothalamic–pituitary–gonadal axis, affecting gonadotropes but not thyrotropes in the pituitary, and kisspeptin neurons but not GnRH neurons in the hypothalamus, thereby contributing to the overall control of reproduction. PMID:25958044

  20. [Drinking behavior and c-fos expression induced by chemical or electrical stimulation of SFO in rat brain].

    PubMed

    Li, Xu-Ping; Jiang, Xing-Hong

    2002-08-01

    To compare the drinking behavior and c-fos expression induced by chemical or electrical stimulation of subfornical organ (SFO) in rat brain. L-glutamic acid microinjection and constant electrical current were used as chemical and electrical stimulation of SFO, respectively. The water intake over 1 h was recorded and Fos expression was examined immunohistochemically. A similar volume of water intake and Fos expression pattern were induced by both methods of stimulation of SFO. These include 11 forebrain areas (organum vasculosum of the lamina terminalis, median preoptic nucleus, hypothalamic paraventricular nucleus, supraoptic nucleus and lateral hypothalamic area, paraventricular nucleus, reunions nucleus and central medial nucleus of thalamus, bed nucleus of the stria terminalis, perifornical dorsal area and substantia innominata) and 4 areas of hindbrain (area postrema, nucleus solitary tract, lateral parabrachial nucleus and dorsal raphe nucleus). The drinking behavior and Fos expression in brain induced by SFO stimulation are the results of activation of the neuronal bodies in SFO.

  1. Tactile Experience Induces c-fos Expression in Rat Barrel Cortex

    PubMed Central

    Filipkowski, Robert K.; Rydz, Marek; Berdel, Bozena; Morys, Janusz; Kaczmarek, Leszek

    2000-01-01

    Understanding gene expression that is responsive to sensory stimulation is central to elucidate molecular mechanisms underlying neuronal plasticity. In this study we demonstrate two new methods of stimulating whiskers that provide major sensory input to rat neocortex. In the first paradigm, animals were placed on the top of a cylinder and their vibrissae were brushed by hand. In the second paradigm, animals were placed for a brief period of time into a new, wired cage resulting in vibrissae stimulation when they explored the new environment. Both approaches induced c-Fos expression in barrel cortex corresponding to the stimulated vibrissae, especially in layer IV. Layers II/III and V/VI also showed c-Fos induction, but there were no detectable changes in layer VIb. The majority of c-Fos-expressing cells are probably not inhibitory neurons, because they do not show parvalbumin staining. Both paradigms, in contrast to the previous methods, are simple to use and do not require anesthesia, restraint of animals, or elaborate experimental setups. PMID:10753978

  2. Spinal nociceptin inhibits AMPA-induced nociceptive behavior and Fos expression in rat spinal cord.

    PubMed

    Menéndez, Luis; Lastra, Ana; Villanueva, Noemí; Hidalgo, Agustín; Baamonde, Ana

    2003-02-01

    The effects of intrathecal nociceptin (NOCI) on the nociceptive behavior (biting, scratching and licking; BSL) and the spinal Fos expression induced by intrathecal administration of N-methyl-D-aspartate (NMDA, 4 microg/rat) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA, 2 microg/rat) were studied. Coadministration of NOCI (3 and 10 nmol/rat) with NMDA did not modify the NMDA-induced BSL or Fos expression. In contrast, NOCI (0.1-3 nmol/rat) dose-dependently inhibited the BSL behavior induced by AMPA. Furthermore, coadministration of NOCI (3 and 10 nmol/rat) significantly reduced the AMPA-induced expression of Fos protein in the superficial layers of the spinal dorsal horn. In order to test whether classical or opioid receptor-like type 1 (ORL1) receptors are involved in the inhibitions by NOCI of AMPA-evoked BSL, the corresponding antagonists were assayed. The administration of the nonselective opioid receptor antagonist, naloxone (10 mg/kg i.p.), did not modify the NOCI-induced inhibition of AMPA-evoked BSL. However, the selective ORL1 receptor antagonist, [N-Phe(1)]nociceptin-(1-13)-NH(2) (90 nmol/rat i.t.), completely prevented the NOCI-mediated inhibition of the nociceptive responses evoked by AMPA. In conclusion, NOCI, acting at ORL1 receptors can, at least in part, induce spinal analgesia by blocking the nociceptive responses produced through the stimulation of AMPA receptors.

  3. Effect of bee venom acupuncture on methamphetamine-induced hyperactivity, hyperthermia and Fos expression in mice.

    PubMed

    Kim, Kee Won; Kim, Hyun Woo; Li, Jing; Kwon, Young Bae

    2011-01-15

    Acupuncture has been used to treat drug addiction by nicotine, alcohol, cocaine and morphine. This study was designed to investigate the effect of bee venom (BV) acupuncture on hyperactivity and hyperthermia induced by acute exposure to methamphetamine (METH, 1mg/kg, s.c.) in mice. Diluted BV (20μl of 0.01, 0.1, 1 and 10mg/ml in saline, s.c.) was administered bilaterally into the Zusanli acupoint (ST36) or control points (SP9 or GB39 or tail base). BV injection into ST36 dose dependently reduced METH-induced hyperactivity and hyperthermia, while BV injection (1mg/ml) into control points did not produce these suppressive effects. METH injection significantly increased Fos expression in several brain regions including nucleus accumbens (NA), caudate putamen (CPU), ventral tegmental area (VTA), substantia nigra (SN) and locus coeruleus (LC). Interestingly, BV (1mg/ml) injection into ST36 further increased METH-induced Fos expression in NA (core and shell), SN and LC. When we performed sciatic denervation or combination treatment of BV and lidocaine (BV diluted in 5% lidocaine solution), the enhancement of Fos elevation by BV was completely blocked in the NA, SN and LC in METH-injected mice, indicating that BV-induced peripheral nerve stimulation played an important role in the BV effect. Furthermore, the effects of BV were completely blocked by the α₂-adrenoceptor antagonist, idazoxan (3mg/kg, i.p.), but not by β-adrenoceptor antagonist, propranolol (10mg/kg, i.p.). Taken together, these findings suggest that BV acupuncture into ST36 may modulate METH-induced hyperactivity, hyperthermia and Fos expression through activation of the peripheral nerve and the central α₂-adrenergic activation. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. The effects of anesthetics on cortical spreading depression elicitation and c-fos expression in rats.

    PubMed

    Kitahara, Y; Taga, K; Abe, H; Shimoji, K

    2001-01-01

    The effects of anesthetics on the generation of cortical spreading depression (CSD) were investigated. Volatile anesthetics halothane, isoflurane, sevoflurane (0.5, 1.0, and 2.0 MAC), and the intravenous anesthetic pentobarbital were studied. Cortical spreading depression was induced by 3M-KCl applied to a surface of brain cortex for 30 minutes. Direct current (DC) potential was recorded, and the number, amplitude, and duration of CSDs were observed. With increasing concentrations of each volatile anesthetic, there was a dose-related reduction in CSD frequency but not in CSD amplitude. At 2.0 MAC of sevoflurane the suppression of CSD was less than with the other volatile anesthetics. In addition, the influence of anesthetics on expression of c-fos mRNA was investigated. Additional animals anesthetized by isoflurane or sevoflurane were studied. Five CSDs were elicited by electric stimulation (0.5 mV, 1 second) in each animal. In situ hybridization with 35S-labeled oligonucleotides was used to evaluate the level of c-fos mRNA. The expression of c-fos was observed in the hemisphere in which CSD was elicited, but there was no difference in expression of c-fos among the groups. We conclude that volatile anesthetics can induce suppression of CSD elicitation in a dose dependent manner, but that at high concentrations sevoflurane is significantly less effective than other volatile agents. Pentobarbital has the least effect on KCl-induced CSD. These data suggest that the choice of anesthetics can impact the results of studies examining membrane depolarization and the ionic changes initiated by CSD.

  5. Striatal dopaminergic stimulation produces c-Fos expression in the PPT and an increase in wakefulness.

    PubMed

    Mena-Segovia, Juan; Giordano, Magda

    2003-10-03

    Striatal activation can modify activity in cortical areas related to specific striatal functions possibly through a process of disinhibition within the basal ganglia. Anatomical studies have shown substantial GABAergic innervation from these nuclei to the pedunculopontine tegmental nucleus (PPT). Thus, dopaminergic stimulation of the striatum could produce PPT disinhibition and result in non-specific cortical activation. To test this hypothesis, d-amphetamine was infused both into the striatum of freely moving rats for motor and electrocorticographic recordings, and into the striatum of animals under deep anesthesia for c-Fos immunohistochemistry. The results show that intrastriatal amphetamine increases wakefulness independent of motor activity, and it increases c-Fos expression in the PPT and adjacent areas. They also suggest that the striatum participates in non-specific cortical activation probably as a result of its relationship with the PPT.

  6. c-FOS expression in the visual system of tree shrews after monocular inactivation.

    PubMed

    Takahata, Toru; Kaas, Jon H

    2017-01-01

    Tree shrews possess an unusual segregation of ocular inputs to sublayers rather than columns in the primary visual cortex (V1). In this study, the lateral geniculate nucleus (LGN), superior colliculus (SC), pulvinar, and V1 were examined for changes in c-FOS, an immediate-early gene, expression after 1 or 24 hours of monocular inactivation with tetrodotoxin (TTX) in tree shrews. Monocular inactivation greatly reduced gene expression in LGN layers related to the blocked eye, whereas normally high to moderate levels were maintained in the layers that receive inputs from the intact eye. The SC and caudal pulvinar contralateral to the blocked eye had greatly (SC) or moderately (pulvinar) reduced gene expressions reflective of dependence on the contralateral eye. c-FOS expression in V1 was greatly reduced contralateral to the blocked eye, with most of the expression that remained in upper layer 4a and lower 4b and lower layer 6 regions. In contrast, much of V1 contralateral to the active eye showed normal levels of c-FOS expression, including the inner parts of sublayers 4a and 4b and layers 2, 3, and 6. In some cases, upper layer 4a and lower 4b showed a reduction of gene expression. Layers 5 and sublayer 3c had normally low levels of gene expression. The results reveal the functional dominance of the contralateral eye in activating the SC, pulvinar, and V1, and the results from V1 suggest that the sublaminar organization of layer 4 is more complex than previously realized. J. Comp. Neurol. 525:151-165, 2017. © 2016 Wiley Periodicals, Inc.

  7. Blocking c-Fos Expression Reveals the Role of Auditory Cortex Plasticity in Sound Frequency Discrimination Learning.

    PubMed

    de Hoz, Livia; Gierej, Dorota; Lioudyno, Victoria; Jaworski, Jacek; Blazejczyk, Magda; Cruces-Solís, Hugo; Beroun, Anna; Lebitko, Tomasz; Nikolaev, Tomasz; Knapska, Ewelina; Nelken, Israel; Kaczmarek, Leszek

    2017-03-17

    The behavioral changes that comprise operant learning are associated with plasticity in early sensory cortices as well as with modulation of gene expression, but the connection between the behavioral, electrophysiological, and molecular changes is only partially understood. We specifically manipulated c-Fos expression, a hallmark of learning-induced synaptic plasticity, in auditory cortex of adult mice using a novel approach based on RNA interference. Locally blocking c-Fos expression caused a specific behavioral deficit in a sound discrimination task, in parallel with decreased cortical experience-dependent plasticity, without affecting baseline excitability or basic auditory processing. Thus, c-Fos-dependent experience-dependent cortical plasticity is necessary for frequency discrimination in an operant behavioral task. Our results connect behavioral, molecular and physiological changes and demonstrate a role of c-Fos in experience-dependent plasticity and learning.

  8. Anxiety-like behaviour and c-fos expression in rats that inhaled vetiver essential oil.

    PubMed

    Saiyudthong, Somrudee; Pongmayteegul, Sirinun; Marsden, Charles A; Phansuwan-Pujito, Pansiri

    2015-01-01

    Vetiver essential oil (VEO) has been used in aromatherapy for relaxation. This study aimed to investigate the effects of VEO on an anxiety-related behavioural model (the elevated plus-maze, EPM) and immediate-early gene c-fos in amygdala, known to be involved in anxiety. Male Wistar rats were administered diazepam (1 mg/kg i.p.) for 30 min or inhalated with VEO (1%, 2.5% or 5% w/w) for 7 min prior to exposure to the EPM. Then, the effects of 2.5% VEO, the anxiolytic dose, on c-fos expression in amygdala were investigated. The rats given either 2.5% VEO or diazepam exhibited an anxiolytic-like profile in the EPM. VEO and diazepam significantly increased c-fos expression in the lateral division of the central amygdaloid nucleus (CeL). Therefore, the anxiolytic properties of VEO might be associated with altering neuronal activation in CeL. However, future studies are needed to investigate the precise mechanism of action of VEO.

  9. Neural Correlates of Birth: Labor Contractions Induce C-Fos Expression In Newborn Rat Brain

    NASA Technical Reports Server (NTRS)

    Ronca, A. E.; Daly, M. E.; Baer, L. A.; Hills, E. M.; Conway, G.; Dalton, Bonnie (Technical Monitor)

    2002-01-01

    At birth, the newborn mammal must make rapid adaptations to the extrauterine environment to survive. We have previously shown that labor contractions augment the appearance of adaptive responses at birth, viz., postpartum breathing and the onset of suckling. Since neuronal activity has been shown to upregulate the activity of immediate early genes (IEGs) in the brain, we analyzed the neural distribution of c-Fos protein expression in newborn rats using immunohistochemistry. Previous studies have reported a burst of c-Fos mRNA expression in mouse and rat brain at birth however relationships to labor and delivery have not been examined. In the present study, we exposed near-term rat fetuses to elements of the vaginal birth process: 1) Simulated labor contractions. 2) Postpartum cooling (22 deg C). 3) Umbilical cord occlusion. and 4) Stroking to mimic postpartum licking by the dam. Cardinally delivered newborns (VG) were compared with those delivered by cesarean section following either prenatal exposure to compressions (C) [simulated labor contractions], or no compressions (NC) [no labor contractions]. Similar patterns of c-fos activation were observed throughout hypothalamic and thalamic nuclei, hippocampus and cerebral cortex in VG and C newborns that were not apparent in NC newborns. Our results indicate that labor contractions play a role in the induction of widespread neural activation in the newborn brain.

  10. Amphetamine-elicited striatal Fos expression is attenuated in neurotensin null mutant mice.

    PubMed

    Fadel, Jim; Dobner, Paul R; Deutch, Ariel Y

    2006-07-10

    Neurotensin (NT) has been suggested to interact with dopamine systems in different forebrain sites to exert both antipsychotic- and psychostimulant-like effects. We previously found that genetic or pharmacological manipulations that disrupt endogenous NT signaling attenuate antipsychotic drug-induced Fos expression in the dorsolateral and central striatum but not other striatal regions. To assess the role of NT in psychostimulant responses, we examined the ability of d-amphetamine (AMP) to induce Fos in wild-type and NT null mutant mice. AMP-elicited Fos expression was significantly attenuated in the medial striatum of NT null mutant mice, but was unaffected in other striatal territories. Similar results were obtained in rats and mice pretreated with the high affinity neurotensin receptor (NTR1) antagonist SR 48692. The effect of the NTR1 antagonist was particularly apparent in the striatal patch (striosome) compartment, as defined by mu-opioid receptor immunoreactivity. These data suggest that NT is required for the full activation by AMP of medial striatal neurons.

  11. Neural Correlates of Birth: Labor Contractions Induce C-Fos Expression In Newborn Rat Brain

    NASA Technical Reports Server (NTRS)

    Ronca, A. E.; Daly, M. E.; Baer, L. A.; Hills, E. M.; Conway, G.; Dalton, Bonnie (Technical Monitor)

    2002-01-01

    At birth, the newborn mammal must make rapid adaptations to the extrauterine environment to survive. We have previously shown that labor contractions augment the appearance of adaptive responses at birth, viz., postpartum breathing and the onset of suckling. Since neuronal activity has been shown to upregulate the activity of immediate early genes (IEGs) in the brain, we analyzed the neural distribution of c-Fos protein expression in newborn rats using immunohistochemistry. Previous studies have reported a burst of c-Fos mRNA expression in mouse and rat brain at birth however relationships to labor and delivery have not been examined. In the present study, we exposed near-term rat fetuses to elements of the vaginal birth process: 1) Simulated labor contractions. 2) Postpartum cooling (22 deg C). 3) Umbilical cord occlusion. and 4) Stroking to mimic postpartum licking by the dam. Cardinally delivered newborns (VG) were compared with those delivered by cesarean section following either prenatal exposure to compressions (C) [simulated labor contractions], or no compressions (NC) [no labor contractions]. Similar patterns of c-fos activation were observed throughout hypothalamic and thalamic nuclei, hippocampus and cerebral cortex in VG and C newborns that were not apparent in NC newborns. Our results indicate that labor contractions play a role in the induction of widespread neural activation in the newborn brain.

  12. Forced expression of stabilized c-Fos in dendritic cells reduces cytokine production and immune responses in vivo

    SciTech Connect

    Yoshida, Ryoko; Suzuki, Mayu; Sakaguchi, Ryota; Hasegawa, Eiichi; Kimura, Akihiro; Shichita, Takashi; Sekiya, Takashi; Shiraishi, Hiroshi; Shimoda, Kouji; Yoshimura, Akihiko

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer Dendritic cells expressing stabilized c-Fos produced less inflammatory cytokines. Black-Right-Pointing-Pointer Dendritic cells expressing stabilized c-Fos activated T cells less efficiently. Black-Right-Pointing-Pointer Transgenic mice expressing stabilized c-Fos were resistant to EAE model. -- Abstract: Intracellular cyclic adenosine monophosphate (cAMP) suppresses innate immunity by inhibiting proinflammatory cytokine production by monocytic cells. We have shown that the transcription factor c-Fos is responsible for cAMP-mediated suppression of inflammatory cytokine production, and that c-Fos protein is stabilized by IKK{beta}-mediated phosphorylation. We found that S308 is one of the major phosphorylation sites, and that the S308D mutation prolongs c-Fos halflife. To investigate the role of stabilized c-Fos protein in dendritic cells (DCs) in vivo, we generated CD11c-promoter-deriven c-FosS308D transgenic mice. As expected, bone marrow-derived DCs (BMDCs) from these Tg mice produced smaller amounts of inflammatory cytokines, including TNF-{alpha}, IL-12, and IL-23, but higher levels of IL-10, in response to LPS, than those from wild-type (Wt) mice. When T cells were co-cultured with BMDCs from Tg mice, production of Th1 and Th17 cytokines was reduced, although T cell proliferation was not affected. Tg mice demonstrated more resistance to experimental autoimmune encephalomyelitis (EAE) than did Wt mice. These data suggest that c-Fos in DCs plays a suppressive role in certain innate and adaptive immune responses.

  13. Expression of c-fos gene in central nervous system of adult medaka (Oryzias latipes) after hypergravity stimulation

    NASA Astrophysics Data System (ADS)

    Shimomura, S.; Ijiri, K.

    The immediate-early genes serve as useful neurobiological tools for mapping brain activity induced by a sensory stimulation. In this study, we have examined brain activity related to gravity perception of medaka (Oryzias latipes) by use of c-fos. The gene, which is homologous to the c-fos genes of other vertebrates, was identified in medaka. Functionally important domains are highly conserved among all the vertebrate species analyzed. Intraperitoneal administration of kainic acid transiently induced the c-fos mRNAs in medaka brain. The results indicate that the expression of c-fos can be utilized as a suitable anatomical marker for the increased neural activities in the central nervous system of medaka. Fish were continuously exposed to 3G hypergravity by centrifugation. Investigation of c-fos mRNA expression showed that c-fos mRNA significantly increased 30 minutes after a start of 3G exposure. The distribution of its transcripts within brains was analyzed by an in situ hybridization method. The 3G-treated medakas displayed c-fos positive cells in their brainstem regions, which are related to vestibular function, such as torus semicircularis, posterior octavu nucleus, nucleus tangentialis and inferior olive. Our results established the method to trace the activated area in the fish brain following gravity stimulation. The method will be a useful tool for understanding gravity perception in the brain.

  14. Central expression of c-Fos in neonatal male and female prairie voles in response to treatment with oxytocin.

    PubMed

    Cushing, Bruce S; Yamamoto, Yukiyo; Hoffman, Gloria E; Carter, C Sue

    2003-07-12

    Early postnatal exposure to both exogenous and endogenous oxytocin (OT) can have long-term effects on behavior and physiology, although the mechanisms of these effects are not known. c-Fos expression was used to investigate the immediate neural effects of neonatal manipulations of OT in male and female prairie voles. On the day of birth prairie vole pups received an intraperitoneal injection of OT, a selective OT antagonist (OTA), or saline (vehicle control), while an additional group was handled but not injected. One hour after treatment brains were collected and fixed via spinning immersion and immunocytochemistry was then used to label for c-Fos immunoreactivity (IR). There were significant differences between males and females. Handled only females displayed significantly higher levels of c-Fos IR in the mediodorsal thalamic nucleus (MD) than males while handled males had higher c-Fos IR in the paraventricular nucleus of the hypothalamus than females. Exogenous OT stimulated neuronal activity in the supraoptic nucleus (SON) in males, while treatment with OTA increased Fos IR in the SON and was associated with reduced Fos IR in the MD in females. The results indicate that neuronal activity and responses to OT are sexually dimorphic in newborn prairie voles. In females changes in Fos expression were stimulated by treatment with OTA, suggesting that endogenous OT affects cellular activity while males responded to exogenous OT.

  15. Differential Expression of FosB Proteins and Potential Target Genes in Select Brain Regions of Addiction and Depression Patients.

    PubMed

    Gajewski, Paula A; Turecki, Gustavo; Robison, Alfred J

    2016-01-01

    Chronic exposure to stress or drugs of abuse has been linked to altered gene expression throughout the body, and changes in gene expression in discrete brain regions are thought to underlie many psychiatric diseases, including major depressive disorder and drug addiction. Preclinical models of these disorders have provided evidence for mechanisms of this altered gene expression, including transcription factors, but evidence supporting a role for these factors in human patients has been slow to emerge. The transcription factor ΔFosB is induced in the prefrontal cortex (PFC) and hippocampus (HPC) of rodents in response to stress or cocaine, and its expression in these regions is thought to regulate their "top down" control of reward circuitry, including the nucleus accumbens (NAc). Here, we use biochemistry to examine the expression of the FosB family of transcription factors and their potential gene targets in PFC and HPC postmortem samples from depressed patients and cocaine addicts. We demonstrate that ΔFosB and other FosB isoforms are downregulated in the HPC but not the PFC in the brains of both depressed and addicted individuals. Further, we show that potential ΔFosB transcriptional targets, including GluA2, are also downregulated in the HPC but not PFC of cocaine addicts. Thus, we provide the first evidence of FosB gene expression in human HPC and PFC in these psychiatric disorders, and in light of recent findings demonstrating the critical role of HPC ΔFosB in rodent models of learning and memory, these data suggest that reduced ΔFosB in HPC could potentially underlie cognitive deficits accompanying chronic cocaine abuse or depression.

  16. Differential Expression of FosB Proteins and Potential Target Genes in Select Brain Regions of Addiction and Depression Patients

    PubMed Central

    Gajewski, Paula A.; Turecki, Gustavo; Robison, Alfred J.

    2016-01-01

    Chronic exposure to stress or drugs of abuse has been linked to altered gene expression throughout the body, and changes in gene expression in discrete brain regions are thought to underlie many psychiatric diseases, including major depressive disorder and drug addiction. Preclinical models of these disorders have provided evidence for mechanisms of this altered gene expression, including transcription factors, but evidence supporting a role for these factors in human patients has been slow to emerge. The transcription factor ΔFosB is induced in the prefrontal cortex (PFC) and hippocampus (HPC) of rodents in response to stress or cocaine, and its expression in these regions is thought to regulate their “top down” control of reward circuitry, including the nucleus accumbens (NAc). Here, we use biochemistry to examine the expression of the FosB family of transcription factors and their potential gene targets in PFC and HPC postmortem samples from depressed patients and cocaine addicts. We demonstrate that ΔFosB and other FosB isoforms are downregulated in the HPC but not the PFC in the brains of both depressed and addicted individuals. Further, we show that potential ΔFosB transcriptional targets, including GluA2, are also downregulated in the HPC but not PFC of cocaine addicts. Thus, we provide the first evidence of FosB gene expression in human HPC and PFC in these psychiatric disorders, and in light of recent findings demonstrating the critical role of HPC ΔFosB in rodent models of learning and memory, these data suggest that reduced ΔFosB in HPC could potentially underlie cognitive deficits accompanying chronic cocaine abuse or depression. PMID:27494187

  17. Expression and colocalization of NMDA receptor and FosB/ΔFosB in sensitive brain regions in rats after chronic morphine exposure.

    PubMed

    Zhang, Qiang; Liu, Qi; Li, Tongzhou; Liu, You; Wang, Lei; Zhang, Zhonghai; Liu, Hongzhi; Hu, Min; Qiao, Yuehua; Niu, Haichen

    2016-02-12

    Research in the last decade demonstrated that the NMDA receptor (NMDAR) has an important role in opiate-induced neural and behavioral plasticity. In addition, increased levels of FosB-like proteins (FosB/ΔFosB) were found to be related to morphine withdrawal behaviors. However, the relationship between NMDAR and FosB/ΔFosB in sensitive brain regions during morphine withdrawal is largely unknown. In this study, we aimed to investigate NMDAR dynamics and FosB/ΔFosB levels in multiple brain regions and whether they are related in sensitive brain regions during morphine abstinence. Quantitative immunohistochemistry was adopted to test NMDAR and FosB/ΔfosB levels during morphine withdrawal in rats. Increased NMDAR and FosB/ΔFosB levels were found in the nucleus accumbens core (AcbC), nucleus accumbens shell (AcbSh), central amygdaloid nucleuscapsular part (CeC), ventral tegmental area (VTA) and cingulate cortex (Cg). Double-immunofluorescence labeling indicated that NMDAR colocalized with Fos/ΔFosB in these five regions. These results suggest that multiple phenotypic regions are mediated by NMDAR and Fos/ΔFosB during morphine withdrawal, such as the motivational (AcbC, AcbSh), limbic (CeC, VTA) and executive (Cg) system pathways, and may be the primary targets of NMDAR and Fos/ΔfosB that impact morphine withdrawal behaviors. Copyright © 2016. Published by Elsevier Ireland Ltd.

  18. Detection of molecular alterations in methamphetamine-activated Fos-expressing neurons from a single rat dorsal striatum using fluorescence-activated cell sorting (FACS)

    PubMed Central

    Liu, Qing-Rong; Rubio, Francisco J.; Bossert, Jennifer M.; Marchant, Nathan J.; Fanous, Sanya; Hou, Xingyu; Shaham, Yavin; Hope, Bruce T.

    2013-01-01

    Methamphetamine and other drugs activate a small proportion of all neurons in the brain. We previously developed a FACS-based method to characterize molecular alterations induced selectively in activated neurons that express the neural activity marker Fos. However, this method requires pooling samples from many rats. We now describe a modified FACS-based method to characterize molecular alterations in Fos-expressing dorsal striatal neurons from a single rat using a multiplex pre-amplification strategy. Fos and NeuN (a neuronal marker) immunohistochemistry indicate that 6–7% of dorsal striatum neurons were activated 90 min after acute methamphetamine injections (5 mg/kg, i.p) while less than 1% of neurons were activated by saline injections. We used FACS to separate NeuN-labeled neurons into Fos-positive and Fos-negative neurons and assessed mRNA expression using RT-qPCR from as little as 5 Fos-positive neurons. Methamphetamine induced 3–20-fold increases of immediate early genes arc, homer-2, c-fos, fosB and its isoforms (ΔfosB and a novel isoform ΔfosB-2) in Fos-positive but not Fos-negative neurons. IEG mRNA induction was 10-fold lower or absent when assessed in unsorted samples from single dorsal striatum homogenates. Our modified method makes it feasible to study unique molecular alterations in neurons activated by drugs or drug-associated cues in complex addiction models. PMID:23895375

  19. Novel spinal pathways identified by neuronal c-Fos expression after urethrogenital reflex activation in female guinea pigs.

    PubMed

    Yuan, S Y; Vilimas, P I; Zagorodnyuk, V P; Gibbins, I L

    2015-03-12

    Pudendal nerve-spinal pathways are involved in urethrogenital sensation, pain and sexual activity. However, details of these pathways and their modulation are unclear. We examined spinal pathways activated by the urethrogenital reflex (UGR) and visualized by c-Fos immunoreactivity in reflexly activated neurons within spinal cord. In anesthetized female guinea pigs, a balloon was inserted into the urethra and inflated with short-repeat or long-continuous distension to activate the UGR. A second balloon recorded reflex contractions of the vagina and uterus. Two control groups had either no balloon or a vaginal balloon (VB) only. Ninety minutes after UGR activation, c-Fos immunoreactivity in L3 and S2 spinal segments was examined. Reflex activated c-Fos immunoreactivity also was investigated in some animals with acute spinal transections at either L4 or T12 levels. There was no significant difference in spinal c-Fos expression between the control groups. Short-repeat distension reliably induced a UGR and a two- to threefold increase in c-Fos-expressing neurons throughout dorsal, intermediate and lateral spinal gray matter at S2 and about twofold increase in superficial dorsal horn at L3. T12 transection had little effect on c-Fos expression at either spinal level. However, after L4 transection, UGR generation was associated with a four- to sixfold increase in c-Fos-expressing neurons in lateral horn (LH) and central canal areas at S2, and but only 20-30% increase at L3. Thus, UGR activates preganglionic neurons projecting to pelvic viscera in both sacral and lumbar spinal cord. The reflex also must activate ascending and descending spinal inhibitory circuits that suppress c-Fos-expression in neurons at both sacral and lumbar spinal levels.

  20. c-Fos expression in rat brainstem following intake of sucrose or saccharin.

    PubMed

    Chen, Ke; Yan, Jianqun; Li, Jinrong; Lv, Bo; Zhao, Xiaolin

    2011-09-01

    To examine whether the activation of brainstem neurons during intake of a sweet tastant is due to orosensory signals or post-ingestive factors, we compared the distribution of c-Fos-like immunoreactivity (c-FLI) in the nucleus of the solitary tract (NST) and parabrachial nucleus (PBN) of brainstem following ingestion of 0.25 Msucrose or 0.005 M saccharin solutions. Immunopositive neurons were localized mainly in the middle zone of the PBN and four rostral-caudal subregions of the NST. Intake of sucrose increased the number of FLI neurons in almost every subnucleus of the PBN (F((2,13)) = 7.610, P = 0.023), in addition to the caudal NST at the level of the area postrema (F((2,13)) = 10.777, P = 0.003) and the NST intermediate zone (F((2,13)) = 7.193, P = 0.014). No significant increase in the number of c-Fos positive neurons was detected in response to saccharin ingestion, although there was a trend towards a modest increase in a few select NST and PBN nuclei. These results suggest that the PBN and NST may be involved in sweet taste perception and modulation of sweet tastant intake, but the significantly enhanced intensity of Fos expression induced by sucrose indicates that PBN/NST neuronal activity is driven by the integrated effects of sweet taste sensation and post-ingestive signals.

  1. Harmful Algal Bloom Toxins: c-Fos Protein Expression in the Brain of Killifish, Fundulus heteroclitus

    DTIC Science & Technology

    2006-04-21

    expression significantly increased in the anterior optic ectum of DA-exposed fish compared to controls (p= 0.055, J.D. Salierno et al. / Aquatic Toxicology ... Aquatic Toxicology 78 (2006) 350–357 Harmful algal bloom toxins alter c-Fos protein expression in the brain of killifish, Fundulus heteroclitus J.D...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 J.D. Salierno et al. / Aquatic Toxicology 78 (2006) 350–357 351 induction can be used as

  2. Nesfatin-1 induces Fos expression and elicits dipsogenic responses in subfornical organ.

    PubMed

    Moreau, Jason M; Ciriello, John

    2013-08-01

    Nesfatin-1 (Nes-1), an 82-amino acid protein cleaved from nucleobindin-2, has been suggested to play a role in ingestive behaviors. Intracerebroventricular (icv) injections of Nes-1 reduce water intake, although the sites of action for this effect are not known. Two series of experiments were done to identify potential sites of action of Nes-1 in drinking behavior. In the first series, icv injections of Nes-1 were made in urethane-anesthetized rats to investigate the distribution of neurons containing Fos-like immunoreactivity (Fos-ir) within the forebrain. Circumventricular organs, including subfornical organ (SFO), were found to contain neurons expressing Fos-ir. Additionally, several hypothalamic, thalamic and limbic nuclei also contained Fos-labeled neurons. As SFO is a pivotal central site in the regulation of water intake, a second series of experiments was done to investigate the role of direct injections of Nes-1 into SFO on water intake in conscious, freely moving rats. Nes-1 (2pmol) injections into SFO induced an increase in water intake compared to vehicle injections. However, when food was made available for ingestion after the Nes-1 injection, the dipsogenic effects of Nes-1 were attenuated. Additionally, the drinking response to Nes-1 was found to be more potent than that observed after injections of ANG II into SFO. Neither simultaneous injections ANG II nor the ANG II type-1 receptor blocker losartan affected the Nes-1 dipsogenic response. Taken together, these results suggest that Nes-1 is a potent dipsogenic agent in SFO, and that Nes-1 may act independently of the SFO angiotensinergic system to elicit the dipsogenic effect. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. c-Fos expression in the paternal mouse brain induced by communicative interaction with maternal mates.

    PubMed

    Zhong, Jing; Liang, Mingkun; Akther, Shirin; Higashida, Chiharu; Tsuji, Takahiro; Higashida, Haruhiro

    2014-09-11

    Appropriate parental care by fathers greatly facilitates health in human family life. Much less is known from animal studies regarding the factors and neural circuitry that affect paternal behavior compared with those affecting maternal behavior. We recently reported that ICR mouse sires displayed maternal-like retrieval behavior when they were separated from pups and caged with their mates (co-housing) because the sires receive communicative interactions via ultrasonic and pheromone signals from the dams. We investigated the brain structures involved in regulating this activity by quantifying c-Fos-immunoreactive cells as neuronal activation markers in the neural pathway of male parental behavior. c-Fos expression in the medial preoptic area (mPOA) was significantly higher in sires that exhibited retrieval behavior (retrievers) than those with no such behavior (non-retrievers). Identical increased expression was found in the mPOA region in the retrievers stimulated by ultrasonic vocalizations or pheromones from their mates. Such increases in expression were not observed in the ventral tegmental area (VTA), nucleus accumbens (NAcc) or ventral palladium (VP). On the following day that we identified the families of the retrievers or non-retrievers, c-Fos expression in neuronal subsets in the mPOA, VTA, NAcc and VP was much higher in the retriever sires when they isolated together with their mates in new cages. This difference was not observed in the singly isolated retriever sires in new cages. The non-retriever sires did not display expression changes in the four brain regions that were assessed. The mPOA neurons appeared to be activated by direct communicative interactions with mate dams, including ultrasonic vocalizations and pheromones. The mPOA-VTA-NAcc-VP neural circuit appears to be involved in paternal retrieval behavior.

  4. Neuronal expression of c-Fos after epicortical and intracortical electric stimulation of the primary visual cortex.

    PubMed

    Neyazi, Belal; Schwabe, Kerstin; Alam, Mesbah; Krauss, Joachim K; Nakamura, Makoto

    2016-11-01

    Electrical stimulation of the primary visual cortex (V1) is an experimental approach for visual prostheses. We here compared the response to intracortical and epicortical stimulation of the primary visual cortex by using c-Fos immunoreactivity as a marker for neuronal activation. The primary visual cortex of male Sprague Dawley rats was unilaterally stimulated for four hours using bipolar electrodes placed either intracortically in layer IV (n=26) or epicortically (n=20). Four different current intensities with a constant pulse width of 200μs and a constant frequency of 10Hz were used, for intracortical stimulation with an intensity of 0μA (sham-stimulation), 10μA, 20μA and 40μA, and for epicortical stimulation 0μA, 400μA, 600μA and 800μA. Subsequently all animals underwent c-Fos immunostaining and c-Fos expression was assessed in layer I-VI of the primary visual cortex within 200μm and 400μm distance to the stimulation site. C-Fos expression was higher after intracortical stimulation compared to epicortical stimulation, even though ten times lower current intensities were applied. Furthermore intracortical stimulation resulted in more focal neuronal activation than epicortical stimulation. C-Fos expression was highest after intracortical stimulation with 20μA compared to all other intensities. Epicortical stimulation showed a linear increase of c-Fos expression with the highest expression at 800μA. Sham stimulation showed similar expression of c-Fos in both hemispheres. The contralateral hemisphere was not affected by intracortical or epicortical stimulation of either intensities. In summary, intracortical stimulation resulted in more focal neuronal activation with less current than epicortical stimulation. This model may be used as a simple but reliable model to evaluate electrodes for microstimulation of the primary visual cortex before testing in more complex settings.

  5. Effects of monocular deprivation on the spatial pattern of visually induced expression of c-Fos protein.

    PubMed

    Nakadate, K; Imamura, K; Watanabe, Y

    2012-01-27

    We studied the pattern of expression of a protein product (c-Fos) of immediate-early gene (IEG) in the visual cortex of rats and mice. The basal expression of c-Fos was very low and visual exposure revealed a large number of c-Fos immunopositive cells in the visual cortex. We found that monocular deprivation during the sensitive period of ocular dominance (OD) plasticity significantly changed both the amount and pattern of c-Fos expression upon monocular stimulation of either eye. The number of immunopositive cells in layer IV of binocular subfields of the primary visual cortex (Oc1B) ipsilateral to the stimulated eye was found to be the most sensitive index of the effects of monocular deprivation during the sensitive period, that is, opened eye stimulation induced significantly larger numbers of c-Fos immunopositive cells, whereas closed eye stimulation induced significantly smaller numbers compared with those induced by monocular stimulation in control animals. In the lateral geniculate nucleus and superior colliculus, the pattern of expression of c-Fos following monocular stimulation was not affected by preceding monocular deprivation. Monocular deprivation imposed after the sensitive period did not affect the pattern of induction of c-Fos. Notably, in age-matched old animals that had been raised in total darkness and then experienced monocular deprivation, the distribution and numbers of c-Fos-expressing cells in visual cortex exhibited the same alterations as found in young animals during the sensitive period. These findings suggest that the present activity mapping method using c-Fos as a molecular marker is useful for examining the activity-dependent regulation of cortical plasticity, and provides an alternative method to conventional electrophysiological recording. This method is particularly powerful when applied to knockout or transgenic mice in which sampling biases in electrophysiological recording have been considered inevitable. Furthermore, these

  6. Nicotine-conditioned place preference induced CREB phosphorylation and Fos expression in the adult rat brain.

    PubMed

    Pascual, Mariano M; Pastor, Veronica; Bernabeu, Ramon O

    2009-11-01

    Experimental evidence indicates that nicotine causes long-lasting changes in the brain associated with behavior. Although much has been learned about factors participating in this process, less is known concerning the mechanisms and brain areas involved in nicotine preference. The objective of this study is to examine the participation of brain structures during the development of nicotine-conditioned place preference (CPP). To identify brain regions activated in CPP, we have measured the levels of phosphorylated cyclic AMP response element binding protein (pCREB) and Fos protein using a behavioral CPP and conditioned place aversion (CPA) paradigms. Rats developed reliable and robust CPP and also CPA. During nicotine preference and reinstatement behaviors, a significant increase of both pCREB and Fos protein expression occurs in the nucleus accumbens (NAc) and ventral tegmental area (VTA) and also in the prefrontal cortex (PFC), dorsal striatum (DStr), amygdala, and hippocampus. These increases were abolished by the administration of mecamylamine or by a CPA protocol, showing a specific activation of pCREB in drug preference animals, mediated by nicotinic receptors. Specifically in the VTA, nicotine-induced preference and reinstatement of the preference caused the activation of dopaminergic and GABAergic cells in different proportions. The results indicate that the phosphorylation of CREB and expression of Fos protein, as indicators of neural activity, accompany the acquisition and maintenance of nicotine-induced CPP but not CPA in mesolimbic areas (NAc, VTA, PFC, and DStr) as well as in memory consolidation structures (hippocampus and amygdala) and nicotinic receptor are involved in this process. Taken together, these studies identify the brain regions where pCREB activity is essential for nicotine preference.

  7. Site specific effects of anosmia and cloacal gland anesthesia on Fos expression induced in male quail brain by sexual behavior

    PubMed Central

    Taziaux, Mélanie; Keller, Matthieu; Ball, Gregory F.; Balthazart, Jacques

    2008-01-01

    In rats, expression of the immediate early gene, c-fos observed in the brain following male copulatory behavior relates mostly to the detection of olfactory information originating from the female and to somatosensory feedback from the penis. However, quail, like most birds, are generally considered to have a relatively poorly developed sense of smell. Furthermore, quail have no intromittent organ (e.g., penis). It is therefore intriguing that expression of male copulatory behavior induces in quail and rats a similar pattern of c-fos expression in the medial preoptic area (mPOA), bed nucleus of the stria terminalis (BSTM) and parts of the amygdala. We analyzed here by immunocytochemistry Fos expression in the mPOA/BSTM/amygdala of male quail that had been allowed to copulate with a female during standardized tests. Before these tests, some of the males had either their nostrils plugged, or their cloacal area anesthetized, or both. A control group was not exposed to females. These manipulations did not affect frequencies of male sexual behavior and all birds exposed to a female copulated normally. In the mPOA, the increased Fos expression induced by copulation was not affected by the cloacal gland anesthesia but was markedly reduced in subjects deprived of olfactory input. Both manipulations affected copulation-induced Fos expression in the BSTM. No change in Fos expression was observed in the amygdala. Thus immediate early gene expression in the mPOA and BSTM of quail is modulated at least in part by olfactory cues and/or somatosensory stimuli originating from the cloacal gland. Future work should specify the nature of these stimuli and their function in the expression of avian male sexual behavior. PMID:18638505

  8. Airjet and FG-7142-induced Fos expression differs in rats selectively bred for high and low anxiety-related behavior.

    PubMed

    Salchner, Peter; Sartori, Simone B; Sinner, Catrin; Wigger, Alexandra; Frank, Elisabeth; Landgraf, Rainer; Singewald, Nicolas

    2006-06-01

    We reported recently that two rat lines bred for either high (HAB) or low (LAB) anxiety-related behavior display differential Fos expression in restricted parts of the fear/anxiety circuitry when exposed to mild anxiety evoked in exploratory anxiety tests. Since different forms of anxiety are thought to activate different parts of the anxiety circuitry, we investigated now whether (1) an aversive stimulus which elicits escape behavior (airjet) and (2) the anxiogenic/panicogenic drug FG-7142 would reveal further differences in Fos expression as a marker of neuronal activation between HAB and LAB rats. Both airjet exposure and FG-7142 induced Fos expression in both lines in various anxiety-related brain areas. HAB rats, which displayed exaggerated escape responses during airjet exposure, exhibited increased Fos expression in brain areas including the hypothalamus, periaqueductal gray and locus coeruleus, as well as blunted Fos activation in the cingulate cortex in response to airjet and/or FG-7142. The results corroborate previous findings showing that trait anxiety affects neuronal excitability in hypothalamic and medial prefrontal areas. Furthermore, by using airjet as well as FG-7142, we now reveal that enhanced trait anxiety is also associated with neuronal hyperexcitability in the locus coeruleus and the periaqueductal gray, suggesting that investigation of an array of different anxiogenic stimuli is important for the detection of altered neuronal processing in trait anxiety.

  9. Repeated Methamphetamine Administration Differentially Alters Fos Expression in Caudate-Putamen Patch and Matrix Compartments and Nucleus Accumbens

    PubMed Central

    Jedynak, Jakub P.; Cameron, Courtney M.; Robinson, Terry E.

    2012-01-01

    Background The repeated administration of psychostimulant drugs produces a persistent and long-lasting increase (“sensitization”) in their psychomotor effects, which is thought to be due to changes in the neural circuitry that mediate these behaviors. One index of neuronal activation used to identify brain regions altered by repeated exposure to drugs involves their ability to induce immediate early genes, such as c-fos. Numerous reports have demonstrated that past drug experience alters the ability of drugs to induce c-fos in the striatum, but very few have examined Fos protein expression in the two major compartments in the striatum—the so-called patch/striosome and matrix. Methodology/Principal Findings In the present study, we used immunohistochemistry to investigate the effects of pretreatment with methamphetamine on the ability of a subsequent methamphetamine challenge to induce Fos protein expression in the patch and matrix compartments of the dorsolateral and dorsomedial caudate-putamen and in the ventral striatum (nucleus accumbens). Animals pretreated with methamphetamine developed robust psychomotor sensitization. A methamphetamine challenge increased the number of Fos-positive cells in all areas of the dorsal and ventral striatum. However, methamphetamine challenge induced Fos expression in more cells in the patch than in the matrix compartment in the dorsolateral and dorsomedial caudate-putamen. Furthermore, past experience with methamphetamine increased the number of methamphetamine-induced Fos positive cells in the patch compartment of the dorsal caudate putamen, but not in the matrix or in the core or shell of the nucleus accumbens. Conclusions/Significance These data suggest that drug-induced alterations in the patch compartment of the dorsal caudate-putamen may preferentially contribute to some of the enduring changes in brain activity and behavior produced by repeated treatment with methamphetamine. PMID:22514626

  10. Preventive role of social interaction for cocaine conditioned place preference: correlation with FosB/DeltaFosB and pCREB expression in rat mesocorticolimbic areas.

    PubMed

    El Rawas, Rana; Klement, Sabine; Salti, Ahmad; Fritz, Michael; Dechant, Georg; Saria, Alois; Zernig, Gerald

    2012-01-01

    The worsening of drug abuse by drug-associated social interaction is a well-studied phenomenon. In contrast, the molecular mechanisms of the beneficial effect of social interaction, if offered as a mutually exclusive choice to drugs of abuse, are under-investigated. In a rat place preference conditioning (CPP) paradigm, four 15 min episodes of social interaction with a gender- and weight-matched male early-adult conspecific inhibited cocaine-induced reinstatement of cocaine CPP, a model of relapse. These protective effects of social interaction were paralleled by a reduced activation, as assessed by Zif268 expression, in brain areas known to play pivotal roles in drug-seeking behavior. Here we show that social interaction during extinction of cocaine CPP also reduced cocaine-CPP-stimulated FosB expression in the nucleus accumbens shell and core. In addition, social interaction during cocaine CPP extinction increased pCREB (cAMP response element binding protein) expression in the nucleus accumbens shell and the cingulate cortex area 1 (Cg1). Our results show that FosB and pCREB may be implicated in the protective effect of social interaction against cocaine-induced reinstatement of CPP. Thus, social interaction, if offered in a context that is clearly distinct from the previously drug-associated one, may profoundly inhibit relapse to cocaine addiction.

  11. Fos expression at the cerebellum following non-contact arousal and mating behavior in male rats

    PubMed Central

    Manzo, Jorge; Miquel, Marta; Toledo, Rebeca; Mayor-Mar, Justo Abraham; Garcia, Luis I.; Aranda-Abreu, Gonzalo E.; Caba, Mario; Hernandez, Maria Elena

    2010-01-01

    The cerebellum is considered a center underlying fine movements, cognition, memory and sexual responses. The latter feature led us to correlate sexual arousal and copulation in male rats with neural activity at the cerebellar cortex. Two behavioral paradigms were used in this investigation: the stimulation of males by distant receptive females (non-contact sexual stimulation), and the execution of up to three consecutive ejaculations. The vermis area of the cerebellum was removed following behavioral experiments, cut into sagittal sections, and analyzed with Fos immunohistochemistry to determine neuronal activation. At the mid-vermis region (sections from the midline to 0.1 mm laterally), non-contact stimulation significantly increased the activity of granule neurons. The number of activated cells increased in every lobule, but lobules 1 and 6 to 9 showed the greatest increment. In sexual behavior tests, males reaching one ejaculation had a high number of activated neurons similar to those counted after non-contact stimulation. However, two or three consecutive ejaculations showed a smaller number of Fos-ir cells. In contrast to the mid-vermis region, sections farthest from the midline (0.1 to 0.9 mm laterally) revealed that only lobule 7 expressed activated neurons. These data suggest that a well-delineated group of granule neurons have a sexual biphasic response at the cerebellar vermis, and that Fos in them is under an active degradation mechanism. Thus, they participate as a neural substrate for male rat sexual responses with an activation-deactivation process corresponding with the sensory stimulation and motor performance occurring during copulation. PMID:17936859

  12. Endomorphins suppress nociception-induced c-Fos and Zif/268 expression in the rat spinal dorsal horn.

    PubMed

    Tateyama, Shingo; Ikeda, Tetsuya; Kosai, Kazuko; Nakamura, Tadashi; Kasaba, Toshiharu; Takasaki, Mayumi; Nishimori, Toshikazu

    2002-09-06

    We evaluated the potency of endomorphin-1 and -2 as endogenous ligands on c-Fos and Zif/268 expression in the spinal dorsal horn by formalin injection to the rat hind paw. Endomorphin-1, -2, or morphine was administered intrathecally or intracerebroventricularly 5 min before formalin injection (5%, 100 microl). All drugs produced marked reductions of formalin-induced c-Fos and Zif/268 immunoreactivity in laminae I and II, and laminae V and VI in the rat lumbar spinal cord. The reductions of Zif/268 expression by endomorphins were greater than those by morphine, while the reductions of c-Fos expression by endomorphins were smaller than those by morphine. These effects of endomorphins were attenuated by pretreatment with naloxone. These results indicate that endomorphin-1 and -2 act as endogenous ligands of mu-opioid receptor in neurons of the spinal dorsal horn and suppress the processing of nociceptive information in the central nervous system.

  13. AP-1(c-Jun/FosB) mediates xFoxD5b expression in Xenopus early developmental neurogenesis.

    PubMed

    Yoon, Jaeho; Kim, Jung-Ho; Lee, Ok-Joo; Lee, Sung-Young; Lee, Seung-Hwan; Park, Jae-Bong; Lee, Jae-Yong; Kim, Sung-Chan; Kim, Jaebong

    2013-01-01

    AP-1 (activator protein-1) is composed of Jun and Fos proteins and functions in cell proliferation, apoptosis and differentiation. Previous studies have demonstrated that different AP-1 complexes participate in the determination of various cell fates. However, the role of different AP-1 complexes during early vertebrate development is not yet fully understood. In the present study, we demonstrate that AP-1(c-Jun/FosB) regulates neurogenesis via FoxD5b expression. We show that FoxD5 was induced by the inhibition of BMP and that FoxD5b plays roles in neurogenesis. Additionally, we show that the FoxD5b promoter region within -1336 and -1316 contains an AP-1 binding site, which is required for the transcriptional regulation of FoxD5b and is induced by the inhibition of BMP signaling in animal cap explants. Moreover, c-Jun, a component of AP-1, directly binds to the AP-1 binding site of the FoxD5b promoter and induces FoxD5b expression cooperatively with FosB, but not with c-Fos or Fra-1. Altogether, these results suggest that AP-1(c-Jun/FosB) may play a role in neurogenesis via the induction of FoxD5b expression during early vertebrate development.

  14. Striatal dopamine and glutamate receptors modulate methamphetamine-induced cortical Fos expression

    PubMed Central

    Gross, Noah B.; Marshall, John F.

    2009-01-01

    Methamphetamine (mAMPH) is a psychostimulant drug that increases extracellular levels of monoamines throughout the brain. It has previously been observed that a single injection of mAMPH increases immediate early gene (IEG) expression in both the striatum and cerebral cortex. Moreover, this effect is modulated by dopamine and glutamate receptors since systemic administration of dopamine or glutamate antagonists has been found to alter mAMPH-induced striatal and cortical IEG expression. However, because dopamine and glutamate receptors are found in extra-striatal as well as striatal brain regions, studies employing systemic injection of dopamine or glutamate antagonists fail to localize the effects of mAMPH-induced activation. In the present experiments, the roles of striatal dopamine and glutamate receptors in mAMPH-induced gene expression in the striatum and cerebral cortex were examined. The nuclear expression of Fos, the protein product of the IEG c-fos, was quantified in both the striatum and the cortex of animals receiving intrastriatal dopamine or glutamate antagonist administration. Intrastriatal infusion of dopamine (D1 or D2) or glutamate [N-methyl-D-aspartic acid (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)] antagonists affected not only mAMPH-induced striatal, but also cortical, Fos expression. Overall, the effects of the antagonists occurred dose-dependently, in both the infused and non-infused hemispheres, with greater influences occurring in the infused hemisphere. Finally, unilateral intrastriatal infusion of dopamine or glutamate antagonists changed the behavior of the rats from characteristic mAMPH-induced stereotypy to rotation ipsilateral to the infusion. These results demonstrate that mAMPH’s actions on striatal dopamine and glutamate receptors modulate the widespread cortical activation induced by mAMPH. It is hypothesized that dopamine release from nigrostriatal terminals modulates activity within striatal

  15. Effects of simulated weightlessness on intramuscular hypertonic saline induced muscle nociception and spinal Fos expression in rats.

    PubMed

    Lei, Jing; Pertovaara, Antti; You, Hao-Jun

    2015-01-12

    We assessed the effects of simulated weightlessness, hindlimb unloading (HU) by 7 days of tail suspension, on noxious mechanically and heat evoked spinal withdrawal reflexes and spinal Fos expression during muscle nociception elicited by intramuscular (i.m.) injection of hypertonic (HT; 5.8%) saline into gastrocnemius muscle in rats. In HU rats, i.m. HT saline-induced secondary mechanical hyperalgesia was enhanced, and secondary heat hypoalgesia was significantly delayed. After 7 days of HU, basal Fos expression in spinal L4-6 segments was bilaterally enhanced only in superficial (I-II) but not middle and deep laminae (III-VI) of the spinal dorsal horn, which finding was not influenced by tail denervation. Unilateral i.m. HT saline injection increased spinal Fos expression bilaterally in both the control rats and 7 days of HU rats. The HT saline-induced bilateral increase of spinal Fos occurred within 0.5h and reached its peak within 1h, after which it gradually returned to the control levels within 8h. Spatial patterns of spinal Fos expression differed between the control group and 7 days of HU group. In superficial laminae, the HT saline-induced increases in Fos expression were higher and in the middle and deep laminae V-VI lower in the 7 days of HU than control rats. It is suggested that supraspinal mechanisms presumably underlie the effects of HU on spinally-organized nociception. Simulated weightlessness may enhance descending facilitation and weaken descending inhibition of nociception. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. c-fos modulates brain-derived neurotrophic factor mRNA expression in mouse hippocampal CA3 and dentate gyrus neurons.

    PubMed

    Dong, Mei; Wu, Yongfei; Fan, Yunxia; Xu, Ming; Zhang, Jianhua

    2006-05-29

    Excess neuronal excitation by glutamate induces neuron cell death, which may contribute to the pathogenesis of acute brain injuries and neurodegenerative diseases. Our previous studies using a mouse with hippocampal c-fos gene deletion showed that c-fos regulates neuronal excitability and excitotoxicity. Moreover, a delayed induction of brain-derived neurotrophic factor (BDNF) protein expression in response to kainic acid (KA) treatment was found in c-fos mutant mice compared to wildtype controls, suggesting that c-fos is important in the temporal control of BDNF induction. To further investigate mechanisms of in vivo regulation of c-fos on BDNF expression, we studied the expression of BDNF mRNA and its colocalization with c-Fos protein in the hippocampal formation in the presence and absence of KA. By in situ hybridization, we observed that the c-fos mutant and wildtype mice exhibited similar basal expression of BDNF in the absence of KA. In contrast, the KA-induced BDNF mRNA levels were significantly different in wildtype and c-fos mutant mice in CA3 and dentate gyrus regions. Our findings indicate that c-fos regulates expression of BDNF in distinct neuron populations of the hippocampal formation in vivo.

  17. Stimulus induced bursts in severe postanoxic encephalopathy.

    PubMed

    Tjepkema-Cloostermans, Marleen C; Wijers, Elisabeth T; van Putten, Michel J A M

    2016-11-01

    To report on a distinct effect of auditory and sensory stimuli on the EEG in comatose patients with severe postanoxic encephalopathy. In two comatose patients admitted to the Intensive Care Unit (ICU) with severe postanoxic encephalopathy and burst-suppression EEG, we studied the effect of external stimuli (sound and touch) on the occurrence of bursts. In patient A bursts could be induced by either auditory or sensory stimuli. In patient B bursts could only be induced by touching different facial regions (forehead, nose and chin). When stimuli were presented with relatively long intervals, bursts persistently followed the stimuli, while stimuli with short intervals (<1s) did not induce bursts. In both patients bursts were not accompanied by myoclonia. Both patients deceased. Bursts in patients with a severe postanoxic encephalopathy can be induced by external stimuli, resulting in stimulus-dependent burst-suppression. Stimulus induced bursts should not be interpreted as prognostic favourable EEG reactivity. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  18. Spatial memory formation differentially affects c-Fos expression in retrosplenial areas during place avoidance training in rats.

    PubMed

    Malinowska, Monika; Niewiadomska, Monika; Wesierska, Malgorzata

    2016-01-01

    The retrosplenial cortex is involved in spatial memory function, but the contribution of its individual areas is not well known. To elucidate the involvement of retrosplenial cortical areas 29c and 30 in spatial memory, we analyzed the expression of c-Fos in these areas in the experimental group of rats that were trained in a spatial place avoidance task, i.e. to avoid shocks presented in an unmarked sector of a stable arena under light conditions. Control rats were trained in the same context as the experimental rats either without (Control-noUS) or with shocks (Control-US) that were delivered in a random, noncontingent manner for three days. On the first day of place avoidance learning, the experimental group exhibited c-Fos induction in area 29c, similar to both control groups. In area 30, similarly high levels of c-Fos expression were observed in the experimental and Control-US groups. On the third day of training, when the experimental group efficiently avoided c-Fos expression in areas 29c and 30 was lower compared with the first day of training. In area 29c c-Fos level was also lower in the experimental than in comparison to the Control-US group. In area 30, c-Fos expression in the experimental group was lower than in both control groups. In conclusion, areas 29c and 30 appear to be activated during spatial memory acquisition on the first day of training, whereas area 30 seems suppressed during long-term memory functioning on the third day of training when rats effectively avoid.

  19. Cannabinoid modulation of zebrafish fear learning and its functional analysis investigated by c-Fos expression.

    PubMed

    Ruhl, Tim; Zeymer, Malou; von der Emde, Gerhard

    2017-02-01

    It has been shown that zebrafish fear learning proceeds in the same way as reported for rodents. However, in zebrafish fear learning it is possible to substitute the use of electric shocks as unconditioned stimulus and utilize the inborn fear responses to the alarm substance Schreckstoff, instead. The skin extract Schreckstoff elicits typical fear reactions such as preferred bottom dwelling, swimming in a tighter shoal, erratic movements and freezing. This natural fear behavior can be transferred from Schreckstoff to any other sensory stimulus by associative conditioning (fear learning). We presented Schreckstoff simultaneously with a red light stimulus and tested the effectiveness of fear learning during memory retrieval. The two brain regions known to be relevant for learning in zebrafish are the medial and the lateral pallium of the dorsal telencephalon, both containing rich expressions of the endocannabinoid receptor CB1. To test the influence of the zebrafish endocannabinoid system on fear acquisition learning, an experimental group of ten fish was pretreated with the CB1 receptor agonist THC (Δ(9)-tetrahydrocannabinol; 100nM for 1h). We found that CB1 activation significantly inhibited acquisition of fear learning, possibly by impairing stimulus encoding processes in pallial areas. This was supported by analyzes of c-Fos expression in the brains of experimental animals. Schreckstoff exposure during fear acquisition learning and memory retrieval during red light presentation increased the number of labelled cells in pallial structures, but in no other brain region investigated (e.g. striatum, thalamus, and habenula). THC administration before fear conditioning significantly decreased c-Fos expression in these structures to a level similar to the control group without Schreckstoff experience, suggesting that Schreckstoff induced fear learning requires brain circuits restricted mainly to pallial regions of the dorsal telencephalon. Copyright © 2016 Elsevier

  20. Fos Expression in Neurons of the Rat Vestibulo-Autonomic Pathway Activated by Sinusoidal Galvanic Vestibular Stimulation

    PubMed Central

    Holstein, Gay R.; Friedrich Jr., Victor L.; Martinelli, Giorgio P.; Ogorodnikov, Dmitri; Yakushin, Sergei B.; Cohen, Bernard

    2012-01-01

    The vestibular system sends projections to brainstem autonomic nuclei that modulate heart rate and blood pressure in response to changes in head and body position with regard to gravity. Consistent with this, binaural sinusoidally modulated galvanic vestibular stimulation (sGVS) in humans causes vasoconstriction in the legs, while low frequency (0.02–0.04 Hz) sGVS causes a rapid drop in heart rate and blood pressure in anesthetized rats. We have hypothesized that these responses occur through activation of vestibulo-sympathetic pathways. In the present study, c-Fos protein expression was examined in neurons of the vestibular nuclei and rostral ventrolateral medullary region (RVLM) that were activated by low frequency sGVS. We found c-Fos-labeled neurons in the spinal, medial, and superior vestibular nuclei (SpVN, MVN, and SVN, respectively) and the parasolitary nucleus. The highest density of c-Fos-positive vestibular nuclear neurons was observed in MVN, where immunolabeled cells were present throughout the rostro-caudal extent of the nucleus. c-Fos expression was concentrated in the parvocellular region and largely absent from magnocellular MVN. c-Fos-labeled cells were scattered throughout caudal SpVN, and the immunostained neurons in SVN were restricted to a discrete wedge-shaped area immediately lateral to the IVth ventricle. Immunofluorescence localization of c-Fos and glutamate revealed that approximately one third of the c-Fos-labeled vestibular neurons showed intense glutamate-like immunofluorescence, far in excess of the stain reflecting the metabolic pool of cytoplasmic glutamate. In the RVLM, which receives a direct projection from the vestibular nuclei and sends efferents to preganglionic sympathetic neurons in the spinal cord, we observed an approximately threefold increase in c-Fos labeling in the sGVS-activated rats. We conclude that localization of c-Fos protein following sGVS is a reliable marker for sGVS-activated neurons of the vestibulo

  1. Fos expression in neurons of the rat vestibulo-autonomic pathway activated by sinusoidal galvanic vestibular stimulation.

    PubMed

    Holstein, Gay R; Friedrich, Victor L; Martinelli, Giorgio P; Ogorodnikov, Dmitri; Yakushin, Sergei B; Cohen, Bernard

    2012-01-01

    The vestibular system sends projections to brainstem autonomic nuclei that modulate heart rate and blood pressure in response to changes in head and body position with regard to gravity. Consistent with this, binaural sinusoidally modulated galvanic vestibular stimulation (sGVS) in humans causes vasoconstriction in the legs, while low frequency (0.02-0.04 Hz) sGVS causes a rapid drop in heart rate and blood pressure in anesthetized rats. We have hypothesized that these responses occur through activation of vestibulo-sympathetic pathways. In the present study, c-Fos protein expression was examined in neurons of the vestibular nuclei and rostral ventrolateral medullary region (RVLM) that were activated by low frequency sGVS. We found c-Fos-labeled neurons in the spinal, medial, and superior vestibular nuclei (SpVN, MVN, and SVN, respectively) and the parasolitary nucleus. The highest density of c-Fos-positive vestibular nuclear neurons was observed in MVN, where immunolabeled cells were present throughout the rostro-caudal extent of the nucleus. c-Fos expression was concentrated in the parvocellular region and largely absent from magnocellular MVN. c-Fos-labeled cells were scattered throughout caudal SpVN, and the immunostained neurons in SVN were restricted to a discrete wedge-shaped area immediately lateral to the IVth ventricle. Immunofluorescence localization of c-Fos and glutamate revealed that approximately one third of the c-Fos-labeled vestibular neurons showed intense glutamate-like immunofluorescence, far in excess of the stain reflecting the metabolic pool of cytoplasmic glutamate. In the RVLM, which receives a direct projection from the vestibular nuclei and sends efferents to preganglionic sympathetic neurons in the spinal cord, we observed an approximately threefold increase in c-Fos labeling in the sGVS-activated rats. We conclude that localization of c-Fos protein following sGVS is a reliable marker for sGVS-activated neurons of the vestibulo

  2. Influence of sleep deprivation on expression of MKK4 and c-fos in the mandibular condylar cartilage of rats.

    PubMed

    Chen, Jinlong; Wu, Gaoyi; Zhu, Guoxiong; Wang, Peihuan; Chen, Hongyu; Zhao, Huaqiang

    2013-12-01

    The aim of this study was to investigate the changes in expression of mitogen-activated protein kinase kinase 4 (MKK4) and c-fos in the mandibular condylar cartilage of rats that had been subjected to sleep deprivation. One hundred and twenty female Wistar rats were randomly divided into 6 groups with 20 in each: sleep deprivation for 2 days, 4 days, 6 days, and 8 days, large-platform controls, and cage controls. After sleep deprivation by the modified multiple platform method the sleep-deprived rats were killed. The large-platform and cage control rats were killed at the same time as the rats deprived of sleep for 8 days. Haematoxylin and eosin were used to record the morphological changes in cartilage, and immunohistochemistry and real-time quantitative polymerase chain reaction (PCR) were used to detect the expression of MKK4 and c-fos. Pathological alterations were apparent after 6 and 8 days of sleep deprivation. Compared with control groups, the expression of MKK4 in the sleep-deprived groups was lower, while that of c-fos was higher. As the duration of sleep deprivation increased, the expression of MKK4 decreased. These results indicate that the variation in expression of MKK4 and c-fos may be correlated with pathological changes induced by sleep deprivation in mandibular condylar cartilage in rats.

  3. Detection of molecular alterations in methamphetamine-activated Fos-expressing neurons from a single rat dorsal striatum using fluorescence-activated cell sorting (FACS).

    PubMed

    Liu, Qing-Rong; Rubio, Francisco J; Bossert, Jennifer M; Marchant, Nathan J; Fanous, Sanya; Hou, Xingyu; Shaham, Yavin; Hope, Bruce T

    2014-01-01

    Methamphetamine and other drugs activate a small proportion of all neurons in the brain. We previously developed a fluorescence-activated cell sorting (FACS)-based method to characterize molecular alterations induced selectively in activated neurons that express the neural activity marker Fos. However, this method requires pooling samples from many rats. We now describe a modified FACS-based method to characterize molecular alterations in Fos-expressing dorsal striatal neurons from a single rat using a multiplex pre-amplification strategy. Fos and NeuN (a neuronal marker) immunohistochemistry indicate that 5-6% of dorsal striatum neurons were activated 90 min after acute methamphetamine injections (5 mg/kg, i.p.) while less than 0.5% of neurons were activated by saline injections. We used FACS to separate NeuN-labeled neurons into Fos-positive and Fos-negative neurons and assessed mRNA expression using RT-qPCR from as little as five Fos-positive neurons. Methamphetamine induced 3-20-fold increases of immediate early genes arc, homer-2, c-fos, fosB, and its isoforms (ΔfosB and a novel isoform ΔfosB-2) in Fos-positive but not Fos-negative neurons. Immediate early gene mRNA induction was 10-fold lower or absent when assessed in unsorted samples from single dorsal striatum homogenates. Our modified method makes it feasible to study unique molecular alterations in neurons activated by drugs or drug-associated cues in complex addiction models. Methamphetamine and other drugs activate a small proportion of all neurons in the brain. We here report an improved method to characterize molecular alterations induced selectively in activated neurons that express the neural activity marker Fos. We used FACS along with targeted PCR pre-amplification to assess acute methamphetamine-induced gene expression from as few as 5 Fos-expressing neurons from a single rat dorsal striatum. Methamphetamine induced 3-20-fold increases of immediate early genes (IEGs) in Fos-positive but not

  4. c-Fos expression after deep brain stimulation of the pedunculopontine tegmental nucleus in the rat 6-hydroxydopamine Parkinson model.

    PubMed

    Saryyeva, Assel; Nakamura, Makoto; Krauss, Joachim K; Schwabe, Kerstin

    2011-11-01

    Deep brain stimulation (DBS) is used to alleviate motor dysfunction in Parkinson's disease (PD). The pedunculopontine nucleus (PPN) may be a potential target for severe freezing and postural instability with 25 Hz stimulation being considered more effective than 130 Hz stimulation. Here we evaluated the expression of c-Fos after 25 Hz and 130 Hz DBS of the pedunculopontine tegmental nucleus (PPTg, i.e., the rodent equivalent to the human PPN) in the rat 6-hydroxydopamine (6-OHDA) PD model. Anaesthetized male Sprague Dawley rats with unilateral 6-OHDA-induced nigrostriatal lesions were stimulated with 25 Hz, 130 Hz, or 0 Hz sham-stimulation for 4h by electrodes implanted into the ipsilateral PPTg. Thereafter the distribution and number of neurons expressing the immediate early gene c-Fos, a marker for acute neuronal activity, was assessed. DBS of the PPTg induced strong ipsilateral c-Fos expression at the stimulation site, with 25 Hz having a more marked impact than 130 Hz. Additionally, c-Fos was strongly expressed in the central gray. In the dorsal part expression was stronger after 25 Hz stimulation, while in the medial and ventral part there was no difference between 25 Hz and 130 Hz stimulation. Expression in the basal ganglia was negligible. In the rat 6-OHDA PD model stimulation of the PPTg did not affect c-Fos expression in the basal ganglia, but had a strong impact on other functional circuitries. PPN stimulation in humans might therefore also have an impact on other systems than the motor system.

  5. Magnesium sulphate attenuates tourniquet-induced hypertension and spinal c-fos mRNA expression: a comparison with ketamine.

    PubMed

    Lee, D H; Jee, D L; Kim, S Y; Kim, J M; Lee, H M

    2006-01-01

    Magnesium and ketamine are well-known N-methyl-D-aspartic acid receptor antagonists. The aim of this study was to determine whether magnesium, in comparison with ketamine, attenuates tourniquet-induced hypertension and spinal c-fos mRNA expression. Rats were divided into four treatment groups: normal (baseline for c-fos mRNA expression); control (saline injection); magnesium injection; and ketamine injection. Arterial blood pressure and c-fos mRNA expression at 60 min were higher in the control than in the magnesium and ketamine groups. Human patients under sevoflurane-oxygen/nitrous oxide anaesthesia were also assigned to receive similar treatments. In humans, arterial blood pressure was increased in the control group at 50 min and thereafter compared with the magnesium and ketamine groups; the magnesium and ketamine groups did not differ. Magnesium and ketamine are equally effective in attenuating tourniquet-induced hypertension and spinal c-fos mRNA expression, suggesting that this effect may be due to reduced pain transmission.

  6. Central Fos expression and conditioned flavor avoidance in rats following intragastric administration of bitter taste receptor ligands.

    PubMed

    Hao, Shuzhen; Dulake, Michelle; Espero, Elvis; Sternini, Catia; Raybould, Helen E; Rinaman, Linda

    2009-03-01

    G protein-coupled receptors that signal bitter taste (T2Rs) are expressed in the mucosal lining of the oral cavity and gastrointestinal (GI) tract. In mice, intragastric infusion of T2R ligands activates Fos expression within the caudal viscerosensory portion of the nucleus of the solitary tract (NTS) through a vagal pathway (Hao S, Sternini C, Raybould HE. Am J Physiol Regul Integr Comp Physiol 294: R33-R38, 2008). The present study was performed in rats to further characterize the distribution and chemical phenotypes of brain stem and forebrain neurons activated to express Fos after intragastric gavage of T2R ligands, and to determine a potential behavioral correlate of this central neural activation. Compared with relatively low brain stem and forebrain Fos expression in control rats gavaged intragastrically with water, rats gavaged intragastrically with T2R ligands displayed significantly increased activation of neurons within the caudal medial (visceral) NTS and caudal ventrolateral medulla, including noradrenergic neurons, and within the lateral parabrachial nucleus, central nucleus of the amygdala, and paraventricular nucleus of the hypothalamus. A behavioral correlate of this Fos activation was evidenced when rats avoided consuming flavors that previously were paired with intragastric gavage of T2R ligands. While unconditioned aversive responses to bitter tastants in the oral cavity are often sufficient to inhibit further consumption, a second line of defense may be provided postingestively by ligand-induced signaling at GI T2Rs that signal the brain via vagal sensory inputs to the caudal medulla.

  7. High ambient temperature increases 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy")-induced Fos expression in a region-specific manner.

    PubMed

    Hargreaves, G A; Hunt, G E; Cornish, J L; McGregor, I S

    2007-03-16

    3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is a popular drug that is often taken under hot conditions at dance clubs. High ambient temperature increases MDMA-induced hyperthermia and recent studies suggest that high temperatures may also enhance the rewarding and prosocial effects of MDMA in rats. The present study investigated whether ambient temperature influences MDMA-induced expression of Fos, a marker of neural activation. Male Wistar rats received either MDMA (10 mg/kg i.p.) or saline, and were placed in test chambers for 2 h at either 19 or 30 degrees C. MDMA caused significant hyperthermia at 30 degrees C and a modest hypothermia at 19 degrees C. The 30 degrees C ambient temperature had little effect on Fos expression in vehicle-treated rats. However MDMA-induced Fos expression was augmented in 15 of 30 brain regions at the high temperature. These regions included (1) sites associated with thermoregulation such as the median preoptic nucleus, dorsomedial hypothalamus and raphe pallidus, (2) the supraoptic nucleus, a region important for osmoregulation and a key mediator of oxytocin and vasopressin release, (3) the medial and central nuclei of the amygdala, important in the regulation of social and emotional behaviors, and (4) the shell of the nucleus accumbens and (anterior) ventral tegmental area, regions associated with the reinforcing effects of MDMA. MDMA-induced Fos expression was unaffected by ambient temperature at many other sites, and was diminished at high temperature at one site (the islands of Calleja), suggesting that the effect of temperature on MDMA-induced Fos expression was not a general pharmacokinetic effect. Overall, these results indicate that high temperatures accentuate key neural effects of MDMA and this may help explain the widespread use of the drug under hot conditions at dance parties as well as the more hazardous nature of MDMA taken under such conditions.

  8. Environmental enrichment and gut inflammation modify stress-induced c-Fos expression in the mouse corticolimbic system.

    PubMed

    Reichmann, Florian; Painsipp, Evelin; Holzer, Peter

    2013-01-01

    Environmental enrichment (EE) has a beneficial effect on rodent behaviour, neuronal plasticity and brain function. Although it may also improve stress coping, it is not known whether EE influences the brain response to an external (psychological) stressor such as water avoidance stress (WAS) or an internal (systemic) stressor such as gastrointestinal inflammation. This study hence explored whether EE modifies WAS-induced activation of the mouse corticolimbic system and whether this stress response is altered by gastritis or colitis. Male C67BL/6N mice were housed under standard or enriched environment for 9 weeks, after which they were subjected to a 1-week treatment with oral iodoacetamide to induce gastritis or oral dextran sulfate sodium to induce colitis. Following exposure to WAS the expression of c-Fos, a marker of neuronal activation, was measured by immunocytochemistry. EE aggravated experimentally induced colitis, but not gastritis, as shown by an increase in the disease activity score and the colonic myeloperoxidase content. In the brain, EE enhanced the WAS-induced activation of the dentate gyrus and unmasked an inhibitory effect of gastritis and colitis on WAS-evoked c-Fos expression within this part of the hippocampus. Conversely, EE inhibited the WAS-evoked activation of the central amygdala and prevented the inhibitory effect of gastritis and colitis on WAS-evoked c-Fos expression in this region. EE, in addition, blunted the WAS-induced activation of the infralimbic cortex and attenuated the inhibitory effect of gastritis and colitis on WAS-evoked c-Fos expression in this area. These data reveal that EE has a region-specific effect on stress-induced c-Fos expression in the corticolimbic system, which is likely to improve stress resilience. The response of the prefrontal cortex - amygdala - hippocampus circuitry to psychological stress is also modified by the systemic stress of gut inflammation, and this interaction between external and internal

  9. Environmental Enrichment and Gut Inflammation Modify Stress-Induced c-Fos Expression in the Mouse Corticolimbic System

    PubMed Central

    Reichmann, Florian; Painsipp, Evelin; Holzer, Peter

    2013-01-01

    Environmental enrichment (EE) has a beneficial effect on rodent behaviour, neuronal plasticity and brain function. Although it may also improve stress coping, it is not known whether EE influences the brain response to an external (psychological) stressor such as water avoidance stress (WAS) or an internal (systemic) stressor such as gastrointestinal inflammation. This study hence explored whether EE modifies WAS-induced activation of the mouse corticolimbic system and whether this stress response is altered by gastritis or colitis. Male C67BL/6N mice were housed under standard or enriched environment for 9 weeks, after which they were subjected to a 1-week treatment with oral iodoacetamide to induce gastritis or oral dextran sulfate sodium to induce colitis. Following exposure to WAS the expression of c-Fos, a marker of neuronal activation, was measured by immunocytochemistry. EE aggravated experimentally induced colitis, but not gastritis, as shown by an increase in the disease activity score and the colonic myeloperoxidase content. In the brain, EE enhanced the WAS-induced activation of the dentate gyrus and unmasked an inhibitory effect of gastritis and colitis on WAS-evoked c-Fos expression within this part of the hippocampus. Conversely, EE inhibited the WAS-evoked activation of the central amygdala and prevented the inhibitory effect of gastritis and colitis on WAS-evoked c-Fos expression in this region. EE, in addition, blunted the WAS-induced activation of the infralimbic cortex and attenuated the inhibitory effect of gastritis and colitis on WAS-evoked c-Fos expression in this area. These data reveal that EE has a region-specific effect on stress-induced c-Fos expression in the corticolimbic system, which is likely to improve stress resilience. The response of the prefrontal cortex – amygdala – hippocampus circuitry to psychological stress is also modified by the systemic stress of gut inflammation, and this interaction between external and internal

  10. CREB, AP‐1, ternary complex factors and MAP kinases connect transient receptor potential melastatin‐3 (TRPM3) channel stimulation with increased c‐Fos expression

    PubMed Central

    Rubil, Sandra; Rössler, Oliver G.

    2016-01-01

    Background and Purpose The rise in intracellular Ca2+ stimulates the expression of the transcription factor c‐Fos. Depending on the mode of entry of Ca2+ into the cytosol, distinct signal transducers and transcription factors are required. Here, we have analysed the signalling pathway connecting a Ca2+ influx via activation of transient receptor potential melastatin‐3 (TRPM3) channels with enhanced c‐Fos expression. Experimental Approach Transcription of c‐Fos promoter/reporter genes that were integrated into the chromatin via lentiviral gene transfer was analysed in HEK293 cells overexpressing TRPM3. The transcriptional activation potential of c‐Fos was measured using a GAL4‐c‐Fos fusion protein. Key Results The signalling pathway connecting TRPM3 stimulation with enhanced c‐Fos expression requires the activation of MAP kinases. On the transcriptional level, three Ca2+‐responsive elements, the cAMP‐response element and the binding sites for the serum response factor (SRF) and AP‐1, are essential for the TRPM3‐mediated stimulation of the c‐Fos promoter. Ternary complex factors are additionally involved in connecting TRPM3 stimulation with the up‐regulation of c‐Fos expression. Stimulation of TRPM3 channels also increases the transcriptional activation potential of c‐Fos. Conclusions and Implications Signalling molecules involved in connecting TRPM3 with the c‐Fos gene are MAP kinases and the transcription factors CREB, SRF, AP‐1 and ternary complex factors. As c‐Fos constitutes, together with other basic region leucine zipper transcription factors, the AP‐1 transcription factor complex, the results of this study explain TRPM3‐induced activation of AP‐1 and connects TRPM3 with the biological functions regulated by AP‐1. © 2015 The British Pharmacological Society PMID:26493679

  11. Brain-Wide Maps of "Fos" Expression during Fear Learning and Recall

    ERIC Educational Resources Information Center

    Cho, Jin-Hyung; Rendall, Sam D.; Gray, Jesse M.

    2017-01-01

    "Fos" induction during learning labels neuronal ensembles in the hippocampus that encode a specific physical environment, revealing a memory trace. In the cortex and other regions, the extent to which "Fos" induction during learning reveals specific sensory representations is unknown. Here we generate high-quality brain-wide…

  12. C-fos and IL-2 gene expression in rat brain cells and splenic lymphocytes after nonantigenic and antigenic stimuli.

    PubMed

    Korneva, E A; Barabanova, S V; Golovko, O I; Nosov, M A; Novikova, N S; Kazakova, T B

    2000-01-01

    Immunostimulatory or immunosuppressive stress models were used: (1) rotation stress (RS) and (2) immobilization (restraint) stress (IS). Intravenous injection of tetanus toxoid (anatoxin) (TT) was chosen as the antigenic stimulus (500 micrograms/kg weight), and intravenous injection of saline solution was used as the control. Splenic lymphocytes (CBA mice) or different brain structures (Wistar and Sprague-Dawley rats) were analyzed. The c-fos and interleukin-2 (IL-2) mRNA expression was measured using a digoxigenin (Dig)-labeled cDNA probe by spot or in situ hybridization. Rotation stress stimulated IL-2 mRNA synthesis in lymphocytes in the presence of ConA and rIL-2 by 40%. IL-2 mRNA synthesis in lymphoid cells obtained from animals after IS and after IS in combination with the administration in vitro of the cytotoxic drug CsA to the splenic lymphocytes was inhibited (30% and 99%), accordingly, as compared with control rats. Induction of c-fos mRNA synthesis in rat brain cells was noted 30 minutes after RS in the hypothalamus (lateralis hypothalamic area, LHA), thalamus, corpus collosum, and sensorimotor zone of the brain cortex. IL-2 mRNA synthesis was shown two hours after RS in the same structures. The increased number of c-fos mRNA-positive cells two hours after TT injection was shown in the posterior hypothalamus area (PHA), LHA, dorsomedial nucleus (DMH), ventromedial nucleus (VMH), and anterior hypothalamus area (AHA) as compared to the effect of i.v. saline injection. Moreover, IL-2 mRNA-positive cell induction was noted in the PHA, DMH, and VMH. Six hours after TT injection, c-fos mRNA expression was decreased in the PHA, LHA, and AHA. Activation of c-fos and IL-2 mRNA was detected in the paraventricularis nucleus 6 hours after TT i.v. injection. Thus, inhibition or stimulation of IL-2 gene expression in lymphoid cells depends on the nature of the stressors. RS or antigenic stimuli induce c-fos and IL-2 gene expression in definite structures of the brain

  13. [Antagonistic effects of selenium on the expression of c-fos in central nerval system of rat included by mercury contaminated rice].

    PubMed

    Cheng, Jin-ping; Wang, Wen-hua; Jia, Jin-ping; Qu, Li-ya; Zheng, Min; Shen, Zhe-ming; Shi, Wei

    2005-03-01

    The objective of this paper is to study the antagonisms between selenium and mercury and the effect of different species mercury on the brain injury. The expression of c-fos mRNA and c-FOS protein in rat brain induced by Hg-contaminated rice was observed by using reverse transcriptions polymerase chain reaction (RT-PCR) and immunocytochemical methods. The results show the Hg-contaminated rice induced significantly the expression of c-fos mRNA and c-FOS protein; selenium could antagonize mercury accumulative level in brain. Antagonistic effects of selenium on the expression of c-fos included by mercury and the molecule mechanism of the antagonisms between selenium and mercury was probed, too.

  14. Electrical activation and c-fos mRNA expression in rat neurosecretory neurones after systemic administration of cholecystokinin.

    PubMed Central

    Hamamura, M; Leng, G; Emson, P C; Kiyama, H

    1991-01-01

    1. The expression of c-fos mRNA in the rat hypothalamus was examined by in situ hybridization following systemic administration of cholecystokinin (CCK), a procedure known to activate magnocellular oxytocin neurons but not magnocellular vasopressin neurones. 2. Conscious male rats were given a single I.P. injection of 50 micrograms/kg CCK, c-fos mRNA signal was apparent in the supraoptic and paraventricular nuclei in rats killed 10 min after injection but not in uninjected or saline-(vehicle) injected rats. The density of c-fos mRNA at both sites was further elevated in rats killed 30 min or 60 min following injection, and was absent in rats killed 4 h after injection. 3. In the paraventricular nucleus the most dense expression of c-fos mRNA following CCK administration was in the medial, mainly parvocellular portion of the nucleus, in an area corresponding to the distribution of corticotrophin-releasing factor mRNA determined by in situ hybridization in adjacent sections. 4. The I.P. injection of CCK increased plasma oxytocin concentrations, measured by specific radioimmunoassay from 13 +/- 5 pg/ml in control rats to 107 +/- 9 pg/ml in the rats killed 10 min after injection, a similar response to that observed previously in urethane-anaesthetized rats. 5. In each of six urethane-anaesthetized rats, recordings were made from single neurones in the supraoptic nucleus, identified antidronomically as projecting to the posterior pituitary and identified electrophysiologically as putative oxytocin neurones. Following I.P. injection of 50 micrograms/kg CCK, the neurones increased their firing rate by a mean of 1.3 +/- 0.2 spikes/s averaged over the 10 min following injection. 6. From the appearance of c-fos mRNA in supraoptic neurones following CCK administration we conclude that this message is expressed in magnocellular oxytocin neurones, since vasopressin neuronal activity and vasopressin release is known to be unaffected by this stimulus, and since the supraoptic

  15. c-Fos expression associated with reinstatement of cocaine-seeking behavior by response-contingent conditioned cues.

    PubMed

    Kufahl, Peter R; Zavala, Arturo R; Singh, Akanksha; Thiel, Kenneth J; Dickey, Erin D; Joyce, Jeffrey N; Neisewander, Janet L

    2009-10-01

    The capability of cocaine cues to generate craving in cocaine-dependent humans, even after extended abstinence, is modeled in rats using cue reinstatement of extinguished cocaine-seeking behavior. We investigated neural activity associated with incentive motivational effects of cocaine cues using c-fos mRNA and Fos protein expression as markers. Unlike preceding studies, we used response-contingent presentation of discrete cues to elicit cocaine seeking. Rats were first trained to press a lever, resulting in cocaine reinforcement and light and tone cues. Rats then underwent extinction training, during which lever presses decreased. On the test day, rats either received response-contingent cocaine cues or received no cues. The cues reinstated extinguished cocaine-seeking behavior on the test day. In general, cue-elicited c-fos mRNA and protein expression were similar and both were enhanced in the prefrontal cortex, ventral tegmental area (VTA), dorsal striatum, and nucleus accumbens. Cues elicited more widespread Fos protein expression relative to our previous research in which cues were presented noncontingently without prior extinction training, including increases in the VTA, substantia nigra, ventral subiculum, and lateral entorhinal cortex. We also observed a correlation between cocaine-seeking behavior and Fos in the agranular insula (AgI) and basolateral amygdala (BLA). The findings suggest that connections between BLA and AgI play a role in cue-elicited incentive motivation for cocaine and that reinstatement of cocaine seeking by response-contingent cues activates a similar corticolimbic circuit as that observed with other modes of cue presentation; however, activation of midbrain and ventral hippocampal regions may be unique to reinstatement by response-contingent cues.

  16. The expression of c-Fos and colocalisation of c-Fos and glucocorticoid receptors in brain structures of low and high anxiety rats subjected to extinction trials and re-learning of a conditioned fear response.

    PubMed

    Lehner, Małgorzata; Wisłowska-Stanek, Aleksandra; Taracha, Ewa; Maciejak, Piotr; Szyndler, Janusz; Skórzewska, Anna; Turzyńska, Danuta; Sobolewska, Alicja; Hamed, Adam; Bidziński, Andrzej; Płaźnik, Adam

    2009-11-01

    We designed an animal model to examine the mechanisms of differences in individual responses to aversive stimuli. We used the rat freezing response in the context fear test as a discriminating variable: low responders (LR) were defined as rats with a duration of freezing response one standard error or more below the mean value, and high responders (HR) were defined as rats with a duration of freezing response one standard error or more above the mean value. We sought to determine the colocalisation of c-Fos and glucocorticoid receptors-immunoreactivity (GR-ir) in HR and LR rats subjected to conditioned fear training, two extinction sessions and re-learning of a conditioned fear. We found that HR animals showed a marked decrease in conditioned fear in the course of two extinction sessions (16 days) in comparison with the control and LR groups. The LR group exhibited higher activity in the cortical M2 and prelimbic areas (c-Fos) and had an increased number of cells co-expressing c-Fos and GR-ir in the M2 and medial orbital cortex after re-learning a contextual fear. HR rats showed increased expression of c-Fos, GR-ir and c-Fos/GR-ir colocalised neurons in the basolateral amygdala and enhanced c-Fos and GR-ir in the dentate gyrus (DG) in comparison with LR animals. Our data indicate that recovery of a context-related behaviour upon re-learning of contextual fear is accompanied in HR animals by a selective increase in c-Fos expression and GRs-ir in the DG area of the hippocampus.

  17. A Fear-Inducing Odor Alters PER2 and c-Fos Expression in Brain Regions Involved in Fear Memory

    PubMed Central

    Pantazopoulos, Harry; Dolatshad, Hamid; Davis, Fred C.

    2011-01-01

    Evidence demonstrates that rodents learn to associate a foot shock with time of day, indicating the formation of a fear related time-stamp memory, even in the absence of a functioning SCN. In addition, mice acquire and retain fear memory better during the early day compared to the early night. This type of memory may be regulated by circadian pacemakers outside of the SCN. As a first step in testing the hypothesis that clock genes are involved in the formation of a time-stamp fear memory, we exposed one group of mice to fox feces derived odor (TMT) at ZT 0 and one group at ZT 12 for 4 successive days. A separate group with no exposure to TMT was also included as a control. Animals were sacrificed one day after the last exposure to TMT, and PER2 and c-Fos protein were quantified in the SCN, amygdala, hippocampus, and piriform cortex. Exposure to TMT had a strong effect at ZT 0, decreasing PER2 expression at this time point in most regions except the SCN, and reversing the normal rhythm of PER2 expression in the amygdala and piriform cortex. These changes were accompanied by increased c-Fos expression at ZT0. In contrast, exposure to TMT at ZT 12 abolished the rhythm of PER2 expression in the amygdala. In addition, increased c-Fos expression at ZT 12 was only detected in the central nucleus of the amygdala in the TMT12 group. TMT exposure at either time point did not affect PER2 or c-Fos in the SCN, indicating that under a light-dark cycle, the SCN rhythm is stable in the presence of repeated exposure to a fear-inducing stimulus. Taken together, these results indicate that entrainment to a fear-inducing stimulus leads to changes in PER2 and c-Fos expression that are detected 24 hours following the last exposure to TMT, indicating entrainment of endogenous oscillators in these regions. The observed effects on PER2 expression and c-Fos were stronger during the early day than during the early night, possibly to prepare appropriate systems at ZT 0 to respond to a fear

  18. Pattern of Fos expression in the brain induced by selective activation of somatostatin receptor 2 in rats

    PubMed Central

    Goebel, Miriam; Stengel, Andreas; Wang, Lixin; Coskun, Tamer; Alsina-Fernandez, Jorge; Rivier, Jean; Taché, Yvette

    2010-01-01

    Central activation of somatostatin (sst) receptors by oligosomatostatin analogs inhibits growth hormone and stress-related rise in catecholamine plasma levels while stimulating grooming, feeding behaviors, gastric transit and acid secretion, which can be mimicked by selective sst2 receptor agonist. To evaluate the pattern of neuronal activation induced by peptide sst receptor agonists, we assessed Fos-expression in rat brain after intracerebroventricular (icv) injection of a newly developed selective sst2 agonist compared to the oligosomatostatin agonist, ODT8-SST, a pan-sst1–5 agonist. Ninety min after injection of vehicle (10µl) or previously established maximal orexigenic dose of peptides (1µg=1nmol/rat), brains were assessed for Fos-immunohistochemistry and doublelabeling. Food and water were removed after injection. The sst2 agonist and ODT8-SST induced a similar Fos distribution pattern except in the arcuate nucleus where only the sst2 agonist increased Fos. Compared to ODT8-SST, the sst2 agonist induced higher Fos-expression by 3.7-fold in the basolateral amygdaloid nucleus, 1.2-fold in the supraoptic nucleus (SON), 1.6-fold in the magnocellular paraventricular hypothalamic nucleus (mPVN), 4.1-fold in the external lateral parabrachial nucleus, and 2.6-fold in both the inferior olivary nucleus and superficial layer of the caudal spinal trigeminal nucleus. Doublelabeling in the hypothalamus showed that ODT8-SST activates 36% of oxytocin, 63% of vasopressin and 79% of sst2 immunoreactive neurons in the mPVN and 28%, 55% and 25% in the SON, respectively. Selective activation of sst2 receptor results in a more robust neuronal activation than the pan-sst1–5 agonist in various brain regions that may have relevance in sst2 mediated alterations of behavioral, autonomic and endocrine functions. PMID:20637739

  19. Water deprivation increases Fos expression in hypothalamic corticotropin-releasing factor neurons induced by right atrial distension in awake rats.

    PubMed

    Benedetti, Mauricio; Rorato, Rodrigo; Castro, Margaret; Machado, Benedito H; Antunes-Rodrigues, Jose; Elias, Lucila L K

    2008-11-01

    Atrial mechanoreceptors, sensitive to stretch, contribute in regulating heart rate and intravascular volume. The information from those receptors reaches the nucleus tractus solitarius and then the paraventricular nucleus (PVN), known to have a crucial role in the regulation of cardiovascular function. Neurons in the PVN synthesize CRF, AVP, and oxytocin (OT). Stimulation of atrial mechanoreceptors was performed in awake rats implanted with a balloon at the junction of the superior vena cava and right atrium. Plasma ACTH, AVP, and OT concentrations and Fos, CRF, AVP, and OT immunolabeling in the PVN were determined after balloon inflation in hydrated and water-deprived rats. The distension of the balloon increased the plasma ACTH concentrations, which were higher in water-deprived than in hydrated rats (P < 0.05). In addition, the distension in the water-deprived group decreased plasma AVP concentrations (P < 0.05), compared with the respective control group. The distension increased the number of Fos- and double-labeled Fos/CRF neurons in the parvocellular PVN, which was higher in the water-deprived than in the hydrated group (P < 0.01). There was no difference in the Fos expression in magnocellular PVN neurons after distension in hydrated and water-deprived groups, compared with respective controls. In conclusion, parvocellular CRF neurons showed an increase of Fos expression induced by stimulation of right atrial mechanoreceptors, suggesting that CRF participates in the cardiovascular reflex adjustments elicited by volume loading. Activation of CRF neurons in the PVN by cardiovascular reflex is affected by osmotic stimulation.

  20. [Puerarin suppresses the proliferation of vscular smooth muscule cells and c-fos and bcl-2 protein expression].

    PubMed

    Xu, Yi-Zhou; Gao, Yan; Li, Pei-Zhang; Wang, Ning-Fu; Xu, Hai-Ying; Tong, Guo-Xin

    2006-03-01

    To observe the role of puerarin on the proliferation of vascular smooth muscle cells(VSMC) induced by thrombin (T) and the effect of puerarin on the c-fos and bcl-2 protein expression. Cell number and cell cycle analysis using flow cytometry were adopted as two different indicators of effects on proliferation of VSMC. Western blot was used to indicate the changes of c-fos and bcl-2 protein after 24 h of treatment of T and puerarin. 1.5 x 10(-5) - 1.5 x 10(-3) mol x L(-1) puerarin could significantly suppress this stimulation of VSMC proliferation and DNA synthesis induced by T. Western blot demonstrated that after 24 hour of treatment with T and puerarin, T could significantly increase c-fos and bcl-2 protein and 1.5 x 10(-5) - 1.5 x 10(-3) mol x L(-1) puerain could significantly suppress this increase. puerarin can suppress the proliferation and DNA synthesis of VSMC promoted by T. This inhibitory effects of puerarin are closely related with the suppression of c-fos and bcl-2 protein.

  1. Effect of hypoxia on metabolic rate, core body temperature, and c-fos expression in the naked mole rat.

    PubMed

    Nathaniel, Thomas I; Otukonyong, Effiong; Abdellatif, Ahmed; Soyinka, Julius O

    2012-10-01

    Recent investigations of hypoxia physiology in the naked mole rat have opened up an interesting line of research into the basic physiological and genomic alterations that accompany hypoxia survival. The extent to which such findings connect the effect of hypoxia to metabolic rate (O₂ consumption), core body temperature (Tb), and transcripts encoding the immediate early gene product (such as c-fos) under a constant ambient temperature (Ta) is not well known. We investigated this issue in the current study. Our first sets of experiments measured Tb and metabolic rates during exposure of naked mole rats to hypoxia over a constant Ta. Hypoxia significantly decreased metabolic rates in the naked mole rat. Although core Tb also decreased during hypoxia, the effect of hypoxia in suppressing core Tb was not significant. The second series of experiments revealed that c-fos protein and mRNA expression in the hippocampus neurons (CA1) increased in naked mole rats that were repeatedly exposed to 3% O₂ for 60 min per day for 5 days when compared to normoxia. Our findings provide evidence for the up-regulation of c-fos and suppression of metabolic rate in hypoxia tolerating naked mole rats under constant ambient temperature. Metabolic suppression and c-fos upregulation constitute part of the physiological complex associated with adaptation to hypoxia.

  2. TGF beta induces a sustained c-fos expression associated with stimulation or inhibition of cell growth in EL2 or NIH 3T3 fibroblasts.

    PubMed

    Liboi, E; Di Francesco, P; Gallinari, P; Testa, U; Rossi, G B; Peschle, C

    1988-02-29

    We have previously indicated that epidermal growth factor (EGF) plays a fundamental role in the proliferation control of EL2 rat fibroblast line. It is shown here that transforming growth factor beta (TGF beta) stimulates both DNA synthesis and proliferation of EL2 cells, while exerting an inhibitory effect on the growth of murine NIH-3T3 fibroblasts. We also report the effect of TGF beta and EGF on c-fos expression in EL2 cells, as compared to that of TGF beta in NIH-3T3 fibroblasts. In EL2 cells EGF induces a transient c-fos expression at both mRNA and protein level, as previously observed in NIH-3T3 fibroblasts treated with platelet-derived or fibroblast growth factor (PDGF, FGF). Conversely, TGF beta induces in EL2 cells a sustained expression of fos mRNA and protein, which are still detectable at least 24 and 7 hr after treatment respectively. In NIH-3T3 fibroblasts TGF beta causes a sustained fos RNA expression, which is not associated, however, with detectable fos protein. We conclude that in fibroblasts stimulated by mitogens c-fos expression may be differentially modulated, depending of the growth factor and the cell line. This is seemingly due to differential regulation of fos gene expression, not only at the transcriptional and/or post-transcriptional level (transient or sustained fos RNA induction by EGF or TGF beta in EL2 cells), but also at the translational level (fos protein(s) induction by TGF beta in EL2 but not NIH-3T3 fibroblasts, possibly related to the stimulatory vs inhibitory effect of this factor on the growth of the former vs the latter line).

  3. Papillomavirus-Associated Tumor Formation Critically Depends on c-Fos Expression Induced by Viral Protein E2 and Bromodomain Protein Brd4

    PubMed Central

    Schneider, Markus; Schuetz, Johanna; Leiprecht, Natalie; Hudjetz, Benjamin; Brodbeck, Stephan; Corall, Silke; Dreer, Marcel; Schwab, Roxana Michaela; Grimm, Martin; Wu, Shwu-Yuan; Stubenrauch, Frank; Chiang, Cheng-Ming; Iftner, Thomas

    2016-01-01

    We investigated the mechanism of how the papillomavirus E2 transcription factor can activate promoters through activator protein (AP)1 binding sites. Using an unbiased approach with an inducible cell line expressing the viral transcription factor E2 and transcriptome analysis, we found that E2 induces the expression of the two AP1 components c-Fos and FosB in a Brd4-dependent manner. In vitro RNA interference confirmed that c-Fos is one of the AP1 members driving the expression of viral oncogenes E6/E7. Mutation analysis and in vivo RNA interference identified an essential role for c-Fos/AP1 and also for the bromodomain protein Brd4 for papillomavirus-induced tumorigenesis. Lastly, chromatin immunoprecipitation analysis demonstrated that E2 binds together with Brd4 to a canonical E2 binding site (E2BS) in the promoter of c-Fos, thus activating c-Fos expression. Thus, we identified a novel way how E2 activates the viral oncogene promoter and show that E2 may act as a viral oncogene by direct activation of c-Fos involved in skin tumorigenesis. PMID:26727473

  4. Bioluminescence imaging of c-fos gene expression accompanying filial imprinting in the newly hatched chick brain.

    PubMed

    Yamaguchi, Shinji; Iikubo, Eiji; Hirose, Naoki; Kitajima, Takaaki; Katagiri, Sachiko; Kawamori, Ai; Fujii-Taira, Ikuko; Matsushima, Toshiya; Homma, Koichi J

    2010-06-01

    Bioluminescence imaging is a powerful tool for examining gene expression in living animals. Previously, we reported that exogenous DNA could be successfully delivered into neurons in the newly hatched chick brain using electroporation. Here, we show the in vivo bioluminescence imaging of c-fos promoter activity and its upregulation, which is associated with filial imprinting. The upregulation of c-fos gene expression correlated with both the strength of the chicks' approach activity to the training object and the acquisition of memory. The present technique should be a powerful tool for analyzing the time changes in neural activity of certain brain areas in real-time during memory formation, using brains of living animals.

  5. Combined Expression of c-jun, c-fos, and p53 Improves Estimation of Prognosis in Oral Squamous Cell Carcinoma.

    PubMed

    Wang, Shan; Xu, Xin; Xu, Fei; Meng, Yan; Sun, Changsheng; Shi, Lei; Zhao, Eryang

    2016-09-13

    To identify the prognostic value of c-jun, c-fos, and p53 in oral cancer, we examined the impact of immunohistochemical expression of these markers on tumor progression in 157 oral squamous cell carcinoma (OSCC). We found that c-jun or c-fos was significantly associated with lymph node metastasis, and coexpression of c-jun/c-fos, or c-jun/c-fos/p53 were significantly associated with lymph node metastasis, poor differentiation and clinical stage. The coexpression of c-jun/c-fos/p53 was identified as independent prognostic factors for overall survival. Simultaneous coexpression of these markers in OSCCs might prove to be a useful indicator for differentiation of low and high-risk patients.

  6. Caffeine elicits c-Fos expression in horizontal diagonal band cholinergic neurons.

    PubMed

    Reznikov, Leah R; Pasumarthi, Ravi K; Fadel, Jim R

    2009-12-09

    Caffeine is a widely self-administered psychostimulant with purported neuroprotective and procognitive effects in rodent models of aging. The cholinergic basal forebrain is important for arousal and attention and is implicated in age-related cognitive decline. Accordingly, we determined the effects of caffeine on cholinergic neuron activation in the rat basal forebrain. Young adult (age 2 months) male rats were treated with caffeine (0, 10, or 50 mg/kg) and killed 2 h later. Caffeine significantly increased c-Fos expression in cholinergic neurons of the horizontal limb of the diagonal band of Broca but not other basal forebrain regions such as the medial septum or substantia innominata. The horizontal limb of the diagonal band of Broca provides cholinergic innervation to the olfactory bulb, suggesting that deficits in this structure may contribute to diminished olfactory function observed in Alzheimer's disease patients. These results suggest that part of the cognitive-enhancing effects of caffeine may be mediated through activation of this part of the cholinergic basal forebrain.

  7. Inhibition of carcinogen induced c-Ha-ras and c-fos proto-oncogenes expression by dietary curcumin

    PubMed Central

    Limtrakul, Porn-ngarm; Anuchapreeda, Songyot; Lipigorngoson, Suwiwek; Dunn, Floyd W

    2001-01-01

    Background We investigated the chemopreventive action of dietary curcumin on 7,12-dimethylbenz(a)anthracene (DMBA)-initiated and 12,0-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumor formation in Swiss albino mice. Curcumin, a yellow coloring matter isolated from roots of Curcuma longa Linn, is a phenolic compound possessing antioxidant, free radical scavenger, and antiinflammatory properties. It has been shown by previously reported work that TPA-induced skin tumors were inhibited by topical application of curcumin, and curcumin has been shown to inhibit a variety of biological activities of TPA. Topical application of curcumin was reported to inhibit TPA-induced c-fos, c-jun and c-myc gene expression in mouse skin. This paper reports the effects of orally administered curcumin, which was consumed as a dietary component at concentrations of 0.2 % or 1 %, in ad libitum feeding. Results Animals in which tumors had been initiated with DMBA and promoted with TPA experienced significantly fewer tumors and less tumor volume if they ingested either 0.2% or 1% curcumin diets. Also, the dietary consumption of curcumin resulted in a significantly decreased expression of ras and fos proto-oncogenes in the tumorous skin, as measured by enhanced chemiluminesence Western blotting detection system (Amersham). Conclusions Whereas earlier work demonstrated that topical application of curcumin to mouse skin inhibited TPA-induced expression of c-fos, c-jun and c-myc oncogenes, our results are the first to show that orally consumed curcumin significantly inhibited DMBA- and TPA-induced ras and fos gene expression in mouse skin. PMID:11231886

  8. Periaqueductal gray c-Fos expression varies relative to the method of conditioned taste aversion extinction employed.

    PubMed

    Mickley, G Andrew; Wilson, Gina N; Remus, Jennifer L; Ramos, Linnet; Ketchesin, Kyle D; Biesan, Orion R; Luchsinger, Joseph R; Prodan, Suzanna

    2011-11-14

    A conditioned taste aversion (CTA) is acquired when an animal consumes a novel taste (CS) and then experiences the symptoms of poisoning (US). Following CTA training, animals will avoid the taste that was previously associated with malaise. This defensive reaction to a learned fear can be extinguished by repeated exposure to the CS alone (CS-only; CSO-EXT). However, following a latency period in which the CS is not presented, the CTA will spontaneously recover (SR). Through the use of an explicitly unpaired extinction procedure (EU-EXT) we have shown that we can speed up extinction and attenuate SR of the CTA. Here we compared and contrasted the ability of CSO and EU extinction procedures to affect c-Fos expression in the periaqueductal gray (PAG). Fluid-deprived Sprague-Dawley rats acquired a strong CTA [via 3 pairings of 0.3% oral saccharin (SAC; the CS) and 81mg/kg i.p. lithium chloride (LiCl; the US)] followed by extinction trials consisting of multiple exposures to either, (a) the CS every-other day (CSO-EXT), or (b) CS and US on alternate days (EU-EXT). A different group of rats did not receive multiple CS exposures and served as a "no extinction" (NE) control. Both extinction procedures resulted in ≥90% reacceptance of SAC (achieving asymptotic extinction). Some of the animals were sacrificed for c-Fos immunohistochemical analysis following asymptotic extinction. Other rats entered a 30-day latency period where they drank water only. These remaining animals were then tested for SR with a final exposure to SAC before being sacrificed for c-Fos immunohistochemistry. As reported previously, rats in the CS-only group exhibited a significant SR of the CTA. However, animals in the EU extinction group reached asymptotic extinction more rapidly than did CSO rats and they did not show SR of the CTA. As compared to rats that retained their CTA, both groups of extinguished rats showed suppression in the number of c-Fos-labeled neurons in all 4 longitudinal columns of

  9. Inhibitory regulation of osteoclast differentiation by interleukin-3 via regulation of c-Fos and Id protein expression.

    PubMed

    Oh, Jaemin; Lee, Myeung Su; Yeon, Jeong-Tae; Choi, Sik-Won; Kim, Hun Soo; Shim, Hyeok; Lee, Sam Youn; Youn, Byung Soo; Yokota, Yoshifumi; Kim, Jung Ha; Kwak, Han Bok

    2012-05-01

    Interleukin-3 (IL-3) is produced under various pathological conditions and is thought to be involved in the pathogenesis of inflammatory diseases; however, its function in bone homeostasis under normal conditions or nature of the downstream molecular targets remains unknown. Here we examined the effect of IL-3 on osteoclast differentiation from mouse and human bone marrow-derived macrophages (BMMs). Although IL-3 can induce osteoclast differentiation of multiple myeloma bone marrow cells, IL-3 greatly inhibited osteoclast differentiation of human BMMs isolated from healthy donors. These inhibitory effects of IL-3 were only observed at early time points (days 0 and 1). IL-3 inhibited the expression of c-Fos and NFATc1 in BMMs treated with RANKL. However, IL-3-mediated inhibition of osteoclast differentiation was not completely reversed by ectopic expression of c-Fos or NFATc1. Importantly, IL-3 induced inhibitor of DNA binding/differentiation (Id)1 in hBMMs, while Id2 were sustained during osteoclast differentiation of mBMMs treated with IL-3. Ectopic expression of NFATc1 in Id2-deficient BMMs completely reversed the inhibitory effect of IL-3 on osteoclast differentiation. Furthermore, inflammation-induced bone erosion was markedly inhibited by IL-3 administration. Taken together, our results suggest that IL-3 plays an inhibitory role in osteoclast differentiation by regulating c-Fos and Ids, and also exerts anti-bone erosion effects.

  10. Amphetamine withdrawal modulates FosB expression in mesolimbic dopaminergic target nuclei: effects of different schedules of administration.

    PubMed

    Murphy, Carol A; Russig, Holger; Pezze, Marie-Astrid; Ferger, Boris; Feldon, Joram

    2003-06-01

    Different patterns of psychostimulant intake can elicit widely varying behavioral and neurochemical consequences. Accordingly, rats were studied during withdrawal from either of two schedules of amphetamine administration, one consisting of 6 days of low-dose (1.5 mg/kg, i.p.) daily intermittent (INT) amphetamine (AMPH) injections, and the other of 6 days of moderately high-dose (1-5 mg/kg, i.p.) escalating (ESC) AMPH injections, for the effects of these treatments on numbers of FosB-positive nuclei and monoamine utilization in dopaminergic target areas. Withdrawal from AMPH pretreatment according to the ESC schedule markedly increased FosB expression in the nucleus accumbens shell and basolateral amygdala. In contrast, withdrawal from INT-AMPH administration did not increase FosB expression in any of the regions examined. Post-mortem neurochemical analyses of these same brain regions did not reveal effects of withdrawal from either INT or ESC administration of AMPH. These results suggest that withdrawal from a moderately high-dose AMPH regimen modifies patterns of gene expression in mesocorticolimbic dopaminergic target nuclei without significantly affecting basal monoamine levels. The strength of these effects in the nucleus accumbens shell and basolateral nucleus of the amygdala are consistent with behavioral and clinical data indicating the importance of these areas in the neuroadaptive changes which characterize addiction and withdrawal states.

  11. c-Fos expression in hypothalamic nuclei of food-entrained rats.

    PubMed

    Angeles-Castellanos, Manuel; Aguilar-Roblero, Raul; Escobar, Carolina

    2004-01-01

    The present study aimed to identify the hypothalamic nuclei involved with food entrainment by using c-Fos-like immunoreactivity (c-Fos-IR) as a marker of functional activation. We studied rats entrained 3 wk to restricted feeding schedules (RF), their ad libitum (AL) controls, and the persistence of c-Fos-IR temporal patterns in entrained-fasted rats. In addition, we included 22-h fasting and 22-h fasting-refeeding groups as controls of fasting and refeeding acute effects. Diurnal patterns of c-Fos-IR were observed in the tuberomammilar nucleus (TM) and suprachiasmatic nucleus (SCN) in AL rats. In all nuclei, except the SCN and ventromedial nucleus (VMH), restricted feeding schedules imposed a temporal pattern of increased c-Fos-IR around mealtime. An increase in c-Fos-IR before and after meal time was observed in dorsomedial nucleus (DMH), lateral nucleus (LH), perifornical area (PeF), and TM, and a marked increase was observed in the paraventricular nucleus (PVN) after feeding. Food-entrained c-Fos-IR patterns persisted after 3 days in fasting in DMH, LH, and PeF. Present data suggest that FEO might not rely on a single nucleus and rather may be a distributed system constituted of interacting nuclei in which the PVN is mainly involved with the response to signals elicited by food ingestion and, therefore, with the entraining pathway. We can suggest that the PeF and TM may be involved with the arousal state during food anticipation and the DMH and LH with the time-keeping mechanism of FEO or its output.

  12. Nucleus accumbens NMDA receptor activation regulates amphetamine cross-sensitization and deltaFosB expression following sexual experience in male rats.

    PubMed

    Beloate, Lauren N; Weems, Peyton W; Casey, Graham R; Webb, Ian C; Coolen, Lique M

    2016-02-01

    Sexual experience in male rats followed by a period of abstinence causes sensitization to d-Amphetamine (Amph) reward, evidenced by an increased conditioned place preference (CPP) for low doses of Amph. Moreover, sexual experience induces neural plasticity within the nucleus accumbens (NAc), including induction of deltaFosB, which plays a key role in Amph reward cross-sensitization. The NMDA receptor subunit NR1 is also upregulated by mating, but the functional relevance of NMDA receptors in sex experience-induced effects is unknown. Here, we examined the influence of intra-NAc MK 801 infusions on sex experience-induced NAc deltaFosB and cFos expression, as well as mating- and Amph-induced CPP in adult male rats. In experiment 1, males received MK 801 or saline into the NAc during each of 4 consecutive days of mating or handling and were tested for Amph CPP and experience-induced deltaFosB 10 days later. Intra-NAc MK 801 during sexual behavior prevented experience-induced increases in Amph CPP and NAc deltaFosB expression without affecting sexual behavior. In experiment 2, the effects of intra-NAc MK 801 on mating-induced CPP were examined by intra-NAc infusion of MK 801 or saline prior to mating on conditioning days. Intra-NAc MK 801 did not affect mating-induced CPP. Next, effects of intra-NAc MK 801 on mating-induced cFos immunoreactivity were examined. MK 801 prevented mating-induced cFos expression in NAc shell and core. Together, these results provide evidence that NAc NMDA receptor activation during sexual behavior plays a key role in mating-induced cFos and deltaFosB expression and subsequent experience-induced cross-sensitization to Amph reward. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Brain region-specific reduction in c-Fos expression associated with an anxiolytic effect of yokukansan in rats.

    PubMed

    Shoji, Hirotaka; Mizoguchi, Kazushige

    2013-08-26

    A traditional Japanese (Kampo) medicine, yokukansan, has long been used to treat neurosis, insomnia, and night crying and irritability in children. Recently, this medicine has reported to improve the behavioral and psychological symptoms of dementia that often become problematic in patients with Alzheimer's disease and other forms of dementia. Several animal studies have reported that yokukansan has an anxiolytic effect. However, the underlying mechanisms are not yet understood. In the present study, we investigated the effects in rats of single and repeated administrations of yokukansan on anxiety-like behaviors, stress responses, and the brain regions involved. Yokukansan dissolved in water (100 or 300 mg/kg) was administered orally to F344/N male rats 1h before each test or for two weeks before the tests began. Locomotor activity and anxiety-related behavior in the open-field test and the elevated plus-maze test, serum corticosterone levels, and restraint stress-induced c-Fos expression in various brain regions as a marker of neuronal activation were evaluated in both the vehicle-treated and yokukansan-treated rats. A single administration of yokukansan had no effect on locomotor activity or anxiety-like behavior; however, repeated administration decreased anxiety-like behavior in a dose-dependent manner. Neither single nor repeated administration of yokukansan had an effect on the basal or stress-induced levels of serum corticosterone. For c-Fos expression, restraint stress increased the number of c-Fos-positive cells in the subdivisions of the prefrontal cortex, amygdala, and hypothalamus. Repeated administration of yokukansan decreased the stress-induced c-Fos expression in the prelimbic cortex and the basolateral and medial amygdaloid nuclei. The present study indicates that repeated oral administration of yokukansan has an anxiolytic effect and that this effect may be associated with attenuated neuronal activity in the medial prefrontal cortex and amygdala

  14. Long-term suppression of methamphetamine-induced c-Fos expression in rat striatum by the injection of c-fos antisense oligodeoxynucleotides absorbed in water-absorbent polymer.

    PubMed

    Semba, Jun'ichi; Wakuta, Maki; Suhara, Tetsuya

    2004-10-01

    The use of water-absorbent polymer (WAP) as a hydrogel carrier for the slow delivery of antisense oligodeoxynucleotides (ODN) in the brain, was recently developed. In this experiment, 15-mer phosphorothioate ODN, complementary to c-fos gene absorbed in WAP, was injected in the rat striatum. The expression of c-Fos-immunoreactivity induced by methamphetamine (6 mg/kg, intraperitoneally) around the injection site was suppressed until 5 days after injection. Using this method, it was observed that unilateral injection with c-fos antisense ODN into the rat striatum caused robust ipsilateral rotations after methamphetamine challenge 4 days post injection. This method is simple, and the biological and behavioral effects of antisense ODN in WAP can be maintained for several days even after a single injection into the brain.

  15. Losartan blocks drinking and cFos expression induced by central ornithine vasotocin in rats.

    PubMed

    Fitts, Douglas A; Zierath, Dannielle K; Wilkins, Emily E; Bassett, John E

    2005-11-15

    We previously reported that an intracerebroventricular (icv) injection of the oxytocin receptor antagonist ornithine vasotocin (OVT) caused water and saline intakes, a pressor response, and Fos-like immunoreactivity (Fos-IR) in the median preoptic nucleus of the rat brain. In the present report, rats receiving an icv injection of isotonic saline vehicle followed by an icv injection of 10 microg of OVT 20 min later drank 5.5+/-1.1 ml of total water and saline intake in 60 min after the OVT; rats receiving 10 microg of losartan before the OVT drank only 0.9+/-0.3 ml of total fluid. In a separate study, rats were treated as above except that they were not allowed to drink and were perfused for analysis of Fos-IR in the median preoptic nucleus at 90 min. Fos-IR in the dorsal part of the median preoptic nucleus was significantly suppressed from 2.69+/-0.57 cells per 10,000 square mum in vehicle-treated rats to 0.89+/-0.20 in losartan-treated rats. Losartan alone had no effect on Fos-IR. Losartan did not reduce intake of saccharin in a dessert test. This suggests that the OVT-induced drinking may result from an activation or disinhibition of angiotensin type AT1 receptors in the median preoptic nucleus.

  16. Spinal neurons that contain gastrin-releasing peptide seldom express Fos or phosphorylate extracellular signal-regulated kinases in response to intradermal chloroquine

    PubMed Central

    Gutierrez-Mecinas, Maria; Polgár, Erika; Todd, Andrew J

    2016-01-01

    Background Gastrin-releasing peptide (GRP) is thought to play a role in the itch evoked by intradermal injection of chloroquine. Although some early studies suggested that GRP was expressed in pruriceptive primary afferents, it is now thought that GRP in the spinal cord is derived mainly from a population of excitatory interneurons in lamina II, and it has been suggested that these are involved in the itch pathway. To test this hypothesis, we used the transcription factor Fos and phosphorylation of extracellular signal-regulated kinases (ERK) to look for evidence that interneurons expressing GRP were activated following intradermal injection of chloroquine into the calf, in mice that express enhanced green fluorescent protein (EGFP) in these cells. Results Injection of chloroquine resulted in numerous Fos- or phospho-ERK (pERK) positive cells in the somatotopically appropriate part of the superficial dorsal horn. The proportion of all neurons in this region that showed Fos or pERK was 18% and 21%, respectively. However, among the GRP–EGFP, only 7% were Fos-positive and 3% were pERK-positive. As such, GRP–EGFP cells were significantly less likely than other neurons to express Fos or to phosphorylate ERK. Conclusions Both expression of Fos and phosphorylation of ERK can be used to identify dorsal horn neurons activated by chloroquine injection. However, these results do not support the hypothesis that interneurons expressing GRP are critical components in the itch pathway. PMID:27270268

  17. Conditioned fear to context is associated with increased Fos expression in the caudal ventrolateral region of the midbrain periaqueductal gray.

    PubMed

    Carrive, P; Leung, P; Harris, J; Paxinos, G

    1997-05-01

    Immunohistochemical detection of Fos was used to determine which regions of the periaqueductal gray are activated during conditioned fear to a context in the rat. More specifically, the aim of the study was to test the role of its lateral and ventrolateral columns in freezing behaviour during fear. Conditioned fear was evoked by re-exposing rats to the same footshock chamber in which they had received footshocks 4 h earlier. Conditioned Re-exposed rats were compared to Not Conditioned Re-exposed and Conditioned Not Re-exposed rats. Freezing was observed in the Conditioned-Re-exposed group only. It was associated with an overall increase in Fos expression in the entire periaqueductal gray that was significantly greater than in the two other groups. The largest and most significant increase in Fos immunoreactivity was found in the ventrolateral column (especially in its caudal part), whereas only a moderate increase was found in the lateral column. The present results argue in favour of the ventrolateral column as the region of the periaqueductal gray that is preferentially involved in expression of conditioned fear. As previous lesion studies suggested, the ventrolateral periaqueductal gray may play a role in mediating the immobility component of freezing induced by fear. Other lines of evidence suggest that it may also play a role in mediating the quiescence immobility associated with deep pain. We propose that the ventrolateral column of the periaqueductal gray acts as an integrating centre mediating behavioural inhibition.

  18. c-fos and HSP70 gene expression in rat brains in high gravitation-induced cerebral ischemia.

    PubMed

    Son, M; Shahed, A R; Werchan, P M; Lee, J C

    1995-11-17

    Previous studies have shown that brief exposures of rodents to high gravitational forces (+Gz) in a specifically designed centrifuge cause global cerebral ischemia. In the present study, the effect of +Gz exposure to +22.5Gz for 15 to 60 s on c-fos and HSP70 gene expression was examined. Northern and RT-PCR analyses to total RNA isolated from brains of rats in different post-exposure times revealed a significant, time-dependent increase in the c-fos mRNA level which returned to near normal by 180 min. The HSP70 mRNA level was increased two-fold at 30 min post exposure, and remained elevated until 180 min. The transient stimulation of c-fos and HSP70 gene expression should serve as useful biomarkers for hypergravic stress on the brain. The present results should aid in design of future experiments in our understanding of the pathophysiology of the high +Gz challenges.

  19. Imipramine-induced c-Fos expression in the medial prefrontal cortex is decreased in the ACTH-treated rats.

    PubMed

    Li, Bingjin; Suemaru, Katsuya; Kitamura, Yoshihisa; Gomita, Yutaka; Araki, Hiroaki; Cui, Ranji

    2013-11-01

    Previous studies have shown that the antidepressive-like effect of tricyclic antidepressants is blocked by repeated treatments with adrenocorticotropic hormone (ACTH). However, little is known about the neuroanatomy underlying the mechanism of the imipramine treatment-resistant depression model. In the present study, first experimental evidence showed no significant difference of the serum imipramine concentrations between the saline and ACTH-treated rats. In further study, imipramine produced significant increases in the c-Fos expression in the medial prefrontal cortex (mPFC), the dentate gyrus of the hippocampus (DGH), and the central nucleus of the amygdala (CeA), in rats repeatedly treated with saline. The imipramine-increased c-Fos immunoreactivity was suppressed in the mPFC of rats repeatedly treated with ACTH. However, there was no significant difference in c-Fos expression in the DGH and CeA between ACTH- and saline-treated rats. These results suggest that the mPFC is maybe involved in effects of the imipramine in the ACTH-treated rats.

  20. Effect of hypergravity on expression of the immediate early gene, c-fos, in central nervous system of medaka (Oryzias latipes)

    NASA Astrophysics Data System (ADS)

    Sayaka, Shimomura-Umemura; Ijiri, Kenichi

    2006-01-01

    Immediate-early genes serve as useful neurobiological tools for mapping brain activity induced by a sensory stimulation. In this study, we have examined brain activity related to gravity perception of medaka (Oryzias latipes) by use of c-fos. The gene, which is homologous to the c-fos genes of other vertebrates, was identified in medaka. Functionally important domains are highly conserved among all the vertebrate species analyzed. Intraperitoneal administration of kainic acid transiently induced the c-fos mRNAs in medaka brains. The results indicate that the expression of c-fos can be utilized as a suitable anatomical marker for the increased neural activities in the central nervous system of medaka. Fish were continuously exposed to 3 g hypergravity by centrifugation. Investigation of c-fos mRNA expression indicated that c-fos mRNA significantly increased 30 min after a start of 3 g exposure. The distribution of its transcripts within the brains was analyzed by an in situ hybridization method. The 3-g treated medakas displayed c-fos positive cells in their brainstem regions, which are related to vestibular function, such as torus semicircularis, nucleus tangentialis, posterior octavu nucleus, and inferior olive. Our results established a method to follow the effect of gravity stimulation, which can be used to investigate gravity perception.

  1. Re-purposing of histological tissue sections for corroborative western blot analysis of hypothalamic metabolic neuropeptide expression following delineation of transactivated structures by Fos immuno-mapping.

    PubMed

    Alenazi, Fahaad S H; Ibrahim, Baher A; Briski, Karen P

    2015-04-01

    Fos immunocytochemistry is a valuable anatomical mapping tool for distinguishing cells within complex tissues that undergo genomic activation, but it is seldom paired with corroborative molecular analytical techniques. Due to preparatory requirements that include protein cross-linking for specimen sectioning, histological tissue sections are regarded as unsuitable for those methods. Our studies show that pharmacological activation of the hindbrain energy sensor AMPK by AICAR elicits estradiol (E)-dependent patterns of Fos immunolabeling of hypothalamic metabolic loci. Here, Western blotting was applied to hypothalamic tissue removed from histological sections of E- versus oil (O)-implanted ovariectomized (OVX) female rat brain to measure levels of metabolic transmitters associated with Fos-positive structures. In both E and O rats, AICAR treatment elicited alterations in pro-opiomelanocortin, neuropeptide Y, SF-1, and orexin-A neuropeptide expression that coincided with patterns of Fos labeling of structures containing neurons that synthesize these neurotransmitters, e.g. arcuate and ventromedial nuclei and lateral hypothalamic area. O, but not E animals also exhibited parallel augmentation of tissue corticotropin-releasing hormone neuropeptide levels and paraventricular nucleus Fos staining. Data demonstrate the utility of immunoblot analysis as a follow-through technique to capitalize on Fos mapping of transactivation sites in the brain. Findings that induction of Fos immunoreactivity coincides with adjustments in hypothalamic metabolic neuropeptide expression affirms that this functional indicator reflects changes in neurotransmission in pathways governing metabolic outflow. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Social experience induces sex-specific fos expression in the amygdala of the juvenile rat.

    PubMed

    Weathington, Jill M; Strahan, J Alex; Cooke, Bradley M

    2012-07-01

    To compare the response of the medial amygdala and central amygdala to juvenile social subjugation (JSS), we used unbiased stereology to quantify the immediate early gene product Fos in prepubertal rats after aggressive or benign social encounters or handling. We estimated the overall number of neurons and the proportion of Fos immunoreactive neurons in the posterodorsal (MePD) and posteroventral medial amygdala (MePV) and the central amygdala (CeA). Experience elicited Fos in a sex- and hemisphere-dependent manner in the MePD. The left MePD was selective for JSS in both sexes, but the right MePD showed a specific Fos response to JSS in males only. In the MePV, irrespective of hemisphere or sex, JSS elicited the greatest amount of Fos, benign social experience elicited an intermediate level, and handling the least. None of the experiential conditions elicited significant levels of Fos in the CeA. We found a previously unreported sex difference in the number of CeA neurons (M>F) that was highly significant and a strong trend toward a sex difference (M>F) in the MePD. These data show that the posterior MeA subnuclei are more responsive to JSS than to benign social interaction, that sex interacts with hemispheric laterality to determine the response of the MePD to JSS and that the MePV responds to social experience and JSS. Taken together, these findings support the hypothesis that juvenile rats process JSS in a sex-specific manner.

  3. Fluorescence Activated Cell Sorting (FACS) and Gene Expression Analysis of Fos-expressing Neurons from Fresh and Frozen Rat Brain Tissue.

    PubMed

    Rubio, F Javier; Li, Xuan; Liu, Qing-Rong; Cimbro, Raffaello; Hope, Bruce T

    2016-08-27

    The study of neuroplasticity and molecular alterations in learned behaviors is switching from the study of whole brain regions to the study of specific sets of sparsely distributed activated neurons called neuronal ensembles that mediate learned associations. Fluorescence Activated Cell Sorting (FACS) has recently been optimized for adult rat brain tissue and allowed isolation of activated neurons using antibodies against the neuronal marker NeuN and Fos protein, a marker of strongly activated neurons. Until now, Fos-expressing neurons and other cell types were isolated from fresh tissue, which entailed long processing days and allowed very limited numbers of brain samples to be assessed after lengthy and complex behavioral procedures. Here we found that yields of Fos-expressing neurons and Fos mRNA from dorsal striatum were similar between freshly dissected tissue and tissue frozen at -80 ºC for 3 - 21 days. In addition, we confirmed the phenotype of the NeuN-positive and NeuN-negative sorted cells by assessing gene expression of neuronal (NeuN), astrocytic (GFAP), oligodendrocytic (Oligo2) and microgial (Iba1) markers, which indicates that frozen tissue can also be used for FACS isolation of glial cell types. Overall, it is possible to collect, dissect and freeze brain tissue for multiple FACS sessions. This maximizes the amount of data obtained from valuable animal subjects that have often undergone long and complex behavioral procedures.

  4. [Gene c-Fos expression in brain of rats resistant and predisposed to emotional stress after intraperitoneal injection of the ACTH(4-10)analog--semax].

    PubMed

    Umriukhin, P E; Koplik, E V; Grivennikov, I A; Miasoedov, N F; Sudakov, K V

    2001-01-01

    The effect of the ACTH(4-10) analog Semax on immediate early gene c-Fos expression was studied in Wistar rats with high and low resistance to emotional stress under the usual conditions and during psychoemotional loading. Fos-immunoreactive cells in the were counted automatically with the help of a computer. It was shown that under the usual conditions the intraperitoneal Semax injection induced immediate early gene c-Fos expression in the lateral septal region in rats predisposed to emotional stress and in the paraventricular hypothalamus in rats of both groups. Preliminary Semax injection decreased the stress-induced c-Fos expression in the paraventricular hypothalamus and medial septum in rats predisposed to emotional stress and tended to reduce the number of stress-induced c-Fos-immunopositive cells in the lateral septum and basolateral amygdala in both groups of animals. The obtained data suggest that Semax differently affects the immediate early c-Fos gene expression in the brain of rats resistant and predisposed to emotional stress and this effect reflects the antistressor properties of the regulatory peptide.

  5. [Chinese herbal medicine enhances sexual function and c-Fos/nNOS expression in the nucleus accumbens of orchidectomized rats].

    PubMed

    Liu, Hongyu; Cui, Jianmei; Zhai, Haifeng; Xue, Jinjuan; Wang, Xiaoyang

    2016-06-01

    There was a decrease in accessory genital organ weight, plasma testosterone, and sexual behavior, as well as a low number of c-Fos-positive cells and a large nNOS-positive cell area in orchidectomized rats. Administration of the herbal medicine increased accessory genital organ weight, testosterone level, mating behavior, and c-Fos-positive cell number, while it decreased the nNOS-positive cell area in orchidectomized rats. An increase of plasma testosterone after administration of "kidney-nourishing" herbal medicine might contribute to the elevated sexual function and activity in orchidectomized rats. In addition, a central nervous system mechanism, such as the functional alteration of NAc, might be involved. Abstract To determine whether the central nervous system is involved in the effect of Chinese herbal medicine on sexual function recovery in orchidectomized rats. Orchidectomized rats were administered intragastrically with a decoction of "kidney-nourishing" Chinese herbal medicine once per day for 28 days. Accessory genital organ weight, plasma testosterone, and mating behavior were investigated. The expression of c-Fos and neuronal nitric oxide synthase (nNOS) in neuronal cells in the nucleus accumbens (NAc) was analyzed by immunohistochemistry.

  6. Inactivation of Median Preoptic Nucleus Causes c-Fos Expression in Hypocretin- and Serotonin-Containing Neurons in Anesthetized Rat

    PubMed Central

    Kumar, Sunil; Szymusiak, Ronald; Bashir, Tariq; Suntsova, Natalia; Rai, Seema; McGinty, Dennis; Alam, Md. Noor

    2008-01-01

    The median preoptic nucleus (MnPN) of the hypothalamus contains sleep-active neurons including sleep-active GABAergic neurons and is involved in the regulation of nonREM/REM sleep. The hypocretinergic (HCRT) neurons of the perifornical-lateral hypothalamic area (PF-LHA) and serotonergic (5-HT) neurons of the dorsal raphe nucleus (DRN) are mostly active during waking and have been implicated in the regulation of arousal. MnPN GABAergic neurons project to the PF-LHA and DRN. It is hypothesized that MnPN promotes sleep by inhibiting multiple arousal systems including HCRT and other wake-active neurons within the PF-LHA and 5-HT neurons in the DRN. We examined the effects of inactivation of MnPN neurons by locally microinjecting 0.2 µl of 1mM or 10mM solutions of a GABAA receptor agonist, muscimol, into the MnPN on Fos expression (Fos-IR) in the PF-LHA neurons including HCRT neurons and 5-HT neurons in the DRN in anesthetized rats. Compared to artificial cerebrospinal fluid control, microinjection of muscimol into the MnPN resulted in significantly higher percentages of HCRT and non-HCRT neurons in the PF-LHA and 5-HT neurons in the DRN that exhibited Fos-IR. The percentage of melanin-concentrating hormone (MCH)+/Fos+ neurons in the PF-LHA did not change after muscimol treatments. These results support a hypothesis that the activation of MnPN neurons contributes to the suppression of wake-promoting systems including HCRT and other unidentified neurons in the PF-LHA and 5-HT neurons in the DRN. These results also suggest that MCH neurons may not be under MnPN inhibitory control. These findings are consistent with a hypothesized role of MnPN in sleep regulation. PMID:18722360

  7. Blockade of 5-Ht3 receptors in the septal area increases Fos expression in selected brain areas.

    PubMed

    Urzedo-Rodrigues, Lilia S; Ferreira, Hilda S; Santana, Rejane Conceição; Luz, Carla Patrícia; Perrone, Camila F; Fregoneze, Josmara B

    2014-04-01

    Serotonin is widely distributed throughout the brain and is involved in a multiplicity of visceral, cognitive and behavioral responses. It has been previously shown that injections of different doses of ondansetron, a 5-HT3 receptor antagonist, into the medial septum/vertical limb of the diagonal band complex (MS/vDB) induce a hypertensive response in rats. On the other hand, administration of m-CPBG, a 5-HT3 agonist, into the MS/vDB inhibits the increase of blood pressure during restraint stress. However, it is unclear which neuronal circuitry is involved in these responses. The present study investigated Fos immunoreactive nuclei (Fos-IR) in different brain areas following the blockade of 5-HT3 receptors located in the MS/vDB in sham and in sinoaortic denervated (SAD) rats. Ondansetron injection into the MS/vDB increases Fos-IR in different brain areas including the limbic system (central amygdala and ventral part of the bed nucleus of the stria terminalis), hypothalamus (medial parvocellular parts of the paraventricular nucleus, anterodorsal preoptic area, dorsomedial hypothalamic nucleus), mesencephalon (ventrolateral periaqueductal gray region) and rhombencephalon (lateral parabrachial nucleus) in sham rats. Barodenervation results in higher Fos expression at the parvocellular and magnocellular part of the paraventricular nucleus, the lateral parabrachial nucleus, the central nucleus of amygdala, the locus coeruleus, the medial part of the nucleus of the solitary tract, the rostral ventrolateral medulla and the caudal ventrolateral medulla following 5-HT3receptor blockade in the MS/vDB. Based on the present results and previous data showing a hypertensive response to ondansetron injected into the MS/vDB, it is reasonable to suggest that 5-HT3receptors in the MS/vDB exert an inhibitory drive that may oscillate as a functional regulatory part of the complex central neuronal network participating in the control of blood pressure.

  8. Motherhood and nursing stimulate c-FOS expression in the rabbit forebrain.

    PubMed

    González-Mariscal, Gabriela; Jiménez, Angeles; Chirino, Rosario; Beyer, Carlos

    2009-08-01

    Mother rabbits nurse once daily with circadian periodicity. The authors investigated brain structures involved in regulating this activity by quantifying c-FOS-immunoreactive (IR) cells in the forebrain of: (1) mothers killed on postpartum Day 1 (PPD 1) after nursing (Group 1) or not given pups (Group 2); (2) mothers killed on PPD 7 after nursing (Group 3) or not given pups on such day (Group 4); (3) unmated virgins (Group 5). Groups 1 through 4 showed similar numbers of c-FOS-IR cells in the preoptic area, an amount around three to fourfold larger than that found in virgins. Nursing increased, on PPD 1 and 7, c-FOS-IR cell number in the lateral septum and paraventricular and supraoptic nuclei. No differences were seen among Groups 1 through 5 in the suprachiasmatic nucleus. In the ventromedial hypothalamus virgins had more c-FOS-IR cells compared with Groups 1 and 2. Results suggest that specific forebrain structures participate in regulating particular aspects of rabbit maternal behavior: the POA and LS seem associated with the establishment of motherhood and the magnocellular nuclei with the occurrence of milk letdown. 2009 APA, all rights reserved

  9. Expression of the c-fos gene in spinal cord and brain cells in rats subjected to stress in conditions of exposure to various types of halothane anesthesia.

    PubMed

    Novikova, N S; Kazakova, T B; Rogers, V; Korneva, E A

    2004-05-01

    The influences of different treatments on the expression of the c-fos gene in the spinal cord and brain (hypothalamus) was studied in rats using various types of anesthesia. Synthesis of c-Fos-like proteins occurred only in the spinal cord in conditions of constant 1.5% halothane anesthesia. Use of induction anesthesia with 1.5% halothane allowed detection of c-Fos-like protein expression in cells of the rat spinal cord (lumbar segments) and brain, both when animals were placed in a hammock and when mechanical pain stimulation or electromagnetic irradiation of the skin with UHF currents were applied. The pattern of brain structures reacting to mechanical pain stimulation with expression of c-Fos-like protein was identified. This type of stimulation was shown to induce increases in the quantity of c-Fos-positive cells in the lateral hypothalamic area (LHA), the ventromedial (VMH) and dorsomedial (DMH) hypothalamic nuclei, and in the ventral hypothalamic area (AHA) by 116%, 167%, 101%, and 157% respectively as compared with controls. Skin irradiation with UHF currents decreased the intensity of mechanical pain stimulation-induced synthesis of c-Fos-like protein in most structures (LHA, VMH, DMN, and AHA by 32.8%, 29%, 15%, and 33% respectively). Only induction halothane anesthesia allowed identification of hypothalamic structures reacting to mechanical pain stimulation and the modifying effects of irradiating the skin with UHF currents on the intensity of these reactions.

  10. Excitatory amino acid receptor antagonists and electroacupuncture synergetically inhibit carrageenan-induced behavioral hyperalgesia and spinal fos expression in rats.

    PubMed

    Zhang, Yu-Qiu; Ji, Guang-Chen; Wu, Gen-Cheng; Zhao, Zhi-Qi

    2002-10-01

    The interaction between electroacupuncture and an N-methyl-D-aspartic acid (NMDA) receptor antagonist, (DL-2-amino-5-phosphonopentanoic acid; AP5), or an (+/-)-alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainite (AMPA/KA) receptor antagonist, (6,7-dinitroquinoxaline-2,3 (1H,4H); DNQX) administered intrathecally on carrageenan-induced thermal hyperalgesia and spinal c-Fos expression was investigated. The latency of paw withdrawal (PWL) from a thermal stimulus was used as a measure of hyperalgesia in awake rats. Intrathecal (i.t.) injection of 1 and 10 nmol AP5, but not DNQX, markedly increased the PWL of the carrageenan-injected paw. At a dose of 100 nmol, either AP5 or DNQX significantly increased the PWL of carrageenan-injected paw, with AP5 being more potent. The PWLs of the non-injected and normal saline (NS)-injected paws were not detectably affected by the administration of NMDA or AMPA/KA receptor antagonists at the doses tested. Unilateral electroacupuncture stimulation of the 'Zu-San-Li' (St 36) and 'Kun-Lun' (UB 60) acupuncture points (60 and 2 Hz alternately, 1-2-3 mA) contralateral to the carrageenan-injected paw significantly elevated the PWLs of carrageenan- and NS-injected paws. Although neither i.t. injection of 0.1 nmol AP5 nor 1 nmol DNQX alone had an effect on the PWL of the carrageenan- and NS-injected paws, both significantly potentiated electroacupuncture-induced analgesia in carrageenan-injected rats, especially 0.1 nmol AP5. Fos expression evoked by intraplantar (i.pl.) injection of carrageenan was examined in the spinal cord with immunohistochemical methods. Three hours after i.pl. injection of carrageenan, the number of Fos-like immunoreactive (Fos-LI) neurons was significantly increased in all the layers of the ipsilateral spinal cord at L(4-5), with the highest density in laminae I-II and V-VI. Intrathecally pre-administered AP5 (10 nmol) or DNQX (100 nmol) significantly reduced the total number of carrageenan-induced Fos

  11. Eff ect of a single asenapine treatment on Fos expression in the brain catecholamine-synthesizing neurons: impact of a chronic mild stress preconditioning.

    PubMed

    Osacka, J; Horvathova, L; Majercikova, Z; Kiss, Alexander

    2017-04-25

    Fos protein expression in catecholamine-synthesizing neurons of the substantia nigra (SN) pars compacta (SNC, A8), pars reticulata (SNR, A9), and pars lateralis (SNL), the ventral tegmental area (VTA, A10), the locus coeruleus (LC, A6) and subcoeruleus (sLC), the ventrolateral pons (PON-A5), the nucleus of the solitary tract (NTS-A2), the area postrema (AP), and the ventrolateral medulla (VLM-A1) was quantitatively evaluated aft er a single administration of asenapine (ASE) (designated for schizophrenia treatment) in male Wistar rats preconditioned with a chronic unpredictable variable mild stress (CMS) for 21 days. Th e aim of the present study was to reveal whether a single ASE treatment may 1) activate Fos expression in the brain areas selected; 2) activate tyrosine hydroxylase (TH)-synthesizing cells displaying Fos presence; and 3) be modulated by CMS preconditioning. Control (CON), ASE, CMS, and CMS+ASE groups were used. CMS included restraint, social isolation, crowding, swimming, and cold. Th e ASE and CMS+ASE groups received a single dose of ASE (0.3 mg/kg, s.c.) and CON and CMS saline (300 μl/rat, s.c.). The animals were sacrificed 90 min aft er the treatments. Fos protein and TH-labeled immunoreactive perikarya were analyzed on double labeled histological sections and enumerated on captured pictures using combined light and fluorescence microscope illumination. Saline or CMS alone did not promote Fos expression in any of the structures investigated. ASE alone or in combination with CMS elicited Fos expression in two parts of the SN (SNC, SNR) and the VTA. Aside from some cells in the central gray tegmental nuclei adjacent to LC, where a small number of Fos profiles occurred, none or negligible Fos occurrence was detected in the other structures investigated including the LC and sLC, PON-A5, NTS-A2, AP, and VLM-A1. CMS preconditioning did not infl uence the level of Fos induction in the SN and VTA elicited by ASE administration. Similarly, the ratio

  12. Urocortin 2 increases c-Fos expression in serotonergic neurons projecting to the ventricular/periventricular system

    PubMed Central

    Hale, Matthew W.; Stamper, Christopher E.; Staub, Daniel R.; Lowry, Christopher A.

    2010-01-01

    Serotonin plays an important role in the regulation of anxiety states and physiological responses to aversive stimuli. Intracerebroventricular (i.c.v.) injection of the stress- and anxiety-related neuropeptide urocortin 2 (Ucn 2) increases c-Fos expression in serotonergic neurons in the dorsal (DRD) and caudal (DRC) parts of the dorsal raphe nucleus. These regions contain a subset of serotonergic neurons that projects via the dorsal raphe periventricular tract to periventricular structures, including the subfornical organ and ependymal layer, and to the ventricular system. To determine if Ucn 2 activates ventricle/periventricular-projecting serotonergic neurons in the midbrain raphe complex we made i.c.v. injections of the retrograde tracer Fluoro-Gold into the lateral ventricle, followed 7 days later by i.c.v. injection of Ucn 2. The DRD at −8.18 mm and the DRC at −8.54 mm and −9.16 mm bregma were analyzed using a combined brightfield and immunofluorescence technique. Approximately 40% of the ventricle/periventricular-projecting neurons in the subdivisions sampled were serotonergic. Urocortin 2 increased c-Fos expression in ventricle/periventricular-projecting serotonergic neurons in the DRC and in non-ventricle/periventricular-projecting serotonergic neurons in the DRD and DRC. Of the total population of ventricle/periventricular-projecting serotonergic neurons in the DRC at −8.54 and −9.16 mm bregma, 35% expressed c-Fos following Ucn 2 injections. These data are consistent with previous studies showing that i.c.v. injection of Ucn 2 activates subpopulations of serotonergic neurons restricted to the mid-rostrocaudal DRD and DRC, and further demonstrate that these include both subsets of serotonergic neurons that do and do not project to the ventricle/periventricular system. PMID:20382145

  13. Activation of peroxisome proliferator activated receptor γ in brain inhibits inflammatory pain, dorsal horn expression of Fos, and local edema

    PubMed Central

    Morgenweck, J.; Abdel-aleem, O.S.; McNamara, K.C.; Donahue, R.R.; Badr, M.Z.; Taylor, B.K.

    2009-01-01

    Systemic administration of thiazolidinediones reduces peripheral inflammation in vivo, presumably by acting at peroxisome proliferator-activated receptor γ (PPARγ) in peripheral tissues. Based on a rapidly growing body of literature indicating the CNS as a functional target of PPARγ actions, we postulated that brain PPARγ modulates peripheral edema and the processing of inflammatory pain signals in the dorsal horn of the spinal cord. To test this in the plantar carrageenan model of inflammatory pain, we measured paw edema, heat hyperalgesia, and dorsal horn expression of the immediate-early gene c-fos after intracerebroventricular (ICV) administration of PPARγ ligands or vehicle. We found that ICV rosiglitazone (0.5–50 µg) or 15d-PGJ2 (50–200 µg), but not vehicle, dose-dependently reduced paw thickness, paw volume and behavioral withdrawal responses to noxious heat. These anti-inflammatory and anti-hyperalgesia effects result from direct actions in the brain and not diffusion to other sites, because intraperitoneal and intrathecal administration of rosiglitazone (50 µg) and 15d-PGJ2 (200 µg) had no effect. PPARγ agonists changed neither overt behavior nor motor coordination, indicating that non-specific behavioral effects do not contribute to PPAR ligand-induced anti-hyperalgesia. ICV administration of structurally dissimilar PPARγ antagonists (either GW9662 or BADGE) reversed the anti-inflammatory and anti-hyperalgesic actions of both rosiglitazone and 15d-PGJ2. To evaluate the effects of PPARγ agonists on a classic marker of noxious stimulus-evoked gene expression, we quantified Fos protein expression in the dorsal horn. The number of carrageenan-induced Fos-like immunoreactive profiles was less in rosiglitazone-treated rats as compared to vehicle controls. We conclude that pharmacological activation of PPARγ in the brain rapidly inhibits local edema and the spinal transmission of noxious inflammatory signals. PMID:19891980

  14. Persistent c-fos expression and NADPH-d reactivity in the medulla and the lumbar spinal cord in rat with short-term peripheral anosmia.

    PubMed

    Kalueff, A V; Maisky, V A; Pilyavskii, A I; Makarchuk, N E

    2001-03-30

    Here we examine hypothesis that short-term peripheral ZnSO(4)-induced anosmia can produce effects on c-fos expression within spinal cord and caudal medulla in male Wistar rats (n=4). Fos-like-immunoreactive cells revealed by avidin-biotin-peroxidase method show a significant bilateral increase in the nucleus proprius (layers 3 and 4) and medial part of layers 5 and 6. In substantia gelatinosa (layer 2(i)) and area 10 Fos-positive neurons were intermixed together with nicotin-amide adenine dineucleotide phosphate-diaphorase (NADPH-d)-reactive cells. Short-term anosmia enhanced c-fos expression in ventral horn (layers 7 and 8), ventrolateral segment and dorsal part of the spinal trigeminal nuclei. In anosmic rats varicose fibres and numerous NADPH-d-stained neurons were present in the gelatinous layer of the spinal trigeminal nucleus caudalis, and a separate population of Fos-positive cells was detected within this layer. Nucleus tractus solitaris also contained a few NADPH-d-reactive, medium sized neurons intermixed with Fos-immunoreactive cells.

  15. Receptor-Selective Agonists Induce Emesis and Fos Expression in the Brain and Enteric Nervous System of the Least Shrew (Cryptotis parva)

    PubMed Central

    Ray, Andrew P.; Chebolu, Seetha; Darmani, Nissar A.

    2009-01-01

    Research on the mechanisms of emesis has implicated multiple neurotransmitters via both central (dorsal vagal complex) and peripheral (enteric neurons and enterochromaffin cells) anatomical substrates. Taking advantage of advances in receptor-specific agonists, and utilizing Fos expression as a functional activity marker, this study demonstrates a strong, but incomplete, overlap in anatomical substrates for a variety of emetogens. We used cisplatin and specific agonists to 5-HT3 serotonergic, D2/D3 dopaminergic, and NK1 tachykininergic receptors to induce vomiting in the least shrew (Cryptotis parva), and quantified the resulting Fos expression. The least shrew is a small mammal whose responses to emetic challenges are very similar to its human counterparts. In all cases, the enteric nervous system, nucleus of the solitary tract, and dorsal motor nucleus of the vagus demonstrated significantly increased Fos immunoreactivity (Fos-IR). However, Fos-IR induction was notably absent from the area postrema following the dopaminergic and NK1 receptor-specific agents. Two brain nuclei not usually discussed regarding emesis, the dorsal raphe nucleus and paraventricular thalamic nucleus, also demonstrated increased emesis-related Fos-IR. Taken together, these data suggest the dorsal vagal complex is part of a common pathway for a variety of distinct emetogens, but there are central emetic substrates, both medullary and diencephalic, that can be accessed without directly stimulating the area postrema. PMID:19699757

  16. Acidity induces c-Fos expression in a subpopulation of human colonic submucosal neurons.

    PubMed

    Tixier, Emmanuelle; Galmiche, Jean-Paul; Neunlist, Michel

    2006-08-14

    Enteric neurons responding to chemical challenge of the mucosa have been characterized in animal models mainly in the myenteric plexus. However, in humans, the existence of enteric neurons responding to chemical stimulation of the mucosa remains currently unknown. Therefore, the aim of our study was to identify and characterize human submucosal neurons activated by mucosal challenge with butyrate or hydrochloric acid. Segments of human colon were placed in a modified Ussing chamber and incubated on the mucosal side with butyric acid (20 mM, pH 6.5), sodium butyrate (20 mM, pH 7.5), hydrochloric acid (10 mM, pH 6.5) or culture medium (pH 7.5). After 90 min of culture, tissues were fixed and microdissected to obtain whole mount preparation of submucosa containing the Meissner's plexus. Neuron specific enolase (NSE), c-Fos, vasoactive intestinal peptide (VIP) and substance P (SP) were detected using immunohistochemical methods. Tetrodotoxin (TTX, 1 microM) was used to inhibit neuronal activity. After 90 min of culture, butyric acid induced a significant 5.6-fold increase in the proportion of c-Fos-immunoreactive neurons compared to control (19 +/- 4% versus 4 +/- 1%, respectively, p < 0.001). 41 +/- 5% of c-Fos-immunoreactive neurons were VIP-immunoreactive and 3 +/- 2% were SP-immunoreactive. Butyric acid did not modify the proportion of VIP-immunoreactive neurons. The increase in c-Fos-immunoreactive neurons induced by butyric acid was reproduced with hydrochloric acid at the same pH but not with sodium butyrate. Finally, preincubation of the tissue with TTX prevented the effect of butyric acid. In conclusion, our results demonstrate that acidic mucosal challenge induced the activation of a population of human submucosal neurons with a specific neurochemical coding.

  17. A circulating ghrelin mimetic attenuates light-induced phase delay of mice and light-induced Fos expression in the suprachiasmatic nucleus of rats.

    PubMed

    Yi, Chun-Xia; Challet, Etienne; Pévet, Paul; Kalsbeek, Andries; Escobar, Carolina; Buijs, Ruud M

    2008-04-01

    Anatomical evidence suggests that the ventromedial arcuate nucleus (vmARC) is a route for circulating hormonal communications to the suprachiasmatic nucleus (SCN). Whether this vmARC-SCN connection is involved in the modulation of circadian activity of the SCN is not yet known. We recently demonstrated, in rats, that intravenous (i.v.) injection of a ghrelin mimetic, GHRP-6, during the daytime activated neurons in the vmARC and reduced the normal endogenous daytime Fos expression in the SCN. In the present study we show that i.v. administration of GHRP-6 decreases light-induced Fos expression at ZT13 in the rat SCN by 50%, indicating that light-induced changes in the SCN Fos expression can also be reduced by GHRP-6. Because it is difficult to study light-induced phase changes in rats, we examined the functional effects of GHRP-6 on light-induced phase shifts in mice and demonstrated that peripherally injected GHRP-6 attenuates light-induced phase delays at ZT13 by 45%. However, light-induced Fos expression in the mice SCN was not blocked by GHRP-6. These results illustrate that acute stimulation of the ghrelinergic system may modulate SCN activity, but that its effect on light-induced phase shifts and Fos expression in the SCN might be species related.

  18. Effects of treadmill running exercise on neuronal expression of c-Fos protein in the medulla oblongata after unilateral phrenicotomy in Wistar rats.

    PubMed

    Tomita, Kazuhide; Takayama, Kiyoshige

    2008-08-08

    The purpose of this study was to examine whether treadmill running exercise after phrenicotomy resulted in change in neuronal expression of c-Fos protein in the medulla oblongata in Wistar rats. All rats were subjected to left-sided unilateral phrenicotomy. In test experiments, rats were trained with treadmill running for 4 weeks, while in control experiments rats were not provided with the opportunity to exercise. c-Fos protein, a transient transcription factor, was immunohistochemically stained by the ABC method, and surveyed in the medulla oblongata. Numbers of c-Fos-immunoreactive (c-Fos-ir) neurons were counted microscopically, and their distribution in the medulla oblongata was mapped. In the dorsal respiratory group (DRG), numbers of c-Fos-ir neurons were found to be significantly increased in the test rats compared with control rats, while in the ventral respiratory group (VRG) no significant differences were found in numbers of c-Fos-ir neurons between test and control rats. These findings suggest that DRG neurons may play more important roles than VRG neurons in recovery of respiration in treadmill exercise after unilateral phrenicotomy in Wistar rats.

  19. Modulatory effect of environmental context and drug history on heroin-induced psychomotor activity and fos protein expression in the rat brain.

    PubMed

    Paolone, Giovanna; Conversi, David; Caprioli, Daniele; Bianco, Paola Del; Nencini, Paolo; Cabib, Simona; Badiani, Aldo

    2007-12-01

    The goal of the present study was to investigate the role of environmental context and drug history in modulating the effects of heroin on locomotor activity and Fos protein expression in the neocortex and striatal complex of the rat. It was found that (1) repeated i.p. administrations of a relatively low dose of heroin (1 mg/kg, i.p.) induced psychomotor sensitization only when the treatment was administered in a relatively 'novel' environment (ie, a unique test environment distinct from the home cage) but not when the same treatment was administered in the home cage; (2) environmental novelty facilitated heroin-induced Fos expression in the caudate, particularly in its most caudal regions; (3) environmental context also modulated heroin-induced Fos expression in the nucleus accumbens and in the neocortex; (4) repeated exposures to heroin dramatically altered its effects on Fos expression in the caudate and in the neocortex; and (5) Fos protein levels in the postero-dorsal caudate, in the shell of the nucleus accumbens, and in the barrel field cortex predicted most of the variance in heroin-induced activity scores, as shown by multiple regression analysis. The present report demonstrates that environment and drug history powerfully interact in shaping the neurobehavioral response to heroin, as previously shown for amphetamine and cocaine. Thus, a full understanding of the mechanisms responsible for the neurobehavioral adaptations produced by addictive drugs will also require taking into due consideration the environment in which drugs are experienced.

  20. Differential involvement of 3', 5'-cyclic adenosine monophosphate-dependent protein kinase in regulation of Fos and tyrosine hydroxylase expression in the heart after naloxone induced morphine withdrawal.

    PubMed

    Almela, Pilar; Cerezo, Manuela; González-Cuello, A; Milanés, M Victoria; Laorden, M Luisa

    2007-01-01

    We previously demonstrated that morphine withdrawal induced hyperactivity of the heart by the activation of noradrenergic pathways innervating the left and right ventricle, as evaluated by noradrenaline (NA) turnover and Fos expression. We investigated whether cAMP-dependent protein kinase (PKA) plays a role in this process by estimating changes in PKA immunoreactivity and the influence of inhibitor of PKA on Fos protein expression, tyrosine hydroxylase (TH) immunoreactivity levels and NA turnover in the left and right ventricle. Dependence on morphine was induced by a 7-day s.c. implantation of morphine pellets. Morphine withdrawal was precipitated on day 8 by an injection of naloxone (5 mg/kg). When opioid withdrawal was precipitated, an increase in PKA immunoreactivity and phospho-CREB (cyclic AMP response element protein) levels were observed in the heart. Moreover, morphine withdrawal induces Fos expression, an enhancement of NA turnover and an increase in the total TH levels. When the selective PKA inhibitor HA-1004 was infused, concomitantly with morphine pellets, it diminished the increase in NA turnover and the total TH levels observed in morphine-withdrawn rats. However, this inhibitor neither modifies the morphine withdrawal induced Fos expression nor the increase of nonphosphorylated TH levels. The present findings indicate that an up-regulated PKA-dependent transduction pathway might contribute to the activation of the cardiac catecholaminergic neurons in response to morphine withdrawal and suggest that Fos is not a target of PKA at heart levels.

  1. Effects of electroacupuncture on ethanol-induced impairments of spatial learning and memory and Fos expression in the hippocampus in rats.

    PubMed

    Lu, Bin; Ma, Zhao; Cheng, Fei; Zhao, Yan; Zhang, Xin; Mao, Huijuan; Shen, Xueyong; Liu, Sheng

    2014-07-25

    It is well established that alcohol impairs spatial learning and memory. Here, we investigated the effects of electroacupuncture (EA) at ST36 or nonacupoint on ethanol-induced learning and memory impairment and the expression of Fos in the hippocampus. Ethanol (5g/kg) was administered intragastrically once a day for 5 consecutive days; 2Hz EA was administered immediately after ethanol exposure. After a 2-day ethanol abstinence, for 6 consecutive days, the rats were submitted to Morris water maze training. Probe trials were performed on 1 day after the final training session. We also applied immunohistochemistry to detect Fos-positive nuclei in the hippocampus. We found that 5-day ethanol exposure markedly decreased spatial learning and memory abilities in the Morris water maze task as indicated by escape latency and time in the target quadrant. EA treatment shortened the time of reaching platform and increased times traveled in the target quadrant (P<0.05). Animals administered with ethanol emitted significantly fewer Fos expression in the hippocampal CA1 area. EA increased Fos expression in the hippocampal CA1 area. Significant correlations were obtained between Fos protein expression in CA1 and time in the target quadrant. Altogether, these results suggest that EA protects against ethanol-induced impairments of spatial learning and memory, which may be involved in the hippocampal CA1 area. EA treatment may provide a novel nonpharmacological strategy for ethanol-induced learning and memory impairment.

  2. Morphine withdrawal-induced c-fos expression in the hypothalamic paraventricular nucleus is dependent on the activation of catecholaminergic neurones.

    PubMed

    Laorden, M Luisa; Núñez, Cristina; Almela, Pilar; Milanés, M Victoria

    2002-10-01

    We previously demonstrated that morphine withdrawal induced hyperactivity of noradrenergic pathways innervating the hypothalamic paraventricular nucleus (PVN) in rats, in parallel with an increase in the neurosecretory activity of the hypothalamus-pituitary-adrenocortical (HPA) axis, as evaluated by corticosterone release. These neuroendocrine effects were dependent on stimulation of alpha-adrenoceptors. In the present study, Fos immunostaining was used as a reflection of neuronal activity and combined with immunostaining for tyrosine hydroxylase (TH) for immunohistochemical identification of active neurones during morphine withdrawal. Dependence on morphine was induced by 7-day chronic subcutaneous implantation of six morphine pellets (75 mg). Morphine withdrawal was precipitated by administration of naloxone (5 mg/kg subcutaneously) on day 8. Fos immunoreactivity in the PVN and also in the nucleus tractus solitarius (NTS)-A2 and ventrolateral medulla (VLM)-A1 cell groups, which project to the PVN, increased during morphine withdrawal. Following withdrawal, Fos immunoreactivity was present in most of the TH-positive neurones of the A2 and A1 neurones. In a second study, the effects of administration of adrenoceptor antagonists on withdrawal-induced Fos expression in the PVN were studied. Pre-treatment with alpha1- or alpha2-adrenoceptor antagonists, prazosin (1 mg/kg intraperitoneally) and yohimbine (1 mg/kg intraperitoneally), respectively, 20 min before naloxone administration to morphine-dependent rats markedly reduced Fos expression in the PVN. Similarly, pre-treatment with the beta antagonist, propranolol (3 mg/kg intraperitoneally), significantly prevented withdrawal-induced Fos expression. Collectively, these results suggest the hypothesis that noradrenergic neurones in the brainstem innervating the PVN are active during morphine withdrawal, and that activation of transcriptional responses mediated by Fos in the HPA axis following withdrawal are dependent

  3. Elevated expression of c-fos in central nervous system correlates with visceral hypersensitivity in irritable bowel syndrome (IBS): a new target for IBS treatment.

    PubMed

    Zhang, Ru; Zou, Ning; Li, Ji; Lv, Hong; Wei, Jing; Fang, Xiu-Cai; Qian, Jia-Ming

    2011-08-01

    Although visceral hypersensitivity is a major pathophysiological feature of irritable bowel syndrome (IBS), its molecular mechanisms are still poorly understood. c-fos is a well-established marker of cell activation. Accumulating evidence demonstrates that norepinephrine (NE) system is dysregulated in IBS; however, very little is known on its mechanism. It is our hypothesis that elevated expression of c-fos in central nervous system (CNS) correlates with visceral hypersensitivity in rat model of IBS. Furthermore, we explored the changes of NE system in IBS patients. The rat model of IBS was induced by heterotypic chronic and acute stress. Tissues obtained from rat model were analyzed for c-fos levels in CNS (frontal lobe, hippocampus, cornu dorsale) and colon by immunohistochemistry. Real-time reverse transcription polymerase chain reaction was used to detect tyrosine hydroxylase (TH) in the colonic tissues obtained from IBS patients. The rat model of IBS was associated with increased expression of c-fos in different parts of CNS (P = 0.001, P = 0.002, and P = 0.002, respectively), but normal in colon (P = 0.207). The clinical parameters (colonic motility and sensation) of rat model were significantly correlated with elevated c-fos in CNS (P < 0.05). Enterochromaffin cells and serotonin in colon were related to the elevated c-fos in CNS (P < 0.05). The TH messenger ribonucleic acid (mRNA level of IBS-D patients was almost four times as much as that of controls. Elevated expression of c-fos in CNS might be one of key mechanisms in etiology of IBS. Therefore, regulation of CNS activation could be a major targeting effect when treating IBS patients.

  4. Multiple Color Stimulus Induced Steady State Visual Evoked Potentials

    DTIC Science & Technology

    2007-11-02

    MULTIPLE COLOR STIMULUS INDUCED STEADY STATE VISUAL EVOKED POTENTIALS M. Cheng, X. Gao, S. Gao, D. Xu Institute of Biomedical Engineering...characteristics of high SNR and effectiveness in short-term identification of evoked responses. In most of the SSVEP experiments, single high...frequency stimuli are used. To characterize the complex rhythms in SSVEP, a new multiple color stimulus pattern is proposed in this paper. FFT and

  5. Food for Song: Expression of C-Fos and ZENK in the Zebra Finch Song Nuclei during Food Aversion Learning

    PubMed Central

    Tokarev, Kirill; Tiunova, Anna

    2011-01-01

    Background Specialized neural pathways, the song system, are required for acquiring, producing, and perceiving learned avian vocalizations. Birds that do not learn to produce their vocalizations lack telencephalic song system components. It is not known whether the song system forebrain regions are exclusively evolved for song or whether they also process information not related to song that might reflect their ‘evolutionary history’. Methodology/Principal Findings To address this question we monitored the induction of two immediate-early genes (IEGs) c-Fos and ZENK in various regions of the song system in zebra finches (Taeniopygia guttata) in response to an aversive food learning paradigm; this involves the association of a food item with a noxious stimulus that affects the oropharyngeal-esophageal cavity and tongue, causing subsequent avoidance of that food item. The motor response results in beak and head movements but not vocalizations. IEGs have been extensively used to map neuro-molecular correlates of song motor production and auditory processing. As previously reported, neurons in two pallial vocal motor regions, HVC and RA, expressed IEGs after singing. Surprisingly, c-Fos was induced equivalently also after food aversion learning in the absence of singing. The density of c-Fos positive neurons was significantly higher than that of birds in control conditions. This was not the case in two other pallial song nuclei important for vocal plasticity, LMAN and Area X, although singing did induce IEGs in these structures, as reported previously. Conclusions/Significance Our results are consistent with the possibility that some of the song nuclei may participate in non-vocal learning and the populations of neurons involved in the two tasks show partial overlap. These findings underscore the previously advanced notion that the specialized forebrain pre-motor nuclei controlling song evolved from circuits involved in behaviors related to feeding. PMID:21695176

  6. c-Fos protein expression is increased in cholinergic neurons of the rodent basal forebrain during spontaneous and induced wakefulness

    PubMed Central

    McKenna, J. T.; Cordeira, J. W.; Jeffrey, B. A.; Ward, C. P.; Winston, S.; McCarley, R. W.; Strecker, R. E.

    2009-01-01

    It has been proposed that cholinergic neurons of the basal forebrain (BF) may play a role in vigilance state control. Since not all vigilance states have been studied, we evaluated cholinergic neuronal activation levels across spontaneously occurring states of vigilance, as well as during sleep deprivation and recovery sleep following sleep deprivation. Sleep deprivation was performed for two hours at the beginning of the light (inactive) period, by means of gentle sensory stimulation. In the rodent BF, we used immunohistochemical detection of the c-Fos protein as a marker for activation combined with labeling for choline acetyl-transferase (ChAT) as a marker for cholinergic neurons. We found c-Fos activation in BF cholinergic neurons was highest in the group undergoing sleep deprivation (12.9% of cholinergic neurons), while the spontaneous wakefulness group showed a significant increase (9.2%), compared to labeling in the spontaneous sleep group (1.8%) and sleep deprivation recovery group (0.8%). A subpopulation of cholinergic neurons expressed c-Fos during spontaneous wakefulness, when possible confounds of the sleep deprivation procedure were minimized (e.g., stress and sensory stimulation). Double-labeling in the sleep deprivation treatment group was significantly elevated in select subnuclei of the BF (medial septum/vertical limb of the diagonal band, horizontal limb of the diagonal band, and the magnocellular preoptic nucleus), when compared to spontaneous wakefulness. These findings support and provide additional confirming data of previous reports that cholinergic neurons of BF play a role in vigilance state regulation by promoting wakefulness. PMID:19716862

  7. Novel cues reinstate cocaine-seeking behavior and induce Fos protein expression as effectively as conditioned cues.

    PubMed

    Bastle, Ryan M; Kufahl, Peter R; Turk, Mari N; Weber, Suzanne M; Pentkowski, Nathan S; Thiel, Kenneth J; Neisewander, Janet L

    2012-08-01

    Cue reinstatement of extinguished cocaine-seeking behavior is a widely used model of cue-elicited craving in abstinent human addicts. This study examined Fos protein expression in response to cocaine cues or to novel cues as a control for activation produced by test novelty. Rats were trained to self-administer cocaine paired with either a light or a tone cue, or received yoked saline and cue presentations, and then underwent daily extinction training. They were then tested for reinstatement of extinguished cocaine-seeking behavior elicited by response-contingent presentations of either the cocaine-paired cue or a novel cue (that is, tone for those trained with a light or vice versa). Surprisingly, conditioned and novel cues both reinstated responding and increased Fos similarly in most brain regions. Exceptions included the anterior cingulate, which was sensitive to test cue modality in saline controls and the dorsomedial caudate-putamen, where Fos was correlated with responding in the novel, but not conditioned, cue groups. In subsequent experiments, we observed a similar pattern of reinstatement in rats trained and tested for sucrose-seeking behavior, whereas rats trained and tested with the cues only reinstated to a novel, and not a familiar, light or tone. The results suggest that novel cues reinstate responding to a similar extent as conditioned cues regardless of whether animals have a reinforcement history with cocaine or sucrose, and that both types of cues activate similar brain circuits. Several explanations as to why converging processes may drive drug and novel cue reinforcement and seeking behavior are discussed.

  8. The effects of apomorphine and D-amphetamine on striatal c-Fos expression in Sprague-Dawley and Long Evans rats and their F1 progeny.

    PubMed

    Saint Marie, Richard L; Neary, Alaina C; Shoemaker, Jody M; Swerdlow, Neal R

    2006-11-13

    We previously reported that Sprague-Dawley (SD) rats are significantly more sensitive than Long Evans (LE) rats to disruption of prepulse inhibition (PPI) of the startle reflex by the dopamine agonists, apomorphine (APO) and D-amphetamine (AMPH). This susceptibility is inherited through F1 (SD x LE) and N2 backcross (F1 x SD) generations via an orderly pattern (SD>N2>F1>LE). Here we examined systemic APO (0.5 mg/kg) and AMPH (4.5 mg/kg) modulation of neural activity in four regions of the striatum suspected to be involved in the dopaminergic regulation of PPI - dorsolateral (dlCPu) and medial (mCPu) caudate/putamen and core (NACc) and medial shell (NACms) regions of nucleus accumbens - under conditions that mimicked those used to assess PPI. Immunohistochemical quantification of c-Fos protein expression was used as the surrogate measure of neural activity in SD and LE rats and their F1 crosses. Vehicle-treatment showed significant regional differences in Fos expression, particularly between the dlCPu and the other three areas, but no strain-related differences were observed. Three of four brain areas examined (dlCPu, mCPu and NACc) exhibited drug-induced changes in Fos expression--APO decreased and AMPH increased Fos expression in each region. The aggregate effect across these three regions revealed Fos expression to be significantly greater in LE compared to SD rats for both drugs, with F1 rats intermediate. This pattern of inheritance (LE>F1>SD) reveals an inverse relationship between striatal Fos expression and PPI sensitivity for these drugs; and a positive relationship with reported heritable differences in D2-linked G-protein binding in the CPu and NACc, and with locomotor activation/suppression by AMPH and APO.

  9. Delta 9-tetrahydrocannabinol suppresses vomiting behavior and Fos expression in both acute and delayed phases of cisplatin-induced emesis in the least shrew.

    PubMed

    Ray, Andrew P; Griggs, Lisa; Darmani, Nissar A

    2009-01-03

    Cisplatin chemotherapy frequently causes severe vomiting in two temporally separated clusters of bouts dubbed the acute and delayed phases. Cannabinoids can inhibit the acute phase, albeit through a poorly understood mechanism. We examined the substrates of cannabinoid-mediated inhibition of both the emetic phases via immunolabeling for serotonin, Substance P, cannabinoid receptors 1 and 2 (CB(1), CB(2)), and the neuronal activation marker Fos in the least shrew (Cryptotis parva). Shrews were injected with cisplatin (10mg/kg i.p.), and one of vehicle, Delta(9)-THC, or both Delta(9)-THC and the CB(1) receptor antagonist SR141716A (2mg/kg i.p.), and monitored for vomiting. Delta(9)-THC-pretreatment caused concurrent decreases in the number of shrews expressing vomiting and Fos-immunoreactivity (Fos-IR), effects which were blocked by SR141716A-pretreatment. Acute phase vomiting induced Fos-IR in the solitary tract nucleus (NTS), dorsal motor nucleus of the vagus (DMNX), and area postrema (AP), whereas in the delayed phase Fos-IR was not induced in the AP at all, and was induced at lower levels in the other nuclei when compared to the acute phase. CB(1) receptor-IR in the NTS was dense, punctate labeling indicative of presynaptic elements, which surrounded Fos-expressing NTS neurons. CB(2) receptor-IR was not found in neuronal elements, but in vascular-appearing structures. All areas correlated with serotonin- and Substance P-IR. These results support published acute phase data in other species, and are the first describing Fos-IR following delayed phase emesis. The data suggest overlapping but separate mechanisms are invoked for each phase, which are sensitive to antiemetic effects of Delta(9)-THC mediated by CB(1) receptors.

  10. Schisandra chinensis and Rhodiola rosea exert an anti-stress effect on the HPA axis and reduce hypothalamic c-Fos expression in rats subjected to repeated stress

    PubMed Central

    XIA, NAN; LI, JIE; WANG, HONGWEI; WANG, JIAN; WANG, YANGTIAN

    2016-01-01

    The aim of the present study was to investigate the effects of Schisandra chinensis (S. chinensis) and Rhodiola rosea (R. rosea) on rats subjected to 5 h of stress, induced by water-floating followed by treadmill exercise. Hypothalamus-pituitary-adrenal (HPA) activity and c-Fos and Fos-related antigen 2 (Fra-2) mRNA expression levels in the hypothalamus of the rats were evaluated. Rats were distributed into four groups: S. chinensis (n=12), R. rosea (n=10), stress control (n=10) and quiet control (n=8). Following a training period of 6 consecutive days, the S. chinensis, R. rosea and stress control groups underwent a 3-h water-floating session in the presence of feline predators immediately followed by 2 h treadmill running to induce psychological and physical stress. Following compound stress induction, the serum levels of corticosterone (CORT), adrenocorticotropic hormone and interleukin-1β and the mRNA expression levels of hypothalamic corticotropin-releasing hormone (CRH), neuropeptide-Y, c-Fos and Fra-2 were evaluated using enzyme-linked immunosorbent assay, radioimmunoassay and quantitative polymerase chain reaction, respectively. The results indicated that S. chinensis and R. rosea markedly decreased the stress-induced elevation of CRH and peripheral CORT levels. The mRNA expression levels of c-Fos and Fra-2 in the hypothalamus were significantly increased after 5 h compound stress, and reduced levels of c-Fos expression were detected in rats treated with R. rosea. Thus, S. chinensis and R. rosea exert an anti-stress effect in rats subjected to stress by balancing the HPA axis, and possibly by reducing the expression of c-Fos in the hypothalamus. PMID:26889268

  11. [Influence of dexamethasone on the expression of immediate early genes c-fos and c-jun in different regions of the neonatal brain].

    PubMed

    Sukhareva, E V; Dygalo, N N; Kalinina, T S

    2016-01-01

    The ratio of the expression levels of the immediate early genes c-jun and c-fos that encode components of the AP-1 transcription complex determines the direction of changes in the expression of genes controlled by the complex, including changes induced by glucocorticoids. The aim of the present work was to assess the levels of mRNA encoded by genes c-jun and c-fos and the ratio of expression levels of these genes in various regions of the neonatal rat brain after the administration of dexamethasone, a selective ligand of the glucocorticoid receptor. The level of mRNA encoded by the immediate early gene c-fos in the hippocampus and prefrontal cortex of 3-day-old rat pups was elevated at 30, 60, and 120 min after dexamethasone administration. The basal level of c-fos gene expression in the brainstem was higher than in the cortex and hippocampus, and administration of the hormone was followed by a reduction in the amount of transcript detectable in the brainstem after 2 h. As a result, the ratio of c-jun to c-fos transcript levels in the brainstem of neonatal rats was doubled after dexamethasone administration. The dexamethasone-induced shift of the ratio of c-jun to c-fos transcript levels in the brainstem of neonatal rats towards a predominance of c-jun reported for the first time in the present work may induce the expression of genes that contain AP-1 response elements in the promoters, since the glucocorticoid receptor can be involved in protein-protein interactions with the Jun/Jun homodimer of the AP-1 complex.

  12. Schisandra chinensis and Rhodiola rosea exert an anti-stress effect on the HPA axis and reduce hypothalamic c-Fos expression in rats subjected to repeated stress.

    PubMed

    Xia, Nan; Li, Jie; Wang, Hongwei; Wang, Jian; Wang, Yangtian

    2016-01-01

    The aim of the present study was to investigate the effects of Schisandra chinensis (S. chinensis) and Rhodiola rosea (R. rosea) on rats subjected to 5 h of stress, induced by water-floating followed by treadmill exercise. Hypothalamus-pituitary-adrenal (HPA) activity and c-Fos and Fos-related antigen 2 (Fra-2) mRNA expression levels in the hypothalamus of the rats were evaluated. Rats were distributed into four groups: S. chinensis (n=12), R. rosea (n=10), stress control (n=10) and quiet control (n=8). Following a training period of 6 consecutive days, the S. chinensis, R. rosea and stress control groups underwent a 3-h water-floating session in the presence of feline predators immediately followed by 2 h treadmill running to induce psychological and physical stress. Following compound stress induction, the serum levels of corticosterone (CORT), adrenocorticotropic hormone and interleukin-1β and the mRNA expression levels of hypothalamic corticotropin-releasing hormone (CRH), neuropeptide-Y, c-Fos and Fra-2 were evaluated using enzyme-linked immunosorbent assay, radioimmunoassay and quantitative polymerase chain reaction, respectively. The results indicated that S. chinensis and R. rosea markedly decreased the stress-induced elevation of CRH and peripheral CORT levels. The mRNA expression levels of c-Fos and Fra-2 in the hypothalamus were significantly increased after 5 h compound stress, and reduced levels of c-Fos expression were detected in rats treated with R. rosea. Thus, S. chinensis and R. rosea exert an anti-stress effect in rats subjected to stress by balancing the HPA axis, and possibly by reducing the expression of c-Fos in the hypothalamus.

  13. Electroacupuncture Suppresses Discrete Cue-Evoked Heroin-Seeking and Fos Protein Expression in the Nucleus Accumbens Core in Rats

    PubMed Central

    Liu, Sheng; Zhu, Fenglei; Lai, Miaojun; Sun, Limin; Liu, Yijun; Zhou, Wenhua

    2012-01-01

    Relapse to drug seeking was studied using a rodent model of reinstatement induced by exposure to drug-related cues. Here, we used intravenous drug self-administration procedures in rats to further investigate the beneficial effects of electroacupuncture (EA) on heroin-seeking behavior in a reinstatement model of relapse. We trained Sprague-Dawley rats to nose-poke for i.v. heroin either daily for 4 h or 25 infusions for 14 consecutive days. Then the rats were abstinent from heroin for two weeks. 2 Hz EA stimulation was conducted once daily for 14 days during heroin abstinence. We tested these animals for contextual and discrete cue-induced reinstatement of active responses. We also applied immunohistochemistry to detect Fos-positive nuclei in the nucleus accumbens (NACc) core and shell after reinstatement test. We found that active responses elicited by both contextual cues and discrete cues were high in the rats trained with heroin than in saline controls. EA treatment significantly reduced active responses elicited by discrete cues. EA stimulation attenuated Fos expression in the core but not the shell of the NACc. Altogether, these results highlight the therapeutic benefit of EA in preventing relapse to drug addiction. PMID:22454660

  14. Anxiety behaviour of the male rat on the elevated plus maze: associated regional increase in c-fos mRNA expression and modulation by early maternal separation.

    PubMed

    Troakes, C; Ingram, C D

    2009-07-01

    Stressful stimuli cause region-specific increases in c-fos expression within the rat brain. Early maternal separation (EMS) is a model of early life adversity that results in long lasting changes to stress and anxiety responses. This study examined the regional distribution of c-fos mRNA after exposure to the elevated plus-maze (EPM) and how EMS altered this pattern. On each of post-natal days 5-21 pups were separated from the dam for 6 h -- control rats remained undisturbed. At 70 days old, male offspring were either exposed to the EPM or left undisturbed in the home cage. After exposure to the EPM, c-fos mRNA expression was significantly increased in specific brain areas, including cingulate cortex, medial amygdala and hippocampus. EMS rats displayed greater anxiety behaviour on the EPM vs. controls. Although EMS caused no overall effect on basal c-fos mRNA, a significant interaction between treatment group and exposure to the EPM occurred in the dentate gyrus and piriform cortex, with lower EPM-induced mRNA levels in EMS rats. The region-specific increase in c-fos mRNA reflects activation of neural circuits associated with EPM-induced anxiety. The effect of EMS on this activation in the two regions suggests these areas may contribute to the differential response to the anxiogenic stress of the EPM.

  15. Differential expression of Fos and Zif268 in the nigrostriatal system after methamphetamine administration in a rat model of Parkinson's disease.

    PubMed

    Ishida, Yasushi; Kawai, Keiichi; Magata, Yasuhiro; Ebihara, Kosuke; Takeda, Ryuichiro; Abe, Hiroshi; Yoshimoto, Mitsuyoshi; Hashiguchi, Hiroyuki; Odagiri, Kei; Matsuo, Hisae; Nishimori, Toshikazu

    2008-12-01

    The goal of this study was to examine the topological specificity of methamphetamine-induced activation of the immediate-early gene proteins, Fos and Zif268, in the nigrostriatal system in a unilateral 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease with or without intrastriatal grafts of fetal ventral mesencephalon. Methamphetamine (3 mg/kg, i.p.) induced Fos-like immunoreactivity (FLI) dominantly in the striatum and the globus pallidus (GP) on the intact side as well as in the substantia nigra pars reticulata (SNr) on the lesioned side in the 6-OHDA rats. Lower levels of methamphetamine-induced FLI in the striatum and GP on the lesioned side were restored by intrastriatal grafts which could completely suppress the methamphetamine-induced rotation. In the striatum, a similar tendency could be observed between Fos and Zif268 immunoreactivity following methamphetamine. However, sparse immunoreactivity of Zif268 could be detected in the GP and SNr on both sides in the 6-OHDA rats. Intrastriatal grafts had little influence on Zif268 expression in these two regions. The differential expression of Fos and Zif268 was observed among the three regions of the nigrostriatal system following methamphetamine in the 6-OHDA rats. This may suggest that Fos and Zif268 therefore possess gene-specific and region-specific functions in the basal ganglia nuclei.

  16. ENaC-expressing neurons in the sensory circumventricular organs become c-Fos activated following systemic sodium changes

    PubMed Central

    Miller, Rebecca L.; Wang, Michelle H.; Gray, Paul A.; Salkoff, Lawrence B.

    2013-01-01

    The sensory circumventricular organs (CVOs) are specialized collections of neurons and glia that lie in the midline of the third and fourth ventricles of the brain, lack a blood-brain barrier, and function as chemosensors, sampling both the cerebrospinal fluid and plasma. These structures, which include the organum vasculosum of the lamina terminalis (OVLT), subfornical organ (SFO), and area postrema (AP), are sensitive to changes in sodium concentration but the cellular mechanisms involved remain unknown. Epithelial sodium channel (ENaC)-expressing neurons of the CVOs may be involved in this process. Here we demonstrate with immunohistochemical and in situ hybridization methods that ENaC-expressing neurons are densely concentrated in the sensory CVOs. These neurons become c-Fos activated, a marker for neuronal activity, after various manipulations of peripheral levels of sodium including systemic injections with hypertonic saline, dietary sodium deprivation, and sodium repletion after prolonged sodium deprivation. The increases seen c-Fos activity in the CVOs were correlated with parallel increases in plasma sodium levels. Since ENaCs play a central role in sodium reabsorption in kidney and other epithelia, we present a hypothesis here suggesting that these channels may also serve a related function in the CVOs. ENaCs could be a significant factor in modulating CVO neuronal activity by controlling the magnitude of sodium permeability in neurons. Hence, some of the same circulating hormones controlling ENaC expression in kidney, such as angiotensin II and atrial natriuretic peptide, may coordinate ENaC expression in sensory CVO neurons and could potentially orchestrate sodium appetite, osmoregulation, and vasomotor sympathetic drive. PMID:24049115

  17. Cocaine-induced c-Fos expression in rats selectively bred for high or low saccharin intake and in rats selected for high or low impulsivity.

    PubMed

    Regier, Paul S; Carroll, Marilyn E; Meisel, Robert L

    2012-08-01

    Sweet preference and impulsivity are predictors of cocaine self-administration; however, no research has been conducted to investigate neuronal activation in key brain reward areas after first time exposure to cocaine in rats that differ in their propensity for cocaine-seeking and -taking behavior. In this study we used rats that had been selectively bred for high vs. low saccharin intake and rats selected for high vs. low impulsivity for food. The goal of this study was to investigate whether there are differences of c-Fos reactivity between high and low phenotypes and determine whether these differences are similar between the two animal models. A group of rats was bred for high or low saccharin intake. Another group of rats was selected as high or low impulsive based on performance in a delay-discounting task. Subsequently, rats were given an acute injection of cocaine or saline and then c-Fos expression was observed and analyzed in several brain regions. The low reward-seeking phenotypes showed higher cocaine-induced c-Fos expression in several of these regions. Low saccharin preferring rats showed higher cocaine-induced c-Fos expression in the nucleus accumbens shell, and low impulsive rats showed higher cocaine-induced c-Fos expression in the orbitofrontal cortex and cingulate gyrus 1 area. In addition, both low impulsive and low saccharin rats had higher cocaine-induced c-Fos in the dorsal medial and dorsal lateral caudate putamen. The results indicate that individual differences in neuronal reactivity exist prior to chronic exposure to drugs of abuse. Furthermore, similar differences between the two animal models may be indicative of a common mechanism underlying vulnerability to drugs of abuse. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Cocaine-induced c-Fos expression in rats selectively bred for high or low saccharin intake and in rats selected for high or low impulsivity

    PubMed Central

    Carroll, Marilyn E.; Meisel, Robert L.

    2013-01-01

    Sweet preference and impulsivity are predictors of cocaine self-administration; however no research has been conducted to investigate neuronal activation in key brain reward areas after first time exposure to cocaine in rats that differ in their propensity for cocaine-seeking and – taking behavior. In this study we used rats that that been selectively bred for high vs. low saccharin intake and rats selected for high vs. low impulsivity for food. The goal of this study was to investigate whether there are differences of c-Fos reactivity between high and low phenotypes and determine whether these differences are similar between the two animal models. A group of rats was bred for either high or low saccharin intake. Another group of rats was selected as high or low impulsive based on performance in a delay-discounting task. Subsequently, rats were given an acute injection of cocaine or saline and then c-Fos expression was observed and analyzed in several brain regions. The low reward-seeking phenotypes showed higher cocaine-induced c-Fos expression in several of these regions. Low saccharin preferring rats showed higher cocaine-induced c-Fos expression in the nucleus accumbens shell, and low impulsive rats showed higher cocaine-induced c-Fos expression in the orbitofrontal cortex and cingulate gyrus 1 area. In addition, both low impulsive and low saccharin rats had higher cocaine-induced c-Fos in the dorsal medial and dorsal lateral caudate putamen. The results indicate that individual differences in neuronal reactivity exist prior to chronic exposure to drugs of abuse. Furthermore, similar differences between the two animal models may be indicative of a common mechanism underlying vulnerability to drugs of abuse. PMID:22613730

  19. Environmental novelty is associated with a selective increase in Fos expression in the output elements of the hippocampal formation and the perirhinal cortex.

    PubMed

    VanElzakker, Michael; Fevurly, Rebecca D; Breindel, Tressa; Spencer, Robert L

    2008-12-01

    If the hippocampus plays a role in the detection of novel environmental features, then novelty should be associated with altered hippocampal neural activity and perhaps also measures of neuroplasticity. We examined Fos protein expression within subregions of rat hippocampal formation as an indicator of recent increases in neuronal excitation and cellular processes that support neuroplasticity. Environmental novelty, but not environmental complexity, led to a selective increase of Fos induction in the final "output" subregion of the dorsal hippocampal trisynaptic circuit (CA1) and a primary projection site (layer five of the lateral entorhinal cortex, ERC), as well as in the perirhinal cortex. There was no selective effect of novelty on Fos expression within "input" elements of the trisynaptic circuit (ERC layer two, the dentate gyrus or CA3) or other comparison brain regions that may be responsive to overall motor-sensory activity or anxiety levels (primary somatosensory and motor cortex or hypothalamic paraventricular nucleus). Test session ambulatory behavior increased with both novelty and environmental complexity and was not significantly correlated with Fos expression patterns in any of the brain regions examined. In contrast, the extent of manipulated environmental novelty was strongly correlated with Fos expression in CA1. These results support the prospect that a novelty-associated signal is generated within hippocampal neurocircuitry, is relayed to cortical projection sites, and specifically up-regulates neuroplasticity-supporting processes with dorsal hippocampal CA1 and ERC layer five. Whether novelty-dependent Fos induction in perirhinal cortex depends on this hippocampal output or reflects an independent process remains to be determined.

  20. Otolith organ or semicircular canal stimulation induces c-fos expression in unipolar brush cells and granule cells of cat and squirrel monkey.

    PubMed

    Sekerková, Gabriella; Ilijic, Ema; Mugnaini, Enrico; Baker, James F

    2005-07-01

    Immediate early gene expression in the cerebellar vermis of cats and squirrel monkeys was stimulated by prolonged whole body rotations. Continuous, earth-horizontal axis rotations that excited only otoliths or high velocity vertical axis rotations that excited only semicircular canals resulted in c-fos immunoreactive nuclei concentrated in the granular layer of lobules X and ventral IX (the nodulus and ventral uvula), which represent the medial parts of the vestibulo-cerebellum. Large clusters of labeled nuclei consisting mainly of granule cells and calretinin-positive unipolar brush cells were present in the granular layer, whereas Purkinje cell nuclei were unlabeled, and labeled basket and stellate cell nuclei were scattered in the molecular layer. In other vermal lobules there was a significant but less dense label than in the nodulus and ventral uvula. Generally, the extent of c-fos labeling of molecular layer interneurons was in relation to nuclear labeling of granular layer neurons: labeling of both basket and stellate cells accompanied nuclear labeling of neurons throughout the depth of the granular layer, whereas only stellate cells were labeled when nuclear labeling was restricted to the superficial granular layer. Yaw horizontal or roll vertical rotations each stimulated c-fos expression in the cat medial vestibulo-cerebellum to approximately the same extent. Low-velocity rotations resulted in much less c-fos expression. Similar, albeit less intense, patterns of c-fos activation were observed in monkeys. Concentrated c-fos expression in the medial vestibulo-cerebellum after exposure to a strong head velocity signal that could originate from either otolith or canal excitation suggests that granule and unipolar brush cells participate in a neuronal network for estimating head velocity, irrespective of the signal source.

  1. Effect of blonanserin on methamphetamine-induced disruption of latent inhibition and c-Fos expression in rats.

    PubMed

    Kuramashi, Aki; Abe, Hiroshi; Koganemaru, Go; Matsuo, Hisae; Ikeda, Tetsuya; Ebihara, Kosuke; Funahashi, Hideki; Takeda, Ryuichiro; Nishimori, Toshikazu; Ishida, Yasushi

    2013-08-09

    To clarify the psychopharmacological profile of blonanserin, a novel antipsychotic, we examined its effect on the methamphetamine-induced disruption of latent inhibition (LI) and the neural activation related to this effect in rats. To evaluate the LI, we used a conditioned emotional response in which a tone (conditioned stimulus) was paired with a mild foot shock (unconditioned stimulus). This paradigm was presented to rats licking water. Methamphetamine-induced (1.0mg/kg, i.p.) disruption of LI was significantly improved by the administration of a higher dose (3.0mg/kg, i.p.) of blonanserin and tended to be improved by 1.0-mg/kg blonanserin and 0.2-mg/kg haloperidol but not by a lower dose (0.3mg/kg) of blonanserin. Immunohistochemical examination showed blonanserin (3.0mg/kg, i.p.) increased c-Fos expression in the shell area but not in the core area of the nucleus accumbens while methamphetamine (3.0mg/kg, i.p.) produced the opposite expression pattern. Blonanserin also increased the number of c-Fos expressions in the central amygdala nucleus but not in the basolateral amygdala nucleus or the prefrontal cortex. Blonanserin ameliorates the methamphetamine-induced disruption of LI, as other antipsychotics do, and a neuronal activation and/or modulation of neurotransmission in the nucleus accumbens is related to the disruption of LI by methamphetamine and to its amelioration by blonanserin. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. FOS EXPRESSION FOLLOWING REGIMENS OF PREDATOR STRESS VERSUS FOOTSHOCK THAT DIFFERENTIALLY AFFECT PREPULSE INHIBITION IN RATS

    PubMed Central

    Baisley, Sarah K.; Cloninger, Christina L.; Bakshi, Vaishali P.

    2011-01-01

    Stress is suggested to exacerbate symptoms and contribute to relapse in patients with schizophrenia and several other psychiatric disorders. A prominent feature of many of these illnesses is an impaired ability to filter information through sensorimotor gating processes. Prepulse inhibition (PPI) is a functional measure of sensorimotor gating, and known to be deficient in schizophrenia and sometimes in post-traumatic stress disorder (PTSD), both of which are also sensitive to stress-induced symptom deterioration. We previously found that a psychological stressor (exposure to a ferret without physical contact), but not footshock, disrupted PPI in rats, suggesting that intense psychological stress/trauma may uniquely model stress-induced sensorimotor gating abnormalities. In the present experiment, we sought to recreate the conditions where we found this behavioral difference, and to explore possible underlying neural substrates. Rats were exposed acutely to ferret stress, footshock, or no stress (control). 90 minutes later, tissue was obtained for Fos immunohistochemistry to assess neuronal activation. Several brain regions (prelimbic, infralimbic, and cingulate cortices, the paraventricular hypothalamic nucleus, the paraventricular thalamic nucleus, and the lateral periaqueductal gray) were equally activated following exposure to either stressor. Interestingly, the medial amygdala and dorsomedial periaqueductal gray had nearly twice as much Fos activation in the ferret-exposed rats as in the footshock-exposed rats, suggesting that higher activation within these structures may contribute to the unique behavioral effects induced by predator stress. These results may have implications for understanding the neural substrates that could participate in sensorimotor gating abnormalities seen in several psychiatric disorders after psychogenic stress. PMID:21843541

  3. Transcutaneous electrical nerve stimulation on Yongquan acupoint reduces CFA-induced thermal hyperalgesia of rats via down-regulation of ERK2 phosphorylation and c-Fos expression.

    PubMed

    Yang, Lin; Yang, Lianxue; Gao, Xiulai

    2010-07-01

    Activation of extracellular signal-regulated kinase-1/2 (ERK1/2) and its involvement in regulating gene expression in spinal dorsal horn, cortical and subcortical neurons by peripheral noxious stimulation contribute to pain hypersensitivity. Transcutaneous electrical nerve stimulation (TENS) is a treatment used in physiotherapy practice to promote analgesia in acute and chronic inflammatory conditions. In this study, a total number of 114 rats were used for three experiments. Effects of complete Freund's adjuvant (CFA)-induced inflammatory pain hypersensitivity and TENS analgesia on ERK1/2 phosphorylation and c-Fos protein expression were examined by using behavioral test, Western blot, and immunostaining methods. We found that CFA injection caused an area of localized swelling, erythema, hypersensitivity to thermal stimuli, the decreased response time of hind paw licking (HPL), as well as upregulation of c-Fos protein expression and ERK2 phosphorylation in the ipsilateral spinal dorsal horn and the contralateral primary somatosensory area of cortex and the amygdala of rats. TENS on Yongquan acupoint for 20 min produced obvious analgesic effects as demonstrated with increased HPL to thermal stimuli of CFA-treated rats. In addition, TENS application suppressed the CFA-induced ERK2 activation and c-Fos protein expression. These results suggest that down-regulation of ERK2 phosphorylation and c-Fos expression were involved in TENS inhibition on CFA-induced thermal hyperalgesia of rats.

  4. Induction of c-fos and c-jun protooncogenes expression by formaldehyde-releasing and epoxy resin-based root-canal sealers in human osteoblastic cells.

    PubMed

    Huang, Fu-Mei; Hsieh, Yih-Shou; Tai, Kuo-Wei; Chou, Ming-Yung; Chang, Yu-Chao

    2002-03-05

    An important requirement for a root-canal sealer is biologic compatibility; most evaluations have focused on general toxicological and local tissue irritating properties. There is only scant information about mutagenicity or carcinogenicity testing for root-canal sealer. It has been shown that c-fos and c-jun are induced rapidly by a variety of chemical and physical stimuli. Numerous works have extensively investigated the induction mechanisms of c-fos and c-jun protooncogenes by these agents; however, little is known about the induction of cellular signaling events and specific gene expression after cell exposure to root-canal sealers. Therefore, we used osteoblastic cell line U2-OS to examine the effect of zinc-oxide eugenol-based (N2 and Endomethasome), epoxy resin-based (AH Plus), and calcium hydroxide-based (Sealapex) root-canal sealers on the expression of c-fos and c-jun protooncogenes to understand in more detail the molecular mechanisms of root-canal sealer-induced genotoxicity. The cytotoxicity decreased in an order of N2 > Endomethasome > AH Plus > Sealapex. In addition, N2, Endomethasome, and AH Plus rapidly induced c-jun and c-fos mRNA levels in cells. However, Sealapex did not induce c-jun and c-fos mRNA expression at detectable levels all time points. Taken together, persistent induction of c-jun and c-fos protooncogenes by formaldehyde-releasing and epoxy resin-based root-canal sealers may be distributed systemically via apex to cause some unexpected adverse effects on human beings. These data should be taken into consideration when choosing a root-canal sealer. Copyright 2001 John Wiley & Sons, Inc.

  5. Induction of Fos expression in the rat forebrain after intragastric administration of monosodium L-glutamate, glucose and NaCl.

    PubMed

    Otsubo, H; Kondoh, T; Shibata, M; Torii, K; Ueta, Y

    2011-11-24

    l-glutamate, an umami taste substance, is a key molecule coupled to a food intake signaling pathway. Furthermore, recent studies have unveiled new roles for dietary glutamate on gut-brain axis communication via activation of gut glutamate receptors and subsequent vagus nerve. In the present study, we mapped activation sites of the rat forebrain after intragastric load of 60 mM monosodium l-glutamate (MSG) by measurement of Fos protein, a functional marker of neuronal activation. The same concentration of d-glucose (sweet) and NaCl (salty) was used as controls. MSG administration exclusively produced enhanced Fos expression in four hypothalamic regions (the medial preoptic area, lateral hypothalamic area, dorsomedial nucleus, and arcuate nucleus). On the other hand, glucose administration exclusively enhanced Fos induction in the nucleus accumbens. Both MSG and glucose enhanced Fos induction in three brain regions (the habenular nucleus, paraventricular nucleus, and central nucleus of the amygdala). However, MSG induced Fos inductions were more potent than those of glucose in the habenular nucleus and paraventricular nucleus. Importantly, the present study identified for the first time two brain areas (the paraventricular and arcuate hypothalamic nuclei) that are more potently activated by intragastric MSG loads compared with glucose and NaCl. Overall, our results suggest significant activation of a neural network comprising the habenular nucleus, amygdala, and the hypothalamic subnuclei following intragastric load with glutamate.

  6. Heterodimers of the transcriptional factors NFATc3 and FosB mediate tissue factor expression for 15(S)-hydroxyeicosatetraenoic acid-induced monocyte trafficking.

    PubMed

    Kotla, Sivareddy; Singh, Nikhlesh K; Kirchhofer, Daniel; Rao, Gadiparthi N

    2017-09-08

    Tissue factor (TF) is expressed in vascular and nonvascular tissues and functions in several pathways, including embryonic development, inflammation, and cell migration. Many risk factors for atherosclerosis, including hypertension, diabetes, obesity, and smoking, increase TF expression. To better understand the TF-related mechanisms in atherosclerosis, here we investigated the role of 12/15-lipoxygenase (12/15-LOX) in TF expression. 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), the major product of human 15-LOXs 1 and 2, induced TF expression and activity in a time-dependent manner in the human monocytic cell line THP1. Moreover, TF suppression with neutralizing antibodies blocked 15(S)-HETE-induced monocyte migration. We also found that NADPH- and xanthine oxidase-dependent reactive oxygen species (ROS) production, calcium/calmodulin-dependent protein kinase IV (CaMKIV) activation, and interactions between nuclear factor of activated T cells 3 (NFATc3) and FosB proto-oncogene, AP-1 transcription factor subunit (FosB) are involved in 15(S)-HETE-induced TF expression. Interestingly, NFATc3 first induced the expression of its interaction partner FosB before forming the heterodimeric NFATc3-FosB transcription factor complex, which bound the proximal AP-1 site in the TF gene promoter and activated TF expression. We also observed that macrophages from 12/15-LOX(-/-) mice exhibit diminished migratory response to monocyte chemotactic protein 1 (MCP-1) and lipopolysaccharide compared with WT mouse macrophages. Similarly, compared with WT macrophages, monocytes from 12/15-LOX(-/-) mice displayed diminished trafficking, which was rescued by prior treatment with 12(S)-HETE, in a peritonitis model. These observations indicate that 15(S)-HETE-induced monocyte/macrophage migration and trafficking require ROS-mediated CaMKIV activation leading to formation of NFATc3 and FosB heterodimer, which binds and activates the TF promoter. © 2017 by The American Society for

  7. Baclofen prevented the changes in c-Fos and brain-derived neutrophic factor expressions during mecamylamine-precipitated nicotine withdrawal in mice.

    PubMed

    Varani, Andrés P; Moutinho Machado, Lirane; Balerio, Graciela N

    2014-11-01

    Previous studies from our laboratory showed that baclofen (BAC, GABAB receptor agonist) prevented the behavioral and neurochemical alterations of nicotine (NIC) withdrawal syndrome. To further investigate the mechanisms underlying these effects, we analyzed the c-Fos and brain-derived neutrophic factor (BDNF) expression during NIC withdrawal and its prevention with BAC. Swiss-Webster mice received NIC (2.5 mg/kg, sc) four times daily, for 7 days. On the 8th day, NIC-treated mice received the nicotinic antagonist mecamylamine (MEC; 2 mg/kg, i.p.) 1 h after the last dose of NIC. A second group of NIC-treated mice received BAC (2 mg/kg, i.p.) prior to MEC administration. Thirty minutes after MEC, mice were sacrificed and the immunohistochemistry assays (c-Fos and BDNF) were performed at different anatomical levels. c-Fos expression decreased in the dentate gyrus of the hippocampus (DG) and the bed nucleus of the stria terminalis (BST), and increased in the habenular (Hb), accumbens shell (AcbSh) nuclei during NIC withdrawal. BAC re-established the modified c-Fos expression only in the DG, BST and AcbSh during NIC withdrawal. Conversely, BDNF expression decreased in the CA1 and CA3 area of the hippocampus, the Hb, and caudate putamen (CPu) during NIC withdrawal. Finally, BAC restored the decreased BDNF expression during NIC withdrawal in the CA1, CA3, Hb, and CPu. The results suggest a relationship between BAC's preventive effect of the expression of NIC withdrawal signs, and its ability to restore the changes in c-Fos and BDNF expression, observed in specific brain areas of NIC-withdrawn mice. © 2014 Wiley Periodicals, Inc.

  8. Waves of c-Fos and Arc Proteins Expression in Neuronal Populations of the Hippocampus in Response to a Single Episode of New Experience.

    PubMed

    Ivashkina, O I; Toropova, K A; Ivanov, A A; Chekhov, S A; Anokhin, K V

    2016-04-01

    Accumulation of c-Fos and Arc proteins in neurons in different regions of the hippocampus after single trial of contextual fear conditioning was studied by using immunohistochemical staining. We found that the dynamics of the c-Fos and Arc expression has a biphasic pattern: the first peak was observed in 15-30 min after learning and the second less pronounced peak in 1-3 h. Induction of Arc occurred earlier than c-Fos and the overall dynamics of the two waves slightly varied in the dentate gyrus and hippocampal CA1 and CA3 fields. The findings open the possibility of mapping the cognitive neural networks of the brain with higher temporal resolution and draw attention to fluctuations of hippocampal activity after a single brief episode of new experience.

  9. [Visual input affects the expression of the early genes c-Fos and ZENK in auditory telencephalic centers of pied flycatcher nestlings during the acoustically-guided freezing].

    PubMed

    Korneeva, E V; Tiunova, A A; Aleksandrov, L I; Golubeva, T B; Anokhin, K V

    2014-01-01

    The present study analyzed expression of transcriptional factors c-Fos and ZENK in 9-day-old pied flycatcher nestlings' (Ficedula hypoleuca) telencephalic auditory centers (field L, caudomedial nidopallium and caudomedial mesopallium) involved in the acoustically-guided defense behavior. Species-typical alarm call was presented to the young in three groups: 1--intact group (sighted control), 2--nestlings visually deprived just before the experiment for a short time (unsighted control) 3--nestlings visually deprived right after hatching (experimental deprivation). Induction of c-Fos as well as ZENK in nestlings from the experimental deprivation group was decreased in both hemispheres as compared with intact group. In the group of unsighted control, only the decrease of c-Fos induction was observed exclusively in the right hemisphere. These findings suggest that limitation of visual input changes the population of neurons involved into the acoustically-guided behavior, the effect being dependant from the duration of deprivation.

  10. Urocortin 2 increases c-Fos expression in topographically organized subpopulations of serotonergic neurons in the rat dorsal raphe nucleus.

    PubMed

    Staub, Daniel R; Spiga, Francesca; Lowry, Christopher A

    2005-05-24

    Corticotropin-releasing factor (CRF)-related peptides modulate stress-related physiology and behavior. Some of the physiological and behavioral effects of CRF-related peptides may be due to actions on CRF type 2 (CRF2) receptors modulating serotonergic systems in the dorsal raphe nucleus (DR). To determine if CRF2 receptor activation has effects on serotonergic neurons in the DR in conscious behaving rats, we gave intracerebroventricular (icv) injections of the selective CRF2 receptor agonist urocortin 2 (0, 0.01, 0.1, or 1.0 mug in 2 microl saline) to adult male Wistar rats and quantified c-Fos expression in topographically organized subpopulations of serotonergic neurons within the DR. In addition, home cage behaviors were recorded for 30 min prior to drug treatment and for 2 h following drug treatment. Two hours following drug treatment, rats were anesthetized, transcardially perfused with fixative, and brain tissues were processed for immunohistochemistry. Urocortin 2, in the absence of any effects on most behavioral endpoints studied, consistently increased c-Fos expression in subpopulations of serotonergic neurons identified by either tryptophan hydroxylase or serotonin immunostaining within specific subdivisions of the DR, particularly the dorsal region of the mid-rostrocaudal and caudal DR (-7.64, -8.18, -8.54, and -9.16 mm bregma). These studies demonstrate that urocortin 2 has selective actions on a subset of DR serotonergic neurons. Urocortin 2 actions on serotonergic systems described here may contribute to delayed behavioral effects of urocortin 2 described previously, including orexigenic, locomotor, and anxiety-related effects in a variety of behavioral tests as well as potentiation of conditioned fear and induction of escape deficits in a model of learned helplessness.

  11. The orexin-1 receptor antagonist SB-334867 decreases anxiety-like behavior and c-Fos expression in the hypothalamus of rats exposed to cat odor.

    PubMed

    Vanderhaven, M W; Cornish, J L; Staples, L G

    2015-02-01

    Increasing evidence suggests that the orexin system is involved in modulating anxiety, and we have recently shown that cat odor-induced anxiety in rats is attenuated by the orexin receptor antagonist SB-334867. In the current experiment, c-Fos expression was used to map changes in neuronal activation following SB-334867 administration in the cat odor anxiety model. Male Wistar rats were exposed to cat odor with or without SB-334867 pre-treatment (10 mg/kg, i.p.). A naïve control group not exposed to cat odor was also used. Following cat odor exposure, brains were processed for c-Fos expression. Vehicle-treated rats showed an increase in anxiety-like behaviors (increased hiding and decreased approach toward the cat odor), and increased c-Fos expression in the posteroventral medial amygdala (MePV), paraventricular hypothalamus (PVN) and dorsal premammillary nucleus (PMd). In rats pretreated with SB-334867, approach scores increased and c-Fos expression decreased in the PVN and PMd. These results provide both behavioral and neuroanatomical evidence for the attenuation of cat odor-induced anxiety in rats via the orexin system. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  12. Effect of postnatal treadmill exercise on c-Fos expression in the hippocampus of rat pups born from the alcohol-intoxicated mothers.

    PubMed

    Sim, Young-Je; Kim, Hong; Shin, Mal-Soon; Chang, Hyun-Kyung; Shin, Min-Chul; Ko, Il-Gyu; Kim, Ki-Jeong; Kim, Tea-Soo; Kim, Bo-Kyun; Rhim, Yong-Taek; Kim, Sangho; Park, Ho-Yoon; Yi, Jae-Woo; Lee, Sam-Jun; Kim, Chang-Ju

    2008-02-01

    Maternal alcohol-intoxication during pregnancy exerts detrimental effects on fetal development and is known to influence learning ability and memory capability by altering neuronal activity in the hippocampus. c-Fos expression represents neuronal activity and plays a crucial role in the brain development. Physical exercise is known to enhance neuronal plasticity and activity. In the present study, we investigated the influence of postnatal treadmill running on the c-Fos expression in the hippocampus of rat pups born from the alcohol-intoxicated mothers. The results obtained show that maternal alcohol-intoxication suppressed c-Fos expression in the hippocampus of rat pups and that postnatal treadmill exercise enhanced c-Fos expression in the hippocampus of these rat pups. The present study suggests that exercise should be considered as a therapeutic means of countering the effects of maternal alcohol-intoxication, and that it may provide a useful strategy for enhancing the neuronal activity of children born from the mothers who abuse alcohol during pregnancy.

  13. Environmental Novelty is Associated with a Selective Increase in Fos Expression in the Output Elements of the Hippocampal Formation and the Perirhinal Cortex

    ERIC Educational Resources Information Center

    VanElzakker, Michael; Fevurly, Rebecca D.; Breindel, Tressa; Spencer, Robert L.

    2008-01-01

    If the hippocampus plays a role in the detection of novel environmental features, then novelty should be associated with altered hippocampal neural activity and perhaps also measures of neuroplasticity. We examined Fos protein expression within subregions of rat hippocampal formation as an indicator of recent increases in neuronal excitation and…

  14. Environmental Novelty is Associated with a Selective Increase in Fos Expression in the Output Elements of the Hippocampal Formation and the Perirhinal Cortex

    ERIC Educational Resources Information Center

    VanElzakker, Michael; Fevurly, Rebecca D.; Breindel, Tressa; Spencer, Robert L.

    2008-01-01

    If the hippocampus plays a role in the detection of novel environmental features, then novelty should be associated with altered hippocampal neural activity and perhaps also measures of neuroplasticity. We examined Fos protein expression within subregions of rat hippocampal formation as an indicator of recent increases in neuronal excitation and…

  15. c-fos sequence necessary for basal expression and induction by epidermal growth factor, 12-O-tetradecanoyl phorbol-13-acetate and the calcium ionophore.

    PubMed Central

    Fisch, T M; Prywes, R; Roeder, R G

    1987-01-01

    We have investigated the sequence requirements for induction of the human c-fos gene by epidermal growth factor (EGF), 12-O-tetradecanoyl-13-acetate (TPA), and the calcium ionophore A23187 by transfecting c-fos promoter mutants into HeLa and A431 cells. Induction by both EGF and TPA in HeLa cells required the presence of the c-fos enhancer located at -317 to -298 relative to the mRNA cap site. A23187, however, did not induce expression of the transfected gene, even though it strongly induced expression of the endogenous gene, suggesting that it has different requirements for induction than do EGF and TPA. We have also investigated the role of promoter sequences downstream of the enhancer in general expression and induction of c-fos. A sequence between -97 and -76, which includes an 8-base-pair perfect direct repeat, was needed for efficient general expression but not for induction of the gene. A factor in nuclear extracts that bound specifically to this sequence was detected by a gel mobility shift assay. A 7-base-pair sequence, located between -63 and -57 relative to the mRNA cap site and previously shown to be important for general expression of mouse c-fos, was also important for general expression of the human gene. In addition, this element was important for inducibility by EGF and TPA, since induction was significantly reduced when internal deletion mutants that retained the enhancer but lacked the -63 to -57 sequence element were analyzed in transfecting assays. Images PMID:3119989

  16. Role of thalamic nuclei in the modulation of Fos expression within the cerebral cortex during hypertonic saline-induced muscle nociception.

    PubMed

    Xiao, Y; Lei, J; Ye, G; Xu, H; You, H-J

    2015-09-24

    It has been proposed that thalamic mediodorsal (MD) and ventromedial (VM) nuclei form thalamic 'nociceptive discriminators' in discrimination of nociceptive afferents, and specifically govern endogenous descending facilitation and inhibition. The present study conducted in rats was to explore the role of thalamic MD and VM nuclei in modulation of cerebral neuronal activities by means of detection of spatiotemporal variations of Fos expression within the cerebral cortex. Following a unilateral intramuscular injection of 5.8% saline into the gastrocnemius muscle, Fos expression within the bilateral, different areas of the cerebral cortex except S2 was significantly increased (P<0.05). Particularly, the increases in Fos expression within the cingulate cortex and the insular cortex occurred at 0.5h, 4h and reached the peak level at 4h, 16h, respectively. Electrolytic lesion of the contralateral thalamic MD and VM nuclei significantly blocked the 5.8% saline intramuscularly induced increases in Fos expression within the bilateral cingulate and insular cortices, respectively. Additionally, the 5.8% saline-induced Fos expression in the cingulate cortex and the insular cortex were dose-dependently attenuated by microinjection of μ-opioid antagonist β-funaltrexamine hydrochloride into the thalamic MD and VM nuclei. It is suggested that (1) the neural circuits of 'thalamic MD nucleus - cingulate cortex' and 'thalamic VM nucleus - insular cortex' form two distinct pathways in the endogenous control of nociception, (2) mirror or contralateral pain is hypothesized to be related to cross-talk of neuronal activities within the bilateral cerebral cortices modulated by μ-opioid receptors within the thalamic MD and VM nuclei.

  17. Novelty, but not operant aversive learning, enhances Fos and Egr-1 expression in the medial prefrontal cortex and hippocampal areas of rats.

    PubMed

    Yochiy, Angélica; Britto, Luiz R G; Hunziker, Maria H L

    2012-12-01

    Immediate early genes (IEG) are presumed to be activated in response to stress, novelty, and learning. Evidence supports the involvement of prefrontal and hippocampal areas in stress and learning, but also in the detection of novel events. This study examined whether a previous experience with shocks changes the pattern of Fos and Egr-1 expression in the medial prefrontal cortex (mPFC), the hippocampal cornus ammonis 1 (CA1), and dentate gyrus (DG) of adult male Wistar rats that learned to escape in an operant aversive test. Subjects previously exposed to inescapable footshocks that learned to escape from shocks were assigned to the treated group (EXP). Subjects from Group Novelty (NOV) rested undisturbed during treatment and also learned to escape in the test. The nonshock group (NSH) rested undisturbed in both sessions. Standard immunohistochemistry procedures were used to detect the proteins in brain sections. The results show that a previous experience with shocks changed the pattern of IEG expression, then demonstrating c-fos and egr-1 induction as experience-dependent events. Compared with NSH and EXP an enhanced Fos expression was detected in the mPFC and CA1 subfield of Group NOV, which also exhibited increased Egr-1 expression in the mPFC and DG in comparison to NSH. No differences were found in the DG for Fos, or in the CA1 for Egr-1. Novelty, and not the operant aversive escape learning, seems to have generated IEG induction. The results suggest novel stimuli as a possible confounding factor in studies on Fos and/or Egr-1 expression in aversive conditions.

  18. Immediate expression of c-fos and c-jun mRNA in a model of intestinal autotransplantation and ischemia-reperfusion in situ

    PubMed Central

    Santos, Maria Mercês; Tannuri, Ana Cristina Aoun; Coelho, Maria Cecilia Mendonça; de Oliveira Gonçalves, Josiane; Serafini, Suellen; da Silva, Luiz Fernando Ferraz; Tannuri, Uenis

    2015-01-01

    OBJECTIVE: Intestinal ischemia-reperfusion injury occurs in several clinical conditions and after intestinal transplantation. The aim of the present study was to investigate the phenomena of apoptosis and cell proliferation in a previously described intestinal ischemia-reperfusion injury autograft model using immunohistochemical markers. The molecular mechanisms involved in ischemia-reperfusion injury repair were also investigated by measuring the expression of the early activation genes c-fos and c-jun, which induce apoptosis and cell proliferation. MATERIALS AND METHODS: Thirty adult male Wistar rats were subjected to surgery for a previously described ischemia-reperfusion model that preserved the small intestine, the cecum and the ascending colon. Following reperfusion, the cecum was harvested at different time points as a representative segment of the intestine. The rats were allocated to the following four subgroups according to the reperfusion time: subgroup 1: 5 min; subgroup 2: 15 min; subgroup 3: 30 min; and subgroup 4: 60 min. A control group of cecum samples was also collected. The expression of c-fos, c-jun and immunohistochemical markers of cell proliferation and apoptosis (Ki67 and TUNEL, respectively) was studied. RESULTS: The expression of both c-fos and c-jun in the cecum was increased beginning at 5 min after ischemia-reperfusion compared with the control. The expression of c-fos began to increase at 5 min, peaked at 30 min, and exhibited a declining tendency at 60 min after reperfusion. A progressive increase in c-jun expression was observed. Immunohistochemical analyses confirmed these observations. CONCLUSION: The early activation of the c-fos and c-jun genes occurred after intestinal ischemia-reperfusion injury, and these genes can act together to trigger cell proliferation and apoptosis. PMID:26039956

  19. [Inhibition of histone deacetylases in the chick brain modulates expression of c-Fos and ZENK transcription factors and facilitates establishment of long-term memory].

    PubMed

    Toropova, K A; Anokhin, K V; Tiunova, A A

    2014-01-01

    The aim of the work was to examine the role of histone acetylation in memory consolidation in newborn chicks. We studied the effects of histone deacetylase inhibitor trichostatin A (TSA) on a "weak" memory for passive avoidance and on expression of two transcription factors c-Fos and ZENK known to play a role in neuronal plasticity in the chick brain. Intraventricular administration of trichostatin A prior to training produced a dose-dependent enhancement of memory when tested 24 hours after the training. It also increased neuronal expression of c-Fos and ZENK proteins: the density of ZENK immunopositive cells increased in the hippocampus and intermediate medial mesopallium and the density of c-Fos immunopositive cells increased in intermediate arcopallium and dorsocaudal nidopallium. Weak passive avoidance training did not produce further enhancement of c-Fos and ZENK expression in any of these brain areas. These data demonstrate possibility of facilitating long-term memory in day-old chicks by a histone deacetylases inhibitor, thus supporting the hypothesis on the role of histone acetylation in long-term memory formation. They also suggest that these effects might be mediated through modulation of transcriptional response in brain areas involved in consolidation of this form of memory.

  20. Differential expression of AP-1 transcription factor genes c-fos and c-jun in the helminth parasites Taenia crassiceps and Taenia solium.

    PubMed

    Morales-Montor, J; Escobedo, G; Rodriguez-Dorantes, M; Téllez-Ascencio, N; Cerbón, M A; Larralde, C

    2004-08-01

    Homologues of c-fos and c-jun from total DNA of Taenia crassiceps and Taenia solium were cloned and sequenced. The amino acid alignment analysis revealed that c-fos DNAs from T. crassiceps and T. solium were highly homologous (96%), and both have high homology compared to several mammalian c-fos proteins (93% to mouse, 96% to rat and 86% to human). The c-jun protein alignment showed higher homology (T. crassiceps and T. solium have 98%), when compared with mouse, rat and human, being 92%, 98% and 93% respectively. RT-PCR amplification of the parasite's total RNA, showed that T. crassiceps expressed both AP-1 complex genes, while T. solium only expressed c-fos. Southern blot hybridization analysis confirmed the true origin of each amplified gene. AP-1 transcription gene expression is regulated by oestradiol in the same fashion as their mammalian counterparts only in T. crassiceps. To study if AP-1 genes are involved in a physiological function of the cyst, reproduction was studied in vitro. Oestradiol treatment stimulated reproduction in T. crassiceps but not in T. solium cysticerci. This is the first report of the detection and functionality of AP-1 transcription factor genes in any species of helminth parasite.

  1. Perinatal protein deprivation facilitates morphine cross-sensitization to cocaine and enhances ΔFosB expression in adult rats.

    PubMed

    Perondi, María Cecilia; Gutiérrez, María Cecilia; Valdomero, Analía; Cuadra, Gabriel Ricardo

    2017-08-30

    Previous studies have indicated that neural changes induced by early nutritional insult cause an altered response to pharmacological treatments, including addictive drugs. This study evaluates the influence of perinatal protein malnutrition in developing cross-sensitization to cocaine-induced rewarding effects in animals pre-exposed to morphine. Different groups of well-nourished (C-rats) and protein-deprived animals (D-rats) were treated twice a day for three days with increasing doses of morphine or with saline. After 3days, the incentive motivational effects of cocaine were assessed in a Conditioned Place Preference paradigm in both groups. In saline pre-treated animals, dose-response curves to cocaine revealed a conditioning effect in D-rats at doses of 5, 7.5 and 10mg/kg, while this effect was observed in C-rats only with 10 and 15mg/kg. Furthermore, when animals of both groups were pre-treated with escalating doses of morphine, cross-sensitization to the conditioning effect of cocaine was elicited only in D-rats with low doses of cocaine (5 and 7.5mg/kg). In contrast, under the same experimental conditions, C-rats show no cross-sensitization. To correlate this differential rewarding response with a molecular substrate linked to the behavioral changes observed after repeated drug exposure, ΔFosB expression was assessed in different brain regions. D-rats showed a significant increase in this transcription factor in the nucleus accumbens, amygdala and medial prefrontal cortex. These results demonstrated that perinatal protein deprivation facilitates rewarding effects and the development of cross-sensitization to cocaine, which correlates with an upregulation of ΔFosB in brain areas related to the reward circuitry. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Androgen receptors and estrogen receptors are colocalized in male rat hypothalamic and limbic neurons that express Fos immunoreactivity induced by mating.

    PubMed

    Gréco, B; Edwards, D A; Michael, R P; Clancy, A N

    1998-01-01

    Conversion of testosterone into estradiol is important for male rat sexual behavior, and both steroids probably contribute to mating. The distributions of neurons containing androgen receptors (AR) and estrogen receptors (ER) overlap, and many AR-immunoreactive (AR-ir) neurons express Fos immunoreactivity (Fos-ir) induced by mating. Because mating-induced Fos-ir in the male rat occurs mainly in AR-ir neurons, and because both steroids are important for mating, we hypothesized that (i) AR-ir and ER-ir are colocalized and that (ii) some of these neurons are activated during mating. We examined, in adjacent sections from the medial preoptic area (MPN) through the central tegmental field (CTF), the expression of ER-ir in: (i) AR-ir-containing neurons, and (ii) Fos-ir-expressive neurons. PG21 anti-AR, OA-11-824 anti-c-fos, H222 or 1D5 anti-ER primary antibodies were visualized, respectively, with cyanine-conjugated, fluorescein- or cyanine-conjugated, and fluorescein-conjugated secondary antibodies in male rats which were killed 1 h after ejaculating with a receptive female. In MPN, bed nucleus of the stria terminalis (BNST), and medial amygdala (MEA), 80-90% of ER-ir labeling occurred in AR-ir-positive neurons but only about 30% of AR-ir neurons were ER-ir-positive. No ER-ir was found in the CTF. This suggests the presence of three types of brain neurons sensitive to gonadal steroid hormones: neurons sensitive to androgens only, neurons sensitive to both androgens and estrogens, and neurons sensitive to estrogens only. About 50% of ER-ir labeling occurred in cells expressing mating-induced Fos-ir but only about 30% of Fos-ir neurons were ER-ir-positive. These findings suggest that, in the MPN, at least two different neuronal populations are activated during mating: the first contains AR-ir only and the second contains AR-ir and ER-ir. In the BNST and MEA, at least three hormonally sensitive populations are activated during mating: the two described above plus a third

  3. Incubation of Methamphetamine Craving Is Associated with Selective Increases in Expression of Bdnf and Trkb, Glutamate Receptors, and Epigenetic Enzymes in Cue-Activated Fos-Expressing Dorsal Striatal Neurons

    PubMed Central

    Rubio, F. Javier; Zeric, Tamara; Bossert, Jennifer M.; Kambhampati, Sarita; Cates, Hannah M.; Kennedy, Pamela J.; Liu, Qing-Rong; Cimbro, Raffaello; Hope, Bruce T.; Nestler, Eric J.

    2015-01-01

    Cue-induced methamphetamine seeking progressively increases after withdrawal (incubation of methamphetamine craving), but the underlying mechanisms are largely unknown. We determined whether this incubation is associated with alterations in candidate genes in dorsal striatum (DS), a brain area implicated in cue- and context-induced drug relapse. We first measured mRNA expression of 24 candidate genes in whole DS extracts after short (2 d) or prolonged (1 month) withdrawal in rats following extended-access methamphetamine or saline (control condition) self-administration (9 h/d, 10 d). We found minimal changes. Next, using fluorescence-activated cell sorting, we compared gene expression in Fos-positive dorsal striatal neurons, which were activated during “incubated” cue-induced drug-seeking tests after prolonged withdrawal, with nonactivated Fos-negative neurons. We found significant increases in mRNA expression of immediate early genes (Arc, Egr1), Bdnf and its receptor (Trkb), glutamate receptor subunits (Gria1, Gria3, Grm1), and epigenetic enzymes (Hdac3, Hdac4, Hdac5, GLP, Dnmt3a, Kdm1a) in the Fos-positive neurons only. Using RNAscope to determine striatal subregion and cell-type specificity of the activated neurons, we measured colabeling of Fos with Drd1 and Drd2 in three DS subregions. Fos expression was neither subregion nor cell-type specific (52.5 and 39.2% of Fos expression colabeled with Drd1 and Drd2, respectively). Finally, we found that DS injections of SCH23390 (C17H18ClNO), a D1-family receptor antagonist known to block cue-induced Fos induction, decreased incubated cue-induced methamphetamine seeking after prolonged withdrawal. Results demonstrate a critical role of DS in incubation of methamphetamine craving and that this incubation is associated with selective gene-expression alterations in cue-activated D1- and D2-expressing DS neurons. PMID:26019338

  4. Melanocortin 4 receptor activates ERK-cFos pathway to increase brain-derived neurotrophic factor expression in rat astrocytes and hypothalamus.

    PubMed

    Ramírez, D; Saba, J; Carniglia, L; Durand, D; Lasaga, M; Caruso, C

    2015-08-15

    Melanocortins are neuropeptides with well recognized anti-inflammatory and anti-apoptotic effects in the brain. Of the five melanocortin receptors (MCR), MC4R is abundantly expressed in the brain and is the only MCR present in astrocytes. We have previously shown that MC4R activation by the α-melanocyte stimulating hormone (α-MSH) analog, NDP-MSH, increased brain-derived neurotrophic factor (BDNF) expression through the classic cAMP-Protein kinase A-cAMP responsive element binding protein pathway in rat astrocytes. Now, we examined the participation of the mitogen activated protein kinases pathway in MC4R signaling. Rat cultured astrocytes treated with NDP-MSH 1 µM for 1 h showed increased BDNF expression. Inhibition of extracellular signal-regulated kinase (ERK) and ribosomal p90 S6 kinase (RSK), an ERK substrate, but not of p38 or JNK, prevented the increase in BDNF expression induced by NDP-MSH. Activation of MC4R increased cFos expression, a target of both ERK and RSK. ERK activation by MC4R involves cAMP, phosphoinositide-3 kinase (PI3K) and the non receptor tyrosine kinase, Src. Both PI3K and Src inhibition abolished NDP-MSH-induced BDNF expression. Moreover, we found that intraperitoneal injection of α-MSH induces BDNF and MC4R expression and activates ERK and cFos in male rat hypothalamus. Our results show for the first time that MC4R-induced BDNF expression in astrocytes involves ERK-RSK-cFos pathway which is dependent on PI3K and Src, and that melanocortins induce BDNF expression and ERK-cFos activation in rat hypothalamus. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Cherubism mice also deficient in c-Fos exhibit inflammatory bone destruction executed by macrophages that express MMP14 despite the absence of TRAP+ osteoclasts.

    PubMed

    Kittaka, Mizuho; Mayahara, Kotoe; Mukai, Tomoyuki; Yoshimoto, Tetsuya; Yoshitaka, Teruhito; Gorski, Jeffrey P; Ueki, Yasuyoshi

    2017-09-15

    Currently, it is believed that osteoclasts positive for tartrate-resistant acid phosphatase (TRAP +) are the exclusive bone-resorbing cells responsible for focal bone destruction in inflammatory arthritis. Recently, a mouse model of cherubism (Sh3bp2(KI/KI) ) with a homozygous gain-of-function mutation in the SH3-domain binding protein 2 (SH3BP2) was shown to develop auto-inflammatory joint destruction. Here, we demonstrate that Sh3bp2(KI/KI) mice also deficient in the FBJ osteosarcoma oncogene (c-Fos) still exhibit noticeable bone erosion at the distal tibia even in the absence of osteoclasts at 12 weeks old. Levels of serum ICTP, a marker of bone resorption generated by matrix metalloproteinases (MMPs), were elevated, while levels of serum CTX, another resorption marker produced by cathepsin K, were not increased. Collagenolytic MMP levels were increased in the inflamed joints of the Sh3bp2(KI/KI) mice deficient in c-Fos. Resorption pits contained a large number of F4/80+ macrophages and genetic depletion of macrophages rescued these erosive changes. Importantly, administration of NSC405020, an MMP14 inhibitor targeted to the hemopexin (PEX) domain, suppressed bone erosion in c-Fos-deficient Sh3bp2(KI/KI) mice. After activation of the NF-κB pathway, M-CSF-dependent macrophages from c-Fos-deficient Sh3bp2(KI/KI) mice expressed increased amounts of MMP14 compared to wild-type macrophages. Interestingly, RANKL-deficient Sh3bp2(KI/KI) mice failed to show notable bone erosion, while c-Fos deletion did restore bone erosion to the RANKL-deficient Sh3bp2(KI/KI) mice, suggesting that osteolytic transformation of macrophages requires both loss-of-function of c-Fos and gain-of-function of SH3BP2 in this model. These data provide the first genetic evidence that cells other than osteoclasts can cause focal bone destruction in inflammatory bone disease and suggest that MMP14 is a key mediator conferring pathological bone-resorbing capacity on c-Fos-deficient Sh3bp2(KI

  6. Differential contributions of NMDA and non-NMDA receptors to spinal Fos expression evoked by superficial tissue and muscle inflammation in the rat.

    PubMed

    Hu, J Y; Zhao, Z Q

    2001-01-01

    The role of N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the spinal cord in the transmission of nociceptive afferents from superficial tissue and muscle was studied by examining the effects of NMDA or non-NMDA receptor antagonists on Fos expression in the spinal dorsal horn. Muscle inflammation was induced by injection of turpentine oil into the gastrocnemius muscle, whereas superficial tissue inflammation was induced by an intraplantar injection of turpentine oil into the hindpaw. The NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP-5), the non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) or normal saline were intrathecally administered 15 min before an intramuscular or intraplantar injection of turpentine oil. Muscle inflammation evoked expression of Fos-like immunoreactive neurons staining in neurons that were predominantly distributed in the middle portions of laminae I-II(outer) and the lateral portions of laminae V-VI of the ipsilateral dorsal horn at the spinal L(4)-L(5). DNQX, but not AP-5, significantly reduced the total number of Fos-like immunoreactive neurons evoked by muscle inflammation. In contrast, superficial tissue inflammation evoked expression of Fos-like immunoreactive neurons in the medial portions of laminae I-II(outer) and V-VI of the ipsilateral dorsal horn at the spinal L(4)-L(5) that was blocked by AP-5, but not by DNQX. Injection of normal saline did not influence the numbers of Fos-LI neurons. These results indicate that different glutamate receptors in the dorsal horn of the spinal cord may mediate nociceptive input from superficial tissue (particularly skin) and muscle. DNQX receptors may mediate transmission of nociceptive information originating in muscle, while NMDA receptors may preferentially mediate transmission of nociceptive information originating in skin.

  7. Characterization of the transduction pathway involved in c-fos and c-jun expression induced by Aggregatibacter actinomycetemcomitans lipopolysaccharides in human gingival fibroblasts.

    PubMed

    Gutiérrez-Venegas, Gloria; Castillo-Alemán, Ramiro

    2008-11-01

    Periodontal disease is an inflammatory disease caused by infection with oral bacteria that results in tooth exfoliation. Lipopolysaccharides (LPS) are a major component of the outer membrane of Gram-negative microorganisms and are involved in the inflammatory response. c-fos and c-jun are involved in pathological conditions such as inflammatory disorders. Inflammatory signaling cascades leading to c-fos activation in human gingival fibroblasts (HGFs) are not well characterized. Thus, we have investigated the kinase pathways involved in c-fos and c-jun activation induced by LPS in human gingival fibroblasts. LPS promoted a dose- and time-dependent increase in c-fos transcription. Phosphoinositide-phospholipase C inhibitor (U-73122), protein kinase A inhibitor (H89), MEK1 inhibitor (PD 98,059), p38 inhibitor (SB203580), and tyrosine kinase inhibitors (genistein and herbimycin) attenuated the LPS effect, while the PI-3 K inhibitor (Wortmannin) had no effect on LPS-induced c-fos transcription. Protein kinase C inhibitors (Ro 31-8220, calphostin C, staurosporine, and chelerythrine chloride) also inhibited LPS-induced c-fos transcription. However, long-term treatment (24 -h) with the PKC activator tetradecanoyl phorbol-13-acetate (PMA) had no significant effect on LPS-induced transcription in HGFs. We also found an increase in c-jun expression in HGF stimulated with LPS. In addition, experiments using pharmacological inhibitors of individual mitogen-activated protein kinases (MAPK) and of protein kinase C (PKC) revealed that p38, ERK 1/2, and PKC are involved in LPS-induced c-jun expression. Our results indicate that LPS-induced c-fos and c-jun expressions are mediated by two different signaling pathways: one through phosphoinositide-phospholipase C via an upstream protein tyrosine kinase, which activates PKC isoforms that are insensitive to phorbol stress, and the second through activation of protein kinase A (PKA). Both kinases regulate the phosphorylation of the

  8. Stimulus-induced drop episodes in Coffin-Lowry syndrome.

    PubMed

    Hahn, Jin S; Hanauer, André

    2012-05-01

    The Coffin-Lowry syndrome (CLS) is a rare but well-defined X-linked semidominant syndrome characterized by psychomotor and growth retardation, and progressive skeletal changes. CLS is caused by loss of function mutations in the Rps6ka3 gene encoding the ribosomal S6 kinase 2 (RSK2) protein. A distinctive paroxysmal disorder has been described in some CLS patients, characterized by episodes of sudden falling, without apparent alteration of consciousness, usually induced by unexpected tactile or auditory stimuli. Duration of episodes is very short, usually lasting a few seconds. The appellation "Stimulus-induced drop episodes" (SIDEs) was proposed for these non-epileptic events in CLS patients. SIDEs are clinically heterogeneous; with some patients exhibiting cataplexy-like events characterized by sudden hypotonia and collapse, and others hyperekplexia-like episodes with a startle response. The pathophysiology of SIDEs is not well understood.

  9. Rhythmic cFos expression in the ventral subparaventricular zone influences general activity rhythms in the Nile grass rat, Arvicanthis niloticus.

    PubMed

    Schwartz, M D; Nuñez, A A; Smale, L

    2009-10-01

    Circadian rhythms in behavior and physiology are very different in diurnal and nocturnal rodents. A pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus is responsible for generating and maintaining circadian rhythms in mammals, and cellular and molecular rhythms within the SCN of diurnal and nocturnal rodents are very similar. The neural substrates determining whether an animal has a diurnal or nocturnal phase preference are thus likely to reside downstream of the SCN. The ventral subparaventricular zone (vSPVZ), a major target of the SCN that is important for the expression of circadian rhythmicity in nocturnal lab rats (Rattus norvegicus), exhibits different rhythms in cFos expression in diurnal Nile grass rats compared to lab rats. We examined the effects of chemotoxic lesions of the cFos-expressing cells of the vSPVZ on activity rhythms of grass rats to evaluate the hypothesis that these cells support diurnality in this species. Male grass rats housed in a 12:12 light:dark (LD) cycle were given bilateral injections of the neurotoxin n-methyl-D-L-aspartic acid (NMA) or vehicle aimed at the vSPVZ; cells in the SCN are resistant to NMA, which kills neurons in other brain regions, but leaves fibers of passage intact. vSPVZ-damaged grass rats exhibited highly unstable patterns of activity in constant darkness (DD) and in the LD cycle that followed. However, crepuscular bouts of activity could be seen in all animals with vSPVZ lesions. Damage to the vSPVZ reduced cFos expression in this area but not in the SCN. Using correlational analyses, we found that the number of cFos-ir cells in the vSPVZ was unrelated to several parameters of the activity rhythms during the initial post-surgical period, when animals were in LD. However, the number of cells expressing cFos in the vSPVZ was positively correlated with general activity during the subjective day relative to the subjective night when the animals were switched to DD, and this pattern persisted

  10. c-Fos expression in the parabrachial nucleus following intraoral bitter stimulation in the rat with dietary-induced zinc deficiency.

    PubMed

    Kawano, Akiyo; Honma, Shiho; Inui-Yamamoto, Chizuko; Ito, Akira; Niwa, Hitoshi; Wakisaka, Satoshi

    2017-03-15

    Zinc deficiency causes various symptoms including taste disorders. In the present study, changes in expression of c-Fos immunoreactivity in neurons of the parabrachial nucleus (PBN), one of the relay nuclei for transmission of gustatory information, after bitter stimulation to the dorsal surface of the tongue were examined in zinc-deficient rats. Experimental zinc-deficient animals were created by feeding a low-zinc diet for 4weeks, and showed the following symptoms of zinc deficiency: low body weight, low serum zinc content and behavioral changes to avoid bitter stimulation. In normal control animals, intraoral application of 1mM quinine caused increased numbers of c-Fos-immunoreactive (c-Fos-IR) neurons in the external lateral subnucleus and external medial subnucleus of the PBN (elPBN and emPBN, respectively) compared with application of distilled water. However, in the zinc-deficient animals, the numbers of c-Fos-IR neurons in the elPBN and emPBN did not differ significantly between application of quinine and distilled water. After feeding the zinc-deficient animals a normal diet for 4weeks, the symptoms of zinc deficiency recovered, and the expression of c-Fos-IR neurons following intraoral bitter stimulation became identical to that in the normal control animals. The present results indicate that dietary zinc deficiency causes alterations to neuronal activities in the gustatory neural circuit, and that these neuronal alterations can be reversed by changing to a normal diet. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Differential Fos expression in the paraventricular nucleus of the hypothalamus, sacral parasympathetic nucleus and colonic motor response to water avoidance stress in Fischer and Lewis rats.

    PubMed

    Million, M; Wang, L; Martinez, V; Taché, Y

    2000-09-22

    The responsiveness of hypothalamic CRF to various stressors is reduced in the young female Lewis relative to the histocompatible Fischer rat. Whether such a difference impacts the brain-gut response to water avoidance stress was investigated by monitoring Fos immunoreactivity in the brain and sacral spinal cord and fecal pellet output. Exposure for 60 min to water avoidance stress increased the number of Fos positive cells in the paraventricular nucleus of the hypothalamus (PVN), nucleus tractus solitarius (NTS), and the parasympathetic nucleus of the lumbo-sacral spinal cord (L6-S1) in both Lewis and Fischer rats compared with non stress groups. The Fos response was lower by 32.0% in the PVN, and 63% in sacral parasympathetic nucleus in Lewis compared with Fischer rats while similar Fos expression was observed in the NTS. Stress-induced defecation was reduced by 52% in Lewis compared with Fischer rats while colonic motor response to CRF injected intracisternally resulted in a similar pattern and magnitude of defecation in both strains. The CRF receptor antagonist [D-Phe12,Nle(21,38)C(a)MeLeu(37)]-CRF(12-41) injected intracisternally antagonized partly the defecation response in Lewis and Fischer rats. These data indicate that a lower activation of PVN and sacral parasympathetic nuclei in Lewis compared with Fisher rats may contribute to the differential colonic motor response and that the blunted CRF hypothalamic response to stress, unlike responsiveness to central CRF plays a role.

  12. Stress-Induced Locomotor Sensitization to Amphetamine in Adult, but not in Adolescent Rats, Is Associated with Increased Expression of ΔFosB in the Nucleus Accumbens

    PubMed Central

    Carneiro de Oliveira, Paulo E.; Leão, Rodrigo M.; Bianchi, Paula C.; Marin, Marcelo T.; Planeta, Cleopatra da Silva; Cruz, Fábio C.

    2016-01-01

    While clinical and pre-clinical evidence suggests that adolescence is a risk period for the development of addiction, the underlying neural mechanisms are largely unknown. Stress during adolescence has a huge influence on drug addiction. However, little is known about the mechanisms related to the interaction among stress, adolescence and addiction. Studies point to ΔFosB as a possible target for this phenomenon. In the present study, adolescent and adult rats (postnatal day 28 and 60, respectively) were restrained for 2 h once a day for 7 days. Three days after their last exposure to stress, the animals were challenged with saline or amphetamine (1.0 mg/kg i.p.) and amphetamine-induced locomotion was recorded. Immediately after the behavioral tests, rats were decapitated and the nucleus accumbens was dissected to measure ΔFosB protein levels. We found that repeated restraint stress increased amphetamine-induced locomotion in both the adult and adolescent rats. Furthermore, in adult rats, stress-induced locomotor sensitization was associated with increased expression of ΔFosB in the nucleus accumbens. Our data suggest that ΔFosB may be involved in some of the neuronal plasticity changes associated with stress induced-cross sensitization with amphetamine in adult rats. PMID:27672362

  13. BONLAC: A Combinatorial Proteomic Technique to Measure Stimulus-induced Translational Profiles in Brain Slices

    PubMed Central

    Bowling, Heather; Bhattacharya, Aditi; Zhang, Guoan; Lebowitz, Joseph Z.; Alam, Danyal; Smith, Peter T.; Kirshenbaum, Kent; Neubert, Thomas A.; Vogel, Christine; Chao, Moses V.; Klann, Eric

    2015-01-01

    Stimulus-triggered protein synthesis is critical for brain health and function. However, due to technical hurdles, de novo neuronal translation is predominantly studied in cultured cells, whereas electrophysiological and circuit analyses often are performed in brain slices. The different properties of these two experimental systems create an information gap about stimulus-induced alterations in the expression of new proteins in mature circuits. To address this, we adapted two existing techniques, BONCAT and SILAC, to a combined proteomic technique, BONLAC, for use in acute adult hippocampal slices. Using BDNF-induced protein synthesis as a proof of concept, we found alterations in expression of proteins involved in neurotransmission, trafficking, and cation binding that differed from those found in a similar screen in cultured neurons. Our results indicate important differences between cultured neurons and slices, and suggest that BONLAC could be used to dissect proteomic changes underlying synaptic events in adult circuits. PMID:26205778

  14. Cardiovascular effects and c-Fos expression in the rat hindbrain in response to innocuous stomach distension.

    PubMed

    Molinari, Claudio; Sabbatini, Maurizio; Grossini, Elena; Mary, David A S G; Cannas, Mario; Vacca, Giovanni

    2006-03-31

    The present work was planned to study the effects of non-noxious gastric distension on hemodynamic variables and on cardiovascular hindbrain areas detected by means of c-Fos immunoreactivity, to determine the afferent and central mechanisms involved. In anesthetized rats, innocuous stomach distension increased arterial blood pressure and heart rate and induced c-Fos immunoreactivity within nucleus tractus solitarii, nucleus ambiguus, ventrolateral medulla and lateral reticular nucleus. Bilateral vagotomy abolished the pressor response and c-Fos immunoreactivity in nucleus ambiguus and ventrolateral medulla. Also, c-Fos immunoreactivity was significantly decreased in nucleus tractus solitarii and lateral reticular nucleus. After bilateral splanchnicotomy the pressor and tachycardic responses caused by gastric distension were reduced. c-Fos immunoreactivity in nucleus tractus solitarii, lateral reticular nucleus and nucleus ambiguus was reduced in comparison to the intact rats. In ventrolateral medulla a preferential localization of c-Fos immunoreactivity was found within its caudal portion. It was shown that such gastric distension, known to activate low threshold mechanoreceptors, induced cardiovascular effects via both vagal and splanchnic afferents and involving their central convergence and interaction in modulating the baroreceptor buffer system.

  15. Distinct Fos-Expressing Neuronal Ensembles in the Ventromedial Prefrontal Cortex Mediate Food Reward and Extinction Memories

    PubMed Central

    Warren, Brandon L.; Mendoza, Michael P.; Cruz, Fabio C.; Leao, Rodrigo M.; Caprioli, Daniele; Rubio, F. Javier; Whitaker, Leslie R.; McPherson, Kylie B.; Bossert, Jennifer M.; Shaham, Yavin

    2016-01-01

    reward seeking, whereas the ventral mPFC inhibits reward seeking. In this paper, we use the Daun02 chemogenetic inactivation procedure to demonstrate that Fos-expressing neuronal ensembles mediating both food reward and extinction memories intermingle within the same ventral mPFC area. PMID:27335401

  16. Distinct Fos-Expressing Neuronal Ensembles in the Ventromedial Prefrontal Cortex Mediate Food Reward and Extinction Memories.

    PubMed

    Warren, Brandon L; Mendoza, Michael P; Cruz, Fabio C; Leao, Rodrigo M; Caprioli, Daniele; Rubio, F Javier; Whitaker, Leslie R; McPherson, Kylie B; Bossert, Jennifer M; Shaham, Yavin; Hope, Bruce T

    2016-06-22

    ventral mPFC inhibits reward seeking. In this paper, we use the Daun02 chemogenetic inactivation procedure to demonstrate that Fos-expressing neuronal ensembles mediating both food reward and extinction memories intermingle within the same ventral mPFC area. Copyright © 2016 the authors 0270-6474/16/366691-13$15.00/0.

  17. Electrical Stimulation Normalizes c-Fos Expression in the Deep Cerebellar Nuclei of Depressive-like Rats: Implication of Antidepressant Activity.

    PubMed

    Huguet, Gemma; Kadar, Elisabet; Temel, Yasin; Lim, Lee Wei

    2017-04-01

    The electrical stimulation of specific brain targets has been shown to induce striking antidepressant effects. Despite that recent data have indicated that cerebellum is involved in emotional regulation, the mechanisms by which stimulation improved mood-related behaviors in the cerebellum remained largely obscure. Here, we investigated the stimulation effects of the ventromedial prefrontal cortex (vmPFC), nucleus accumbens (NAc), and lateral habenular nucleus on the c-Fos neuronal activity in various deep cerebellar and vestibular nuclei using the unpredictable chronic mild stress (CMS) animal model of depression. Our results showed that stressed animals had increased number of c-Fos cells in the cerebellar dentate and fastigial nuclei, as well as in the spinal vestibular nucleus. To examine the stimulation effects, we found that vmPFC stimulation significantly decreased the c-Fos activity within the cerebellar fastigial nucleus as compared to the CMS sham. Similarly, there was also a reduction of c-Fos expression in the magnocellular part of the medial vestibular nucleus in vmPFC- and NAc core-stimulated animals when compared to the CMS sham. Correlational analyses showed that the anxiety measure of home-cage emergence escape latency was positively correlated with the c-Fos neuronal activity of the cerebellar fastigial and magnocellular and parvicellular parts of the interposed nuclei in CMS vmPFC-stimulated animals. Interestingly, there was a strong correlation among activation in these cerebellar nuclei, indicating that the antidepressant-like behaviors were possibly mediated by the vmPFC stimulation-induced remodeling within the forebrain-cerebellar neurocircuitry.

  18. Maternal separation in early life modifies anxious behavior and Fos and glucocorticoid receptor expression in limbic neurons after chronic stress in rats: effects of tianeptine.

    PubMed

    Trujillo, Verónica; Durando, Patricia E; Suárez, Marta M

    2016-01-01

    Early-life adversity can lead to long-term consequence persisting into adulthood. Here, we assess the implications of an adverse early environment on vulnerability to stress during adulthood. We hypothesized that the interplay between early and late stress would result in a differential phenotype regarding the number of neurons immunoreactive for glucocorticoid receptor (GR-ir) and neuronal activity as assessed by Fos immunoreactivity (Fos-ir) in brain areas related to stress responses and anxiety-like behavior. We also expected that the antidepressant tianeptine could correct some of the alterations induced in our model. Male Wistar rats were subjected to daily maternal separation (MS) for 4.5 h during the first 3 weeks of life. As adults, the rats were exposed to chronic stress for 24 d and they were treated daily with tianeptine (10 mg/kg intraperitoneal) or vehicle (isotonic saline). Fos-ir was increased by MS in all structures analyzed. Chronic stress reduced Fos-ir in the hippocampus, but increased it in the paraventricular nucleus. Furthermore, chronic stress increased GR-ir in hippocampus (CA1) and amygdala in control non-MS rats. By contrast, when MS and chronic stress were combined, GR-ir was decreased in these structures. Additionally, whereas tianeptine did not affect Fos-ir, it regulated GR-ir in a region-dependent manner, in hippocampus and amygdala opposing in some cases the stress or MS effects. Furthermore, tianeptine reversed the MS- or stress-induced anxious behavior. The interplay between MS and chronic stress observed indicates that MS rats have a modified phenotype, which is expressed when they are challenged by stress in later life.

  19. Behavioral responses and Fos activation following painful stimuli in a rodent model of Parkinson's disease.

    PubMed

    Tassorelli, Cristina; Armentero, Marie-Therese; Greco, Rosaria; Fancellu, Roberto; Sandrini, Giorgio; Nappi, Giuseppe; Blandini, Fabio

    2007-10-24

    In Parkinson's disease (PD), the motor dysfunction caused by degeneration of the nigrostriatal pathway is often associated with alterations of pain perception. This is likely related to the role that the nigrostriatal system may play in the processing of noxious, somatosensory stimuli. To further address this issue, we used a rodent model of PD, based on the unilateral, intrastriatal injection of neurotoxin 6-hydroxydopamine (6-OHDA). We investigated the effects of the nigrostriatal lesion on behavioral responses to pain tests designed to explore different aspects of nociception, such as the formalin test and the tail flick test; we also explored modifications in the expression of Fos protein, a marker of neuronal activation, in supraspinal nuclei involved in the integration of pain perception and stress-related behavior. Rats bearing the nigrostriatal lesion showed complex alterations in pain perception, including hyperalgesic responses to the tonic, inflammatory pain elicited by formalin injection, but only when the stimulus was delivered ipsilaterally to the lesion. This phenomenon was associated with delayed responses to the phasic, thermal stimulus induced by the tail flick test. The hyperalgesic response to the formalin test was accompanied by reduced Fos expression in the paraventricular nucleus of the hypothalamus, which is part of a network (the medial pain system) that mediates motivational-affective aspects of pain. Our results confirm that a unilateral alteration of central dopaminergic transmission disrupts the neural mechanisms underlying proper integration of painful stimuli, particularly in the hemibody ipsilateral to the dopaminergic denervation.

  20. Thapsigargin induces rapid, transient growth inhibition and c-fos expression followed by sustained growth stimulation in mouse keratinocyte cultures.

    PubMed

    Harmon, C S; Ducote, J; Xiong, Y

    1996-08-01

    Although the sesquiterpene lactone thapsigargin has been shown to possess hyperplastic and tumor-promoting activities when applied topically to mouse skin in vivo, the cellular mechanism(s) which underlie these effects are unclear. We show here that thapsigargin treatment of Primary mouse epidermal keratinocytes increased intracellular free Ca2+ concentration (Cai) in a concentration-dependent manner. Thapsigargin induced a rapid, transient elevation in keratinocyte Cai, in part due to the release of Ca2+ from intracellular stores. This response was followed by a sustained elevation in Ca2+, resulting entirely from calcium influx. Thapsigargin elicited a biphasic effect on keratinocyte DNA synthesis: a rapid inhibitory effect (50-60% inhibition at 4-8 h), followed by a very marked and sustained elevation. Prolonged treatment of keratinocytes with thapsigargin at relatively high concentrations resulted in cytotoxicity (inhibition of neutral red uptake). The rapid antiproliferative effect of thapsigargin was not associated with cytotoxicity, as determined by either neutral red uptake or by trypan blue exclusion, and was not blocked by pretreatment with Ro 31-7349, a selective inhibitor of protein kinase C. The rapid antiproliferative effect of thapsigargin was associated with rapid, transient activation of keratinocyte c-fos expression and rapid inhibition of total protein synthesis. Taken together, these findings raise the possibility that the hyperplastic and tumor-promoting activities of thapsigargin on epidermis in vivo result from direct keratinocyte growth stimulation as a consequence of a prolonged elevation in levels of Cai.

  1. Scheduled feeding restores memory and modulates c-Fos expression in the suprachiasmatic nucleus and septohippocampal complex.

    PubMed

    Ruby, Norman F; Fisher, Nathan; Patton, Danica F; Paul, Matthew J; Fernandez, Fabian; Heller, H Craig

    2017-07-28

    Disruptions in circadian timing impair spatial memory in humans and rodents. Circadian-arrhythmic Siberian hamsters (Phodopus sungorus) exhibit substantial deficits in spatial working memory as assessed by a spontaneous alternation (SA) task. The present study found that daily scheduled feeding rescued spatial memory deficits in these arrhythmic animals. Improvements in memory persisted for at least 3 weeks after the arrhythmic hamsters were switched back to ad libitum feeding. During ad libitum feeding, locomotor activity resumed its arrhythmic state, but performance on the SA task varied across the day with a peak in daily performance that corresponded to the previous daily window of food anticipation. At the end of scheduled feeding, c-Fos brain mapping revealed differential gene expression in entrained versus arrhythmic hamsters in the suprachiasmatic nucleus (SCN) that paralleled changes in the medial septum and hippocampus, but not in other neural structures. These data show that scheduled feeding can improve cognitive performance when SCN timing has been compromised, possibly by coordinating activity in the SCN and septohippocampal pathway.

  2. Newly paired zebra finches have higher dopamine levels and immediate early gene Fos expression in dopaminergic neurons.

    PubMed

    Banerjee, Sunayana B; Dias, Brian G; Crews, David; Adkins-Regan, Elizabeth

    2013-12-01

    Most birds are socially monogamous, yet little is known about the neural pathways underlying avian monogamy. Recent studies have implicated dopamine as playing a role in courtship and affiliation in a socially monogamous songbird, the zebra finch (Taeniopygia guttata). In the present study, we sought to understand the specific contribution to pair formation in zebra finches of the mesolimbic dopaminergic pathway that projects from the midbrain ventral tegmental area to the nucleus accumbens. We observed that paired birds had higher levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid in the ventral medial striatum, where the nucleus accumbens is situated, than unpaired birds. Additionally, we found that the percentage of dopaminergic neurons expressing immediate early gene Fos, a marker of neuronal activity, was higher in the ventral tegmental area of paired birds than in that of unpaired birds. These data are consistent with a role for the mesolimbic dopaminergic pathway in pair formation in zebra finches, suggesting the possibility of a conserved neural mechanism of monogamy in birds and mammals.

  3. IP{sub 3}-dependent intracellular Ca{sup 2+} release is required for cAMP-induced c-fos expression in hippocampal neurons

    SciTech Connect

    Zhang, Wenting; Tingare, Asmita; Ng, David Chi-Heng; Johnson, Hong W.; Schell, Michael J.; Lord, Rebecca L.; Chawla, Sangeeta

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer cAMP-induced c-fos expression in hippocampal neurons requires a submembraneous Ca{sup 2+} pool. Black-Right-Pointing-Pointer The submembraneous Ca{sup 2+} pool derives from intracellular ER stores. Black-Right-Pointing-Pointer Expression of IP{sub 3}-metabolizing enzymes inhibits cAMP-induced c-fos expression. Black-Right-Pointing-Pointer SRE-mediated and CRE-mediated gene expression is sensitive to IP{sub 3}-metabolizing enzymes. Black-Right-Pointing-Pointer Intracellular Ca{sup 2+} release is required for cAMP-induced nuclear translocation of TORC1. -- Abstract: Ca{sup 2+} and cAMP are widely used in concert by neurons to relay signals from the synapse to the nucleus, where synaptic activity modulates gene expression required for synaptic plasticity. Neurons utilize different transcriptional regulators to integrate information encoded in the spatiotemporal dynamics and magnitude of Ca{sup 2+} and cAMP signals, including some that are Ca{sup 2+}-responsive, some that are cAMP-responsive and some that detect coincident Ca{sup 2+} and cAMP signals. Because Ca{sup 2+} and cAMP can influence each other's amplitude and spatiotemporal characteristics, we investigated how cAMP acts to regulate gene expression when increases in intracellular Ca{sup 2+} are buffered. We show here that cAMP-mobilizing stimuli are unable to induce expression of the immediate early gene c-fos in hippocampal neurons in the presence of the intracellular Ca{sup 2+} buffer BAPTA-AM. Expression of enzymes that attenuate intracellular IP{sub 3} levels also inhibited cAMP-dependent c-fos induction. Synaptic activity induces c-fos transcription through two cis regulatory DNA elements - the CRE and the SRE. We show here that in response to cAMP both CRE-mediated and SRE-mediated induction of a luciferase reporter gene is attenuated by IP{sub 3} metabolizing enzymes. Furthermore, cAMP-induced nuclear translocation of the CREB coactivator TORC1 was inhibited by

  4. Dopamine D1-like receptors agonist SKF 38393 increases cFOS expression in the paraventricular nucleus of the hypothalamus--impact of acute and chronic cocaine.

    PubMed

    Chocyk, A; Czyrak, A; Wedzony, K

    2008-09-01

    The present study indicates that activation of dopamine D1-like receptors by administration of SKF 38393 leads to dose-dependent (doses: 5, 10 and 20 mg/kg) increases in the expression of cFos proteins in the rat paraventricular nucleus of the hypothalamus (PVN). This effect was abolished by administration of SCH 23390, a dopamine D1-like receptor antagonist (0.5 and 1 mg/kg, given 30 min before SKF 38393--10 mg/kg), suggesting that the apparent effect is specific for activation of dopamine D1-like receptors. Expression of cFos after SKF 38393 (10 mg/kg) was observed in some, but not all, CRF-immunoreactive neurons, as well as in small portion of oxytocin- but not vasopressin-immunoreactive neurons (double-immunofluorescence experiments). There were also certain populations of nuclei that showed expression of cFos but did not co-localize with the above markers. We also found that both acute and repeated (once daily for 5 consecutive days) exposure to cocaine (25 mg/kg) attenuated the induction of cFos expression triggered by SKF 38393 when administered 24 hours after single or the last dose of cocaine (25 mg/kg). Attenuation was observed at the same level after single and chronic exposure to cocaine, indicating a rapid functional down-regulation of dopamine D1-like receptors that are resistant to subsequent doses of cocaine. These data provide evidence for the functional role of dopamine D1-like receptors in the PVN and indicate a functional adaptation of dopamine D1-like receptors following a single dose of cocaine without further progression of adaptation or resistance of D1-like receptor-mediated genomic function in the course of repeated cocaine intake.

  5. Nalfurafine prevents 5'-guanidinonaltrindole- and compound 48/80-induced spinal c-fos expression and attenuates 5'-guanidinonaltrindole-elicited scratching behavior in mice.

    PubMed

    Inan, S; Dun, N J; Cowan, A

    2009-09-29

    The aims of the present study were to establish if nalfurafine, a kappa opioid agonist, inhibits compulsive scratching in mice elicited by the s.c. administration (behind the neck) of 5'-guanidinonaltrindole (GNTI), a kappa opioid antagonist; to assess if nalfurafine prevents c-fos expression provoked by GNTI or compound 48/80, two chemically diverse pruritogens; and to distinguish on the basis of neuroanatomy, those neurons in the brainstem activated by either GNTI-induced itch or formalin-induced pain (both compounds given s.c. to the right cheek). Pretreatment of mice with nalfurafine (0.001-0.03 mg/kg s.c.) attenuated GNTI (0.3 mg/kg)-evoked scratching dose-dependently. A standard antiscratch dose of nalfurafine (0.02 mg/kg) had no marked effect on the spontaneous locomotion of mice. Tolerance did not develop to the antiscratch activity of nalfurafine. Both GNTI and compound 48/80 provoked c-fos expression on the lateral side of the superficial layer of the dorsal horn of the cervical spinal cord and pretreating mice with nalfurafine inhibited c-fos expression induced by both pruritogens. In contrast to formalin, GNTI did not induce c-fos expression in the trigeminal nucleus suggesting that pain and itch sensations are projected differently along the sensory trigeminal pathway. Our data indicate that the kappa opioid system is involved, at least in part, in the pathogenesis of itch; and that nalfurafine attenuates excessive scratching and prevents scratch-induced neuronal activity at the spinal level. On the basis of our results, nalfurafine holds promise as a potentially useful antipruritic in human conditions involving itch.

  6. Decline in c-myc mRNA expression but not the induction of c-fos mRNA expression is associated with differentiation of SH-SY5Y human neuroblastoma cells

    SciTech Connect

    Jalava, A.M.; Heikkilae, J.E.; Akerman, K.E.O. )

    1988-11-01

    The induction of differentiation in SH-SY5Y human neuroblastoma cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) is accompanied by a rapid and a transient expression of c-fos mRNA and a down-regulation of c-myc RNA. The TPA-induced expression of c-fos mRNA was inhibited by H-7, a specific inhibitor of protein kinase C (PK-C). Dioctanoylglycerol (DiC{sub 8}) failed to induce differentiation of SH-SY5Y cells or to down-regulate c-myc mRNA but it did induce the expression of c-fos mRNA. Treatment of IMR-32 human neuroblastoma cells with TPA did not cause differentiation although c-fos mRNA was induced. Since PK-C in SH-SY5Y cells was activated by both TPA and DiC{sub 8} it is suggested that the activation of PK-C alone is not sufficient to induce differentiation in SH-SY5Y cells. The down-regulation of c-myc mRNA rather than the induction of c-fos mRNA seems to be associated with differentiation process in SH-SY5Y cells.

  7. Contribution of REM sleep to Fos and FRA expression in the vestibular nuclei of rat leading to vestibular adaptation during the STS-90 Neurolab Mission.

    PubMed

    Pompeiano, O

    2007-01-01

    1. Electrophysical studies performed in ground-based experiments have shown that VN neurons respond to labyrinthine signals following stimulation of macular gravity receptors. Additional evidence indicates that VN neurons may also respond to extralabyrinthine signals of pontine origin, which occur during the PGO waves typical of REM sleep (Bizzi et al., 1964a, b; cf. also Pompeiano, 1967, 1970, 1974 for ref.). 2. In a previous study (Pompeiano et al., 2002) changes in Fos and FRA expression were used to identify the short-term (Fos) and the long-term (FRA) molecular changes which affect the VN neurons at different time points of the space flight. In particular, while Fos protein persists in the brain tissue only for a few hours (6-8 hrs) after its induction, FRA proteins, which can also be induced in the same experimental conditions, persist in the brain tissue for longer periods of time (i.e. from 12/24 hrs to days). 3. In order to relate the changes in gene expression which occurred in the VN during the space flight either to gravity changes or to REM sleep, we investigated in a recent study (Centini et al, 2006) the changes in Fos and FRA expression which occurred in different phases of the sleep-waking cycle, thus being indicative of the animal state. We could then compare the results obtained during the space lab Mission with those previously observed either in ground-based experiments during the physiological state of waking and slow-wave (SWS) or during neurochemically induced episodes of PS, as obtained after microinjection of appropriate agents in dorsal pontine structures of rats. 4. Our findings indicated that a waking state possibly associated with episodes of SWS, occurred at FD2 and FD14, i.e. at launch and after exposure of the animal to microgravity. It appeared also that at the reentry (R + 1) rather than at launch (FD2), an increase in Fos and FRA expression affected the noradrenergic LC neurons, as well as several related structures. These

  8. Electroacupuncture attenuates morphine withdrawal signs and c-Fos expression in the central nucleus of the amygdala in freely moving rats.

    PubMed

    Liu, Sheng; Zhou, Wenhua; Liu, Huifen; Yang, Guodong; Zhao, Weikang

    2005-05-24

    Experimental efforts for understanding the mechanisms of electroacupuncture (EA) for opiate addiction are partially hampered by restraint stress. In unrestrained animals, it is difficult to perform EA stimulation at acupuncture points frequently selected on the four limbs. The present study was performed to evaluate the effect of EA at the acupuncture point Shen-Shu (BL.23) on morphine withdrawal signs and c-Fos expression of the amygdala in freely moving rats or restrained rats. We applied immunohistochemistry to detect c-Fos-positive nuclei. Corticosterone levels and behavioral responses were measured during EA stimulation. The needles were bilaterally inserted and fixed at BL.23, and 100-Hz electric stimulation was conducted 30 min before naloxone-precipitated withdrawal. In both freely moving rats and restrained rats, EA significantly reduced the signs of morphine withdrawal. Notably, EA stimulation in freely moving rats attenuated c-Fos expression in the central nucleus of the amygdala while EA in restrained animals increased this response. In addition, the restrained rats emitted greater levels of vocalization and facial expression than freely moving rats during EA stimulation. Corticosterone levels were also significantly higher in restrained animals after EA stimulation. The new EA paradigm demonstrated in the present study might help the analysis of certain physiological responses induced by EA that would otherwise have been hindered by restraint stress.

  9. Repeated forced swim stress enhances CFA-evoked thermal hyperalgesia and affects the expressions of pCREB and c-Fos in the insular cortex.

    PubMed

    Imbe, H; Kimura, A; Donishi, T; Kaneoke, Y

    2014-02-14

    Stress affects brain activity and promotes long-term changes in multiple neural systems. Exposure to stressors causes substantial effects on the perception and response to pain. In several animal models, chronic stress produces lasting hyperalgesia. The insular (IC) and anterior cingulate cortices (ACC) are the regions exhibiting most reliable pain-related activity. And the IC and ACC play an important role in pain modulation via the descending pain modulatory system. In the present study we examined the expression of phospho-cAMP response element-binding protein (pCREB) and c-Fos in the IC and ACC after forced swim stress (FS) and complete Freund's adjuvant (CFA) injection to clarify changes in the cerebral cortices that affect the activity of the descending pain modulatory system in the rats with stress-induced hyperalgesia. FS (day 1, 10min; days 2-3, 20min) induced an increase in the expression of pCREB and c-Fos in the anterior IC (AIC). CFA injection into the hindpaw after the FS shows significantly enhanced thermal hyperalgesia and induced a decrease in the expression of c-Fos in the AIC and the posterior IC (PIC). Quantitative image analysis showed that the numbers of c-Fos-immunoreactive neurons in the left AIC and PIC were significantly lower in the FS+CFA group (L AIC, 95.9±6.8; L PIC, 181.9±23.1) than those in the naive group (L AIC, 151.1±19.3, p<0.05; L PIC, 274.2±37.3, p<0.05). These findings suggest a neuroplastic change in the IC after FS, which may be involved in the enhancement of CFA-induced thermal hyperalgesia through dysfunction of the descending pain modulatory system. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Ionotropic glutamatergic neurotransmission in the ventral tegmental area modulates DeltaFosB expression in the nucleus accumbens and abstinence syndrome in morphine withdrawal rats.

    PubMed

    Wang, Hui-Ling; Xiang, Xiao-Hui; Guo, Yuan; Wu, Wei-Ran; Cao, Dong-Yuan; Wang, Hui-Sheng; Zhao, Yan

    2005-12-19

    The present study sought to assess whether the blockade of ionotropic glutamate receptors in the ventral tegmental area could modulate morphine withdrawal in morphine-dependent rats and the expression of stable DeltaFosB isoforms in the nucleus accumbens during morphine withdrawal. Rats were injected (i.p.) with increasing doses of morphine for 1 week to develop physical dependence, and withdrawal was then precipitated by one injection of naloxone (2 mg/kg, i.p.). Abstinence signs such as jumping, wet-dog shake, writhing posture, weight loss, and Gellert-Holtzman scale score were recorded to evaluate naloxone-induced morphine withdrawal. Two ionotropic glutamate receptor antagonists, dizocilpine (MK-801) and 6, 7-dinitroquinnoxaline-2, 3-dione (DNQX), were microinjected unilaterally into the ventral tegmental area 30 min before naloxone precipitation. A second injection of naloxone (2 mg/kg i.p.) was given 1 h after the first naloxone injection to sustain a maximal level of withdrawal so that the expression of stable DeltaFosB isoforms in the nucleus accumbens could be measured. This would enable determination of the correlation between the MK-801 or DNQX-induced decrease in somatic withdrawal signs and the change in neuronal activity in the nucleus accumbens. The results showed that both MK-801 and DNQX significantly alleviated all symptoms of morphine withdrawal except for weight loss and reduced the expression of stable DeltaFosB isoforms within the nucleus accumbens. These data suggest that ionotropic glutamatergic neurotransmission in the ventral tegmental area regulates the levels of stable DeltaFosB isoforms in the nucleus accumbens, which play a very important role in modulating opiate withdrawal.

  11. Stimulus-induced reflex epileptic spasms in 5p- syndrome.

    PubMed

    Shirai, Kentaro; Saito, Yoshiaki; Yokoyama, Atushi; Nishimura, Yoko; Tamasaki, Akiko; Maegaki, Yoshihiro

    2016-02-01

    Here we describe two patients with 5p- syndrome who suffered from epilepsy characterised by stimulus-induced epileptic spasms manifesting as head nodding. In patient 1, a series of spasms were exclusively triggered by eating, and were associated with diffuse high-voltage slow waves on ictal EEG, particularly presenting as a positive slow potential at the left mid-temporal area. Clusters of sharp waves with negative polarity emerged in the same area during the inter-spasm periods during eating. In patient 2, spasms were provoked by either eating or micturition. Ictal EEG of clustered spasms after micturition showed positive slow or triphasic waves, which correlated with each spasm, over the bifrontal and vertex areas. These findings suggest that the focal cortical areas act as trigger regions in reflex epilepsies, and that a spasm-generator responsible for the execution of reflex spasms exists either in other cortical areas or in the subcortical structures. Although epilepsy is an unusual complication of 5p- syndrome, this syndrome may have a propensity to develop reflex epilepsy, particularly epileptic spasms. However, identification of responsible genes and their roles in this phenotype requires further investigations.

  12. Differential expression of the two Drosophila fos/kayak transcripts during oogenesis and embryogenesis.

    PubMed

    Souid, Sami; Yanicostas, Constantin

    2003-05-01

    The Dfos/kayak gene encodes a bZIP protein, DFos, required in a large variety of differentiation and morphogenetic processes throughout Drosophila development. The recent availability of an expressed sequence tag (EST) sequence led us to identify a novel kay mRNA encoding a deduced DFos isoform showing a specific NH(2)-terminal region. To gain further insight into the function and the regulation of this gene, we have investigated the expression pattern of the two kay mRNA isoforms, kay-RA and kay-RB, during oogenesis and embryogenesis by whole-mount in situ hybridization. Results show that, although the two kay RNA isoforms display fully distinct patterns of transcription during oogenesis, they show partially overlapping expression profiles in embryos. These data reveal a previously unsuspected level of complexity in the regulation of the expression of the kay gene. In addition, they suggest a possible requirement for this gene in the invagination processes during early gastrula stages.

  13. Immediate early gene expression in cat visual cortex during and after the critical period: differences between EGR-1 and Fos proteins.

    PubMed

    Kaplan, I V; Guo, Y; Mower, G D

    1996-02-01

    Immediate early gene (IEG) expression in the cat visual cortex is highly responsive to visual input and may initiate genetic mechanisms responsible for neuronal plasticity. The present study used immunohistochemical methods to address two issues regarding IEG expression in response to visual input. One was to define the differential response of distinct IEG families by comparing EGR-1 (also termed zif-268, NGFI-A, and Krox-24) and Fos proteins. The second was to determine whether IEG expression, in addition to reflecting neural activity, is related to the state of plasticity by comparing young and adult visual cortex. Immunoreactivity of the two IEG proteins was compared between 5-week-old and adult cats under three conditions of visual input: ambient light to assess basal levels of expression, 1 week of darkness to assess the effect of reduced activity, and exposure to light after 1 week of darkness to determine rapid changes in expression as a result of visual input. At both ages, there were marked differences in the expression of the two IEG proteins. EGR-1 responded to visual input with sustained changes in its level of expression. It showed high basal levels, reduced expression in darkness, and a rapid return to high constitutive levels with the introduction of light. Fos showed a markedly different profile. It had very low basal expression which was not demonstrably affected by darkness and its principal response was a marked transient induction upon exposure to light after darkness. These unique changes in expression highlight the complex response across IEGs to environmental input and suggest a genetic "on/off' signaling mechanism. There were marked differences in the laminar distribution of EGR-1 and Fos proteins between young and adult cats. In young animals, cells in all visual cortical layers showed high levels of EGR-1 and Fos proteins. In adults, immunostaining was largely specific to cells located above and below layer IV and only very faint labeling

  14. Delayed wave of c-Fos expression in the dorsal hippocampus involved specifically in persistence of long-term memory storage

    PubMed Central

    Katche, Cynthia; Bekinschtein, Pedro; Slipczuk, Leandro; Goldin, Andrea; Izquierdo, Ivan A.; Cammarota, Martin; Medina, Jorge H.

    2009-01-01

    Memory formation is a temporally graded process during which transcription and translation steps are required in the first hours after acquisition. Although persistence is a key characteristic of memory storage, its mechanisms are scarcely characterized. Here, we show that long-lasting but not short-lived inhibitory avoidance long-term memory is associated with a delayed expression of c-Fos in the hippocampus. Importantly, this late wave of c-Fos is necessary for maintenance of inhibitory avoidance long-term storage. Moreover, inhibition of transcription in the dorsal hippocampus 24 h after training hinders persistence but not formation of long-term storage. These findings indicate that a delayed phase of transcription is essential for maintenance of a hippocampus-dependent memory trace. Our results support the hypothesis that recurrent rounds of consolidation-like events take place late after learning in the dorsal hippocampus to maintain memories. PMID:20018662

  15. The role of CD4-dependent signaling in interleukin-16 induced c-Fos expression and facilitation of neurite outgrowth in cerebellar granule neurons.

    PubMed

    Fenster, Catherine P; Chisnell, Hope K; Fry, Carl R; Fenster, Steven D

    2010-11-26

    Neuronal interleukin 16 (NIL-16) is the larger neural-specific splice variant of the interleukin-16 (IL16) gene and shows restricted expression to post-mitotic neurons of the mammalian hippocampus and cerebellum. Although the N-terminus of NIL-16 is unique to the neuronal variant, the C-terminus is identical to pro-IL-16, the IL-16 precursor expressed primarily in T-cells. IL-16 was originally described as a proinflammatory cytokine and has diverse immunoregulatory effects which involve signaling through CD4. NIL-16-expressing neurons can secrete IL-16 and may express CD4; moreover, treatment of cultured cerebellar granule neurons (CGCs) with IL-16 increases the expression of c-Fos, an immediate-early gene which transcriptionally regulates genes directing survival, proliferation, and growth. Taken together, we hypothesize that IL-16 functions as a neuroregulatory cytokine which signals through neuronal CD4 receptors. In this study, we investigated the role of CD4 in IL-16-induced c-Fos expression in CGCs, as well as the effects of IL-16 on neuronal survival and growth. We detected components involved in IL-16-signaling in lymphocytes, including CD4 and the associated tyrosine kinase p56(lck), in CGCs using qRT-PCR and immunoblotting. We also show that IL-16 induces c-Fos expression in wild-type CGCs, but not CD4-deficient CGCs or following inhibition of p56(lck). Finally, treatment of CGCs with IL-16 enhanced neurite outgrowth, an effect also observed in CD4-deficient CGCs. Taken together, our results indicate that IL-16-signaling affects neuronal gene expression and growth through CD4-dependent and independent pathways. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  16. Expression of c-fos in auditory and non-auditory brain regions of the gerbil after manipulations that induce tinnitus.

    PubMed

    Wallhäusser-Franke, E; Mahlke, C; Oliva, R; Braun, S; Wenz, G; Langner, G

    2003-12-01

    Subjective tinnitus is a phantom sound sensation that does not result from acoustic stimulation and is audible to the affected subject only. Tinnitus-like sensations in animals can be evoked by procedures that also cause tinnitus in humans. In gerbils, we investigated brain activation after systemic application of sodium salicylate or exposure to loud noise, both known to be reliable tinnitus-inductors. Brains were screened for neurons containing the c-fos protein. After salicylate injections, auditory cortex was the only auditory area with consistently increased numbers of immunoreactive neurons compared to controls. Exposure to impulse noise led to prolonged c-fos expression in auditory cortex and dorsal cochlear nucleus. After both manipulations c-fos expression was increased in the amygdala, in thalamic midline, and intralaminar areas, in frontal cortex, as well as in hypothalamic and brainstem regions involved in behavioral and physiological defensive reactions. Activation of these non-auditory areas was attributed to acute stress, to aversive-affective components and autonomous reactions associated with the treatments and a resulting tinnitus. The present findings are in accordance with former results that provided evidence for suppressed activation in auditory midbrain but enhanced activation of the auditory cortex after injecting high doses of salicylate. In addition, our present results provide evidence that acute stress coinciding with a disruption of hearing may evoke activation of the auditory cortex. We interpret these results in favor of our model of central tinnitus generation.

  17. Chronic light deprivation inhibits appetitive associative learning induced by ethanol and its respective c-Fos and pCREB expression.

    PubMed

    Varela, Patrícia; Escosteguy-Neto, João Carlos; Coelho, Carolina Tesone; Mello, Luiz Eugênio; da Silveira, Dartiu Xavier; Santos-Junior, Jair Guilherme

    2014-11-01

    To address the role of mixed anxiety/mood disorder on appetitive associative learning, we verify whether previous chronic light deprivation changes ethanol-induced conditioned place preference and its respective expression of c-Fos and pCREB, markers of neuronal activity and plasticity. The experimental group was maintained in light deprivation for 24 h for a period of 4 wk. Subsequently, it was adapted to a standard light-dark cycle for 1 wk. As a control, some mice were maintained in standard cycle for a period of 4 wk (Naïve group). Then, all animals were submitted to behavioral tests to assess emotionality: elevated plus maze; open field; and forced swim. After that, they were submitted to ethanol-induced conditioned place preference. Ninety minutes after the place preference test, they were perfused, and their brains processed for c-Fos and pCREB immunohistochemistry. Light deprivation induced anxiety-like trait (elevated plus maze), despair (forced swim), and hyperlocomotion (open field), common features seen in other animal models of depression. Ethanol-induced conditioned place preference was accompanied by increases on c-Fos and pCREB in the hippocampus, prefrontal cortex and striatum. Interestingly, mice previously submitted to light deprivation did not develop either acquisition and/or expression of ethanol-induced conditioned place preference or increases in c-Fos and pCREB. Therefore, chronic light deprivation mimics several behavioral aspects of other animal models of depression. Furthermore, it could be useful to study the neurochemical mechanisms involved in the dual diagnosis. However, given its likely deleterious effects on appetitive associative memory, it should be used with caution to investigate the cognitive aspects related to the dual diagnosis.

  18. Effects of intracerebroventricular losartan on angiotensin II-mediated pressor responses and c-fos expression in near-term ovine fetus.

    PubMed

    Shi, Lijun; Mao, Caiping; Thornton, Simon N; Sun, Wanping; Wu, Jiawei; Yao, Jiaming; Xu, Zhice

    2005-12-26

    The renin-angiotensin system plays an important role in cardiovascular control. Intracerebroventricular (i.c.v.) angiotensin (ANG) II causes a reliable pressor response in the fetus at 90% gestation. To determine the roles of brain AT1 and AT2 receptors in this response, the effects of the central AT1 and AT2 receptor antagonists losartan and PD123319 were investigated in chronically prepared near-term ovine fetuses. Losartan at 0.5 mg/kg (i.c.v.) abolished central ANG II-induced pressor responses. High-dose losartan (5 mg/kg, i.c.v.) showed a potentiation of the pressor response to i.c.v. ANG II, accompanied by bradycardia. Associated with the pressor responses, c-fos expression in the cardiovascular controlling areas was significantly different between the low and high doses of losartan. These areas included the subfornical organ, median preoptic nucleus, organum vasculosum of the lamina terminalis, and paraventricular nuclei in the forebrain, and the tractus solitarius nuclei, lateral parabrachial nuclei in the hindbrain. Low-dose losartan markedly reduced c-fos in these areas after i.c.v. ANG II, while the high-dose losartan together with ANG II elicited a much stronger FOS-immunoreactivity in these areas than that induced by i.c.v. ANG II alone. This is a novel finding, that c-fos expression in the brain can be both activated and inhibited under the same condition. Central ANG II-induced fetal pressor responses were not altered by PD123319 (0.8 mg/kg). These results indicate that i.c.v. losartan at a high and a low dose has strikingly different effects on central ANG II-induced pressor responses in fetuses at late gestation, and that the AT1 mechanism plays an important role in fetal cardiovascular regulation.

  19. Expression of arthritis-causing HLA-B27 on Hela cells promotes induction of c-fos in response to in vitro invasion by Salmonella typhimurium.

    PubMed Central

    Ikawa, T; Ikeda, M; Yamaguchi, A; Tsai, W C; Tamura, N; Seta, N; Trucksess, M; Raybourne, R B; Yu, D T

    1998-01-01

    HLA-B27 confers a very strong genetic predisposition to development of a reactive arthritis after infection by bacteria such as Salmonella typhimurium. This study examines the role of HLA-B27 in the initiation of the earliest host activities after exposure to Salmonella, namely activation of the immediate early genes in the epithelial cells. Our major finding is that in Hela cells, the expression of c-fos was induced by Salmonella invasion only when the cells expressed the transfected HLA-B27 gene, but not the HLA-A1 gene or a truncated HLA-B27 gene lacking the exons encoding the cytoplasmic domain. C-fos is potentially capable of complexing with members of the c-jun family to become the AP-1 transcription complex. Parallel to c-fos expression, we found that only with the HLA-B27 transfectant was there expression of AP-1. AP-1 potentially controls the expression of a large number of genes. On screening a panel of proinflammatory molecules, we found that Salmonella invasion induced expression of monocyte chemoattractant protein-1 in the HLA-B27 cells. Since each of these separate positive findings belong to the same cascade of events after cell activation, together they reinforce the hypothesis that HLA-B27 plays a modulatory role in the early signal transduction events induced by Salmonella invasion. This hypothesis adds another item to the list of allele-specific activities carried out by HLA class I molecules. If similar activation also occurs in the joints, it may play a major role in arthritis. PMID:9421489

  20. Beta-adrenoceptor Activation by Norepinephrine Enhances Lipopolysaccharide-induced Matrix Metalloproteinase-9 Expression Through the ERK/JNK-c-Fos Pathway in Human THP-1 Cells

    PubMed Central

    Yin, Xiang; Zhou, Linli; Han, Fei; Han, Jie; Zhang, Yuanyuan; Sun, Zewei; Zhao, Wenting; Wang, Zhen

    2017-01-01

    Aim: Atherosclerosis is a chronic inflammatory disease, which leads to thrombosis and acute coronary syndrome. Matrix metalloproteinase-9 (MMP-9) is involved in the stability of the extracellular matrix (ECM) and atherosclerosis plaque. Until now, it is established that lipopolysaccharide (LPS) and norepinephrine (NE) are associated with the pathological process of atherosclerosis. However, the combined effect of LPS and NE on MMP-9 is unclear. We investigated the combined effect of LPS and NE on MMP-9 expression in human monocytes and the mechanism involved in the process. Methods: THP-1 cells were cultured and treated with LPS and/or NE. MMP-9 and TIMP-1 gene and protein expression were detected by real time PCR and ELISA, respectively. MMP-9 activity was detected by gelatin zymography. Adrenoceptor antagonists and MAPKs inhibitors were used to clarify the mechanism. Pathway-related proteins were detected by Western blot. Results: We found that NE enhances LPS-induced MMP-9 and TIMP-1 expression as well as MMP-9 activity in THP-1 cells. This effect is reversed by the beta (β)-adrenoceptor antagonist propranolol, extracellular signal-regulated kinases (ERK) inhibitor U0126, and c-Jun N-terminal kinase (JNK) inhibitor SP600125. NE enhances LPS-induced ERK/JNK phosphorylation. NE up-regulates LPS-induced c-Fos expression, which is counteracted by propranolol, U0126, and SP600125. Furthermore, c-Fos silence reverses the effect of NE on MMP-9 activity. Conclusions: Our results suggest that NE enhances LPS-induced MMP-9 expression through β-adrenergic receptor and downstream ERK/JNK-c-Fos pathway. This study may help us to understand the combined effect and mechanism of NE/LPS on MMP-9 expression. PMID:27237101

  1. Hypovolemic hemorrhage induces Fos expression in the rat hypothalamus: Evidence for involvement of the lateral hypothalamus in the decompensatory phase of hemorrhage.

    PubMed

    Göktalay, G; Millington, W R

    2016-05-13

    This study tested the hypothesis that the hypothalamus participates in the decompensatory phase of hemorrhage by measuring Fos immunoreactivity and by inhibiting neuronal activity in selected hypothalamic nuclei with lidocaine or cobalt chloride. Previously, we reported that inactivation of the arcuate nucleus inhibited, but did not fully prevent, the fall in arterial pressure evoked by hypotensive hemorrhage. Here, we report that hemorrhage (2.2 ml/100g body weight over 20 min) induced Fos expression in a high percentage of cells in the paraventricular, supraoptic and arcuate nuclei of the hypothalamus as shown previously. Lower densities of Fos immunoreactive cells were also found in the medial preoptic area (mPOA), anterior hypothalamus, lateral hypothalamus (LH), dorsomedial hypothalamus, ventromedial hypothalamus (VMH) and posterior hypothalamus. Bilateral injection of lidocaine (2%; 0.1 μl or 0.3 μl) or cobalt chloride (5mM; 0.3 μl) into the tuberal portion of the LH immediately before hemorrhage was initiated reduced the magnitude of hemorrhagic hypotension and bradycardia significantly. Lidocaine injection into the VMH also attenuated the fall in arterial pressure and heart rate evoked by hemorrhage although inactivation of the mPOA or rostral LH was ineffective. These findings indicate that hemorrhage activates neurons throughout much of the hypothalamus and that a relatively broad area of the hypothalamus, extending from the arcuate nucleus laterally through the caudal VMH and tuberal LH, plays an important role in the decompensatory phase of hemorrhage.

  2. Acupuncture attenuates repeated nicotine-induced behavioral sensitization and c-Fos expression in the nucleus accumbens and striatum of the rat.

    PubMed

    Chae, Younbyoung; Yang, Chae Ha; Kwon, Young Kyu; Kim, Mi Ryeo; Pyun, Kwang-Ho; Hahm, Dae-Hyun; Lee, Hye-Jung; Shim, Insop

    2004-03-25

    Repeated injections of nicotine can produce behavioral sensitization, as evidenced by an enhanced locomotor response to a subsequent injection of the drug. Behavioral sensitization has been suggested as a model for studying drug addiction. Acupuncture as a therapeutic intervention is widely used for treatment for many functional disorders, such as substance abuse and mental dysfunction. We examined the effect of acupuncture on nicotine-induced behavioral locomotor activity and c-fos expression in the nucleus accumbens and striatum utilizing the immunocytochemical detection of the Fos protein. The rats were given repeated daily nicotine injections (0.4 mg/kg s.c., twice daily for 7 days) followed by one challenging injection on the 4th day after the last daily injection. Acupuncture at zusanli (ST36), but not control, significantly attenuated expected increase in nicotine-induced locomotor activity and Fos-like-immunoreactivity in the nucleus accumebns and striatum to subsequent nicotine challenge. These findings suggest that acupuncture has a therapeutic effect on nicotine addiction, possibly by modulating postsynaptic neuronal activity in the nucleus accumbens and the striatum.

  3. Effect of NMDA receptor antagonist MK-801 on light-induced Fos expression in the suprachiasmatic nuclei and on melatonin production in the Syrian hamster.

    PubMed

    Vuillez, P; Jacob, N; Teclemariam-Mesbah, R; Van Rossum, A; Vivien-Roels, B; Pévet, P

    1998-09-01

    In mammals, circadian rhythms generated by the suprachiasmatic nuclei (SCN) are daily synchronized by a light-dark cycle. Photic information is transmitted to the SCN mainly through the direct retinohypothalamic tract, the neurotransmitters involved being excitatory amino acids. It is also commonly accepted that photoperiodic information coming from the retina via the SCN is transduced by the pineal into a nocturnal signal, i.e. melatonin production. Light exposure at night induces (1) an inhibition of melatonin synthesis and (2) an expression of c-fos in numerous cells of SCN. To determine the role of the NMDA receptor in these effects, we treated Syrian hamsters with ip injections of MK-801, a noncompetitive NMDA receptor antagonist. Several subpopulations of light-sensitive cells in the SCN are affected by MK-801. According to previous studies, MK-801 inhibits light-induced Fos immunoreactivity mainly in the most ventral part of the SCN. However, we observed that numerous other cells are still activated by light. When light is applied in the middle of the night, MK-801 pretreatment does not reduce Fos-ir in the dorsal SCN. At the beginning of the night, labeled cells in this part of the nucleus appear even more numerous after MK-801. We also found that MK-801 fails to reduce the light-induced inhibition of melatonin synthesis. Moreover, in control animals, which received no light stimulation, ip injection of MK-801 induces by itself a dose-dependent inhibition of melatonin production.

  4. UV-induced DNA damage is an intermediate step in UV-induced expression of human immunodeficiency virus type 1, collagenase, c-fos, and metallothionein

    SciTech Connect

    Stein, B.; Rahmsdorf, H.J.; Steffen, A.; Litfin, M.; Herrlich, P. )

    1989-11-01

    UV irradiation of human and murine cells enhances the transcription of several genes. Here we report on the primary target of relevant UV absorption, on pathways leading to gene activation, and on the elements receiving the UV-induced signal in the human immunodeficiency virus type 1 (HIV-1) long terminal repeat, in the gene coding for collagenase, and in the cellular oncogene fos. In order to induce the expression of genes, UV radiation needs to be absorbed by DNA and to cause DNA damage of the kind that cannot be repaired by cells from patients with xeroderma pigmentosum group A. UV-induced activation of the three genes is mediated by the major enhancer elements (located between nucleotide positions -105 and -79 of HIV-1, between positions -72 and -65 of the collagenase gene, and between positions -320 and -299 of fos). These elements share no apparent sequence motif and bind different trans-acting proteins; a member of the NF kappa B family binds to the HIV-1 enhancer, the heterodimer of Jun and Fos (AP-1) binds to the collagenase enhancer, and the serum response factors p67 and p62 bind to fos. DNA-binding activities of the factors recognizing the HIV-1 and collagenase enhancers are augmented in extracts from UV-treated cells. The increase in activity is due to posttranslational modification. While AP-1 resides in the nucleus and must be modulated there, NF kappa B is activated in the cytoplasm, indicating the existence of a cytoplasmic signal transduction pathway triggered by UV-induced DNA damage. In addition to activation, new synthesis of AP-1 is induced by UV radiation.

  5. Chronic wheel running affects cocaine-induced c-Fos expression in brain reward areas in rats.

    PubMed

    Zlebnik, Natalie E; Hedges, Valerie L; Carroll, Marilyn E; Meisel, Robert L

    2014-03-15

    Emerging evidence from human and animal studies suggests that exercise is a highly effective treatment for drug addiction. However, most work has been done in behavioral models, and the effects of exercise on the neurobiological substrates of addiction have not been identified. Specifically, it is unknown whether prior exercise exposure alters neuronal activation of brain reward circuitry in response to drugs of abuse. To investigate this hypothesis, rats were given 21 days of daily access to voluntary wheel running in a locked or unlocked running wheel. Subsequently, they were challenged with a saline or cocaine (15 mg/kg, i.p.) injection and sacrificed for c-Fos immunohistochemistry. The c-Fos transcription factor is a measure of cellular activity and was used to quantify cocaine-induced activation of reward-processing areas of the brain: nucleus accumbens (NAc), caudate putamen (CPu), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC). The mean fold change in cocaine-induced c-Fos cell counts relative to saline-induced c-Fos cell counts was significantly higher in exercising compared to control rats in the NAc core, dorsomedial and dorsolateral CPu, the prelimbic area, and the OFC, indicating differential cocaine-specific cellular activation of brain reward circuitry between exercising and control animals. These results suggest neurobiological mechanisms by which voluntary wheel running attenuates cocaine-motivated behaviors and provide support for exercise as a novel treatment for drug addiction. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Incubation of methamphetamine craving is associated with selective increases in expression of Bdnf and trkb, glutamate receptors, and epigenetic enzymes in cue-activated fos-expressing dorsal striatal neurons.

    PubMed

    Li, Xuan; Rubio, F Javier; Zeric, Tamara; Bossert, Jennifer M; Kambhampati, Sarita; Cates, Hannah M; Kennedy, Pamela J; Liu, Qing-Rong; Cimbro, Raffaello; Hope, Bruce T; Nestler, Eric J; Shaham, Yavin

    2015-05-27

    Cue-induced methamphetamine seeking progressively increases after withdrawal (incubation of methamphetamine craving), but the underlying mechanisms are largely unknown. We determined whether this incubation is associated with alterations in candidate genes in dorsal striatum (DS), a brain area implicated in cue- and context-induced drug relapse. We first measured mRNA expression of 24 candidate genes in whole DS extracts after short (2 d) or prolonged (1 month) withdrawal in rats following extended-access methamphetamine or saline (control condition) self-administration (9 h/d, 10 d). We found minimal changes. Next, using fluorescence-activated cell sorting, we compared gene expression in Fos-positive dorsal striatal neurons, which were activated during "incubated" cue-induced drug-seeking tests after prolonged withdrawal, with nonactivated Fos-negative neurons. We found significant increases in mRNA expression of immediate early genes (Arc, Egr1), Bdnf and its receptor (Trkb), glutamate receptor subunits (Gria1, Gria3, Grm1), and epigenetic enzymes (Hdac3, Hdac4, Hdac5, GLP, Dnmt3a, Kdm1a) in the Fos-positive neurons only. Using RNAscope to determine striatal subregion and cell-type specificity of the activated neurons, we measured colabeling of Fos with Drd1 and Drd2 in three DS subregions. Fos expression was neither subregion nor cell-type specific (52.5 and 39.2% of Fos expression colabeled with Drd1 and Drd2, respectively). Finally, we found that DS injections of SCH23390 (C17H18ClNO), a D1-family receptor antagonist known to block cue-induced Fos induction, decreased incubated cue-induced methamphetamine seeking after prolonged withdrawal. Results demonstrate a critical role of DS in incubation of methamphetamine craving and that this incubation is associated with selective gene-expression alterations in cue-activated D1- and D2-expressing DS neurons. Copyright © 2015 the authors 0270-6474/15/358232-13$15.00/0.

  7. C-Fos expression in trigeminal nucleus neurons after chemical irritation of the cornea: reduction by selective blockade of nociceptor chemosensitivity.

    PubMed

    Martinez, S; Belmonte, C

    1996-04-01

    The distribution and number of trigeminal brainstem and higher order sensory neurons expressing the protein product of the proto-oncogene c-fos after noxious stimulation of the cornea was studied in the rat using immunocytochemistry. The possibility that attenuation of nociceptive messages from the cornea by diltiazem reduced Fos-like immunoreactivity of spinal trigeminal neurons was also examined. A group of animals were killed 2-3 h after corneal stimulation. One cornea was stimulated with: a drop of 10 mM acetic acid; with acid plus mechanical scratching of the corneal epithelium; or with a drop of saline of 56 degrees C. Half of the animals treated with acid had been pretreated ipsilaterally with topical diltiazem (10 mM). Control rats received either saline in one eye or no treatment. Another group of animals were killed 7-8 h after stimulation with acetic acid. Fos-like immunoreactive neurons were counted in serial brainstem sections using an anti-Fos primary antiserum and processed according to the avidin-biotin complex method. In rats killed 2-3 h after corneal stimulation with acid, heat, or acid plus mechanical injury, labelled neurons were found in laminae I and II of the intermediate zone between caudalis and interpolaris subnuclei of the ipsilateral spinal trigeminal nucleus and, in a reduced number, in the symmetrical zones of the contralateral side. In animals stimulated with noxious heat or combined mechanical and chemical injury, a few scattered cells were also labelled in the ipsilateral junction between the cervical spinal cord and the caudalmost part of the trigeminal subnucleus caudalis. In rats killed 7 h after stimulation with acid, stained neurons were observed in the same areas of the trigeminal nucleus as in rats killed at shorter times, but in lower numbers; in these animals, no immunoreactive cells were found in deeper laminae or in higher sensory relay nuclei. Pretreatment with diltiazem significantly reduced the number of cells of the

  8. Exposure to an open-field arena increases c-Fos expression in a distributed anxiety-related system projecting to the basolateral amygdaloid complex.

    PubMed

    Hale, M W; Hay-Schmidt, A; Mikkelsen, J D; Poulsen, B; Shekhar, A; Lowry, C A

    2008-08-26

    Anxiety states and anxiety-related behaviors appear to be regulated by a distributed and highly interconnected system of brain structures including the basolateral amygdala. Our previous studies demonstrate that exposure of rats to an open-field in high- and low-light conditions results in a marked increase in c-Fos expression in the anterior part of the basolateral amygdaloid nucleus (BLA) compared with controls. The neural mechanisms underlying the anatomically specific effects of open-field exposure on c-Fos expression in the BLA are not clear, however, it is likely that this reflects activation of specific afferent input to this region of the amygdala. In order to identify candidate brain regions mediating anxiety-induced activation of the basolateral amygdaloid complex in rats, we used cholera toxin B subunit (CTb) as a retrograde tracer to identify neurons with direct afferent projections to this region in combination with c-Fos immunostaining to identify cells responding to exposure to an open-field arena in low-light (8-13 lux) conditions (an anxiogenic stimulus in rats). Adult male Wistar rats received a unilateral microinjection of 4% CTb in phosphate-buffered saline into the basolateral amygdaloid complex. Rats were housed individually for 11 days after CTb injections and handled (HA) for 2 min each day. On the test day rats were either, 1) exposed to an open-field in low-light conditions (8-13 lux) for 15 min (OF); 2) briefly HA or 3) left undisturbed (control). We report that dual immunohistochemical staining for c-Fos and CTb revealed an increase in the percentage of c-Fos-immunopositive basolateral amygdaloid complex-projecting neurons in open-field-exposed rats compared with HA and control rats in the ipsilateral CA1 region of the ventral hippocampus, subiculum and lateral entorhinal cortex. These data are consistent with the hypothesis that exposure to the open-field arena activates an anxiety-related neuronal system with convergent input to the

  9. Expression of beta2-microglobulin and c-fos mRNA: is there an influence of high- or low-flux dialyzer membranes?

    PubMed

    Haufe, C C; Eismann, U; Deppisch, R M; Stein, G

    2001-02-01

    Dialysis-related amyloidosis is an important complication of long-term hemodialysis (HD) therapy with several pathogenetic factors. One of them is the influence of the dialyzer membrane type on the synthesis of beta2-microglobulin (beta2m). In vitro results are controversial. Thus, the hypothesis of whether in vivo beta2m generation is induced by the HD procedure and whether this induction depends on the type of the used dialyzer membrane should be tested. The aim of the present study was to investigate the influence of "biocompatible" high-flux versus "bioincompatible" low-flux HD on in vivo beta2m generation as well as the induction of the early activation gene c-fos in peripheral blood cells. Six nondiabetic HD patients [mean age 46 (21 to 69) years; Kt/V> 1.2] were included in a randomized crossover study using either a low-flux (cellulosic/cuprophan) or a high-flux (polyamide) dialyzer membrane. At the end of a four-week run-in period for each membrane, whole blood samples were taken before, immediately at, and four hours after the end of the dialysis session. MRNA was extracted, and after transcription to cDNA, quantitative polymerase chain reaction was performed for the beta2m gene, the early response gene c-fos, and the GAP-DH housekeeping gene. Based on the applied method for detection of specific mRNA, the results were given as ratio of beta2m or c-fos cDNA per GAP-DH cDNA. General cell activation during HD was indicated by increasing mRNA expression of c-fos related to the time course of the dialysis session, whereas beta2m did not change significantly. However, no difference was found when comparing the low-flux and the high-flux dialyzer membranes. Despite the evidence for activation of peripheral blood cells, as indicated by increasing c-fos message, no sign of beta2m mRNA induction during HD procedure with different dialyzer membranes was seen. Our results suggest that there is post-transcriptional regulation of beta2m generation and/or release as

  10. Effect of teicoplanin on the expression of c-myc and c-fos proto-oncogenes in MCF-7 breast cancer cell line

    PubMed Central

    Ashouri, Saeideh; Khujin, Maryam Hosseindokht; Kazemi, Mohammad; Kheirollahi, Majid

    2016-01-01

    Background: Teicoplanin is a member of vancomycin-ristocetin family of glycopeptide antibiotics. It mediated wound healing by increasing neovascularization possibly through activation of MAP kinase signaling pathway. The aim of this study is an evaluation of c-myc and c-fos genes expression after treatment of cells by teicoplanin and determines whether this glycopeptide antibiotic exerts its proliferation effects by influencing the expression of these genes. Hence, this study was designed to elucidate one possible mechanism underlying teicoplanin effects on cell proliferation using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Materials and Methods: Breast cancer cell line, MCF-7, was cultured, and three different concentrations of teicoplanin were added to the plates. We measured the cell proliferation rate by MTT assay. After cell harvesting, total RNA was extracted to synthesize single-stranded cDNA. Real-time polymerase chain reaction was performed, and the data were analyzed. Results: It was observed that the level of c-fos and c-myc genes’ expressions was decreased at all three different concentrations of teicoplanin. Conclusion: it could be concluded that although teicoplanin is considered as an enhancing cell growth and proliferation, but probably its effect is not through MAP kinase signaling pathway or perhaps even has inhibitory effect on the expression of some genes such as c-myc and c-fos in this pathway. Hence, the mechanism of action of teicoplanin for increasing cell propagation, through cell signaling pathways or chromosomal abnormalities, remains unclear, and further studies should be conducted. PMID:28028512

  11. Cue-Induced Food Seeking After Punishment Is Associated With Increased Fos Expression in the Lateral Hypothalamus and Basolateral and Medial Amygdala.

    PubMed

    Campbell, Erin J; Barker, David J; Nasser, Helen M; Kaganovsky, Konstantin; Dayas, Christopher V; Marchant, Nathan J

    2017-02-20

    In humans, relapse to unhealthy eating habits following dieting is a significant impediment to obesity treatment. Food-associated cues are one of the main triggers of relapse to unhealthy eating during self-imposed abstinence. Here we report a behavioral method examining cue-induced relapse to food seeking following punishment-induced suppression of food taking. We trained male rats to lever press for food pellets that were delivered after a 10-s conditional stimulus (CS) (appetitive). Following training, 25% of reinforced lever presses resulted in the presentation of a compound stimulus consisting of a novel CS (aversive) and the appetitive CS followed by a pellet and footshock. After punishment-imposed abstinence, we tested the rats in an extinction test where lever pressing resulted in the presentation of either the appetitive or aversive CS. We then compared activity of lateral hypothalamus (LH) and associated extrahypothalamic regions following this test. We also assessed Fos expression in LH orexin and GABA neurons. We found that cue-induced relapse of food seeking on test was higher in rats tested with the appetitive CS compared to the aversive CS. Relapse induced by the appetitive CS was associated with increased Fos expression in LH, caudal basolateral amygdala (BLA), and medial amygdala (MeA). This relapse was also associated with increased Fos expression in LH orexin and VGAT-expressing neurons. These data show that relapse to food seeking can be induced by food-associated cues after punishment-imposed abstinence, and this relapse is associated with increased activity in LH, caudal BLA, and MeA. (PsycINFO Database Record

  12. Fluorescent visualisation of the hypothalamic oxytocin neurones activated by cholecystokinin-8 in rats expressing c-fos-enhanced green fluorescent protein and oxytocin-monomeric red fluorescent protein 1 fusion transgenes.

    PubMed

    Katoh, A; Shoguchi, K; Matsuoka, H; Yoshimura, M; Ohkubo, J-I; Matsuura, T; Maruyama, T; Ishikura, T; Aritomi, T; Fujihara, H; Hashimoto, H; Suzuki, H; Murphy, D; Ueta, Y

    2014-05-01

    The up-regulation of c-fos gene expression is widely used as a marker of neuronal activation elicited by various stimuli. Anatomically precise observation of c-fos gene products can be achieved at the RNA level by in situ hybridisation or at the protein level by immunocytochemistry. Both of these methods are time and labour intensive. We have developed a novel transgenic rat system that enables the trivial visualisation of c-fos expression using an enhanced green fluorescent protein (eGFP) tag. These rats express a transgene consisting of c-fos gene regulatory sequences that drive the expression of a c-fos-eGFP fusion protein. In c-fos-eGFP transgenic rats, robust nuclear eGFP fluorescence was observed in osmosensitive brain regions 90 min after i.p. administration of hypertonic saline. Nuclear eGFP fluorescence was also observed in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) 90 min after i.p. administration of cholecystokinin (CCK)-8, which selectively activates oxytocin (OXT)-secreting neurones in the hypothalamus. In double transgenic rats that express c-fos-eGFP and an OXT-monomeric red fluorescent protein 1 (mRFP1) fusion gene, almost all mRFP1-positive neurones in the SON and PVN expressed nuclear eGFP fluorescence 90 min after i.p. administration of CCK-8. It is possible that not only a plane image, but also three-dimensional reconstruction image may identify cytoplasmic vesicles in an activated neurone at the same time.

  13. The hypophagic factor oleoylethanolamide differentially increases c-fos expression in appetite regulating centres in the brain of wild type and histamine deficient mice.

    PubMed

    Umehara, Hayato; Fabbri, Roberta; Provensi, Gustavo; Passani, M Beatrice

    2016-11-01

    Histaminergic neurons in the hypothalamic tuberomamillary nucleus (TMN) establish connections with virtually all brain areas. Recent evidence suggests that feeding-related motivation is correlated with the activation of a subpopulation of histamine neurons in the ventral TMN that project to hypothalamic and subcortical areas controlling feeding behaviour. Oleoylethanolamide (OEA) is a hypophagic lipid-amide released by the small intestine in response to daily fat intake that indirectly activates hypothalamic oxytocin-neurons in the paraventricular (PVN) and supraoptic (SON) nuclei. We recently showed that OEA requires the integrity of neuronal histamine to fully display its hypophagic effect. Here we aimed to investigate if differences exist in OEA-induced c-Fos expression in several brain regions of fasted, histidine decarboxylase (HDC)-KO mice that do not synthesize histamine, and wild type (WT) littermates. All the brain regions examined receive histaminergic innervation and are involved in different aspects of feeding behaviour. We found that OEA increased c-Fos expression in the SON, arcuate nucleus (ARC) and the amygdala of WT mice, but not HDC-KO mice, whereas neither genotype nor treatment differences were observed in the lateral and dorsomedial hypothalamus. Furthermore, oxytocin-immunostaining was markedly increased in the neurohypophysis of WT and not in HDC-KO mice. Of note, OEA increased c-Fos expression in the nucleus of solitary tract of both genotypes. Our findings suggest that the TMN serves as a relay station to elaborate peripheral signals that control homeostatic and adaptive behavioural responses. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Enhancement of delay eyelid conditioning by microcurrent electrical stimulation of the medial prefrontal cortex is triggered by the expression of Fos protein in guinea pigs

    PubMed Central

    ZHENG, YA-JUAN; DONG, YU-CHEN; ZHU, CHAO; ZHAO, MEI-SHENG

    2016-01-01

    Eyelid conditioning, including delay eyelid conditioning and trace eyelid conditioning, has been used extensively to study neural structures and mechanisms of learning and memory as a form of associative learning. In the present study, microcurrent electrical stimulation was used to stimulate the medial prefrontal cortex (mPFC) to induce delay eyelid conditioning in guinea pigs. The acquisition rate and relative latency of the conditioned eyelid response (CR) and the startle eyelid response (SR) were analyzed. The mPFC sites in the guinea pigs were examined under a light microscope following Nissl staining. In addition, the expression of Fos protein in neurons was detected using immunohistochemistry and western blot analysis. The results indicated that the acquisition rates of CR and SR were increased significantly (P<0.05), whilst the relative latencies of CR and SR were decreased significantly (P<0.05). Lesions were observed in the mPFC regions in the training group when compared with the control group. In addition, immunohistochemistry and western blot analysis revealed that Fos expression was significantly increased in the training group when compared with the sham group for the control and resident-intruder test guinea pigs (P<0.05). Therefore, the enhancement of delay eyelid conditioning by microcurrent electrical stimulation of the mPFC in guinea pigs was triggered by the expression of Fos protein. The observations of the present study further expand the understanding of conditioned reflexes and may aid future investigations into the formation of eyelid conditioning and the mechanisms underlying the circuit in various conditions. PMID:26998030

  15. Individual Variations in Maternal Care Early in Life Correlate with Later Life Decision-Making and c-Fos Expression in Prefrontal Subregions of Rats

    PubMed Central

    van Hasselt, Felisa N.; de Visser, Leonie; Tieskens, Jacintha M.; Cornelisse, Sandra; Baars, Annemarie M.; Lavrijsen, Marla; Krugers, Harm J.; van den Bos, Ruud; Joëls, Marian

    2012-01-01

    Early life adversity affects hypothalamus-pituitary-adrenal axis activity, alters cognitive functioning and in humans is thought to increase the vulnerability to psychopathology–e.g. depression, anxiety and schizophrenia- later in life. Here we investigated whether subtle natural variations among individual rat pups in the amount of maternal care received, i.e. differences in the amount of licking and grooming (LG), correlate with anxiety and prefrontal cortex-dependent behavior in young adulthood. Therefore, we examined the correlation between LG received during the first postnatal week and later behavior in the elevated plus maze and in decision-making processes using a rodent version of the Iowa Gambling Task (rIGT). In our cohort of male and female animals a high degree of LG correlated with less anxiety in the elevated plus maze and more advantageous choices during the last 10 trials of the rIGT. In tissue collected 2 hrs after completion of the task, the correlation between LG and c-fos expression (a marker of neuronal activity) was established in structures important for IGT performance. Negative correlations existed between rIGT performance and c-fos expression in the lateral orbitofrontal cortex, prelimbic cortex, infralimbic cortex and insular cortex. The insular cortex correlations between c-fos expression and decision-making performance depended on LG background; this was also true for the lateral orbitofrontal cortex in female rats. Dendritic complexity of insular or infralimbic pyramidal neurons did not or weakly correlate with LG background. We conclude that natural variations in maternal care received by pups may significantly contribute to later-life decision-making and activity of underlying brain structures. PMID:22693577

  16. Enhancement of delay eyelid conditioning by microcurrent electrical stimulation of the medial prefrontal cortex is triggered by the expression of Fos protein in guinea pigs.

    PubMed

    Zheng, Ya-Juan; Dong, Yu-Chen; Zhu, Chao; Zhao, Mei-Sheng

    2016-03-01

    Eyelid conditioning, including delay eyelid conditioning and trace eyelid conditioning, has been used extensively to study neural structures and mechanisms of learning and memory as a form of associative learning. In the present study, microcurrent electrical stimulation was used to stimulate the medial prefrontal cortex (mPFC) to induce delay eyelid conditioning in guinea pigs. The acquisition rate and relative latency of the conditioned eyelid response (CR) and the startle eyelid response (SR) were analyzed. The mPFC sites in the guinea pigs were examined under a light microscope following Nissl staining. In addition, the expression of Fos protein in neurons was detected using immunohistochemistry and western blot analysis. The results indicated that the acquisition rates of CR and SR were increased significantly (P<0.05), whilst the relative latencies of CR and SR were decreased significantly (P<0.05). Lesions were observed in the mPFC regions in the training group when compared with the control group. In addition, immunohistochemistry and western blot analysis revealed that Fos expression was significantly increased in the training group when compared with the sham group for the control and resident-intruder test guinea pigs (P<0.05). Therefore, the enhancement of delay eyelid conditioning by microcurrent electrical stimulation of the mPFC in guinea pigs was triggered by the expression of Fos protein. The observations of the present study further expand the understanding of conditioned reflexes and may aid future investigations into the formation of eyelid conditioning and the mechanisms underlying the circuit in various conditions.

  17. Light-induced c-Fos expression in the SCN and behavioural phase shifts of Djungarian hamsters with a delayed activity onset.

    PubMed

    Schöttner, Konrad; Vuillez, Patrick; Challet, Etienne; Pévet, Paul; Weinert, Dietmar

    2015-06-01

    C-Fos expression in the suprachiasmatic nucleus (SCN) and phase shifts of the activity rhythm following photic stimulation were investigated in Djungarian hamsters (Phodopus sungorus) of two different circadian phenotypes. Wild-type (WT) hamsters display robust daily patterns of locomotor activity according to the light/dark conditions. Hamsters of the DAO (delayed activity onset) phenotype, however, progressively delay the activity onset, whereas activity offset remains coupled to "light-on". Although the exact reason for the delayed activity onset is not yet clarified, it is connected with a disturbed interaction between the light/dark cycle and the circadian clock. The aim was to test the link between photoreception and the behavioral output of the circadian system in hamsters of both phenotypes, to get further insight in the underlying mechanism of the DAO phenomenon. Animals were exposed to short light pulses at different times during the dark period to analyze phase shifts of the activity rhythm and expression of Fos protein in the SCN. The results indicate that the photosensitive phase in DAO hamsters is shifted like the activity onset. Also, phase shifts were significantly smaller in DAO hamsters. At the same time, levels of Fos expression did not differ between phenotypes regarding the circadian phase. The results provide evidence that the shifted photosensitivity of the circadian system in DAO hamsters does not differ from that of WT animals, and lead us to conclude that processes within the SCN that enable light information to reset the circadian pacemaker might offer an explanation for the DAO phenomenon.

  18. VDR/RXR and TCF4/β-catenin cistromes in colonic cells of colorectal tumor origin: impact on c-FOS and c-MYC gene expression.

    PubMed

    Meyer, Mark B; Goetsch, Paul D; Pike, J Wesley

    2012-01-01

    Many of the transcriptional and growth regulating activities of 1α,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] in the intestine and colon are recapitulated in the human colorectal cancer cell LS180. We therefore used this line together with chromatin immunoprecipitation-seq and gene expression analyses to identify the vitamin D receptor (VDR)/retinoid X receptor (RXR) and transcription factor 7-like 2 (TCF7L2/TCF4)/β-catenin cistromes and the genes that they regulate. VDR and RXR colocalized to predominantly promoter distal, vitamin D response element-containing sites in a largely ligand-dependent manner. These regulatory sites control the expression of both known as well as novel 1,25-(OH)(2)D(3) target genes. TCF4 and β-catenin cistromes partially overlapped, contained TCF/lymphoid enhancer-binding factor consensus elements, and were only modestly influenced by 1,25-(OH)(2)D(3). However, the two heterodimer complexes colocalized at sites near a limited set of genes that included c-FOS and c-MYC; the expression of both genes was modulated by 1,25-(OH)(2)D(3). At the c-FOS gene, both VDR/RXR and TCF4/β-catenin bound to a single distal enhancer located 24 kb upstream of the transcriptional start site. At the c-MYC locus, however, binding was noted at a cluster of sites between -139 and -165 kb and at a site located -335 kb upstream. Examined as isolated enhancer fragments, these regions exhibited basal and 1,25-(OH)(2)D(3)-inducible activities that were interlinked to both VDR and β-catenin activation. These data reveal additional complexity in the regulation of target genes by 1,25-(OH)(2)D(3) and support a direct action of both VDR and the TCF4/β-catenin regulatory complex at c-FOS and c-MYC.

  19. Acute injection of drugs with low addictive potential (delta(9)-tetrahydrocannabinol, 3,4-methylenedioxymethamphetamine, lysergic acid diamide) causes a much higher c-fos expression in limbic brain areas than highly addicting drugs (cocaine and morphine).

    PubMed

    Erdtmann-Vourliotis, M; Mayer, P; Riechert, U; Höllt, V

    1999-08-25

    It is regarded as a common pharmacological property responsible for the addictive potential of drugs of abuse that they are able to activate brain areas involved in the sensation of pleasure, especially the nucleus accumbens. To investigate the connection between addictive potential and stimulation of critical brain areas in more detail, we studied c-fos accumulation in response to various addicting drugs in direct comparison. The substances were injected into drug-naive rats, and c-fos mRNA levels were measured throughout the brain by in situ hybridization. Cocaine in a high dose of 50 mg/kg yielded only a discrete c-fos expression in the medial and central striatum. Morphine (50 mg/kg) caused a weak c-fos synthesis in the lateral septum. THC (delta(9)-tetrahydrocannabinol), 25 mg/kg, induced c-fos mRNA again in the lateral septum and furthermore in large parts of the striatum including the nucleus accumbens. LSD (lysergic acid diamide), 1 mg/kg, elicited a similar c-fos expression pattern as THC, but there was additionally a very strong hybridization signal in the cerebral cortex, especially in the upper layers, and in the ventral part of the periaqueductal gray. The widest range of brain areas was activated by MDMA (3, 4-methylenedioxymethamphetamine, 'ecstasy'), 6 mg/kg. In addition to the regions that responded to LSD, there was a very pronounced c-fos signal in the nucleus accumbens core and shell and in the mammillary nuclei. Taken together, our study revealed that the drugs with the highest addictive potential, cocaine and morphine, yielded a very low c-fos synthesis throughout the brain whereas the brain regions closely linked to pleasure (especially the nucleus accumbens) responded strongly to drugs with an apparently lower addictive potential (THC, LSD, MDMA).

  20. Suckling and sucrose ingestion suppress persistent hyperalgesia and spinal Fos expression after forepaw inflammation in infant rats.

    PubMed

    Ren, K; Blass, E M; Zhou, Q; Dubner, R

    1997-02-18

    Sweet taste and nonnutritive suckling produce analgesia to transient noxious stimuli in infant rats and humans. The present study evaluated the pain-modulating effects of sucrose and suckling in a rat model of persistent pain and hyperalgesia that mimics the response to tissue injury in humans. Fore- and hindpaw withdrawal latencies from a 30 degrees or 48 degrees C brass stylus were determined in 10-day-old rats following paw inflammation induced by complete Freund's adjuvant (CFA; 1:1 injected s.c. in a 0.01 ml volume). CFA markedly decreased escape latencies to both 48 degrees and 30 degrees C stimulation, thereby demonstrating thermal hyperalgesia and mechanical allodynia. The combination of nonnutritive suckling and sucrose (7.5%, 0.01-0.06 ml/min) infusion markedly increased escape latencies to forepaw stimulation in both CFA-treated and control rats. In contrast, intraoral sucrose and suckling did not increase hindpaw withdrawal latencies in either control or CFA-inflamed rats. The effect was specific to sweet taste because neither water nor isotonic saline infusion affected forepaw escape latencies. Parallel findings were obtained for CFA-induced Fos-like immunoreactivity (Fos-LI), a marker of neuronal activation. Fos-LI was selectively induced in cervical and lumbar regions ipsilateral to forepaw and hindpaw inflammation, respectively. Suckling-sucrose treatment significantly reduced Fos-LI at the cervical but not at the lumbar regions. These findings demonstrate: (i) the development of persistent pain and hyperalgesia in 10-day-old rats that can be attenuated by endogenous pain-modulating systems activated by taste and nonnutritive suckling; (ii) the mediation of the sucrose-suckling analgesia and antihyperalgesia at the spinal level; and (iii) a differential rostrocaudal maturation of descending pain-modulating systems to the spinal cord of 10-day-old rats. These findings may provide new clinical approaches for engaging endogenous analgesic mechanisms in

  1. Regional Fos-expression induced by γ-hydroxybutyrate (GHB): comparison with γ-butyrolactone (GBL) and effects of co-administration of the GABAB antagonist SCH 50911 and putative GHB antagonist NCS-382.

    PubMed

    van Nieuwenhuijzen, P S; McGregor, I S; Chebib, M; Hunt, G E

    2014-09-26

    γ-Hydroxybutyrate (GHB) has a complex array of neural actions that include effects on its own high-affinity GHB receptor, the release of neuroactive steroids, and agonist actions at GABAA and GABAB receptors. We previously reported partial overlap in the c-Fos expression patterns produced by GHB and the GABAB agonist, baclofen in rats. The present study extends these earlier findings by examining the extent to which GHB Fos expression and behavioral sedation are prevented by (2S)-(+)-5,5-dimethyl-2-morpholineacetic acid (SCH 50911), a GABAB antagonist, and NCS-382, a putative antagonist at the high-affinity GHB receptor. We also compare Fos expression caused by GHB and its precursor γ-butyrolactone (GBL), which is a pro-drug for GHB but lacks the high sodium content of the parent GHB molecule. Both GHB (1,000 mg/kg) and GBL (600 mg/kg) induced rapid sedation in rats that lasted over 90 min and caused similar Fos expression patterns, albeit with GBL causing greater activation of the nucleus accumbens (core and shell) and dentate gyrus (granular layer). Pretreatment with SCH 50911 (100mg/kg) partly reversed the sedative effects of GHB and significantly reduced GHB-induced Fos expression in only four regions: the tenia tecta, lateral habenula, dorsal raphe and laterodorsal tegmental nucleus. NCS-382 (50mg/kg) had no effect on GHB-induced sedation or Fos expression. When given alone, both NCS-382 and SCH 50911 increased Fos expression in the bed nucleus of the stria terminalis, central amygdala, parasubthalamic nucleus and nucleus of the solitary tract. SCH 50911 alone affected the Islands of Calleja and the medial, central and paraventricular thalamic nuclei. Overall, this study shows a surprising lack of reversal of GHB-induced Fos expression by two relevant antagonists, both of which have marked intrinsic actions. This may reflect the limited doses tested but also suggests that GHB Fos expression reflects mechanisms independent of GHB and GABAB receptors.

  2. Chronic stress disrupts fear extinction and enhances amygdala and hippocampal Fos expression in an animal model of post-traumatic stress disorder.

    PubMed

    Hoffman, Ann N; Lorson, Nickolaus G; Sanabria, Federico; Foster Olive, M; Conrad, Cheryl D

    2014-07-01

    Chronic stress may impose a vulnerability to develop maladaptive fear-related behaviors after a traumatic event. Whereas previous work found that chronic stress impairs the acquisition and recall of extinguished fear, it is unknown how chronic stress impacts nonassociative fear, such as in the absence of the conditioned stimulus (CS) or in a novel context. Male rats were subjected to chronic stress (STR; wire mesh restraint 6 h/d/21d) or undisturbed (CON), then tested on fear acquisition (3 tone-footshock pairings), and two extinction sessions (15 tones/session) within the same context. Then each group was tested (6 tones) in the same context (SAME) or a novel context (NOVEL), and brains were processed for functional activation using Fos immunohistochemistry. Compared to CON, STR showed facilitated fear acquisition, resistance to CS extinction on the first extinction day, and robust recovery of fear responses on the second extinction day. STR also showed robust freezing to the context alone during the first extinction day compared to CON. When tested in the same or a novel context, STR exhibited higher freezing to context than did CON, suggesting that STR-induced fear was independent of context. In support of this, STR showed increased Fos-like expression in the basolateral amygdala and CA1 region of the hippocampus in both the SAME and NOVEL contexts. Increased Fos-like expression was also observed in the central amygdala in STR-NOVEL vs. CON-NOVEL. These data demonstrate that chronic stress enhances fear learning and impairs extinction, and affects nonassociative processes as demonstrated by enhanced fear in a novel context.

  3. Post-weaning social isolation attenuates c-Fos expression in GABAergic interneurons in the basolateral amygdala of adult female rats.

    PubMed

    Lukkes, Jodi L; Burke, Andrew R; Zelin, Naomi S; Hale, Matthew W; Lowry, Christopher A

    2012-12-05

    Previous studies have found that adolescent social isolation of rats can lead to an increased anxiety state during adulthood, while chronic anxiety states are associated with dysregulated local GABAergic inhibition within the basolateral amygdala (BL). Therefore, we investigated the effects of post-weaning social isolation of female rats, in combination with a challenge with the anxiogenic drug, N-methyl-beta-carboline-3-carboxamide (FG-7142), on a subset of GABAergic interneurons in the BL in adulthood using dual immunohistochemical staining for c-Fos and parvalbumin. Juvenile female rats were reared in isolation or in groups of three for a 3-week period from weaning to mid-adolescence, after which all rats were group-housed for an additional 2 weeks. Group-reared rats and isolation-reared rats injected with FG-7142 had increased c-Fos expression in GABAergic interneurons in the anterior part of the BL compared to group-reared rats and isolation-reared rats, respectively, injected with vehicle. Isolation rearing had a main effect to decrease c-Fos expression in GABAergic interneurons in the anterior part of the BL compared to group-reared rats. These data suggest that post-weaning social isolation of female rats leads to dysregulation of a parvalbumin-containing subset of local GABAergic interneurons in the anterior part of the BL, which have previously been implicated in the pathophysiology of chronic anxiety states. These cellular changes may lead to an increased vulnerability to stress- and anxiety-related responses in adulthood.

  4. The non-peptide neurokinin-1 antagonist, RPR 100893, decreases c-fos expression in trigeminal nucleus caudalis following noxious chemical meningeal stimulation.

    PubMed

    Cutrer, F M; Moussaoui, S; Garret, C; Moskowitz, M A

    1995-02-01

    The effect of RPR 100893, a selective and specific neurokinin-1 antagonist, or its enantiomer RPR 103253 was examined on c-fos antigen expression in brain stem and upper cervical cord 2 h after intracisternal capsaicin injection (30.5 micrograms/ml) in pentobarbital-anesthetized Hartley guinea-pigs. Positive cells were counted at three levels corresponding to obex, -2.25 mm and -6.75 mm in 18 sections (50 microns). Immunoreactivity was strongly expressed within laminae I and IIo of trigeminal nucleus caudalis, area postrema and the leptomeninges. Moderate labeling was present in the nucleus of the solitary tract and the medullary lateral reticular nucleus, whereas few positive cells were found in the ventral portion of the medullary reticular nucleus and Rexed laminae III-V and X. The distribution of labeled cells was consistent with previously reported results following subarachnoid placement of the noxious agents, blood or carrageenin. Pretreatment with RPR 100893 (1, 10 and 100 micrograms/kg, i.v.) but not its enantiomer (100 micrograms/kg, i.v.) 30 min prior to capsaicin injection significantly reduced the number of positive cells in the trigeminal nucleus caudalis (P < 0.01) in a dose-dependent manner, but not within area postrema or nucleus of the solitary tract. These results indicate that (i) the instillation of capsaicin into the subarachnoid space is an effective stimulus for the induction of c-fos antigen within trigeminal nucleus caudalis, presumably through activation of trigeminovascular afferents, and (ii) the neurokinin-1 antagonist RPR 100893 reduces the number of positive cells selectively within this nucleus. The findings are significant because drugs which alleviate vascular headaches decrease the number of c-fos-positive cells within trigeminal nucleus caudalis following noxious meningeal stimulation. Hence, strategies aimed at blocking the neurokinin-1 receptor may be useful for treating migraine and cluster headache.

  5. Topical dura mater application of CFA induces enhanced expression of c-fos and glutamate in rat trigeminal nucleus caudalis: attenuated by KYNA derivate (SZR72).

    PubMed

    Lukács, M; Warfvinge, K; Tajti, J; Fülöp, F; Toldi, J; Vécsei, L; Edvinsson, L

    2017-12-01

    Migraine is a debilitating neurological disorder where trigeminovascular activation plays a key role. We have previously reported that local application of Complete Freund's Adjuvant (CFA) onto the dura mater caused activation in rat trigeminal ganglion (TG) which was abolished by a systemic administration of kynurenic acid (KYNA) derivate (SZR72). Here, we hypothesize that this activation may extend to the trigeminal complex in the brainstem and is attenuated by treatment with SZR72. Activation in the trigeminal nucleus caudalis (TNC) and the trigeminal tract (Sp5) was achieved by application of CFA onto the dural parietal surface. SZR72 was given intraperitoneally (i.p.), one dose prior CFA deposition and repeatedly daily for 7 days. Immunohistochemical studies were performed for mapping glutamate, c-fos, PACAP, substance P, IL-6, IL-1β and TNFα in the TNC/Sp5 and other regions of the brainstem and at the C1-C2 regions of the spinal cord. We found that CFA increased c-fos and glutamate immunoreactivity in TNC and C1-C2 neurons. This effect was mitigated by SZR72. PACAP positive fibers were detected in the fasciculus cuneatus and gracilis. Substance P, TNFα, IL-6 and IL-1β immunopositivity were detected in fibers of Sp5 and neither of these molecules showed any change in immunoreactivity following CFA administration. This is the first study demonstrating that dural application of CFA increases the expression of c-fos and glutamate in TNC neurons. Treatment with the KYNA analogue prevented this expression.

  6. [Effects of teprenone on expression of heat shock protein 70 and c-fos in stomach following prednisolone ingestion: experiment with rats].

    PubMed

    Lü, Bin; Zhang, Lu; Fan, Yi-Hong; Xu, Yi

    2008-01-22

    To estimate the effect of teprenone on the expression of heat shock protein (HSP) 70 and c-fos in stomach following prednisolone ingestion. Fifty male Sprague-Dawley rats were randomly into 5 equal groups: normal control group, undergoing gastric perfusion of normal saline (NS) for 7 days, and since the 4 th day undergoing fasting for 4 days; model control group, undergoing gastric perfusion of NS for 7 days, and since the 4 th day undergoing fasting and subcutaneous injection of prednisolone 40 mg/kg for 4 days; and 3 model therapy groups, undergoing gastric perfusion with low, middle, and high dose of teprenone (50 mg/kg, 100 mg/kg, and 200 mg/kg respectively) for 7 days and undergoing fasting and subcutaneous injection of prednisolone 40 mg/kg since the 4 th day. Twenty-four hours after the last administration of drugs, the rats were killed with their stomachs taken out. The gastric ulcer index (UI) was measured. HE staining was used to observe the injury index of the gastric mucosa. The mRNA expression of HSP70 in the gastric tissue was semi-quantitatively detected with reverse transcription-polymerase chain reaction. The protein expression of c-fos in the gastric tissue was detected with immunohistochemical staining. The injury index of the gastric mucosa of the model control group was 5.5, significantly higher than that of the normal control group (0, P = 0.000), and the injury indexes of the 3 teprenone groups were all significantly lower than that of the model control group dose-dependently (all P < 0.01). The UI of the model control group was 44.5, significantly higher than that of the normal control group (0, P = 0.000), and the UI values of the 3 teprenone groups were 32.5, 23.0, and 23.0 respectively, all significantly lower than that of the model control group dose-dependently (all P < 0.01). The expression value of c-fos of the model control group was 42 +/- 8, significantly higher than that of the normal control group (P < 0.01), and that expression

  7. Autoregulation of fos: the dyad symmetry element as the major target of repression.

    PubMed Central

    König, H; Ponta, H; Rahmsdorf, U; Büscher, M; Schönthal, A; Rahmsdorf, H J; Herrlich, P

    1989-01-01

    Fos and Jun co-operatively repress the fos promoter. Removal of all putative Fos/Jun binding sites from the fos promoter neither obliterates the repression by Fos/Jun in transient cotransfection experiments in NIH3T3 cells nor the turn-off kinetics of serum-induced fos expression in stably transfected NIH3T3 cells. The dyad symmetry element (DSE) suffices to subject a promoter to this type of repression. However, one of the putative Fos/Jun binding sites (-292 to -299 and thus located immediately adjacent to the DSE), determines the very low level of basal expression. Images PMID:2511006

  8. Inhibition of osteoclast differentiation and bone resorption by rotenone, through down-regulation of RANKL-induced c-Fos and NFATc1 expression.

    PubMed

    Kwak, Han Bok; Lee, Byeong Ki; Oh, Jaemin; Yeon, Jeong-Tae; Choi, Sik-Won; Cho, Hae Joong; Lee, Myeung Su; Kim, Jeong-Joong; Bae, Ji-Myung; Kim, Seong Hwan; Kim, Hun Soo

    2010-03-01

    Osteoclasts are responsible for bone erosion in diseases as diverse as osteoporosis, periodontitis, and rheumatoid arthritis. Natural plant-derived products have received recent attention as potential therapeutic and preventative drugs in human disease. The effect of rotenone in RANKL-induced osteoclast differentiation was examined in this study. Rotenone inhibited RANKL-mediated osteoclast differentiation in bone marrow macrophages (BMMs) in a dose-dependent manner without any evidence of cytotoxicity. The mRNA expression of c-Fos, NFATc1, TRAP, and OSCAR in RANKL-treated BMMs was inhibited by rotenone treatment. Rotenone strongly inhibited p38 and ERK phosphorylation and I-kappaB degradation in RANKL-stimulated BMMs, and did not inhibit JNK phosphorylation. Further, RANKL-induced c-Fos and NFATc1 protein expression was suppressed by rotenone. Rotenone additionally inhibited the bone resorptive activity of differentiated osteoclasts. A lipopolysaccharide (LPS)-induced bone erosion study was also performed to assess the effects of rotenone in vivo. Mice treated with rotenone demonstrated marked attenuation of bone erosion based on Micro CT and histologic analysis of femurs. These results collectively suggested that rotenone demonstrated inhibitory effects on osteoclast differentiation in vitro and suppressed inflammatory bone loss in vivo. Rotenone may therefore serve as a useful drug in the prevention of bone loss.

  9. Induction of interleukin 6 and interleukin 8 expression by Broncho-Vaxom (OM-85 BV) via C-Fos/serum responsive element.

    PubMed Central

    Keul, R.; Roth, M.; Papakonstantinou, E.; Nauck, M.; Perruchoud, A. P.; Block, L. H.

    1996-01-01

    BACKGROUND: Broncho-Vaxom (OM-85 BV) increases the resistance of the respiratory tract to bacterial infections by modulating host immune responses. The compound increases serum IgG levels but decreases IgE levels in patients suffering from chronic bronchitis or chronic obstructive pulmonary disease. It increases concentrations of gamma-interferon (IFN-gamma), IgA, and interleukin (IL)-2 in bronchoalveolar lavage fluid of patients with bronchitis. Treatment with OM-85 BV increases the number of T helper and natural killer cells. In this study the effects of OM-85 BV on transcription of cytokines is investigated in human lung fibroblasts. METHODS: Transcription and synthesis of IL-6 and IL-8 were assessed in cultured primary human lung fibroblasts using standard methods of Northern blot analysis for the level of mRNAs and enzyme linked immunosorbent assay for proteins. RESULTS: Broncho-Vaxom (OM-85 BV) at different concentrations induced transcription of IL-6 and IL-8. The effect of the drug on transcription of IL-6 and IL-8 genes correlated with secretion of the proteins into cell supernatants. OM-85 BV-dependent expression of the interleukin genes involved C-Fos/serum responsive element (C-Fos/SRE). CONCLUSIONS: The data suggest that the various immunopharmacological activities of OM-85 BV that have been described in clinical studies may be explained by its ability to induce expression of IL-6 and IL-8. Images PMID:8711646

  10. Copulation or sensory cues from the female augment Fos expression in arginine vasopressin neurons of the posterodorsal medial amygdala of male rats

    PubMed Central

    2014-01-01

    Background The posterodorsal part of the medial amygdala is essential for processing reproductively salient sensory information in rodents. This is the initial brain structure where information from olfactory system and male hormones intersect. The neurochemical identity of the neurons participating in the sensory processing in medial amygdala remains presently undetermined. Many neurons in this brain structure express arginine vasopressin in a testosterone-dependent manner, suggesting that this neuropeptide is maintained by the androgenic milieu. Method Here we use Fos, a protein expressed by recently active neurons, to quantify activation of arginine vasopressin neurons after exposure to odor from physically inaccessible female. We compare it to mating with accessible female and to reproductively innocuous odor. Results We show that inaccessible female activate arginine vasopressin neurons in the male posterodorsal medial amygdala. The magnitude of activation is not further enhanced when physical access with resultant mating is granted, even though it remains undetermined if same population of AVP neurons is activated by both inaccessible female and copulation. We also show that arginine vasopressin activation cannot be fully accounted for by mere increase in the number of Fos and AVP neurons. Conclusion These observations posit a role for the medial amygdala arginine vasopressin in reproductive behaviors, suggesting that these neurons serve as integrative node between the hormonal status of the animal and the availability of reproductive opportunities. PMID:24926317

  11. Expression of c-fos mRNA in the Basal Ganglia Associated with Contingent Tolerance to Amphetamine-Induced Hypophagia

    PubMed Central

    Bachand, Kimberlee D.; Guthrie, Kathleen M.; Wolgin, David L.

    2009-01-01

    Tolerance to the hypophagic effect of psychostimulants is contingent on having access to food while intoxicated. Rats given chronic injections of such drugs with access to food learn to suppress stereotyped movements, which interfere with feeding. In contrast, controls given the drug after food access do not learn to suppress stereotypy and, therefore, do not become tolerant. To determine the role of the basal ganglia in this phenomenon, we used in situ hybridization to measure the expression of c-fos mRNA, a marker for neural activation, in the brains of tolerant and nontolerant rats. Rats given chronic amphetamine injections prior to food access learned to suppress stereotyped movements, whereas yoked controls given the drug after feeding did not. Following an acute injection of amphetamine, both of these groups had higher levels of c-fos mRNA than saline-treated controls throughout the striatum, in the nucleus accumbens core, the ventral pallidum and layers V–VI of the motor cortex. In contrast, tolerant rats, which had learned to suppress stereotypy, had higher levels of c-fos mRNA than both amphetamine- and saline-treated controls in the entopeduncular nucleus, globus pallidus, subthalamic nucleus, pedunculopontine nucleus, nucleus accumbens shell, olfactory tubercle, somatosensory cortex, and layers II–IV of motor cortex. These data suggest that the learned suppression of amphetamine-induced stereotypy involves the activation of dorsal striatal pathways previously implicated in response selection as well as the ventral striatum, long implicated in appetitive motivation and reinforcement. PMID:19084559

  12. Upregulation of N-methyl-D-aspartate receptor subunits and c-Fos expressing genes in PC12D cells by nobiletin.

    PubMed

    Kimura, Junko; Nemoto, Kiyomitsu; Degawa, Masakuni; Yokosuka, Akihito; Mimaki, Yoshihiro; Shimizu, Kosuke; Oku, Naoto; Ohizumi, Yasushi

    2014-01-01

    The N-methyl-D-aspartate (NMDA) receptor plays a key role in learning and memory. Our recent studies have shown that nobiletin from citrus peels activates the cAMP response element-binding protein (CREB) signaling pathway and ameliorates NMDA receptor antagonist-induced learning impairment by activating extracellular signal-regulated kinase. For the first time, we have shown that nobiletin significantly upregulated mRNA expression of the NMDA receptor subunits NR1, NR2A, and NR2B in PC12D cells. Furthermore, c-Fos mRNA expression also increased due to the action of nobiletin. Our results indicate that nobiletin modulates the expression of essential genes for learning and memory by activating the CREB signaling pathway, and suggest that this action mechanism of nobiletin plays a crucial role in improving NMDA receptor antagonist-induced learning impairment in model animals with dementia.

  13. c-Fos immunoreactivity in the pig brain following deoxynivalenol intoxication: focus on NUCB2/nesfatin-1 expressing neurons.

    PubMed

    Gaigé, Stéphanie; Bonnet, Marion S; Tardivel, Catherine; Pinton, Philippe; Trouslard, Jérôme; Jean, André; Guzylack, Laurence; Troadec, Jean-Denis; Dallaporta, Michel

    2013-01-01

    Deoxynivalenol (DON), produced by the cereal-contaminating Fusarium fungi, is a major trichothecene responsible for mycotoxicoses in farm animals, including swine. The main effect of DON-intoxication is food intake reduction and the consequent body weight loss. The present study aimed to identify brain structures activated during DON intoxication in pigs. To this goal, we used c-Fos staining which constitutes a useful approach to identify activated neurons. We showed that per os administration of Fusarium graminearum extracts (containing the equivalent of 1mg DON per kg of body weight) induced an increase in c-Fos immunoreactivity in several central structures, including the ventrolateral medulla (VLM), dorsal vagal complex (DVC), paraventricular nucleus of the hypothalamus (PVN), arcuate nucleus (Arc), supraoptic nucleus (SON) and amygdala (CeA). Moreover, we coupled c-Fos staining with phenotypic markers detection in order to specify the neuronal populations activated during DON intoxication. This phenotypic characterization revealed the activation of catecholaminergic but not of serotoninergic neurons in response to the toxin. In this context, we also paid a particular attention to NUCB2/nesfatin-1 positive cells, since nesfatin-1 is known to exert a satiety effect. We report here, for the first time in the pig brain, the presence of NUCB2/nesfatin-1 neurons in the VLM, DVC, PVN, Arc and SON, and their activation during DON intoxication. Taken together, these data show that DON stimulates the main structures involved in food intake in pigs and suggest that catecholaminergic and NUCB2/nesfatin-1 neurons could contribute in the anorexigenic effects of the mycotoxin.

  14. Assessment of HTLV-1 proviral load, LAT, BIM, c-FOS and RAD51 gene expression in adult T cell leukemia/lymphoma.

    PubMed

    Ramezani, Samaneh; Shirdel, Abbas; Rafatpanah, Houshang; Akbarin, Mohammad Mehdi; Tarokhian, Hanieh; Rahimi, Hossein; Bari, Alireza; Jahantigh, Hamid Reza; Rezaee, Seyed Abdolrahim

    2017-08-01

    Adult T cell leukemia/lymphoma (ATLL) is a life-threatening malignancy of HTLV-1 infected Th lymphocytes. In the present study host-virus interactions were investigated by assessment of HTLV-1 proviral load (PVL) and host gene expression. A cross-sectional study was carried out on 18 ATLL, 10 HAM/TSP patients and 18 HTLV-1 asymptomatic carriers (ACs). DNA and mRNA of the peripheral blood mononuclear cells were extracted for PVL and LAT, BIM, c-FOS and RAD51 gene expression measurement using qRT-PCR. The mean PVL in ATLL patients was 11,430 ± 3770 copies/10(4) which was statistically higher than ACs, 530 ± 119 copies/10(4), (p < 0.001). The expression of BIM, and c-FOS in ATLL patients were higher than HTLV-1 ACs; however, there were no statistically significant differences. The expression of RAD51 as an essential player on DNA repair showed around 160 times increase in ATLL group (166 ± 95) compared to ACs (1.04 ± 0.34) which is statistically significant (p < 0.001). Interestingly, there was a positive correlation between RAD51 expression and HTLV-PVL. The expression of LAT as a central adaptor in TCR signaling interestingly was around 36 times higher in ATLL group than ACs (ATLL; 41.33 ± 19.91 vs. ACs; 1.15 ± 0.22, p < 0.001). This finding showed that TCR signaling pathway mainly provides the growth factors for transformed cells. Furthermore, the overexpression of RAD51 which has been induced in HTLV-1 infected cells as a consequence of virus replication is not able to overcome the DNA damage toward cell transformation.

  15. Modulation of p53, c-fos, RARE, cyclin A, and cyclin D1 expression in human leukemia (HL-60) cells exposed to arsenic trioxide

    PubMed Central

    Yedjou, Clement G.; Tchounwou, Paul B.

    2010-01-01

    Arsenic trioxide (As2O3) has recently been successfully used to treat all-trans retinoic acid (ATRA) resistant relapsing acute promyelocytic leukemia. However, its molecular mechanisms of action are poorly understood. In the present study, we used the human leukemia (HL-60) cell line as a test model to study the cellular and molecular mechanisms of anti-cancer properties of As2O3. We hypothesized that As2O3-induced expression of stress genes and related proteins may play a role in the cellular and molecular events leading to cell cycle modulation in leukemic cells. To test this hypothesis, we performed Western blot analysis to assess the expression of specific cellular response proteins including p53, c-fos, RARE, Cyclin A, and Cyclin D1. Densitometric analysis was performed to determine the relative abundance of these proteins. Western Blot and densitometric analyses demonstrated a strong dose-response relationship with regard to p53 and RARE expression within the dose range of 0-8μg/mL. Expression of c-fos was slightly up-regulated at 2μg/mL, and down-regulated within the dose-range of 4-8 μg/mL. A statistically significant down-regulation of this protein was detected at the 6 and 8 μg/mL dose levels. No statistically significant differences (p>0.05) in Cyclin D1 expression was found between As2O3-treated cells and the control. Cyclin A expression in As2O3-treated HL-60 cells was up-regulated at 6μg/mL, suggesting that it is required for S phase and passage through G2 phase in cell cycle progression. Taken together, these results indicate that As2O3 has the potential to induce cell cycle arrest through activation of the 53-kDa tumor suppressor protein and repression of the c-fos transcription factor. Up-regulation of RARE by As2O3 indicates that its cytotoxicity may be mediated through interaction/binding with the retinoic acid receptor, and subsequent inhibition of growth and differentiation. PMID:19444595

  16. Reduced induction of c-fos but not of c-myc expressions in a nontumorigenic revertant R1 of EJ-ras-transformed NIH/3T3 cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA)

    SciTech Connect

    Suzuki, Hiroaki; Fujita, Hisakazu; Ogiso, Yoshifumi; Oda, Atsushi; Kuzumaki, Noboru; Uchino, Junichi )

    1989-10-01

    It has been reported that both c-fos and c-myc mRNAs are induced in NIH/3T3 cells after 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment. The authors have studied the effect of TPA on the expression of c-fos and c-myc in EJ-ras-transformed NIH/3T3 and its nontumorigenic flat revertant R1 cells. Although TPA treatment induces c-myc mRNA, as in the case of NIH/3T3 cells, the induced level of c-fos mRNA is greatly reduced not only in slow growing EJ-ras-transformed NIH/3T3 but also in quiescent R1 cells. In addition, serum-induced c-fos expression is also reduced in EJ-ras-transformed NIH/3T3 and R1 cells. These observations suggest that the pathway from TPA to c-fos gene is different from that to c-myc gene and that the former pathway is down-regulated in association not with the transformed phenotype, but with EJ-ras expression, and it is possible that this reduced induction of c-fox is not specific to TPA.

  17. Radiation hepatology of the rat: The effects of the proliferation stimulus induced by subtotal hepatectomy

    SciTech Connect

    Geraci, J.P.; Mariano, M.S.

    1994-11-01

    The effect of an 80 to 90% hepatectomy in stimulating proliferation immediately after irradiation of the liver was studied. A dose of 15 Gy was not lethal for animals with intact livers, but all animals with subtotal hepatectomies exposed to this dose died from apparent liver failure 28 to 60 days after exposure. To elucidate the mechanism for this mortality, plasma aspartate aminotransferase, retention of intravenous injected rose bengal, liver weight and liver hydroxyproline content were measured 0 to 90 days after 15 Gy irradiation of the liver to determine temporal changes in necrosis, function, mass and fibrosis, respectively, in animals with either intact livers or livers with subtotal resection. Irradiation of the liver had no significant effect on these parameters in animals with intact livers. In subtotally hepatectomized animals the same radiation dose that suppressed liver mass restoration significantly increased hepatocyte necrosis within 7 days, which was followed by increased liver hydroxyproline concentration and hepatic dysfunction. This radiation-induced temporal change in hepatic dysfunction correlated with increased concentration of hydroxyproline but not with liver mass, indicating that liver fibrosis was the cause of hepatic dysfunction. Since similar sequelae are produced in intact livers after higher doses and longer intervals after irradiation, the proliferation stimulus induced by partial hepatectomy must accelerate the expression of damage and lower the radiation tolerance of the liver. However, in subtotally hepatectomized animals radiation-induced hepatocyte necrosis precedes fibrosis, whereas the reverse is normally true for animals with intact livers. 35 refs., 5 figs.

  18. CRAC channels are required for [Ca(2+)]i oscillations and c-fos gene expression after muscarinic acetylcholine receptor activation in leukemic T cells.

    PubMed

    Mashimo, Masato; Yurie, Yukako; Kawashima, Koichiro; Fujii, Takeshi

    2016-09-15

    T lymphocytes express muscarinic acetylcholine receptors (mAChRs) involved in regulating their proliferation, differentiation and cytokine release. Activation of M1, M3 or M5 mAChRs increases the intracellular Ca(2+) concentration ([Ca(2+)]i) through inositol-1,4,5-phosphate (IP3)-mediated Ca(2+) release from endoplasmic reticulum Ca(2+) stores. In addition, T lymphocytes express Ca(2+)-release activated Ca(2+) (CRAC) channels to induce Ca(2+) influx and to regulate diverse immune functions. Our aim in the present study was to assess the role of CRAC channels during mAChR activation in the Ca(2+)-dependent transduction that contributes to the regulation of T cell function. Changes in [Ca(2+)]i following mAChR activation on human leukemic T cells, CCRF-CEM (CEM), were monitored using fura-2, based on the ratio of 510nm fluorescences elicited by excitation at 340nm and 380nm (R340/380). We demonstrate that CEM cells express mainly M3 and M5 mAChRs, but little the M1 subtype, and that oxotremorine-M (Oxo-M), an mAChR agonist, induces an initial transient increase in [Ca(2+)]i followed by repetitive [Ca(2+)]i oscillations. Removing extracellular Ca(2+) or pharmacological blockade of CRAC channels abolished the [Ca(2+)]i oscillations without affecting the initial [Ca(2+)]i transient induced by Oxo-M. Moreover, CRAC channel blockade also suppressed Oxo-M-induced c-fos and interleukin-2 expression. These results suggest that upon M3 or M5 mAChR activation, IP3-mediated Ca(2+) release induces extracellular Ca(2+) influx through CRAC channels, which generates repetitive [Ca(2+)]i oscillations and, in turn, enhances c-fos gene expression in T lymphocytes. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Effects of alcohol exposure during development on play behavior and c-Fos expression in response to play behavior

    PubMed Central

    Lawrence, R. Charles; Bonner, H. Cale; Newsom, Ryan J.; Kelly, Sandra J.

    2008-01-01

    Developmental exposure to alcohol can produce characteristic physiological and cognitive deficits, often termed Fetal Alcohol Spectrum Disorder (FASD). More recently, social deficits have been shown to occur both in FASD and animal models of FASD; the behavioral and neural bases of these deficits remain to be determined. It was hypothesized that changes in sensory processing may in part underlie the social deficits seen in FASD. This study used a rat model of FASD and social play, a behavior critical to adult social functioning, to begin to examine this hypothesis. Somatosensory cues from dorsal contact to the nape of the neck, critical to the initiation of pinning, were systematically degraded by administration of different doses of xylocaine, a topical anesthetic. Neuronal activity after one hour of play was assessed by measurement of c-Fos immunoreactivity (IR) in different brain regions. Ethanol-exposed rats showed an increase frequency of pinning during social play and were more sensitive to the degradation of somatosensory cues compared to the control groups, suggesting difficulties in processing somatosensory cues. Neuronal activity in the somatosensory cortex induced by play was significantly decreased in the ethanol-exposed group compared to the non-treated group. The c-Fos IR in the nucleus accumbens was altered in a sexually dimorphic manner in the ethanol-exposed group. Thus, the behavioral and brain measures are consistent with the hypothesis that ethanol exposure during development induces alterations in social play via deficits in processing somatosensory cues that are important to social play. PMID:18160143

  20. Cyclodextrin-Complexed Ocimum basilicum Leaves Essential Oil Increases Fos Protein Expression in the Central Nervous System and Produce an Antihyperalgesic Effect in Animal Models for Fibromyalgia

    PubMed Central

    Nascimento, Simone S.; Araújo, Adriano A. S.; Brito, Renan G.; Serafini, Mairim R.; Menezes, Paula P.; DeSantana, Josimari M.; Lucca Júnior, Waldecy; Alves, Pericles B.; Blank, Arie F.; Oliveira, Rita C. M.; Oliveira, Aldeidia P.; Albuquerque-Júnior, Ricardo L. C.; Almeida, Jackson R. G. S.; Quintans-Júnior, Lucindo J.

    2014-01-01

    O. basilicum leaves produce essential oils (LEO) rich in monoterpenes. The short half-life and water insolubility are limitations for LEO medical uses. β-Cyclodextrin (β-CD) has been employed to improve the pharmacological properties of LEO. We assessed the antihyperalgesic profile of LEO, isolated or complexed in β-CD (LEO/β-CD), on an animal model for fibromyalgia. Behavioral tests: mice were treated every day with either LEO/β-CD (25, 50 or 100 mg/kg, p.o.), LEO (25 mg/kg, p.o.), tramadol (TRM 4 mg/kg, i.p.) or vehicle (saline), and 60 min after treatment behavioral parameters were assessed. Therefore, mice were evaluated for mechanical hyperalgesia (von Frey), motor coordination (Rota-rod) and muscle strength (Grip Strength Metter) in a mice fibromyalgia model. After 27 days, we evaluated the central nervous system (CNS) pathways involved in the effect induced by experimental drugs through immunofluorescence protocol to Fos protein. The differential scanning analysis (DSC), thermogravimetry/derivate thermogravimetry (TG/DTG) and infrared absorption spectroscopy (FTIR) curves indicated that the products prepared were able to incorporate the LEO efficiently. Oral treatment with LEO or LEO-βCD, at all doses tested, produced a significant reduction of mechanical hyperalgesia and we were able to significantly increase Fos protein expression. Together, our results provide evidence that LEO, isolated or complexed with β-CD, produces analgesic effects on chronic non-inflammatory pain as fibromyalgia. PMID:25551603

  1. The effect of electroacupuncture on extinction responding of heroin-seeking behavior and FosB expression in the nucleus accumbens core.

    PubMed

    Hu, Airong; Lai, Miaojun; Wei, Jianzi; Wang, Lina; Mao, Huijuan; Zhou, Wenhua; Liu, Sheng

    2013-02-08

    Augmentation of extinction with learning enhancing therapy may offer an effective strategy to combat heroin relapse. Our lab previously found that electroacupuncture (EA) not only significantly reduced cue-induced reinstatement of heroin seeking but also exhibited a promoting effect on the ability of learning and memory. In the present study, we further investigated the effects of EA on the extinction of heroin-seeking behavior in rats with a history of intravenous heroin self-administration. We trained Sprague-Dawley rats to nose-poke for i.v. heroin either daily for 4h or 25 infusions for 14 consecutive days; then the rats underwent 7 daily 3h extinction sessions in the operant chamber. To assess EA's effects on the extinction response of heroin-associated cues, 2Hz EA was administered 1h before each of the 7 extinction sessions. We also applied immunohistochemistry to detect FosB-positive nuclei in the nucleus accumbens core. We found that EA treatment facilitated the extinction response of heroin seeking but did not alter the locomotor activity in an open field testing environment. EA stimulation attenuated the FosB expression in the core of the nucleus accumbens, a brain region involved in the learning and execution of motor responses. Altogether, these results suggest that EA may provide a novel nonpharmacological approach to enhance extinction learning when combined with extinction therapy for the treatment of heroin addiction.

  2. Cyclodextrin-complexed Ocimum basilicum leaves essential oil increases Fos protein expression in the central nervous system and produce an antihyperalgesic effect in animal models for fibromyalgia.

    PubMed

    Nascimento, Simone S; Araújo, Adriano A S; Brito, Renan G; Serafini, Mairim R; Menezes, Paula P; DeSantana, Josimari M; Lucca, Waldecy; Alves, Pericles B; Blank, Arie F; Oliveira, Rita C M; Oliveira, Aldeidia P; Albuquerque, Ricardo L C; Almeida, Jackson R G S; Quintans, Lucindo J

    2014-12-29

    O. basilicum leaves produce essential oils (LEO) rich in monoterpenes. The short half-life and water insolubility are limitations for LEO medical uses. β-Cyclodextrin (β-CD) has been employed to improve the pharmacological properties of LEO. We assessed the antihyperalgesic profile of LEO, isolated or complexed in β-CD (LEO/β-CD), on an animal model for fibromyalgia. Behavioral tests: mice were treated every day with either LEO/β-CD (25, 50 or 100 mg/kg, p.o.), LEO (25 mg/kg, p.o.), tramadol (TRM 4 mg/kg, i.p.) or vehicle (saline), and 60 min after treatment behavioral parameters were assessed. Therefore, mice were evaluated for mechanical hyperalgesia (von Frey), motor coordination (Rota-rod) and muscle strength (Grip Strength Metter) in a mice fibromyalgia model. After 27 days, we evaluated the central nervous system (CNS) pathways involved in the effect induced by experimental drugs through immunofluorescence protocol to Fos protein. The differential scanning analysis (DSC), thermogravimetry/derivate thermogravimetry (TG/DTG) and infrared absorption spectroscopy (FTIR) curves indicated that the products prepared were able to incorporate the LEO efficiently. Oral treatment with LEO or LEO-βCD, at all doses tested, produced a significant reduction of mechanical hyperalgesia and we were able to significantly increase Fos protein expression. Together, our results provide evidence that LEO, isolated or complexed with β-CD, produces analgesic effects on chronic non-inflammatory pain as fibromyalgia.

  3. The effect of daily caffeine exposure on lever-pressing for sucrose and c-Fos expression in the nucleus accumbens in the rat.

    PubMed

    Retzbach, Edward P; Dholakia, Paulomi H; Duncan-Vaidya, Elizabeth A

    2014-08-01

    Recent reports suggest that caffeine exposure increases the motivation to consume drugs of abuse. As such, it may also enhance the motivation to consume palatable food. Because caffeine is a common constituent in over-the-counter weight-loss supplements, it is important to better understand the relationship between caffeine and food intake. The purpose of this study was to measure the effects of daily intermittent caffeine exposure on lever pressing for sucrose in rats and to assess the impact of caffeine on neuronal activation in the nucleus accumbens (NAc). Male Sprague-Dawley rats that received either saline or caffeine (1, 5, 20mg/kgi.p.) daily were tested on a fixed ratio 4 schedule for sucrose in operant chambers for 10days and then again following a 5-day treatment withdrawal period. After behavioral testing, a subset of the animals was sacrificed to measure the impact of caffeine on neuronal activation in the NAc using c-Fos as a marker. There was a significant increase in active lever presses for sucrose in the rats that had received 5mg/kg of caffeine when compared with the saline group. This treatment effect was no longer present after the withdrawal period. Acute, but not chronic, caffeine exposure elevated c-Fos expression in the NAc. These data suggest that intermittent daily caffeine exposure increases lever pressing for sucrose in rats, but leaves no lasting effect. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Activations of c-fos/c-jun signaling are involved in the modulation of hypothalamic superoxide dismutase (SOD) and neuropeptide Y (NPY) gene expression in amphetamine-mediated appetite suppression

    SciTech Connect

    Hsieh, Y.-S.; Yang, S.-F.; Chiou, H.-L.; Kuo, D.-Y. . E-mail: dykuo@csmu.edu.tw

    2006-04-15

    Amphetamine (AMPH) is known as an anorectic agent. The mechanism underlying the anorectic action of AMPH has been attributed to its inhibitory action on hypothalamic neuropeptide Y (NPY), an appetite stimulant in the brain. This study was aimed to examine the molecular mechanisms behind the anorectic effect of AMPH. Results showed that AMPH treatment decreased food intake, which was correlated with changes of NPY mRNA level, but increased c-fos, c-jun and superoxide dismutase (SOD) mRNA levels in hypothalamus. To determine if c-fos or c-jun was involved in the anorectic response of AMPH, infusions of antisense oligonucleotide into the brain were performed at 1 h before daily AMPH treatment in freely moving rats, and the results showed that c-fos or c-jun knockdown could block this anorectic response and restore NPY mRNA level. Moreover, c-fos or c-jun knockdown could partially block SOD mRNA level that might involve in the modulation of NPY gene expression. It was suggested that c-fos/c-jun signaling might involve in the central regulation of AMPH-mediated feeding suppression via the modulation of NPY gene expression.

  5. Fos and jun cooperate in transcriptional regulation via heterologous activation domains.

    PubMed Central

    Abate, C; Luk, D; Gagne, E; Roeder, R G; Curran, T

    1990-01-01

    The products of c-fos and c-jun (Fos and Jun) function in gene regulation by interacting with the AP-1 binding site. Here we have examined the contribution of Fos and Jun toward transcriptional activity by using Fos and Jun polypeptides purified from Escherichia coli. Fos contained a transcriptional activation domain as well as a region which exerted a negative influence on transcriptional activity in vitro. Moreover, distinct activation domains in both Fos and Jun functioned cooperatively in transcriptional stimulation. Thus, regulation of gene expression by Fos and Jun results from an integration of several functional domains in a bimolecular complex. Images PMID:2119000

  6. Cell-type-specific expression and regulation of a c-fos-NGF fusion gene in neurons and astrocytes of transgenic mice.

    PubMed

    Onténiente, B; Horellou, P; Neveu, I; Makeh, I; Suzuki, F; Bourdet, C; Grimber, G; Colin, P; Brachet, P; Mallet, J

    1994-02-01

    A mouse line transgenic for nerve growth factor (NGF) was developed using the mouse prepro-NGF cDNA inserted within a plasmid containing the proximal region (-10 to -550 bp) of the c-fos promoter and the transcription termination and polyadenylation signals of the rabbit beta-globin gene. No significant modification of gross behavior or central nervous system anatomy was detected in adult animals as assessed by immunohistochemistry and in situ hybridization for NGF and choline acetyltransferase. The expression of the transgene and the possible regulation of its expression by agents acting on the promoter were investigated in vitro. Despite the presence of an additional pool of NGF mRNA specific to the transgene, basal levels of NGF in the supernatant of transgenic astrocytes were similar to normal ones. On the other hand, transgenic neurons spontaneously synthesized and released levels of NGF two to three times higher than normal neurons, while mRNA levels were barely detectable by conventional Northern blotting. The tissue-specificity of NGF expression was respected, with higher levels in hippocampal than neocortical neurons. Increases of NGF mRNA by agents acting on the promoter could be observed in normal and transgenic astrocytes only after inhibition of the protein synthesis by cycloheximide, suggesting a similar rapid turnover of normal and transgenic transcripts. Cyclic AMP agonists specifically increased the secretion of NGF protein by transgenic astrocytes and neurons, while activators of the protein kinase C had a similar effect on transgenic and normal cells. Differences between amounts of NGF secreted by neurons and astrocytes with regards to their respective content in mRNA suggest that transgenic transcripts are subject to normal cell- and tissue-specific post-transcriptional regulations. Agents acting on the c-fos promoter through the protein kinase C or cyclic AMP routes differentially increased the secretion of NGF by transgenic astrocytes or

  7. Reactive Oxygen Species-Dependent c-Fos/Activator Protein 1 Induction Upregulates Heme Oxygenase-1 Expression by Bradykinin in Brain Astrocytes.

    PubMed

    Hsieh, Hsi-Lung; Wang, Hui-Hsin; Wu, Cheng-Ying; Yang, Chuen-Mao

    2010-12-15

    Heme oxygenase-1 (HO-1) plays a crucial role in tissue pathological changes such as brain injuries. Our previous studies have demonstrated that bradykinin (BK) induces the expression of several inflammatory proteins, including matrix metalloproteinase-9 and COX-2, via mitogen-activated protein kinases and nuclear factor-κB (NF-κB) in rat brain astrocytes (RBA-1). However, the molecular mechanisms underlying BK-induced HO-1 expression in RBA-1 cells remain poorly defined. Here we demonstrated that BK induced HO-1 expression and enzymatic activity via a B(2) BK receptor-activated reactive oxygen species (ROS)-dependent signaling pathway. NADPH oxidase (Nox)-dependent ROS generation led to activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun-N-terminal kinase (JNK) and then activated the downstream molecules NF-κB and c-Jun, respectively. The c-Fos, an activator protein 1 (AP-1) subunit, was upregulated by activation of NF-κB and c-Jun, which bound to HO-1 promoter and thereby turned on transcription of HO-1 gene. The rat HO-1 promoter containing a putative AP-1 cis-binding site was identified as a crucial domain linking to BK action. Taken together, these results suggested that in RBA-1 cells, activation of ERK/NF-κB and JNK/c-Jun cascades by a Nox/ROS-dependent event enhancing c-Fos/AP-1 activity is essential for HO-1 upregulation and activation induced by BK. Moreover, ROS-dependent NF-E2-related factor 2 activation also contributes to HO-1 induction by BK in astrocytes.

  8. Endothelin stimulates phospholipase C, Na+/H+ exchange, c-fos expression, and mitogenesis in rat mesangial cells.

    PubMed Central

    Simonson, M S; Wann, S; Mené, P; Dubyak, G R; Kester, M; Nakazato, Y; Sedor, J R; Dunn, M J

    1989-01-01

    A recently described peptide hormone, endothelin, is a potent vasoconstrictor, but it is unclear whether endothelin has other biological actions. These experiments extend the range of biological actions of endothelin to stimulation of mitogenesis. Endothelin at low concentrations (0.1-10 nM) induced mitogenesis by quiescent rat glomerular mesangial cells in culture. Mitogenesis induced by endothelin was accompanied by activation of phospholipase C with increased inositol phosphate turnover and increments of intracellular [Ca2+]. Endothelin also activated Na+/H+ exchange, causing cytosolic alkalinization, and enhanced transcription of the c-fos protooncogene, additional biochemical signals closely linked to proliferation. In addition to being a vasoconstrictor, endothelin thus also functions as a mitogen, presumably through activation of phospholipase C. Images PMID:2536405

  9. Influence of Pre-Training Predator Stress on the Expression of c-fos mRNA in the Hippocampus, Amygdala, and Striatum Following Long-Term Spatial Memory Retrieval

    PubMed Central

    VanElzakker, Michael B.; Zoladz, Phillip R.; Thompson, Vanessa M.; Park, Collin R.; Halonen, Joshua D.; Spencer, Robert L.; Diamond, David M.

    2011-01-01

    We have studied the influence of pre-training psychological stress on the expression of c-fos mRNA following long-term spatial memory retrieval. Rats were trained to learn the location of a hidden escape platform in the radial-arm water maze, and then their memory for the platform location was assessed 24 h later. Rat brains were extracted 30 min after the 24-h memory test trial for analysis of c-fos mRNA. Four groups were tested: (1) Rats given standard training (Standard); (2) Rats given cat exposure (Predator Stress) 30 min prior to training (Pre-Training Stress); (3) Rats given water exposure only (Water Yoked); and (4) Rats given no water exposure (Home Cage). The Standard trained group exhibited excellent 24 h memory which was accompanied by increased c-fos mRNA in the dorsal hippocampus and basolateral amygdala (BLA). The Water Yoked group exhibited no increase in c-fos mRNA in any brain region. Rats in the Pre-Training Stress group were classified into two subgroups: good and bad memory performers. Neither of the two Pre-Training Stress subgroups exhibited a significant change in c-fos mRNA expression in the dorsal hippocampus or BLA. Instead, stressed rats with good memory exhibited significantly greater c-fos mRNA expression in the dorsolateral striatum (DLS) compared to stressed rats with bad memory. This finding suggests that stressed rats with good memory used their DLS to generate a non-spatial (cue-based) strategy to learn and subsequently retrieve the memory of the platform location. Collectively, these findings provide evidence at a molecular level for the involvement of the hippocampus and BLA in the retrieval of spatial memory and contribute novel observations on the influence of pre-training stress in activating the DLS in response to long-term memory retrieval. PMID:21738501

  10. The Expression of Fos, Jun and AP-1 DNA Binding Activity in Rat Supraoptic Nucleus Neurons Following Acute Versus Repeated Osmotic Stimulation

    DTIC Science & Technology

    1995-06-22

    stimulation. This pattern has been observed previously in the hippocampus after treatment with the seizure-inducing drug , metrazole (Sonnenberg et al... fosB , and fra-1 and -2. fra refers to ~OS­ ~elated ~ntigen. Western blot experiments and employment of less stringent nucleic acid hybridization...fos, fra-l and fosB , only form heterodimeric complexes with Jun-related proteins (Nakabeppu et al., 1988; Rauscher et al., 1988b) The AP-l site of many

  11. The nonpeptide oxytocin receptor agonist WAY 267,464: receptor-binding profile, prosocial effects and distribution of c-Fos expression in adolescent rats.

    PubMed

    Hicks, C; Jorgensen, W; Brown, C; Fardell, J; Koehbach, J; Gruber, C W; Kassiou, M; Hunt, G E; McGregor, I S

    2012-07-01

    Previous research suggests that the nonpeptide oxytocin receptor (OTR) agonist WAY 267,464 may only partly mimic the effects of oxytocin in rodents. The present study further explored these differences and related them to OTR and vasopressin 1a receptor (V(1a) R) pharmacology and regional patterns of c-Fos expression. Binding data for WAY 267,464 and oxytocin were obtained by displacement binding assays on cellular membranes, while functional receptor data were generated by luciferase reporter assays. For behavioural testing, adolescent rats were tested in a social preference paradigm, the elevated plus-maze (EPM) and for locomotor activity changes following WAY 267,464 (10 and 100 mg/kg, i.p.) or oxytocin (0.1 and 1 mg/kg, i.p.). The higher doses were also examined for their effects on regional c-Fos expression. Results showed that WAY 267,464 had higher affinity (K(i) ) at the V(1a) R than the OTR (113 versus 978 nm). However, it had no functional response at the V(1a) R and only a weak functional effect (EC(50) ) at the OTR (881 nm). This suggests WAY 267,464 is an OTR agonist with weak affinity and a possible V(1a) R antagonist. Oxytocin showed high binding at the OTR (1.0 nm) and V(1a) R (503 nm), with a functional EC(50) of 9.0 and 59.7 nm, respectively, indicating it is a potent OTR agonist and full V(1a) R agonist. WAY 267,464 (100 mg/kg), but not oxytocin, significantly increased the proportion of time spent with a live rat, over a dummy rat, in the social preference test. Neither compound affected EPM behaviour, whereas the higher doses of WAY 267,464 and oxytocin suppressed locomotor activity. WAY 267,464 and oxytocin produced similar c-Fos expression in the paraventricular hypothalamic nucleus, central amygdala, lateral parabrachial nucleus and nucleus of the solitary tract, suggesting a commonality of action at the OTR with the differential doses employed. However, WAY 267,464 caused greater c-Fos expression in the medial amygdala and the supraoptic

  12. Chrysotile effects on the expression of anti-oncogene P53 and P16 and oncogene C-jun and C-fos in Wistar rats' lung tissues.

    PubMed

    Cui, Yan; Wang, Yuchan; Deng, Jianjun; Hu, Gongli; Dong, Faqin; Zhang, Qingbi

    2017-09-13

    Chrysotile is the most widely used form of asbestos worldwide. China is the world's largest consumer and second largest producer of chrysotile. The carcinogenicity of chrysotile has been extensively documented, and accumulative evidence has shown that chrysotile is capable of causing lung cancer and other forms of cancer. However, molecular mechanisms underlying the tumorigenic effects of chrysotile remained poorly understood. To explore the carcinogenicity of chrysotile, Wistar rats were administered by intratracheal instillation (by an artificial route of administration) for 0, 0.5, 2, or 8 mg/ml of natural chrysotile (from Mangnai, Qinghai, China) dissolved in saline, repeated once a month for 6 months (a repeated high-dose exposure which may have little bearing on the effects following human exposure). The lung tissues were analyzed for viscera coefficients and histopathological alterations. Expression of P53, P16, C-JUN, and C-FOS was measured by western blotting and qRT-PCR. Our results found that chrysotile exposure leads the body weight to grow slowly and lung viscera coefficients to increase in a dose-dependent manner. General sample showed white nodules, punctiform asbestos spots, and irregular atrophy; moreover, HE staining revealed inflammatory infiltration, damage of alveolar structures, agglomerations, and pulmonary fibrosis. In addition, chrysotile can induce inactivation of the anti-oncogene P53 and P16 and activation of the proto-oncogenes C-JUN and C-FOS both in the messenger RNA and protein level. In conclusion, chrysotile induced an imbalanced expression of cancer-related genes in rats' lung tissue. These results contribute to our understanding of the carcinogenic mechanism of chrysotile.

  13. Changing and shielded magnetic fields suppress c-Fos expression in the navigation circuit: input from the magnetosensory system contributes to the internal representation of space in a subterranean rodent.

    PubMed

    Burger, Tomás; Lucová, Marcela; Moritz, Regina E; Oelschläger, Helmut H A; Druga, Rastislav; Burda, Hynek; Wiltschko, Wolfgang; Wiltschko, Roswitha; Nemec, Pavel

    2010-09-06

    The neural substrate subserving magnetoreception and magnetic orientation in mammals is largely unknown. Previous experiments have demonstrated that the processing of magnetic sensory information takes place in the superior colliculus. Here, the effects of magnetic field conditions on neuronal activity in the rodent navigation circuit were assessed by quantifying c-Fos expression. Ansell's mole-rats (Fukomys anselli), a mammalian model to study the mechanisms of magnetic compass orientation, were subjected to natural, periodically changing, and shielded magnetic fields while exploring an unfamiliar circular arena. In the undisturbed local geomagnetic field, the exploration of the novel environment and/or nesting behaviour induced c-Fos expression throughout the head direction system and the entorhinal-hippocampal spatial representation system. This induction was significantly suppressed by exposure to periodically changing and/or shielded magnetic fields; discrete decreases in c-Fos were seen in the dorsal tegmental nucleus, the anterodorsal and the laterodorsal thalamic nuclei, the postsubiculum, the retrosplenial and entorhinal cortices, and the hippocampus. Moreover, in inactive animals, magnetic field intensity manipulation suppressed c-Fos expression in the CA1 and CA3 fields of the hippocampus and the dorsal subiculum, but induced expression in the polymorph layer of the dentate gyrus. These findings suggest that key constituents of the rodent navigation circuit contain populations of neurons responsive to magnetic stimuli. Thus, magnetic information may be integrated with multimodal sensory and motor information into a common spatial representation of allocentric space within this circuit.

  14. Changing and shielded magnetic fields suppress c-Fos expression in the navigation circuit: input from the magnetosensory system contributes to the internal representation of space in a subterranean rodent

    PubMed Central

    Burger, Tomáš; Lucová, Marcela; Moritz, Regina E.; Oelschläger, Helmut H. A.; Druga, Rastislav; Burda, Hynek; Wiltschko, Wolfgang; Wiltschko, Roswitha; Němec, Pavel

    2010-01-01

    The neural substrate subserving magnetoreception and magnetic orientation in mammals is largely unknown. Previous experiments have demonstrated that the processing of magnetic sensory information takes place in the superior colliculus. Here, the effects of magnetic field conditions on neuronal activity in the rodent navigation circuit were assessed by quantifying c-Fos expression. Ansell's mole-rats (Fukomys anselli), a mammalian model to study the mechanisms of magnetic compass orientation, were subjected to natural, periodically changing, and shielded magnetic fields while exploring an unfamiliar circular arena. In the undisturbed local geomagnetic field, the exploration of the novel environment and/or nesting behaviour induced c-Fos expression throughout the head direction system and the entorhinal–hippocampal spatial representation system. This induction was significantly suppressed by exposure to periodically changing and/or shielded magnetic fields; discrete decreases in c-Fos were seen in the dorsal tegmental nucleus, the anterodorsal and the laterodorsal thalamic nuclei, the postsubiculum, the retrosplenial and entorhinal cortices, and the hippocampus. Moreover, in inactive animals, magnetic field intensity manipulation suppressed c-Fos expression in the CA1 and CA3 fields of the hippocampus and the dorsal subiculum, but induced expression in the polymorph layer of the dentate gyrus. These findings suggest that key constituents of the rodent navigation circuit contain populations of neurons responsive to magnetic stimuli. Thus, magnetic information may be integrated with multimodal sensory and motor information into a common spatial representation of allocentric space within this circuit. PMID:20219838

  15. Effect of rhynchophylline on the expression of p-CREB and sc-Fos in triatum and hippocampal CA1 area of methamphetamine-induced conditioned place preference rats.

    PubMed

    Liu, Wei; Peng, Qiu-Xian; Lin, Xiao-Liang; Luo, Chao-Hua; Jiang, Ming-Jin; Mo, Zhi-Xian; Yung, Ken Kin-Lam

    2014-01-01

    To explore the effect of rhynchophylline (Rhy) on the expression of p-CREB and c-Fos in the striatum and hippocampal CA1 area of methamphetamine-induced conditioned place preference (CPP) rat, methamphetamine (2 mg/kg) was injected to rats and the conditioned place preference was observed in these rats treated with or without Rhy. An immunohistochemistry assay was used to determine the expression of p-CREB and c-Fos in the striatum and hippocampal CA1 area. Methamphetamine induced significant behavior alteration in CPP, while after pretreatment with rhynchophylline or ketamine, the time of staying in methamphetamine-paired compartment of rats was significantly reduced. Methamphetamine also increased the number of p-CREB positive cells in the striatum and hippocampal CA1 zone, as well as p-Fos positive cells. However, the compound Rhy could attenuate the effect. These findings show that Rhy can suppress the acquisition of CPP in rats induced by methamphetamine and the action may be related with the reduced expression of p-CREB and p-Fos in the striatum and hippocampus.

  16. Reinforcing properties of pups versus cocaine for fathers and associated central expression of Fos and tyrosine hydroxylase in mandarin voles (Microtus mandarinus).

    PubMed

    Wang, Jianli; Tai, Fadao; Yu, Peng; Wu, Ruiyong

    2012-04-21

    The reciprocal interaction of pups and cocaine on reward effects in rodent mothers is known. However,it remains unclear whether such effects are apparent in father-offspring bonding. The mandarin vole (Microtus mandarinus) is a monogamous rodent with a high level of paternal care. We investigated the reinforcing properties of pups on vole fathers using a conditioned place preference paradigm across the postpartum period and looked for interactions and differences between the reinforcing effects of pups and cocaine. We also measured neuronal Fos and tyrosine hydroxylase (TH) expression underlying the preferences of fathers for pups or cocaine. Our data showed that fathers developed strong preferences for pups at various times (postnatal day 5–9, 13–17 and 19–23) without cocaine conditioning. Fathers showed a reduced preference for pups following simultaneous conditioning with cocaine. Although they preferred cocaine over postnatal day (PND) 5–9 pups, this preference was not detected for PND 13–17 pups. Fathers preferring cocaine exhibited an increase in Fos-immunoreactive neurons in the accumbens,medial nucleus of the amygdala, cingulate cortex, medial preoptic area and ventral tegmental area and had more TH-IR neurons in the ventral tegmental area compared to fathers preferring PND 5–9 pups. These results showed that similar to cocaine, mandarin vole pups elicit significant reward value to their fathers, but that paternal motivation is impaired by cocaine. A preference for cocaine over pups arose from the release of more dopamine and activation of a greater number of neurons within specific reward-associated neuronal subsets. 2012 Elsevier B.V. All rights reserved

  17. Effects of chemical stimulation of the lateral wings of the dorsal raphe nucleus on panic-like defensive behaviors and Fos protein expression in rats.

    PubMed

    Matthiesen, Melina; Spiacci, Ailton; Zangrossi, Hélio

    2017-03-06

    The lateral wings subnucleus of the dorsal raphe nucleus (lwDR) has been implicated in the modulation of panic-like behaviors, such as escape. Infusion of non- excitotoxic doses of the excitatory amino acid kainic acid into this subnucleus promptly evokes a vigorous escape response. In addition, rats exposed to panic-inducing situations show an increase in Fos protein expression in neurons within the lwDR. In the present study, we first investigated whether key structures associated with the mediation of escape behavior are recruited after chemical stimulation of the lwDR with kainic acid. We next investigated whether the infusion of the GABAA receptor antagonist bicuculline into the lwDR also evoked escape responses measured both in a circular arena and in the rat elevated T-maze. The effects of bicuculline in the circular arena were compared to those caused by the infusion of this antagonist into the ventrolateral periaqueductal gray (vlPAG), an area in close vicinity to the lwDR. The results showed that kainic acid infusion into the lwDR increased Fos protein immunostaining in brain structures deeply involved in panic-like defensive behaviors, such as the periaqueductal gray and hypothalamus, but not the amygdala. As observed with kainic acid, bicuculline evoked a pronounced escape response in the circular arena when microinjected in the lwDR, but not in the vlPAG. The escape-promoting effect of bicuculline in the lwDR was also evidenced in the elevated T-maze. These findings strength the view that dysfunction in mechanisms controlling escape in the lwDR is critically implicated in the pathophysiology of panic disorder.

  18. Resilience and reduced c-Fos expression in P2X7 receptor knockout mice exposed to repeated forced swim test.

    PubMed

    Boucher, A A; Arnold, J C; Hunt, G E; Spiro, A; Spencer, J; Brown, C; McGregor, I S; Bennett, M R; Kassiou, M

    2011-08-25

    There is considerable evidence suggesting genetic factors play an important role in the pathophysiology of depression, possibly by increasing susceptibility to repeated environmental stressors. Recent linkage studies have associated a polymorphism of the gene coding for the P2X7 receptor (P2X7R) with both major depressive disorder and bipolar disorder. Here we assessed whether P2X7 deletion affected the behavioural and neural response to repeated stress. P2X7R knockout (P2X7-/-) mice were subjected to the forced swim test for three consecutive days and neuronal activation in response to the third exposure was assessed using c-Fos immunohistochemistry. In addition, anxiety was evaluated in another group of P2X7-/- mice using the elevated plus maze (EPM) and light dark emergence (LDE) tests. Equivalent levels of immobility were observed in P2X7-/- mice and wild-type (WT) mice on the first exposure to forced swim, but much greater immobility was seen in WT mice on second and third exposures. This suggests that P2X7-/- mice exhibit an impaired adaptive coping response to repeated stress. Reinforcing this view, c-Fos expression in the dentate gyrus of the hippocampus and in the basolateral amygdala was seen in WT mice but not P2X7-/- mice following repeated forced swim. In addition, decreased locomotor activity was detected in P2X7-/- mice without any specific effects on anxiety in the LDE test. However, P2X7-/- mice showed greater anxiety-like behaviour in the EPM. These data suggest that the P2X7R may be involved in the adaptive mechanisms elicited by exposure to repeated environmental stressors that leads to the development of depression-like behaviours. This suggests that P2X7R antagonists may be useful therapeutics for the treatment of major depression, possibly by increasing resilience in the face of repeated stress.

  19. L-DOPA-induced dyskinesia in adult rats with a unilateral 6-OHDA lesion of dopamine neurons is paralleled by increased c-fos gene expression in the subthalamic nucleus.

    PubMed

    Soghomonian, Jean-Jacques

    2006-05-01

    Levodopa (L-DOPA), the metabolic precursor of dopamine, is widely used as a pharmacological agent for the symptomatic treatment of Parkinson's disease. However, long-term L-DOPA use results in abnormal involuntary movements such as dyskinesias. There is evidence that abnormal cell signaling in the basal ganglia is involved in L-DOPA-induced dyskinesia. The subthalamic nucleus (STN) plays a key role in the circuitry of the basal ganglia and in the pathophysiology of Parkinson's disease. However, the contribution of the STN to L-DOPA-induced dyskinesias remains unclear. The objective of this work was to study the effects of acute or chronic systemic administration of L-DOPA to adult rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of dopamine neurons on c-fos expression in the STN and test the hypothesis that these effects correlate with L-DOPA-induced dyskinesias. c-fos mRNA expression was measured in the STN by in situ hybridization histochemistry at the single cell level. Our results confirm earlier evidence that the chronic administration of L-DOPA to rats with a unilateral 6-OHDA lesion increases c-fos expression in the STN. We also report that c-fos expression can be increased following an acute injection of L-DOPA to 6-OHDA-lesioned rats but not following a chronic injection of L-DOPA to sham-operated, unlesioned rats. Finally, we provide evidence that the occurrence and severity of dyskinesia is correlated with c-fos mRNA levels in the ipsilateral STN. These results suggest that altered cell signaling in the STN is involved in some of the behavioral effects induced by systemic L-DOPA administration.

  20. Expression patterns of c-Fos early gene and phosphorylated ERK in the rat brain following 1-h immobilization stress: concomitant changes induced in association with stress-related sleep rebound.

    PubMed

    Keshavarzy, Fatemeh; Bonnet, Chantal; Behzadi, Gila; Bezhadi, Gila; Cespuglio, Raymond

    2015-01-01

    An immobilization stress (IS) of 1 h applied at the beginning of the dark phase is followed by a sleep rebound. During the restraint, serotonin released by the dorsal raphe nucleus within the arcuate area stimulates the availability of corticotropin-like intermediate lobe peptide (CLIP or ACTH18-39). Three hours after the restraint, CLIP, through its hypnogenic properties, contributes to the sleep rebound that follows the IS. Here, we immunohistochemically evaluated protein expression of the immediate early gene, c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) in hypothalamic (preoptic area [POA], paraventricular nucleus [PVN], arcuate nucleus [ARC]) and brain stem (dorsal raphe [DR], locus coeruleus [LC]) nuclei involved in the acute response to stress and the subsequent stress-related sleep rebound (recovery period). Immediately after the 1-h restraint, c-Fos and p-ERK expression increased in all structures studied, particularly in PVN and LC. Three hours later, the number of p-ERK- and c-Fos-positive neurons was reduced in PVN and LC (p < 0.001) as well as in DR (p < 0.01) compared to control animals. In contrast, both c-Fos and p-ERK expression in POA neurons (p < 0.01) and c-Fos expression in ARC neurons (p < 0.001) were increased 3 h after the IS. The marked activation observed in PVN and LC nucleus immediately after the IS confirms that these structures are clearly reactive to stress. However, the high activity observed in POA and ARC neurons during the recovery period, not described to date, highlights the particular part played by these structures in the stress-related sleep rebound. An unbalance in the above processes may contribute to pathological outcomes, such as anxiety and depression.

  1. Activation of endogenous c-fos proto-oncogene expression by human T-cell leukemia virus type I-encoded p40 sup tax protein in the human T-cell line, Jurkat

    SciTech Connect

    Nagata, Kinya; Ohtani, Kiyoshi; Nakamura, Masataka; Sugamura, Kazuo )

    1989-08-01

    The authors examined the ability of the trans-acting factor p40{sup tax} of human T-cell leukemia virus type I (HTLV-I), which is thought to be a crucial molecule in T-cell transformation by HTLV-I, to activate expression of a set of endogenous cellular genes related to T-cell proliferation. For this purpose, they established a subclone (JPX-9) of Jurkat cells that was stably transfected with an expression plasmid containing the p40{sup tax} gene, whose expression is definitively dependent on heavy-metal ions. Expression of the interleukin-2 receptor {alpha} chain in JPX-9 cells was induced in response to the induction of p40{sup tax} expression, as has been demonstrated by others in transient transfection experiments with Jurkat cells. In addition, they found that significant enhancement of expression of the nuclear proto-oncogene c-fos was closely associated with expression of p40{sup tax}. Continuous enhancement in the level of c-fos mRNA was observed in the presence of p40{sup tax}. These results suggest that (i) in addition to the interleukin-2-interleukin-2 receptor system, cellular genes such as c-fos, which regulate normal T-cell growth, are also activated directly or indirectly by p40{sup tax} and (ii) p40{sup tax}-induced modulation of gene expression plays a crucial role in T-cell transformation by HTLV-I.

  2. PRENATAL ETHANOL EXPOSURE INCREASES ETHANOL INTAKE AND REDUCES C-FOS EXPRESSION IN INFRALIMBIC CORTEX OF ADOLESCENT RATS

    PubMed Central

    Fabio, Maria Carolina; March, Samanta M.; Molina, Juan Carlos; Nizhnikov, Michael E; Spear, Norman E; Pautassi, Ricardo Marcos

    2013-01-01

    Prenatal ethanol exposure significantly increases later predisposition for alcohol intake, but the mechanisms associated with this phenomenon remain hypothetical. This study analyzed (Exp. 1) ethanol intake in adolescent inbred WKAH/Hok Wistar rats prenatally exposed to ethanol (2.0 g/kg) or vehicle, on gestational days 17–20. Subsequent Experiments (2, 3 and 4) tested several variables likely to underlie the effect of gestational ethanol on adolescent ethanol preference, including ethanol-induced locomotor activation (LMA), ethanol-induced emission of ultrasonic vocalizations (USVs) after exposure to a rough exteroceptive stimulus, and induction of the immediate early gene C-fos in brain areas associated with processing of reward stimuli and with the retrieval and extinction of associative learning. Prenatal ethanol induced a two-fold increase in ethanol intake. Adolescents exhibited significant ethanol-induced LMA, emitted more aversive than appetitive USVs, and postnatal ethanol administration significantly exacerbated the emission of USVs. These effects, however, were not affected by prenatal ethanol. Adolescents prenatally exposed to ethanol as fetuses exhibited reduced neural activity in infralimbic cortex (but not in prelimbic cortex or nucleus accumbens core or shell), an area that has been implicated in the extinction of drug-mediated associative memories. Ethanol metabolism was not affected by prenatal ethanol. Late gestational exposure to ethanol significantly heightened drinking in the adolescent offspring of an inbred rat strain. Ethanol-induced LMA and USVs were not associated with differential ethanol intake due to prenatal ethanol exposure. Prenatal ethanol, however, altered basal neural activity in the infralimbic prefrontal cortex. Future studies should analyze the functionality of medial prefrontal cortex after prenatal ethanol and its potential association with predisposition for heightened ethanol intake. PMID:23266368

  3. Prenatal ethanol exposure increases ethanol intake and reduces c-Fos expression in infralimbic cortex of adolescent rats.

    PubMed

    Fabio, Maria Carolina; March, Samanta M; Molina, Juan Carlos; Nizhnikov, Michael E; Spear, Norman E; Pautassi, Ricardo Marcos

    2013-02-01

    Prenatal ethanol exposure significantly increases later predisposition for alcohol intake, but the mechanisms associated with this phenomenon remain hypothetical. This study analyzed (Experiment 1) ethanol intake in adolescent inbred WKAH/Hok Wistar rats prenatally exposed to ethanol (2.0g/kg) or vehicle, on gestational days 17-20. Subsequent Experiments (2, 3 and 4) tested several variables likely to underlie the effect of gestational ethanol on adolescent ethanol preference, including ethanol-induced locomotor activation (LMA), ethanol-induced emission of ultrasonic vocalizations (USVs) after exposure to a rough exteroceptive stimulus, and induction of the immediate early gene C-fos in brain areas associated with processing of reward stimuli and with the retrieval and extinction of associative learning. Prenatal ethanol induced a two-fold increase in ethanol intake. Adolescents exhibited significant ethanol-induced LMA, emitted more aversive than appetitive USVs, and postnatal ethanol administration significantly exacerbated the emission of USVs. These effects, however, were not affected by prenatal ethanol. Adolescents prenatally exposed to ethanol as fetuses exhibited reduced neural activity in infralimbic cortex (but not in prelimbic cortex or nucleus accumbens core or shell), an area that has been implicated in the extinction of drug-mediated associative memories. Ethanol metabolism was not affected by prenatal ethanol. Late gestational exposure to ethanol significantly heightened drinking in the adolescent offspring of an inbred rat strain. Ethanol-induced LMA and USVs were not associated with differential ethanol intake due to prenatal ethanol exposure. Prenatal ethanol, however, altered basal neural activity in the infralimbic prefrontal cortex. Future studies should analyze the functionality of medial prefrontal cortex after prenatal ethanol and its potential association with predisposition for heightened ethanol intake.

  4. Induction of c-fos mRNA expression in an in vitro hippocampal slice model of adult rats after kainate but not gamma-aminobutyric acid or bicuculline treatment.

    PubMed

    Massamiri, T; Khrestchatisky, M; Ben-Ari, Y

    1994-01-17

    Levels of gene expression following in vitro treatment of rat hippocampal slices with kainate, gamma-aminobutyric acid (GABA), or bicuculline were measured by the reverse transcription-coupled polymerase chain reaction method. Following a short-term exposure to kainate, c-fos gene expression was induced by 12-fold in the adult, but not the newborn, hippocampus. Under the same experimental conditions, zifl268 and brain-derived neurotrophic factor (BDNF) gene expression were unchanged. Our results also demonstrate a lack of induction of c-fos, zifl268 and BDNF after short-time treatment of either adult or newborn hippocampal slices with GABA or bicuculline. The relevance of the differential induction of gene expression in the adult and newborn in an in vitro hippocampal slice model as compared to previously described in vivo models is discussed.

  5. Chemical divisions in the medial geniculate body and surrounding paralaminar nuclei of the rat: quantitative comparison of cell density, NADPH diaphorase, acetyl cholin esterase and basal expression of c-fos.

    PubMed

    Olucha-Bordonau, Francisco E; Pérez-Villalba, Ana; Teruel-Martí, Vicent; Ruiz-Torner, Amparo

    2004-11-01

    Quantitative methods of cell density, the intensities of both acetyl cholinesterase (AChE) and NADPH diaphorase (NADPHd), as well as the basal expression of c-fos, have been carried out in order to study the anatomical divisions of the medial geniculate body (MGB) and the group of nuclei located ventromedially to the MGB called the paralaminar complex (PL). The MGB was composed of the dorsal (MGd), and the ventral (MGv) divisions. We included the medial, or the magnocellular division (MGm), in the PL complex. MGd was composed of a dorsolateral (DL) core and a belt. The belt was composed of the suprageniculate (SG), the deep dorsal (DD), the caudo-medial (CM) and the caudo-dorsal (CD) nuclei. In the MGv, the basal expression of c-fos was the only way to trace a clear boundary between the ovoid (Ov) and the ventrolateral (VL) divisions. However, the marginal zone (MZ) was clearly and contrastingly different. The PL was considered to be composed of: the MGm, the posterior intralaminar nucleus (PIN), the peripeduncular nucleus (PP) and the nucleus subparafascicularis lateralis (SPFL). The MGm and the PIN share most of the chemical features, meanwhile both SPFL and PP displayed different patterns of NADPHd reactivity. The study of cell density on Giemsa stained sections confirmed main divisions of the area. AChE and NADPHd methods allowed the main MGB divisions to be discriminated. The differences between subdivisions were emphasized when cell density and c-fos activity were quantified in each nucleus. Each MGB division displayed a different pattern of c-fos activity under basal conditions. Thus, c-fos basal expression was a particular feature in each MGB or PL nucleus.

  6. Induction of deltaFosB in reward-related brain structures after chronic stress.

    PubMed

    Perrotti, Linda I; Hadeishi, Yuki; Ulery, Paula G; Barrot, Michel; Monteggia, Lisa; Duman, Ronald S; Nestler, Eric J

    2004-11-24

    Acute and chronic stress differentially regulate immediate-early gene (IEG) expression in the brain. Although acute stress induces c-Fos and FosB, repeated exposure to stress desensitizes the c-Fos response, but FosB-like immunoreactivity remains high. Several other treatments differentially regulate IEG expression in a similar manner after acute versus chronic exposure. The form of FosB that persists after these chronic treatments has been identified as DeltaFosB, a splice variant of the fosB gene. This study was designed to determine whether the FosB form induced after chronic stress is also DeltaFosB and to map the brain regions and identify the cell populations that exhibit this effect. Western blotting, using an antibody that recognizes all Fos family members, revealed that acute restraint stress caused robust induction of c-Fos and full-length FosB, as well as a small induction of DeltaFosB, in the frontal cortex (fCTX) and nucleus accumbens (NAc). The induction of c-Fos (and to some extent full-length FosB) was desensitized after 10 d of restraint stress, at which point levels of DeltaFosB were high. A similar pattern was observed after chronic unpredictable stress. By use of immunohistochemistry, we found that chronic restraint stress induced DeltaFosB expression predominantly in the fCTX, NAc, and basolateral amygdala, with lower levels of induction seen elsewhere. These findings establish that chronic stress induces DeltaFosB in several discrete regions of the brain. Such induction could contribute to the long-term effects of stress on the brain.

  7. Peptide YY directly inhibits ghrelin-activated neurons of the arcuate nucleus and reverses fasting-induced c-Fos expression.

    PubMed

    Riediger, Thomas; Bothe, Christine; Becskei, Csilla; Lutz, Thomas A

    2004-01-01

    The hypothalamic arcuate nucleus (Arc) monitors and integrates hormonal and metabolic signals involved in the maintenance of energy homeostasis. The orexigenic peptide ghrelin is secreted from the stomach during negative status of energy intake and directly activates neurons of the medial arcuate nucleus (ArcM) in rats. In contrast to ghrelin, peptide YY (PYY) is released postprandially from the gut and reduces food intake when applied peripherally. Neurons in the ArcM express ghrelin receptors and neuropeptide Y receptors. Thus, PYY may inhibit feeding by acting on ghrelin-sensitive Arc neurons. Using extracellular recordings, we (1) characterized the effects of PYY on the electrical activity of ghrelin-sensitive neurons in the ArcM of rats. In order to correlate the effect of PYY on neuronal activity with the energy status, we (2) investigated the ability of PYY to reverse fasting-induced c-Fos expression in Arc neurons of mice. In addition, we (3) sought to confirm that PYY reduces food intake under our experimental conditions. Superfusion of PYY reversibly inhibited 94% of all ArcM neurons by a direct postsynaptic mechanism. The PYY-induced inhibition was dose-dependent and occurred at a threshold concentration of 10(-8)M. Consistent with the opposite effects of ghrelin and PYY on food intake, a high percentage (50%) of Arc neurons was activated by ghrelin and inhibited by PYY. In line with this inhibitory action, peripherally injected PYY partly reversed the fasting-induced c-Fos expression in Arc neurons of mice. Similarly, refeeding of food-deprived mice reversed the fasting-induced activation in the Arc. Furthermore, peripherally injected PYY reduced food intake in 12-hour fasted mice. Thus the activity of Arc neurons correlated with the feeding status and was not only reduced by feeding but also by administration of PYY in non-refed mice. In conclusion, our current observations suggest that PYY may contribute to signaling a positive status of energy intake

  8. Microinjection of the SH2 domain of the 85-kilodalton subunit of phosphatidylinositol 3-kinase inhibits insulin-induced DNA synthesis and c-fos expression.

    PubMed Central

    Jhun, B H; Rose, D W; Seely, B L; Rameh, L; Cantley, L; Saltiel, A R; Olefsky, J M

    1994-01-01

    We have investigated the functional role of the SH2 domain of the 85-kDa subunit (p85) of the phosphatidylinositol 3-kinase in the insulin signal transduction pathway. Microinjection of a bacterial fusion protein containing the N-terminal SH2 domain of p85 inhibited insulin- and other growth factor-induced DNA synthesis by 90% and c-fos protein expression by 80% in insulin-responsive rat fibroblasts. The specificity of the fusion protein was examined by in vitro precipitation experiments, which showed that the SH2 domain of p85 can independently associate with both insulin receptor substrate 1 and the insulin receptor itself in the absence of detectable binding to other phosphoproteins. The microinjection results were confirmed through the use of an affinity-purified antibody directed against p85, which gave the same phenotype. Additional studies were carried out in another cell line expressing mutant insulin receptors which lack the cytoplasmic tyrosine residues with which p85 interacts. Microinjection of the SH2 domain fusion protein also inhibited insulin signaling in these cells, suggesting that association of p85 with insulin receptor substrate 1 is a key element in insulin-mediated cell cycle progression. In addition, coinjection of purified p21ras protein with the p85 fusion protein or the antibody restored DNA synthesis, suggesting that ras function is either downstream or independent of p85 SH2 domain interaction. Images PMID:7935461

  9. c-Fos expression in neurons projecting from the preoptic and lateral hypothalamic areas to the ventrolateral periaqueductal gray in relation to sleep states

    PubMed Central

    Hsieh, Kung-Chiao; Gvilia, Irma; Kumar, Sunil; Uschakov, Aaron; McGinty, Dennis; Alam, M. Noor; Szymusiak, Ronald

    2011-01-01

    The ventrolateral division of the periaqueductal gray (vlPAG) and the adjacent deep mesencephalic reticular nucleus have been implicated in the control of sleep. The preoptic hypothalamus, which contains populations of sleep-active neurons, is an important source of afferents to the vlPAG. The perifornical lateral hypothalamus (LH) contains populations of wake-active neurons and also projects strongly to the vlPAG. We examined nonREM and REM sleep-dependent expression of c-Fos protein in preoptic-vlPAG and LH-vlPAG projection neurons identified by retrograde labeling with Fluoro-gold (FG). Separate groups of rats (n=5) were subjected to 3 hours total sleep deprivation (TSD) followed by 1 hour recovery sleep (RS), or to 3 hours of selective REM sleep deprivation (RSD) followed by RS. A third group of rats (n=5) was subjected to TSD without opportunity for RS (awake group). In the median preoptic nucleus (MnPN), the percentage of FG+ neurons that were also Fos+ was higher in TSD-RS animals compared to both RSD-RS rats and awake rats. There were significant correlations between time spent in deep nonREM sleep during the 1-hour prior to sacrifice across groups and the percentage of double-labeled cells in MnPN and ventrolateral preoptic area (VLPO). There were no significant correlations between percentage of double labeled neurons and time spent in REM sleep for any of the preoptic nuclei examined. In the LH, percentage of double-labeled neurons was highest in awake rats, intermediate in TSD-RS rats and lowest in the RSD-RS group. These results suggest that neurons projecting from MnPN and VLPO to the vlPAG are activated during nonREM sleep and support the hypothesis that preoptic neurons provide inhibitory input to vlPAG during sleep. Suppression of excitatory input to the vlPAG from the LH during sleep may have a permissive effect on REM sleep generation. PMID:21601616

  10. n-3 polyunsaturated fatty acids stimulate osteoclastogenesis through PPARγ-mediated enhancement of c-Fos expression, and suppress osteoclastogenesis through PPARγ-dependent inhibition of NFkB activation.

    PubMed

    Nakanishi, Atsuko; Tsukamoto, Ikuyo

    2015-11-01

    n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been reported to suppress osteoclastogenesis in vivo. In this study, the effect of PUFAs on receptor for activation of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis was examined using bone marrow-derived monocytes/macrophage precursor cells (BMMs) or bone marrow cells (BMCs) in vitro. EPA and DHA stimulated the osteoclastic differentiation of BMMs, but n-6 PUFAs, linoleic acid and arachidonic acid had no effect. The stimulation of osteoclastogenesis of BMMs by EPA and DHA was associated with enhancement of the gene expressions of c-Fos, tartrate-resistant acid phosphatase, cathepsin K and peroxisome proliferator-activated receptor-γ (PPARγ) and the protein levels of c-Fos, PPARγ and nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent-1 (NFATc1). The PPARγ agonists, rosiglitazone and GW1929, also stimulated the osteoclastogenesis of BMMs. The PPARγ antagonists, T0070907 and GW9662, inhibited the stimulations of osteoclastogenesis and c-Fos expression by EPA or DHA. However, EPA and DHA inhibited the osteoclastogenesis in BMCs including BMMs and mesenchymal stem cells (MSCs). This inhibition was associated with suppression of the expression of RANKL and nuclear factor-κB (NFκB)-regulating genes, cyclooxygenase 2, TNFα and IL-6 in BMCs and MSCs. The agonists and antagonists of PPARγ showed that the inhibitions of NFκB transcriptional activity and osteoclastogenesis by EPA and DHA were PPARγ-dependent. These results suggest that EPA and DHA directly act on BMMs and stimulate osteoclastogenesis through enhancing c-Fos expression mediated by PPARγ but suppress osteoclastogenesis through the PPARγ-dependent inhibition of NFκB activation of MSCs in BMCs. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Study of Fos, androgen receptor and testosterone expression in the sub-regions of medial amygdala, bed nucleus of stria terminalis and medial preoptic area in male Mandarin voles in response to chemosensory stimulation.

    PubMed

    He, Fengqin; Wu, Ruiyong; Yu, Peng

    2014-01-01

    In many rodent species, including mandarin voles (Microtus mandarinus), the behavioral response to odors is regulated by a network of steroid-sensitive ventral forebrain nuclei including the medial amygdala (Me), bed nucleus of the striaterminalis (BNST), and medial preoptic area (MPOA). Although it is well-known that Me, BNST, and MPOA are closely interconnected, function independently in regulating odor-guided social behaviors, little is known about how order information is processed in the sub-regions of Me, BNST, and MPOA. In order to answer this question, we let male mandarin voles expose to two different odors including female vaginal fluid (FVF) and male flank gland secretion (MFGS) and detect the expression of Fos, androgen receptor (AR) and testosterone (T) in the sub-regions of Me, BNST, and MPOA. We found that FVF stimulus caused increased Fos, AR and T expression in the posterior subdivision of the Me (MeP), the posterior medial subdivision of the BNST (BNSTpm), and the medial preoptic nucleus (MPN), while MFGS stimulus did not change Fos, AR and T expression neither in the MeP, BNSTpm, and MPN nor in the anterior subdivision of the Me (MeA), the posterointermediate subdivision of the BNST (BNSTpi), and the lateral subdivision of the MPOA (MPOAl). Serum testosterone levels were increased after 1h in males exposed to FVF. This study provides insight in understanding the relationship between female odor stimulation and Fos, AR and T expression in specific brain areas in males, and the regulatory role of testosterone in this biochemical process. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Anxiogenic-like activity of 3,4-methylenedioxy-methamphetamine ("Ecstasy") in the social interaction test is accompanied by an increase of c-fos expression in mice amygdala.

    PubMed

    Navarro, José Francisco; Rivera, Alicia; Maldonado, Enrique; Cavas, María; de la Calle, Adelaida

    2004-03-01

    3,4-Methylenedioxymethamphetamine (MDMA) is a synthetic amphetamine popularly known as "Ecstasy." Animal studies examining acute effects of MDMA on anxiety are unclear because although an anxiolytic-like action of MDMA in different animal models of anxiety has been described, there is also substantial evidence supporting an anxiogenic-like effect of this drug. To date, several studies have examined c-fos expression following MDMA administration in rats. However, there is no information about the MDMA-induced c-fos expression in mice previously tested in an animal model of anxiety. In this study, male mice were injected with MDMA (1, 8 and 15 mg/kg ip) and assessed for changes on anxiety and for the expression of the immediate early gene c-fos in the amygdala (central, basolateral and basomedial). Anxiety was evaluated by the "social interaction test." Ten behavioral categories were recorded: body care, digging, nonsocial exploration, exploration from a distance, social investigation, threat, attack, avoidance/flee, defense/submission and immobility. As compared with the control group, mice treated with MDMA (all doses) showed a decrease in mean duration and total time spent in social investigation behaviors, whereas avoidance/flee behaviors were significantly increased after treatment with this compound (8 and 15 mg/kg). Likewise, a significant increase in c-fos expression was found in the basolateral (all doses) and central (15 mg/kg) amygdala after MDMA administration. Overall, these findings indicate that MDMA exhibits an anxiogenic-like profile in the social interaction test in mice, and that central and basolateral amygdala might be involved in these anxiogenic-like effects of the drug.

  13. Immunohistochemical analysis of the expression of cellular transcription NFκB (p65), AP-1 (c-Fos and c-Jun), and JAK/STAT in leprosy.

    PubMed

    Silva, Luciana Mota; Hirai, Kelly Emi; de Sousa, Jorge Rodrigues; de Souza, Juarez; Fuzii, Hellen Thais; Dias, Leonidas Braga; Carneiro, Francisca Regina Oliveira; de Souza Aarão, Tinara Leila; Quaresma, Juarez Antonio Simões

    2015-05-01

    Leprosy is a disease whose clinical spectrum depends on the cytokine patterns produced during the early stages of the immune response. The main objective of this study was to describe the activation pattern of cellular transcription factors and to correlate these factors with the clinical forms of leprosy. Skin samples were obtained from 16 patients with the tuberculoid (TT) form and 14 with the lepromatous (LL) form. The histologic sections were immunostained with anti-c-Fos and anti-c-Jun monoclonal antibodies for investigation of AP-1, anti-NFκB p65 for the study of NFκB, and anti-JAK2, STAT1, STAT3, and STAT4 for investigation of the JAK/STAT pathway. Cells expressing STAT1 were more frequent in the TT form than in LL lesions (P = .0096), in agreement with the protective immunity provided by IFN-γ. STAT4 was also more highly expressed in the TT form than in the LL form (P = .0098). This transcription factor is essential for the development of a Th1 response because it is associated with interleukin-12. NFκB (p65) and STAT4 expression in the TT form showed a strong and significant correlation (r = 0.7556 and P = .0007). A moderate and significant correlation was observed between JAK2 and STAT4 in the TT form (r = 0.6637 and P = .0051), with these factors responding to interleukin-12 in Th1 profiles. The results suggest that STAT1, JAK2, and NFκB, together with STAT4, contribute to the development of cell-mediated immunity, which is able to contain the proliferation of Mycobacterium leprae.

  14. Effects of 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) on histopathology, oxidative stress, and expression of c-fos, c-jun and p16 in rat stomachs.

    PubMed

    Li, Ruijin; Tian, Jingjing; Li, Wanqing; Xie, Jingfang

    2013-05-01

    2-Amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) is one of the most abundant heterocyclic amines (HCAs) generated from overcooking meat at high temperatures. To understand the possible mechanism of PhIP-associated stomach cancer, the effects of PhIP on morphology, oxidative stress, gene expression of c-fos, c-jun and p16 in rat stomachs were investigated. The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) PhIP (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase (GPx) activities, while increased catalase (CAT) activity compared with the control. With the elevated doses of PhIP, malondialdehyde (MDA) contents, protein carbonyl (PCO) contents and DNA-protein crosslinks (DPC) coefficients were significantly raised in a dose-dependent manner; (3) PhIP at the doses of 10mg/kg and/or 15mg/kg significantly inhibited p16 mRNA and protein expression, whereas enhanced c-fos and c-jun expression relative to control. The data indicated that PhIP could cause stomach injury, oxidative stress in rat stomachs as well as the activation of c-fos and c-jun and inactivation of p16, which may play a role in the pathogenesis of PhIP-associated stomach cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Ginsenosides Have a Suppressive Effect on c-Fos Expression in Brain and Reduce Cardiovascular Responses Increased by Noxious Stimulation to the Rat Tooth

    PubMed Central

    Jung, Ji-Yeon; Seong, Kyung-Joo; Moon, In-Ohk; Cho, Jin-Hyoung; Kim, Sun-Hun

    2013-01-01

    The purpose of this study is to investigate the antinociceptive effects of ginsenosides on toothache. c-Fos immunoreactive (IR) neurons were examined after noxious intrapulpal stimulation (NS) by intrapulpal injection of 2 M KCl into upper and lower incisor pulps exposed by bone cutter in Sprague Dawley rats. The number of Fos-IR neurons was increased in the trigeminal subnucleus caudalis (Vc) and the transitional region between Vc and subnucleus interpolaris (Vi) by NS to tooth. The intradental NS raised arterial blood pressure (BP) and heart rate (HR). The number of Fos-IR neurons was also enhanced in thalamic ventral posteromedial nucleus (VPMN) and centrolateral nucleus (CLN) by NS to tooth. The intradental NS increased the number of Fos-IR neurons in the nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM), hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN), central cardiovascular regulation centers. Ginsenosides reduced the number of c-Fos-IR increased by NS to tooth in the trigeminal Vc and thalamic VPMN and CLN. Naloxone, an opioid antagonist, did not block the effect of ginsenoside on the number of Fos-IR neurons enhanced by NS to tooth in the trigeminal Vc and thalamic VPMN and CLN. Ginsenosides ameliorated arterial BP and HR raised by NS to tooth and reduced the number of Fos-IR neurons increased by NS to tooth in the NTS, RVLM, hypothalamic SON, and PVN. These results suggest that ginsenosides have an antinociceptive effect on toothache through non-opioid system and attenuates BP and HR increased by NS to tooth. PMID:23626473

  16. Effect of estrogen and tamoxifen on the expression pattern of AP-1 factors in MCF-7 cells: role of c-Jun, c-Fos, and Fra-1 in cell cycle regulation.

    PubMed

    Babu, R L; Naveen Kumar, M; Patil, Rajeshwari H; Devaraju, K S; Ramesh, Govindarajan T; Sharma, S Chidananda

    2013-08-01

    The activated transcription factor ERα plays an important role in the breast development and progression of cancer. In a non-classical pathway ER interacts with other transcription factors AP-1, NFkB, SP1, etc. AP-1 transcription factors control rapid responses of mammalian cells to stimuli that impact proliferation, differentiation, and transformation. AP-1 factors are leucine zipper proteins belonging to members of the Jun family (c-Jun, JunB, and JunD) and Fos family (c-Fos, FosB, Fra-1, and Fra-2) proteins. Although AP-1 factors are well characterized, not much is known about the expression pattern of the AP-1 factors in breast cancer cells. Hence to determine which AP-1 factors are expressed and regulated by estrogen, we used human breast cancer MCF-7 cells as in vitro model system. The MCF-7 cells were treated with or without estradiol-17β (E2) or antiestrogen tamoxifen (TMX) and the cell proliferation and viability was assessed by MTT assay. The expression of different AP-1 factors was analyzed by semi-quantitative RT-PCR. The cells treated with E2 found to increase the cell proliferation by more than 35 % and TMX an antiestrogen decreased by 29 % compared to control. The E2 found to induce the expression of c-Jun, Fra-1, and c-Fos, while TMX decreased the expression. In addition TMX also decreased the mRNA levels of Jun-D and Fra-2. These results suggest that the AP-1 factors c-Jun, c-Fos, and Fra-1 may be involved in the proliferation and transformation of MCF-7 cells. E2 also found to induce cyclin D1 and cyclin E1 mRNA transcripts of cell cycle regulators while TMX significantly decreased compared to control. Further E2 induced the anti-apoptotic Bcl-2 and TMX decreased mRNA transcripts. The data presented here support the E2-ERα-mediated MCF-7 cell proliferation and confirms the role of AP-1 factors in cell cycle regulation.

  17. Detection of conspecific pheromones elicits fos expression in GABA and calcium-binding cells of the rat vomeronasal system-medial extended amygdala.

    PubMed

    Pereno, German Leandro; Balaszczuk, Verónica; Beltramino, Carlos A

    2011-03-01

    The olfactory accessory system is specialized in the detection of pheromones, being an afferent to medial extended amygdala. In spite of the fact that numerous phenotypes are found in these structures, in the current literature, there are no detailed descriptions about the phenotype of neurons in the vomeronasal system-medial extended amygdala after their activation by pheromonal stimuli. Using immunohistochemistry for fos and dual immunohistochemistry for fos and phenotypes, here we show that females have a greater number of activated neurons by the pheromonal stimulus. Likewise, a great colocalization of fos with GABA, calretinin, and calbindin was observed in the vomeronasal system-medial extended amygdala. These data suggest that in amygdaloid areas, neuronal excitability is controlled by GABAergic neurons that contain different calcium-binding proteins, indicating the important role of inhibitory control on the incoming sensory pheromonal and olfactory inputs controlled and processed by the vomeronasal system.

  18. Brain development is impaired in c-fos -/- mice.

    PubMed

    Velazquez, Fabiola N; Prucca, César G; Etienne, Olivier; D'Astolfo, Diego S; Silvestre, David C; Boussin, François D; Caputto, Beatriz L

    2015-07-10

    c-Fos is a proto-oncogene involved in diverse cellular functions. Its deregulation has been associated to abnormal development and oncogenic progression. c-fos-/- mice are viable but present a reduction in their body weight and brain size. We examined the importance of c-Fos during neocortex development at 13.5, 14.5 and 16.5 days of gestation. At E14.5, neocortex thickness, apoptosis, mitosis and expression of markers along the different stages of Neural Stem Progenitor Cells (NSPCs) differentiation in c-fos-/- and wild-type mice were analyzed. A ~15% reduction in the neocortex thickness of c-fos-/- embryos was observed which correlates with a decrease in the number of differentiated cells and an increase in apoptosis at the ventricular zone. No difference in mitosis rate was observed, although the mitotic angle was predominantly vertical in c-fos-/- embryos, suggesting a reduced trend of NSPCs to differentiate. At E13.5, changes in differentiation markers start to be apparent and are still clearly observed at E16.5. A tendency of more AP-1/DNA complexes present in nuclear extracts of cerebral cortex from c-fos-/- embryos with no differences in the lipid synthesis activity was found. These results suggest that c-Fos is involved in the normal development of NSPCs by means of its AP-1 activity.

  19. [Food-procuring stereotype movements is accompanied by changes of c-Fos gene expression in the amygdala and modulation of heart rate in rats].

    PubMed

    Dovgan', O V; Vlasenko, O V; Buzyka, T V; Maĭs'kyĭ, V O; Piliavs'kyĭ, O I; Maznychenko, A V

    2012-01-01

    The distribution of Fos-immunoreactive (Fos-ir) and NADPH Diaphorase reactive (NADPH-dr-) neurons in the different subnuclei of amygdala and insular cortex (on the level -2,12 to -3,14 mm from bregma), and the associated changes of heart rate (HR) in intact, food-deprivated and executed food-procuring movements of rats were studied. In comparison with other groups of animals, the mean number of the Fos-ir neurons in the central nucleus of amygdala (Ce) and the insular cortex (GI/DI) at all studied levels was significantly greater in the executed food-procuring movements in rats. The main focus of localization of the Fos-ir neurons was found in lateral part of the Ce (58.5 +/- 1.9 units in 40-microm-thick section) at the level -2.56 mm. The mean number of Fos-ir neurons was significantly greater also in the lateral and capsular parts of the Ce. The mean number of Fos-ir neurons in the GI/DI was 165.5 +/- 3.2 cells in section. The number and density of NADPH-d reactive neurons was not significantly different in the brain structures of all animal groups studied. The double stained neurons (Fos-ir + NADPH-dr) were registered in medial, basolateral, anterior cortical amygdaloid nuclei and substantia innominata (SI) in rats after realization food-procuring movements. It was found that realization of food-procuring movements by the forelimb during repeated sessions was accompanied with the gradual decline of mean values of the HR (from 5% to 12% of control level) with subsequent renewal of them to the initial values (tonic component). The analysis of dynamics of the HR changes during realization of separate purposeful motion has shown the transient period of the HR suppression (500 ms), which coincided with the terminal phase of grasping of food pellet (phasic component). We suggest that the revealed focuses of localization of Fos-ir neurons in the lateral and medial subregions of amigdaloid Ce and also GI/DI, and SI testified that these structures of brain are involved

  20. Bi-directional effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on fear-related behavior and c-Fos expression after fear conditioning in rats

    PubMed Central

    Meloni, Edward G.; Venkataraman, Archana; Donahue, Rachel J.; Carlezon, William A.

    2015-01-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP) is implicated in stress regulation and learning and memory. PACAP has neuromodulatory actions on brain structures within the limbic system that could contribute to its acute and persistent effects in animal models of stress and anxiety-like behavior. Here, male Sprague-Dawley rats were implanted with intracerebroventricular (ICV) cannula for infusion of PACAP-38 (0.5, 1, or 1.5 ug) or vehicle followed 30 min later by fear conditioning. Freezing was measured early (1, 4, and 7days) or following a delay (7, 10, and 13 days)after conditioning. PACAP (1.5 μg) produced a bi-phasic response in freezing behavior across test days: relative to controls, PACAP-treated rats showed a reduction in freezing when tested 1 or 7 Days after fear conditioning that evolved into a significant elevation in freezing by the third test session in the early, but not delayed, group. Corticosterone (CORT) levels were significantly elevated in PACAP-treated rats following fear conditioning, but not at the time of testing (Day 1). Brain c-Fos expression revealed PACAP-dependent alterations within, as well as outside of, areas typically implicated in fear conditioning. Our findings raise the possibility that PACAP disrupts fear memory consolidation by altering synaptic plasticity within neurocircuits normally responsible for encoding fear-related cues, producing a type of dissociation or peritraumatic amnesia often seen in people early after exposure to a traumatic event. However, fear memories are retained such that repeated testing and memory reactivation (e.g. re-experiencing) causes the freezing response to emerge and persist at elevated levels. PACAP systems may represent an axis on which stress and exposure to trauma converge to promote maladaptive behavioral responses characteristic of psychiatric illnesses such as post-traumatic stress disorder (PTSD). PMID:26590791

  1. Bi-directional effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on fear-related behavior and c-Fos expression after fear conditioning in rats.

    PubMed

    Meloni, Edward G; Venkataraman, Archana; Donahue, Rachel J; Carlezon, William A

    2016-02-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP) is implicated in stress regulation and learning and memory. PACAP has neuromodulatory actions on brain structures within the limbic system that could contribute to its acute and persistent effects in animal models of stress and anxiety-like behavior. Here, male Sprague-Dawley rats were implanted with intracerebroventricular (ICV) cannula for infusion of PACAP-38 (0.5, 1, or 1.5 μg) or vehicle followed 30 min later by fear conditioning. Freezing was measured early (1, 4, and 7 days) or following a delay (7, 10, and 13 days) after conditioning. PACAP (1.5 μg) produced a bi-phasic response in freezing behavior across test days: relative to controls, PACAP-treated rats showed a reduction in freezing when tested 1 or 7 days after fear conditioning that evolved into a significant elevation in freezing by the third test session in the early, but not delayed, group. Corticosterone (CORT) levels were significantly elevated in PACAP-treated rats following fear conditioning, but not at the time of testing (Day 1). Brain c-Fos expression revealed PACAP-dependent alterations within, as well as outside of, areas typically implicated in fear conditioning. Our findings raise the possibility that PACAP disrupts fear memory consolidation by altering synaptic plasticity within neurocircuits normally responsible for encoding fear-related cues, producing a type of dissociation or peritraumatic amnesia often seen in people early after exposure to a traumatic event. However, fear memories are retained such that repeated testing and memory reactivation (e.g., re-experiencing) causes the freezing response to emerge and persist at elevated levels. PACAP systems may represent an axis on which stress and exposure to trauma converge to promote maladaptive behavioral responses characteristic of psychiatric illnesses such as post-traumatic stress disorder (PTSD). Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. FOS Target Acquisition Test

    NASA Astrophysics Data System (ADS)

    Koratkar, Anuradha

    1994-01-01

    FOS onboard target acquisition software capabilities will be verified by this test -- point source binary, point source firmware, point source peak-up, wfpc2 assisted realtime, point source peak-down, taled assisted binary, taled assisted firmware, and nth star binary modes. The primary modes are tested 3 times to determine repeatability. This test is the only test that will verify mode-to-mode acquisition offsets. This test has to be conducted for both the RED and BLUE detectors.

  3. Osteoblasts are target cells for transformation in c-fos transgenic mice

    PubMed Central

    1993-01-01

    We have generated transgenic mice expressing the proto-oncogene c-fos from an H-2Kb class I MHC promoter as a tool to identify and isolate cell populations which are sensitive to altered levels of Fos protein. All homozygous H2-c-fosLTR mice develop osteosarcomas with a short latency period. This phenotype is specific for c-fos as transgenic mice expressing the fos- and jun-related genes, fosB and c-jun, from the same regulatory elements do not develop any pathology despite high expression in bone tissues. The c-fos transgene is not expressed during embryogenesis but is expressed after birth in bone tissues before the onset of tumor formation, specifically in putative preosteoblasts, bone- forming osteoblasts, osteocytes, as well as in osteoblastic cells present within the tumors. Primary and clonal cell lines established from c-fos-induced tumors expressed high levels of exogenous c-fos as well as the bone cell marker genes, type I collagen, alkaline phosphatase, and osteopontin/2ar. In contrast, osteocalcin/BGP expression was either low or absent. All cell lines were tumorigenic in vivo, some of which gave rise to osteosarcomas, expressing exogenous c- fos mRNA, and Fos protein in osteoblastic cells. Detailed analysis of one osteogenic cell line, P1, and several P1-derived clonal cell lines indicated that bone-forming osteoblastic cells were transformed by Fos. The regulation of osteocalcin/BGP and alkaline phosphatase gene expression by 1,25-dihydroxyvitamin D3 was abrogated in P1-derived clonal cells, whereas glucocorticoid responsiveness was unaltered. These results suggest that high levels of Fos perturb the normal growth control of osteoblastic cells and exert specific effects on the expression of the osteoblast phenotype. PMID:8335693

  4. Vesicular acetylcholine transporter knock down-mice are more susceptible to inflammation, c-Fos expression and sickness behavior induced by lipopolysaccharide.

    PubMed

    Leite, Hércules Ribeiro; Oliveira-Lima, Onésia Cristina de; Pereira, Luciana de Melo; Oliveira, Vinícius Elias de Moura; Prado, Vania Ferreira; Prado, Marco Antônio Máximo; Pereira, Grace Schenatto; Massensini, André Ricardo

    2016-10-01

    In addition to the well-known functions as a neurotransmitter, acetylcholine (ACh) can modulate of the immune system. Nonetheless, how endogenous ACh release inflammatory responses is still not clear. To address this question, we took advantage of an animal model with a decreased ACh release due a reduction (knockdown) in vesicular acetylcholine transporter (VAChT) expression (VAChT-KD(HOM)). These animals were challenged with lipopolysaccharide (LPS). Afterwards, we evaluated sickness behavior and quantified systemic and cerebral inflammation as well as neuronal activation in the dorsal vagal complex (DVC). VAChT-KD(HOM) mice that were injected with LPS (10mg/kg) showed increased mortality rate as compared to control mice. In line with this result, a low dose of LPS (0.1mg/kg) increased the levels of pro-inflammatory (TNF-α, IL-1β, and IL-6) and anti-inflammatory (IL-10) cytokines in the spleen and brain of VAChT-KD(HOM) mice in comparison with controls. Similarly, serum levels of TNF-α and IL-6 were increased in VAChT-KD(HOM) mice. This excessive cytokine production was completely prevented by administration of a nicotinic receptor agonist (0.4mg/kg) prior to the LPS injection. Three hours after the LPS injection, c-Fos expression increased in the DVC region of VAChT-KD(HOM) mice compared to controls. In addition, VAChT-KD(HOM) mice showed behavioral changes such as lowered locomotor and exploratory activity and reduced social interaction after the LPS challenge, when compared to control mice. Taken together, our results show that the decreased ability to release ACh exacerbates systemic and cerebral inflammation and promotes neural activation and behavioral changes induced by LPS. In conclusion, our findings support the notion that activity of cholinergic pathways, which can be modulated by VAChT expression, controls inflammatory and neural responses to LPS challenge. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Fos protein expression in olfactory-related brain areas after learning and after reactivation of a slowly acquired olfactory discrimination task in the rat.

    PubMed

    Roullet, Florence; Liénard, Fabienne; Datiche, Frédérique; Cattarelli, Martine

    2005-01-01

    Fos protein immunodetection was used to investigate the neuronal activation elicited in some olfactory-related areas after either learning of an olfactory discrimination task or its reactivation 10 d later. Trained rats (T) progressively acquired the association between one odor of a pair and water-reward in a four-arm maze. Two groups of pseudotrained rats were used: PO rats were not water restricted and were submitted to the olfactory stimuli in the maze without any reinforcement, whereas PW rats were water-deprived and systematically received water in the maze without any odorous stimulation. When the discrimination task was well mastered, a significantly lower Fos immunoreactivity was observed in T rats compared to PW and PO rats in most of the analyzed brain areas, which could reflect the post-acquisition consolidation process. Following memory reactivation, differences in Fos immunoreactivity between trained and some pseudotrained rats were found in the anterior part of piriform cortex, CA3, and orbitofrontal cortex. We also observed that Fos labeling was significantly higher in trained rats after memory reactivation than after acquisition of the olfactory task in most of the brain areas examined. Our results support the assumption of a differential involvement of neuronal networks after either learning or reactivation of an olfactory discrimination task.

  6. Effects of acute heat exposure on prosencephalic c-Fos expression in normohydrated, water-deprived and salt-loaded rats.

    PubMed

    Santana, Rejane; de De Castro E Silva, Emilio; Reis de Oliveira, Irismar; Fregoneze, Josmara B

    2007-04-13

    In the present study, the distribution pattern of c-Fos protein immunoreactivity (Fos-IR) in prosencephalic areas of the brain involved in thermoregulatory and osmoregulatory responses was investigated, in rats exposed or not exposed to a hyperthermic environment, under three different conditions: normohydration, dehydration induced by water deprivation and hyperosmolarity induced by an acute intragastric salt load. Normohydrated, water-deprived or salt-loaded male Wistar rats (270+/-30 g) were submitted or not to acute heat exposure (33 degrees C for 45 min). A separate group of animals was submitted to the same experimental protocol and had blood samples collected before and after the heating period to measure serum osmolarity and sodium. The brains were processed for c-Fos immunohistochemistry using the avidin-biotin peroxidase method. After analyzing Fos-IR in the brains of animals in the present study, three different types of prosencephalic areas were identified: (1) those that respond to hydrational and to heat conditions, with an interaction between these two factors (PaMP and SON); (2) those that respond to hydrational and to heat conditions, but with no interaction between these factors (MnPO, LSV and OVLT); and (3) those that respond only to hydrational status (SFO and PaLM).

  7. Fos Protein Expression in Olfactory-Related Brain Areas after Learning and after Reactivation of a Slowly Acquired Olfactory Discrimination Task in the Rat

    ERIC Educational Resources Information Center

    Roullet, Florence; Lienard, Fabienne; Datiche, Frederique; Cattarelli, Martine

    2005-01-01

    Fos protein immunodetection was used to investigate the neuronal activation elicited in some olfactory-related areas after either learning of an olfactory discrimination task or its reactivation 10 d later. Trained rats (T) progressively acquired the association between one odor of a pair and water-reward in a four-arm maze. Two groups of…

  8. TMJ inflammation increases Fos expression in the nucleus raphe magnus induced by subsequent formalin injection of the masseter or hindpaw of rats.

    PubMed

    Oh, Sang-Hoon; Imbe, Hiroki; Iwai-Liao, Yasutomo

    2006-08-01

    The study was designed to examine the effect of persistent temporomandibular joint (TMJ) inflammation on neuronal activation in the descending pain modulatory system in response to noxious stimulus. Formalin was injected into the left masseter muscle or hindpaw of rats 10 days after injection of the left TMJ with saline or complete Freund's adjuvant (CFA). The results showed that 10-day persistent TMJ inflammation (induced by CFA) alone did not induce a significant increase in Fos-like immunoreactive (Fos-LI) neurons in the rostral ventromedial medulla (RVM) or locus coeruleus (LC), but that formalin injection of the masseter muscle or hindpaw induced a significant increase in Fos-LI neurons in the RVM and LC of rats with and without TMJ inflammation (P < 0.05). However, persistent TMJ inflammation significantly increased Fos-LI neurons in the nucleus raphe magnus (NRM) induced by subsequent formalin injection of the masseter muscle and hindpaw (70.2% increase and 53.8% increase, respectively, over the control TMJ-saline-injected rats; P < 0.05). The results suggest that persistent TMJ inflammation increases neuronal activity, in particularly in the NRM, by the plastic change of the descending pain modulatory system after ipsilateral application of a noxious stimulus to either orofacial area or a spatially remote body area.

  9. Reciprocal Patterns of c-Fos Expression in the Medial Prefrontal Cortex and Amygdala after Extinction and Renewal of Conditioned Fear

    ERIC Educational Resources Information Center

    Knapska, Ewelina; Maren, Stephen

    2009-01-01

    After extinction of conditioned fear, memory for the conditioning and extinction experiences becomes context dependent. Fear is suppressed in the extinction context, but renews in other contexts. This study characterizes the neural circuitry underlying the context-dependent retrieval of extinguished fear memories using c-Fos immunohistochemistry.…

  10. Reciprocal Patterns of c-Fos Expression in the Medial Prefrontal Cortex and Amygdala after Extinction and Renewal of Conditioned Fear

    ERIC Educational Resources Information Center

    Knapska, Ewelina; Maren, Stephen

    2009-01-01

    After extinction of conditioned fear, memory for the conditioning and extinction experiences becomes context dependent. Fear is suppressed in the extinction context, but renews in other contexts. This study characterizes the neural circuitry underlying the context-dependent retrieval of extinguished fear memories using c-Fos immunohistochemistry.…

  11. Enriched environment attenuates nicotine self-administration and induces changes in ΔFosB expression in the rat prefrontal cortex and nucleus accumbens.

    PubMed

    Venebra-Muñoz, Arturo; Corona-Morales, Aleph; Santiago-García, Juan; Melgarejo-Gutiérrez, Montserrat; Caba, Mario; García-García, Fabio

    2014-06-18

    Environment enrichment conditions have important consequences on subsequent vulnerability to drugs of abuse. The present work examined whether exposure to an enriched environment (EE) decreases oral self-consumption of nicotine. Wistar rats were housed either in a standard environment (SE, four rats per standard cage) or in an EE during 60 days after weaning. EE consisted of eight animals housed in larger cages containing a variety of objects such as boxes, toys, and burrowing material that were changed three times a week. After this period, animals were exposed to nicotine for 3 weeks, where animals chose freely between water and a nicotine solution (0.006% in water). Fluid consumption was evaluated on a daily basis. ΔFosB immunohistochemistry in the prefrontal cortex and nucleus accumbens was also performed. Rats of the EE group consumed less nicotine solution (0.25±0.04 mg/kg/day) than SE rats (0.54±0.05 mg/kg/day). EE increased the number of ΔFos-immunoreactive (ΔFos-ir) cells in the nucleus accumbens core and shell and in the prefrontal cortex, compared with animals in the standard condition. However, rats exposed to nicotine in the SE showed higher ΔFos-ir cells in the nucleus accumbens core and shell than nonexposed rats. Nicotine consumption did not modify ΔFos-ir cells in these brain areas in EE animals. These results support the idea of a possible protective effect of the EE on reward sensitivity and the development of an addictive behavior to nicotine.

  12. Interleukin-1beta up-regulates the expression of thrombopoietin and transcription factors c-Jun, c-Fos, GATA-1, and NF-E2 in megakaryocytic cells.

    PubMed

    Chuen, Carmen Ka Yee; Li, Karen; Yang, Mo; Fok, Tai Fai; Li, Chi Kong; Chui, Cecilia Mei Yan; Yuen, Patrick Man Pan

    2004-02-01

    The multifunctional cytokine interleukin-1beta (IL-1beta) plays a central role in the body's immune and inflammatory responses. The mechanism of IL-1beta on thrombocytosis and megakaryocytopoiesis has remained controversial. In previous reports, we have demonstrated the expression of IL-1 receptors (IL-1RI and IL-1RII) and enhancing effects of IL-1beta on primary human megakaryocytic (MK) cells. In this study, we investigated the possible direct effects of IL-1beta on the expression of thrombopoietin (TPO) and transcription factors c-Jun, c-Fos, GATA-1, and p45 nuclear factor-E2 (NF-E2) in MK cell lines CHRF and Meg-01. Our results demonstrated that IL-1beta up-regulated messenger RNA (mRNA) and protein expressions of these transcription factors in a dose- and time-dependent manner. In CHRF cells, mRNA: c-Jun [3.4-fold, peaked at 15 minutes], c-Fos [4.2-fold, 15 minutes], GATA-1 [4.0-fold, 60 minutes], NF-E2 [3.2-fold, 120 minutes] and protein expression: c-Jun [3.0-fold, 30 minutes], c-Fos [1.7-fold, 30 minutes], GATA-1 [11.5-fold, 60 minutes], NF-E2 [12.5-fold, 120 minutes] were evidently enhanced after treatment with IL-1beta. The response to IL-1beta was consistent in the total cell and nuclear extracts and was significantly reduced by pretreatment with actinomycin D or cycloheximide. An IL-1-receptor antagonist (IL-1RA) inhibited the stimulatory effects of IL-1beta on these transcription factors by as much as 78%. TPO expression was increased by more than 9.9-fold on stimulation with IL-1beta. A TPO-neutralizing antibody did not significantly reduce the effects of IL-1beta. We conclude that IL-1beta up-regulates the expression of TPO, c-Jun, c-Fos, GATA-1, and NF-E2 in MK cells. The mechanism might be mediated by IL-1beta receptors and require transcription or protein synthesis. The direct involvement of IL-1beta in the MK lineage may provide an explanation for the phenomenon of thrombocytosis during inflammatory responses.

  13. Long-lasting c-fos and NGF mRNA expressions and loss of perikaryal parvalbumin immunoreactivity in the development of epileptogenesis after ethacrynic acid-induced seizure.

    PubMed

    Suzukawa, J; Omori, K; Okugawa, G; Fujiseki, Y; Heizmann, C W; Inagaki, C

    1999-07-10

    A single cerebroventricular injection of ethacrynic acid (EA), a Cl(-)-ATPase inhibitor, induces generalized tonic-clonic convulsions in mice. To clarify whether such convulsive stimulus triggers a long-lasting rearrangement of the neural circuitry culminating in seizure susceptibility, we examined molecular, cellular and behavioral changes following the EA-induced seizure. The expression of immediate early gene c-fos mRNA as an index for cellular activation increased biphasically, with an early transient increase at 60 min and a late prolonged increase on the 10th to 14th day post-EA administration, most remarkably in the hippocampus and pyriform cortex. On the 14th day post-EA seizure, subconvulsive dose of kainic acid (5-17.5 mg/kg) caused severe (stage 5) seizure in 77% of the mice, with 70% mortality. In addition, the expression of nerve growth factor (NGF) also showed biphasic increases with close spatiotemporal correlation with c-fos expression. Moreover, the number of cell somata and the density of axon fibers of parvalbumin (PARV)-positive cells, a subpopulation of GABAergic interneurons, decreased in area dentata, CA1 and CA3 on the 7th and 14th day post-EA seizure. In area dentata and CA1, the density of glutamic acid decarboxylase (GAD)-positive cells also decreased on the 14th day. Thus, the transient EA-induced seizures appear to develop seizure susceptibility by causing damage of a subpopulation of inhibitory interneurons along with increases in the expression of c-fos and NGF in limbic structures.

  14. FosB Null Mutant Mice Show Enhanced Methamphetamine Neurotoxicity: Potential Involvement of FosB in Intracellular Feedback Signaling and Astroglial Function

    PubMed Central

    Kuroda, Kumi O; Ornthanalai, Veravej G; Kato, Tadafumi; Murphy, Niall P

    2010-01-01

    Previous studies show that (1) two members of fos family transcription factors, c-Fos and FosB, are induced in frontal brain regions by methamphetamine; (2) null mutation of c-Fos exacerbates methamphetamine-induced neurotoxicity; and (3) null mutation of FosB enhances behavioral responses to cocaine. Here we sought a role of FosB in responses to methamphetamine by studying FosB null mutant (−/−) mice. After a 10 mg/kg methamphetamine injection, FosB(−/−) mice were more prone to self-injury. Concomitantly, the intracellular feedback regulators of Sprouty and Rad-Gem-Kir (RGK) family transcripts had lower expression profiles in the frontoparietal cortex and striatum of the FosB(−/−) mice. Three days after administration of four 10 mg/kg methamphetamine injections, the frontoparietal cortex and striatum of FosB(−/−) mice contained more degenerated neurons as determined by Fluoro-Jade B staining. The abundance of the small neutral amino acids, serine, alanine, and glycine, was lower and/or was poorly induced after methamphetamine administration in the frontoparietal cortex and striatum of FosB(−/−) mice. In addition, methamphetamine-treated FosB(−/−) frontoparietal and piriform cortices showed more extravasation of immunoglobulin, which is indicative of blood–brain barrier dysfunction. Methamphetamine-induced hyperthermia, brain dopamine content, and loss of tyrosine hydroxylase immunoreactivity in the striatum, however, were not different between genotypes. These data indicate that FosB is involved in thermoregulation-independent protective functions against methamphetamine neurotoxicity in postsynaptic neurons. Our findings suggest two possible mechanisms of FosB-mediated neuroprotection: one is induction of negative feedback regulation within postsynaptic neurons through Sprouty and RGK. Another is supporting astroglial function such as maintenance of the blood–brain barrier, and metabolism of serine and glycine, which are important

  15. FosB null mutant mice show enhanced methamphetamine neurotoxicity: potential involvement of FosB in intracellular feedback signaling and astroglial function.

    PubMed

    Kuroda, Kumi O; Ornthanalai, Veravej G; Kato, Tadafumi; Murphy, Niall P

    2010-02-01

    Previous studies show that (1) two members of fos family transcription factors, c-Fos and FosB, are induced in frontal brain regions by methamphetamine; (2) null mutation of c-Fos exacerbates methamphetamine-induced neurotoxicity; and (3) null mutation of FosB enhances behavioral responses to cocaine. Here we sought a role of FosB in responses to methamphetamine by studying FosB null mutant (-/-) mice. After a 10 mg/kg methamphetamine injection, FosB(-/-) mice were more prone to self-injury. Concomitantly, the intracellular feedback regulators of Sprouty and Rad-Gem-Kir (RGK) family transcripts had lower expression profiles in the frontoparietal cortex and striatum of the FosB(-/-) mice. Three days after administration of four 10 mg/kg methamphetamine injections, the frontoparietal cortex and striatum of FosB(-/-) mice contained more degenerated neurons as determined by Fluoro-Jade B staining. The abundance of the small neutral amino acids, serine, alanine, and glycine, was lower and/or was poorly induced after methamphetamine administration in the frontoparietal cortex and striatum of FosB(-/-) mice. In addition, methamphetamine-treated FosB(-/-) frontoparietal and piriform cortices showed more extravasation of immunoglobulin, which is indicative of blood-brain barrier dysfunction. Methamphetamine-induced hyperthermia, brain dopamine content, and loss of tyrosine hydroxylase immunoreactivity in the striatum, however, were not different between genotypes. These data indicate that FosB is involved in thermoregulation-independent protective functions against methamphetamine neurotoxicity in postsynaptic neurons. Our findings suggest two possible mechanisms of FosB-mediated neuroprotection: one is induction of negative feedback regulation within postsynaptic neurons through Sprouty and RGK. Another is supporting astroglial function such as maintenance of the blood-brain barrier, and metabolism of serine and glycine, which are important glial modulators of nerve cells.

  16. Ionic conditions modulate stimulus-induced capacitance changes in isolated neurohypophysial terminals of the rat.

    PubMed

    Marrero, Héctor G; Lemos, José R

    2010-01-15

    Peptidergic nerve terminals of the neurohypophysis (NH) secrete both oxytocin and vasopressin upon stimulation with peptide-specific bursts of action potentials from magnocellular neurons. These bursts vary in both frequency and action potential duration and also induce in situ ionic changes both inside and outside the terminals in the NH. These temporary effects include the increase of external potassium and decrease of external calcium, as well as the increase in internal sodium and chloride concentrations. In order to determine any mechanism of action that these ionic changes might have on secretion, stimulus-induced capacitance recordings were performed on isolated terminals of the NH using action potential burst patterns of varying frequency and action potential width. The results indicate that in NH terminals: (1) increased internal chloride concentration improves the efficiency of action potential-induced capacitance changes, (2) increasing external potassium increases stimulus-induced capacitance changes, (3) decreasing external calcium decreases the capacitance induced by low frequency broadened action potentials, while no capacitance change is observed with high frequency un-broadened action potentials, and (4) increasing internal sodium increases the capacitance change induced by low frequency bursts of broadened action potentials, more than for high frequency bursts of narrow action potentials. These results are consistent with previous models of stimulus-induced secretion, where optimal secretory efficacy is determined by particular characteristics of action potentials within a burst. Our results suggest that positive effects of increased internal sodium and external potassium during a burst may serve as a compensatory mechanism for secretion, counterbalancing the negative effects of reduced external calcium. In this view, high frequency un-broadened action potentials (initial burst phase) would condition the terminals by increasing internal sodium for

  17. C-Fos Regulation by the MAPK and PKC Pathways in Intervertebral Disc Cells

    PubMed Central

    Yokoyama, Katsuya; Hiyama, Akihiko; Arai, Fumiyuki; Nukaga, Tadashi; Sakai, Daisuke; Mochida, Joji

    2013-01-01

    Background The gene encoding c-fos is an important factor in the pathogenesis of joint disease in patients with osteoarthritis. However, it is unknown whether the signal mechanism of c-fos acts in intervertebral disc (IVD) cells. We investigated whether c-fos is activated in relation to mitogen-activated protein kinases (MAPKs) and the protein kinase C (PKC) pathway in nucleus pulposus (NP) cells. Methodology/Results Reverse transcription-polymerase chain reaction and western blotting analyses were used to measure the expression of c-fos in rat IVD cells. Transfections were performed to determine the effects of c-fos on target gene activity. The effect of c-fos protein expression was examined in transfection experiments and in a 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide cell viability assay. Phorbol 12-myristate 13-acetate (PMA), the most commonly used phorbol ester, binds to and activates protein kinase C (PKC), causing a wide range of effects in cells and tissues. PMA induced the expression of c-fos gene transcription and protein expression, and led to activation of the MAPK pathways in NP cells. The c-fos promoter was suppressed completely in the presence of the MAPK inhibitor PD98059, an inhibitor of the MEK/ERK kinase cascade, but not in the presence of SKF86002, SB202190, or SP600125. The effects of the PKC pathway on the transcriptional activity of the c-fos were evaluated. PKCγ and PKCδ suppressed the promoter activity of c-fos. Treatment with c-fos inhibited aggrecan and Col2 promoter activities and the expression of these genes in NP cells. Conclusions This study demonstrated, for the first time, that the MAPK and PKC pathways had opposing effects on the regulation of c-fos in NP cells. Thus, the expression of c-fos can be suppressed in the extracellular matrix of NP cells. PMID:24023832

  18. c-FOS suppresses ovarian cancer progression by changing adhesion

    PubMed Central

    Oliveira-Ferrer, L; Rößler, K; Haustein, V; Schröder, C; Wicklein, D; Maltseva, D; Khaustova, N; Samatov, T; Tonevitsky, A; Mahner, S; Jänicke, F; Schumacher, U; Milde-Langosch, K

    2014-01-01

    Background: C-Fos was initially described as oncogene, but was associated with favourable prognosis in ovarian cancer (OvCa) patients. The molecular and functional aspects underlying this effect are still unknown. Methods: Using stable transfectants of SKOV3 and OVCAR8 cells, proliferation, migration, invasion and apoptotic potential of c-FOS-overexpressing clones and controls were compared. Adherence to components of the extracellular matrix was analysed in static assays, and adhesion to E-selectin, endothelial and mesothelial cells in dynamic flow assays. The effect of c-FOS in vivo was studied after intraperitoneal injection of SKOV3 clones into SCID mice, and changes in gene expression were determined by microarray analysis. Results: Tumour growth after injection into SCID mice was strongly delayed by c-FOS overexpression, with reduction of lung metastases and circulating tumour cells. In vitro, c-FOS had only weak influence on proliferation and migration, but was strongly pro-apoptotic. Adhesion to components of the extracellular matrix (collagen I, IV) and to E-selectin, endothelial and mesothelial cells was significantly reduced in c-FOS-overexpressing OvCa cells. This corresponds to deregulation of adhesion proteins and glycosylation enzymes in microarray analysis. Conclusion: In addition to its known pro-apoptotic effect, c-FOS might influence OvCa progression by changing the adhesion of OvCa cells to peritoneal surfaces. PMID:24322891

  19. Stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs): an intriguing EEG phenomenon.

    PubMed

    Silveira, Mariana Ribeiro Marcondes da; Andrade, Joaquina; Garzon, Eliana

    2013-12-01

    SIRPIDs, an acronym for stimulus-induced rhythmic, periodic, or ictal discharges, were first named in 2004. This is a pattern observed in continuous electroencephalogram (CEEG) consistently elicited by stimulation in comatose patients. The pathophysiology of SIRPIDs probably involves dysregulation of subcortico-cortical projections, particularly thalamocortical circuit, in a markedly abnormal brain with hyperexci-table cortex. This may explain some studies found an association of prolonged periodic epileptiform discharges (PEDs) activity and a higher incidence of concurrent electrographic seizures and SIRPIDs. An association of SIRPIDs and poor prognosis has already been described. However, it is not yet possible to assert whether these discharges can cause neuronal injury or if they are simply a marker of severe brain injury. Objective of this paper is to review clinical relevance and pathophysiology of SIRPIDs, as well as its role as a brain response in the critically ill patient.

  20. Right atrial stretch alters fore- and hind-brain expression of c-fos and inhibits the rapid onset of salt appetite

    PubMed Central

    De Gobbi, Juliana Irani Fratucci; Menani, Jose Vanderlei; Beltz, Terry G; Johnson, Ralph F; Thunhorst, Robert L; Johnson, Alan Kim

    2008-01-01

    The inflation of an intravascular balloon positioned at the superior vena cava and right atrial junction (SVC-RAJ) reduces sodium or water intake induced by various experimental procedures (e.g. sodium depletion; hypovolaemia). In the present study we investigated if the stretch induced by a balloon at this site inhibits a rapid onset salt appetite, and if this procedure modifies the pattern of immunohistochemical labelling for Fos protein (Fos-ir) in the brain. Male Sprague–Dawley rats with SVC-RAJ balloons received a combined treatment of furosemide (Furo; 10 mg (kg bw)−1) plus a low dose of the angiotensin-converting enzyme inhibitor captopril (Cap; 5 mg (kg bw)−1). Balloon inflation greatly decreased the intake of 0.3 m NaCl for as long as the balloon was inflated. Balloon inflation over a 3 h period following Furo–Cap treatment decreased Fos-ir in the organum vasculosum of the lamina terminalis and the subfornical organ and increased Fos-ir in the lateral parabrachial nucleus and caudal ventrolateral medulla. The effect of balloon inflation was specific for sodium intake because it did not affect the drinking of diluted sweetened condensed milk. Balloon inflation and deflation also did not acutely change mean arterial pressure. These results suggest that activity in forebrain circumventricular organs and in hindbrain putative body fluid/cardiovascular regulatory regions is affected by loading low pressure mechanoreceptors at the SVC-RAJ, a manipulation that also attenuates salt appetite. PMID:18556369

  1. Stimulus-induced myoclonus treated effectively with clonazepam in genetically confirmed Coffin–Lowry syndrome☆

    PubMed Central

    Arslan, Elif Acar; Ceylaner, Serdar; Turanlı, Güzide

    2014-01-01

    Purpose Coffin–Lowry syndrome (CLS) is a rare X-linked semidominant syndromic genetic disorder that is characterized by typical facial and radiologic findings, psychomotor and growth retardation, and various skeletal anomalies. A distinctive paroxysmal disorder called stimulus-bound myoclonus is clinically heterogeneous and is generally characterized by a sudden loss of muscle tone that is regained within a few seconds and is induced by sudden auditory or tactile stimulus. As the pathophysiology of stimulus-induced drop episodes (SIDEs) is not well understood, there is no definite therapy for those episodes. Methods We report a 15-year-old female with stimulus-induced drop episodes occurring many times a day that resulted in failure to perform her daily activities. Because her SIDEs were misdiagnosed as atonic seizures, she was treated with several antiepileptic drugs, including valproic acid, levetiracetam, lamotrigine, primidone, carbamazepine, and clobazam. Results We realized that her clinical and radiological findings, together with SIDEs, are compatible with Coffin–Lowry syndrome. All of her medications were discontinued following the diagnosis of SIDE, and she was started on clonazepam. After treatment, she became more independent and was able to perform her daily activities. Subsequently, her episodes decreased from 3 times a day to 1–2 times a month. Sodium oxybate and fluoxetine were added to the treatment protocol without remarkable improvement. Her genetic analysis revealed a heterozygous variation of CLS. Conclusion We conclude that SIDE should be included in a differential diagnosis of epileptic seizures in patients with CLS and that clonazepam is an effective choice in the treatment of SIDEs. PMID:25667906

  2. Brief pup exposure induces Fos expression in the lateral habenula and serotonergic caudal dorsal raphe nucleus of paternally experienced male California mice (Peromyscus californicus).

    PubMed

    de Jong, T R; Measor, K R; Chauke, M; Harris, B N; Saltzman, W

    2010-09-01

    Fathers play a substantial role in infant care in a small but significant number of mammalian species, including humans. However, the neural circuitry controlling paternal behavior is much less understood than its female counterpart. In order to characterize brain areas activated by paternal care, male California mice were separated from their female mate and litter for 3 h and then exposed to a pup or a control object (a glass pebble with the approximate size and oblong shape of a newborn pup) for 10 min. All males receiving a pup showed a strong paternal response towards it, whereas males receiving a pebble interacted with it only occasionally. Despite the clear behavioral differences, exposure to a pup did not increase Fos-like immunoreactivity (Fos-LIR) compared to a pebble in brain areas previously found to be associated with parental care, including the medial preoptic nucleus and medial bed nucleus of the stria terminalis. Pup exposure did, however, significantly increase Fos-LIR in the lateral habenula (LHb) and in predominantly serotonergic neurons in the caudal dorsal raphe nucleus (DRC), as compared to pebble exposure. Both the LHb and DRC are known to be involved in the behavioral responses to strong emotional stimuli; therefore, these areas might play a role in controlling parental behavior in male California mice.

  3. Structure, chromosome location, and expression of the mouse zinc finger gene Krox-20: multiple gene products and coregulation with the proto-oncogene c-fos.

    PubMed Central

    Chavrier, P; Janssen-Timmen, U; Mattéi, M G; Zerial, M; Bravo, R; Charnay, P

    1989-01-01

    We have analyzed the structure and the regulation of Krox-20, a mouse zinc finger-encoding gene which is transiently activated following serum stimulation of quiescent fibroblast cells in culture. The gene is localized on chromosome 10, band B5, in the mouse, and the homologous human gene also maps to chromosome 10 (region q21.1 to q22.1). Alternative splicing of the 5'-most intron of the Krox-20 gene gives rise to mRNAs encoding putative zinc finger proteins with different N termini. The first exon contains a sequence element with strong similarity to the c-fos proto-oncogene serum response element (SRE). This element can functionally substitute for the c-fos SRE, and it binds the same nuclear protein. It is probably responsible for the serum induction of Krox-20, possibly in combination with a weaker SRE located in the 5'-flanking region of the gene. Our findings suggest that c-fos, Krox-20, and a number of immediate-early serum response genes are coregulated and that the SRE and its cognate protein are essential components of this regulatory pathway. Images PMID:2496302

  4. Medial prefrontal cortical injections of c-fos antisense oligonucleotides transiently lower c-Fos protein and mimic amphetamine withdrawal behaviours.

    PubMed

    Persico, A M; Schindler, C W; Davis, S C; Ambrosio, E; Uhl, G R

    1998-02-01

    Prefrontal cerebral cortical areas display decreased expression of several transcription factor/immediate-early genes, including c-fos, during amphetamine withdrawal. Antisense strategies can help to test possible roles for this prefrontal c-fos down-regulation in the behavioural correlates of amphetamine withdrawal. Medial prefrontal cortical injections delivering 1.7 nmoles of anti c-fos oligonucleotides revealed an approximately 3 h half-life for phosphothioate and a 15 min half-life for phosphodiester oligonucleotides. Antisense phosphothioates complementary to the c-fos translational start site reduced levels of c-Fos protein, while exerting modest and variable effects on c-fos messenger RNA levels. Neither missense phosphorothioate nor antisense phosphodiester oligonucleotides significantly reduced levels of either c-fos messenger RNA or protein. Animals injected with anti c-fos phosphothioate oligonucleotides into the medial prefrontal cortex displayed marked reductions in linear locomotor activity and repetitive movements measured in a novel environment, effects not seen when missense oligonucleotides were used or when animals were accustomed to the activity monitor prior to antisense oligonucleotide injection. Behavioural changes produced by prefrontal cortical injections of c-fos antisense oligonucleotides closely mimic alterations recorded during amphetamine withdrawal. Prefrontal c-fos could thus conceivably play roles in the neurobiological underpinnings of psychostimulant withdrawal and of responses to stressors such as exposure to novel environments.

  5. Exposure to high- and low-light conditions in an open-field test of anxiety increases c-Fos expression in specific subdivisions of the rat basolateral amygdaloid complex.

    PubMed

    Hale, Matthew W; Bouwknecht, J Adriaan; Spiga, Francesca; Shekhar, Anantha; Lowry, Christopher A

    2006-12-11

    Anxiety states and anxiety-related behaviors appear to be regulated by a distributed and highly interconnected system of forebrain structures including the basolateral amygdaloid complex (basolateral amygdala). Despite a wealth of research examining the role of the basolateral amygdala in anxiety-related behaviors and anxiety states, the specific subdivisions of the basolateral amygdala that are involved in responses to anxiogenic stimuli have not been examined. In this study, we investigated the effects of exposure to a novel open-field environment, with either low- or high-levels of illumination, on expression of the protein product of the immediate-early gene c-Fos in subdivisions of the rat basolateral amygdala. The subdivisions studied included the lateral, ventrolateral and ventromedial parts of the lateral amygdaloid nucleus, the anterior, posterior and ventral parts of the basolateral amygdaloid nucleus and the anterior and posterior part of the basomedial amygdaloid nucleus. Small increases in the number of c-Fos-immunoreactive cells were observed in several, but not all, of the subdivisions of the basolateral amygdala studied following exposure of rats to either the high- or low-light conditions, compared to home cage or handled control groups. Open-field exposure in both the high- and low-light conditions resulted in a marked increase in c-Fos expression in the anterior part of the basolateral amygdaloid nucleus compared to either home cage or handled control groups. These findings point toward anatomical and functional heterogeneity within the basolateral amygdaloid complex and an important role of the anterior part of the basolateral amygdaloid nucleus in the neural mechanisms underlying physiological or behavioral responses to this anxiety-related stimulus.

  6. Ca2+ influx through CRAC channels activates cytosolic phospholipase A2, leukotriene C4 secretion, and expression of c-fos through ERK-dependent and -independent pathways in mast cells.

    PubMed

    Chang, Wei-Chiao; Nelson, Charmaine; Parekh, Anant B

    2006-11-01

    Cytosolic phospholipase A2 (cPLA2) is a Ca2+-dependent enzyme that mediates agonist-dependent arachidonic acid release in most cell types. Arachidonic acid can then be metabolized by the 5-lipoxygenase enzyme to generate the proinflammatory signal leukotriene C4 (LTC4). Here we report that Ca2+ entry through store-operated CRAC (Ca2+ release-activated Ca2+) channels activates the extracellular signal-regulated kinases (ERKs), members of the mitogen-activated protein kinase family, within minutes and this is necessary for stimulation of cPLA2. Ca2+ entry activates ERK indirectly, via recruitment of Ca2+-dependent protein kinase C alpha and betaI. Ca2+ influx also promotes translocation of cytosolic 5-lipoxygenase to the nuclear membrane, a key step in the activation of this enzyme. Translocation is dependent on ERK activation. A role for gene activation is shown by the finding that CRAC channel opening results in increased transcription and translation of c-fos. Inhibition of ERK activation failed to prevent c-fos expression. Our results show that CRAC channel activation elicits short-term effects through the co-coordinated regulation of two metabolic pathways (cPLA2 and 5-lipoxygenase), which results in the generation of both intra- and intercellular messengers within minutes, as well as longer term changes involving gene activation. These short-term effects are mediated via ERK, whereas, paradoxically, c-fos expression is not. Ca2+ influx through CRAC channels can therefore activate different signaling pathways at the same time, culminating in a range of temporally diverse responses.

  7. Using c-fos to study neuronal ensembles in corticostriatal circuitry of addiction

    PubMed Central

    Cruz, Fabio C.; Rubio, F. Javier; Hope, Bruce T.

    2014-01-01

    Learned associations between drugs and environment play an important role in addiction and are thought to be encoded within specific patterns of sparsely distributed neurons called neuronal ensembles. This hypothesis is supported by correlational data from in vivo electrophysiology and cellular imaging studies in relapse models in rodents. In particular, cellular imaging with the immediate early gene c-fos and its protein product Fos has been used to identify sparsely distributed neurons that were strongly activated during conditioned drug behaviors such as drug self-administration and context- and cue-induced reinstatement of drug seeking. Here we review how Fos and the c-fos promoter have been employed to demonstrate causal roles for Fos-expressing neuronal ensembles in prefrontal cortex and nucleus accumbens in conditioned drug behaviors. This work has allowed identification of unique molecular and electrophysiological alterations within Fos-expressing neuronal ensembles that may contribute to the development and expression of learned associations in addiction. PMID:25446457

  8. Pyrroloquinoline Quinine Inhibits RANKL-Mediated Expression of NFATc1 in Part via Suppression of c-Fos in Mouse Bone Marrow Cells and Inhibits Wear Particle-Induced Osteolysis in Mice

    PubMed Central

    Smith, Wanli; Zhu, Shu; Zhu, Jinyu; Zhu, Qingsheng

    2013-01-01

    The effects of pyrroloquinoline quinine (PQQ) on RANKL-induced osteoclast differentiation and on wear particle-induced osteolysis were examined in this study. PQQ inhibited RANKL-mediated osteoclast differentiation in bone marrow macrophages (BMMs) in a dose-dependent manner without any evidence of cytotoxicity. The mRNA expression of c-Fos, NFATc1, and TRAP in RANKL-treated BMMs was inhibited by PQQ treatment. Moreover, RANKL-induced c-Fos and NFATc1 protein expression was suppressed by PQQ. PQQ additionally inhibited the bone resorptive activity of differentiated osteoclasts. Further a UHMWPE-induced murine calvaria erosion model study was performed to assess the effects of PQQ on wear particle-induced osteolysis in vivo. Mice treated with PQQ demonstrated marked attenuation of bone erosion based on Micro-CT and histologic analysis of calvaria. These results collectively suggested that PQQ demonstrated inhibitory effects on osteoclast differentiation in vitro and may suppress wear particle-induced osteolysis in vivo, indicating that PQQ may therefore serve as a useful drug in the prevention of bone loss. PMID:23613773

  9. Accumbal FosB/DeltaFosB immunoreactivity and conditioned place preference in alcohol-preferring AA rats and alcohol-avoiding ANA rats treated repeatedly with cocaine.

    PubMed

    Marttila, Kristiina; Petteri Piepponen, T; Kiianmaa, Kalervo; Ahtee, Liisa

    2007-07-30

    Transcription factor DeltaFosB has been implicated in the psychomotor responses and rewarding effects of drugs of abuse. In the present study, we compared the effects of cocaine on the expression of DeltaFosB-like proteins by immunohistochemistry in striatal brain areas of alcohol-preferring (AA) and alcohol-avoiding (ANA) rats. Cocaine was administered using a previously verified treatment paradigm that sensitized the locomotor response to cocaine in AA but not in ANA rats. We also studied the rewarding effects of cocaine with a conditioned place preference (CPP) paradigm in both lines of rats. Cocaine treatment increased the FosB/DeltaFosB immunoreactivity (IR) in the nucleus accumbens of AA rats but not in ANA rats. In addition, after repeated saline injections the accumbal FosB/DeltaFosB IR was significantly greater in saline-injected AA rats than in ANA rats. In the caudate-putamen cocaine significantly increased FosB/DeltaFosB IR, but no differences were found between the rats of two lines. In the CPP experiment, AA rats treated with cocaine 2.5 mg/kg preferred the cocaine-associated compartment, in contrast to ANA rats, which did not show such a preference. In conclusion, our findings show that AA rats are more sensitive to cocaine than ANA rats, and suggest that one possible mediator for this increased sensitivity could be the increased expression of fosB-derived proteins in the nucleus accumbens of AA rats.

  10. Genome-Wide Analysis Reveals PADI4 Cooperates with Elk-1 to Activate c-Fos Expression in Breast Cancer Cells

    PubMed Central

    Stadler, Sonja; Cherrington, Brian D.; Causey, Corey P.; Thompson, Paul R.; Roberson, Mark S.; Kraus, W. Lee; Coonrod, Scott A.

    2011-01-01

    Peptidylarginine deiminase IV (PADI4) catalyzes the conversion of positively charged arginine and methylarginine residues to neutrally charged citrulline, and this activity has been linked to the repression of a limited number of target genes. To broaden our knowledge of the regulatory potential of PADI4, we utilized chromatin immunoprecipitation coupled with promoter tiling array (ChIP-chip) analysis to more comprehensively investigate the range of PADI4 target genes across the genome in MCF-7 breast cancer cells. Results showed that PADI4 is enriched in gene promoter regions near transcription start sites (TSSs); and, surprisingly, this pattern of binding is primarily associated with actively transcribed genes. Computational analysis found potential binding sites for Elk-1, a member of the ETS oncogene family, to be highly enriched around PADI4 binding sites; and coimmunoprecipitation analysis then confirmed that Elk-1 physically associates with PADI4. To better understand how PADI4 may facilitate gene transactivation, we then show that PADI4 interacts with Elk-1 at the c-Fos promoter and that, following Epidermal Growth Factor (EGF) stimulation, PADI4 catalytic activity facilitates Elk-1 phosphorylation, histone H4 acetylation, and c-Fos transcriptional activation. These results define a novel role for PADI4 as a transcription factor co-activator. PMID:21655091

  11. Genome-wide analysis reveals PADI4 cooperates with Elk-1 to activate c-Fos expression in breast cancer cells.

    PubMed

    Zhang, Xuesen; Gamble, Matthew J; Stadler, Sonja; Cherrington, Brian D; Causey, Corey P; Thompson, Paul R; Roberson, Mark S; Kraus, W Lee; Coonrod, Scott A

    2011-06-01

    Peptidylarginine deiminase IV (PADI4) catalyzes the conversion of positively charged arginine and methylarginine residues to neutrally charged citrulline, and this activity has been linked to the repression of a limited number of target genes. To broaden our knowledge of the regulatory potential of PADI4, we utilized chromatin immunoprecipitation coupled with promoter tiling array (ChIP-chip) analysis to more comprehensively investigate the range of PADI4 target genes across the genome in MCF-7 breast cancer cells. Results showed that PADI4 is enriched in gene promoter regions near transcription start sites (TSSs); and, surprisingly, this pattern of binding is primarily associated with actively transcribed genes. Computational analysis found potential binding sites for Elk-1, a member of the ETS oncogene family, to be highly enriched around PADI4 binding sites; and coimmunoprecipitation analysis then confirmed that Elk-1 physically associates with PADI4. To better understand how PADI4 may facilitate gene transactivation, we then show that PADI4 interacts with Elk-1 at the c-Fos promoter and that, following Epidermal Growth Factor (EGF) stimulation, PADI4 catalytic activity facilitates Elk-1 phosphorylation, histone H4 acetylation, and c-Fos transcriptional activation. These results define a novel role for PADI4 as a transcription factor co-activator.

  12. Effect of resveratrol on c-fos expression of rat trigeminal spinal nucleus caudalis and C1 dorsal horn neurons following mustard oil-induced acute inflammation.

    PubMed

    Matsumoto, Yasuhiro; Komatsu, Kyouhei; Shimazu, Yoshihito; Takehana, Shiori; Syouji, Yumiko; Kobayashi, Ayumu; Takeda, Mamoru

    2017-10-01

    The dietary constituent, resveratrol, was recently identified as a transient receptor potential ankyrin 1 (TRPA1) antagonist, voltage-dependent sodium ion (Na(+) ) channel, and cyclooxygenase-2 (COX-2) inhibitor. The aim of the present study was to investigate whether pretreatment with resveratrol attenuates acute inflammation-induced sensitization of nociceptive processing in rat spinal trigeminal nucleus caudalis (SpVc) and upper cervical (C1) dorsal horn neurons, via c-fos immunoreactivity. Mustard oil (MO), a TRPA1 channel agonist, was injected into the whisker pads of rats to induce inflammation. Pretreatment with resveratrol significantly decreased the mean thickness of inflammation-induced edema in whisker pads compared with those of untreated, inflamed rats. Ipsilateral of both the superficial and deep laminae of SpVc and C1 dorsal horn, there were significantly more c-fos-immunoreactive SpVc/C1 neurons in inflamed rats compared with naïve rats, and resveratrol pretreatment significantly decreased that number relative to untreated, inflamed rats. These results suggest that systemic administration of resveratrol attenuates acute inflammation-induced augmented nociceptive processing of trigeminal SpVc and C1 neurons. These findings support resveratrol as a potential therapeutic agent for use in alternative, complementary medicine to attenuate, or even prevent, acute trigeminal inflammatory pain. © 2017 Eur J Oral Sci.

  13. Taste aversion learning induced c-fos expression in the nucleus of the solitary tract after spontaneous flavor intake: role of the inter-stimulus interval.

    PubMed

    Mediavilla, Cristina; Bernal, Antonio; Puerto, Amadeo

    2007-09-01

    Taste aversion learning (TAL) can be induced by associating a flavor intake with the immediate or delayed (30 min) intragastric administration of a noxious substance, e.g., hypertonic NaCl. The objective of this study was to analyze the induction of c-Fos immunoreactivity in the intermediate nucleus of the solitary nucleus (iNST) after acquisition of a contiguous or delayed TAL, offering the flavor for voluntary consumption in both cases. The behavioral results obtained indicate that, although the learning was established under both experimental conditions, an increase in c-Fos induction was only produced in the group that learned by means of a non-delayed TAL. Immunohistochemical analyses revealed the participation of different brain structures in these two TAL modalities. Thus, the nucleus of the solitary tract may be involved in the TAL procedure in which voluntary flavor intake and intragastric administration of the noxious visceral stimulus are contiguous but not in delayed TAL, which would depend on other anatomical circuits that do not include the iNST.

  14. Stimulus-induced transition of clustering firings in neuronal networks with information transmission delay

    NASA Astrophysics Data System (ADS)

    Wang, Qingyun; Zhang, Honghui; Chen, Guanrong

    2013-07-01

    We study the evolution of spatiotemporal dynamics and transition of clustering firing synchronization on spiking Hodgkin-Huxley neuronal networks as information transmission delay and the periodic stimulus are varied. In particular, it is shown that the tuned information transmission delay can induce a clustering anti-phase synchronization transition with the pacemaker, where two equal clusters can alternatively synchronize in anti-phase firing. More interestingly, we show that the periodic stimulus can drive the delay-induced clustering anti-phase firing synchronization bifurcate to the collective perfect synchronization, which is routed by the complex process including collective chaotic firings and clustering out-of-phase synchronization of the neuronal networks. In addition, the periodic stimulus induced clustering firings of the spiking neuronal networks are robust to the connectivity probability of small world networks. Furthermore, the different stimulus frequency induced complexity is also investigated. We hope that the results of this paper can provide insights that could facilitate the understanding of the joint impact of information transmission delays and periodic stimulus on controlling dynamical behaviors of realistic neuronal networks.

  15. Overexpression of c-fos increases recombination frequency in human osteosarcoma cells.

    PubMed

    van den Berg, S; Rahmsdorf, H J; Herrlich, P; Kaina, B

    1993-05-01

    We have shown previously that overexpression of c-Ha-ras, v-mos or c-fos increases the spontaneous level of chromosomal aberrations and gene mutations in NIH 3T3 cells, and that reduction of the Fos protein level inhibits aberration induction by c-Ha-ras and v-mos and also by irradiation with ultraviolet light (van den Berg et al., Mol. Carcinogenesis, 4, 460-466). In order to examine whether fos is also involved in DNA recombination, thymidine kinase (tk) deficient human osteosarcoma cells containing two versions of the herpes simplex virus tk gene inactivated by base insertion were either transiently or stably transfected with various fos expression plasmids. The frequency of tk+ revertants was significantly enhanced both upon transient transfection with RSV-promoter-fos gene constructs and by stimulation of Fos synthesis in stably transfected cells harbouring an inducible metallothionein promoter-fos construct. No such increases were observed in cells transfected with plasmids containing a truncated version of c-fos. The data indicate that c-fos is involved in generating various types of genetic changes including homologous recombination; a role of c-fos in genetic instability may contribute to its action in tumor promotion and progression.

  16. Hepatocyte growth factor-stimulated renal tubular mitogenesis: effects on expression of c-myc, c-fos, c-met, VEGF and the VHL tumour-suppressor and related genes.

    PubMed Central

    Clifford, S. C.; Czapla, K.; Richards, F. M.; O'Donoghue, D. J.; Maher, E. R.

    1998-01-01

    Hepatocyte growth factor (HGF/SF) is a potent renal proximal tubular cell (PTEC) mitogen involved in renal development. HGF/SF is the functional ligand for the c-met proto-oncogene, and germline c-met mutations are associated with familial papillary renal cell carcinoma. Somatic von Hippel-Lindau disease tumour-suppressor gene (VHL) mutations are frequently detected in sporadic clear cell renal cell carcinomas (RCC), and germline VHL mutations are the commonest cause of familial clear cell RCC. pVHL binds to the positive regulatory components of the trimeric elongin (SIII) complex (elongins B and C) and has been observed to deregulate expression of the vascular endothelial growth factor (VEGF) gene. HGF/SF has similarly been reported to up-regulate expression of the VEGF gene in non-renal experimental systems. To investigate the mechanism of HGF/SF action in PTECs and, specifically, to examine potential interactions between the HGF/c-met and the VHL-mediated pathways for renal tubular growth control, we have isolated untransformed PTECs from normal kidneys, developed conditions for their culture in vitro and used these cells to investigate changes in mRNA levels of the VHL, elongin A, B and C, VEGF, c-myc, c-fos and c-met genes after HGF/SF exposure. Significant elevations in the mRNA levels of VEGF, c-myc, c-fos, c-met and elongins A, B and C, but not VHL, were detected after HGF/SF stimulation of human PTECs (P < 0.02), with a consistent order of peak levels observed over successive replicates (c-fos at 1 h, VEGF at 2-4 h, c-myc, at 4 h, followed by c-met and all three elongin subunits at 8 h). This study highlights the spectrum of changes in gene expression observed in PTECs after HGF/SF stimulation and has identified possible candidate mediators of the HGF/SF-induced mitogenic response. Our evidence would suggest that the changes in PTEC VEGF expression induced by HGF/SF are mediated by a VHL-independent pathway. Images Figure 1 PMID:9652757

  17. DeltaFosB in the nucleus accumbens is critical for reinforcing effects of sexual reward

    PubMed Central

    Pitchers, Kyle K.; Frohmader, Karla S.; Vialou, Vincent; Mouzon, Ezekiell; Nestler, Eric J.; Lehman, Michael N.; Coolen, Lique M.

    2010-01-01

    Sexual behavior in male rats is rewarding and reinforcing. However, little is known about the specific cellular and molecular mechanisms mediating sexual reward or the reinforcing effects of reward on subsequent expression of sexual behavior. The current study tests the hypothesis that ΔFosB, the stably expressed truncated form of FosB, plays a critical role in the reinforcement of sexual behavior and experience-induced facilitation of sexual motivation and performance. Sexual experience was shown to cause ΔFosB accumulation in several limbic brain regions including the nucleus accumbens (NAc), medial prefrontal cortex, ventral tegmental area and caudate putamen, but not the medial preoptic nucleus. Next, the induction of c-Fos, a downstream (repressed) target of ΔFosB, was measured in sexually experienced and naïve animals. The number of mating-induced c-Fos-IR cells was significantly decreased in sexually experienced animals compared to sexually naïve controls. Finally, ΔFosB levels and its activity in the NAc were manipulated using viral-mediated gene transfer to study its potential role in mediating sexual experience and experience-induced facilitation of sexual performance. Animals with ΔFosB over-expression displayed enhanced facilitation of sexual performance with sexual experience relative to controls. In contrast, the expression of ΔJunD, a dominant-negative binding partner of ΔFosB, attenuated sexual experience-induced facilitation of sexual performance, and stunted long-term maintenance of facilitation compared to GFP and ΔFosB over-expressing groups. Together, these findings support a critical role for ΔFosB expression in the NAc for the reinforcing effects of sexual behavior and sexual experience-induced facilitation of sexual performance. PMID:20618447

  18. Estrogen receptor alpha, fos-related antigen-2, and c-Jun coordinately regulate human UDP glucuronosyltransferase 2B15 and 2B17 expression in response to 17beta-estradiol in MCF-7 cells.

    PubMed

    Hu, Dong Gui; Mackenzie, Peter I

    2009-08-01

    UDP-glucuronosyltransferase 2B15 and 2B17 expression is up-regulated by 17beta-estradiol in MCF-7 breast cancer cells, as assessed by quantitative real-time polymerase chain reaction. Using 5'-deletion mapping and site-directed mutagenesis, we demonstrate that 17beta-estradiol activation of UGT2B15 gene transcription is mediated by a 282-base pair fragment positioned -454 to -172 nucleotides from the translation start site. This region contains two putative activator protein-1 (AP-1) elements, one imperfect estrogen response element (ERE), and two consensus ERE half-sites. We propose that these five sites act as an estrogen response unit (ERU), because mutation in any site reduces activation of the UGT2B15 promoter by 17beta-estradiol. Despite the presence of two AP-1 elements, the UGT2B15 promoter is not responsive to the AP-1 activator phorbol 12-myristate 13-acetate. Although electrophoretic mobility shift assays (EMSA) indicate that the AP-1 proteins c-Jun and Fos-related antigen 2 (Fra-2) bound to the distal AP-1 site, binding of Jun or Fos family members to the proximal AP-1 site was not detected by EMSA. Chromatin immunoprecipitation assays showed a 17beta-estradiol-induced recruitment of estrogen receptor (ER) alpha, c-Jun, and Fra-2 to the 282-bp ERU. The involvement of these three transcription factors in the stimulation of UGT2B15 gene expression by 17beta-estradiol was confirmed by siRNA silencing experiments. Mutagenesis and siRNA experiments indicate that UGT2B17 expression is also regulated by 17beta-estradiol via the ERU, which is fully conserved in both promoters. Because UGT2B15 and UGT2B17 inactivate steroid hormones by glucuronidation, the regulation of their genes by 17beta-estradiol may maintain steroid hormone homeostasis and prevent excessive estrogen signaling activity.

  19. Gonadotropin-releasing hormone (GnRH) agonist triptorelin inhibits estradiol-induced serum response element (SRE) activation and c-fos expression in human endometrial, ovarian and breast cancer cells.

    PubMed

    Gründker, Carsten; Günthert, Andreas R; Hellriegel, Martin; Emons, Günter

    2004-11-01

    The majority of human endometrial (>80%), ovarian (>80%) and breast (>50%) cancers express GnRH receptors. Their spontaneous and epidermal growth-factor-induced proliferation is dose- and time-dependently reduced by treatment with GnRH and its agonists. In this study, we demonstrate that the GnRH agonist triptorelin inhibits estradiol (E2)-induced cancer cell proliferation. The proliferation of quiescent estrogen receptor alpha (ER alpha)-/ER beta-positive, but not of ER alpha-negative/ER beta-positive endometrial, ovarian and breast cancer cell lines, was significantly stimulated (P<0.001) (ANOVA) after treatment with E2 (10(-8) M). This effect was time- and dose-dependently antagonized by simultaneous treatment with triptorelin. The inhibitory effect was maximal at 10(-5) M concentration of triptorelin (P<0.001). In addition, we could show that, in ER alpha-/ER beta-positive cell lines, E2 induces activation of serum response element (SRE) and expression of the immediate early-response gene c-fos. These effects were blocked by triptorelin (P<0.001). E2-induced activation of estrogen-response element (ERE) was not affected by triptorelin. The transcriptional activation of SRE by E2 is due to ER alpha activation of the mitogen-activated protein kinase (MAPK) pathway. This pathway is impeded by GnRH, resulting in a reduction of E2-induced SRE activation and, in consequence, a reduction of E2-induced c-fos expression. This causes downregulation of E2-induced cancer cell proliferation.

  20. TGF-β Effects on Prostate Cancer Cell Migration and Invasion Require FosB.

    PubMed

    Barrett, Cachétne S X; Millena, Ana C; Khan, Shafiq A

    2017-01-01

    Activator Protein-1 (AP-1) family (cJun, JunB, JunD, cFos, FosB, Fra1, and Fra2) plays a central role in the transcriptional regulation of many genes that are associated with cell proliferation, differentiation, migration, metastasis, and survival. Many oncogenic signaling pathways converge at the AP-1 transcription complex. Transforming growth factor beta (TGF-β) is a multifunctional regulatory cytokine that regulates many aspects of cellular function, including cellular proliferation, differentiation, migration, apoptosis, adhesion, angiogenesis, immune surveillance, and survival. This study investigated, the role of FOS proteins in TGF-β signaling in prostate cancer cell proliferation, migration, and invasion. Steady state expression levels of FOS mRNA and proteins were determined using RT-PCR and western blotting analyses. DU145 and PC3 prostate cancer cells were exposed to TGF-β1 at varying time and dosage, RT-PCR, western blot, and immunofluorescence analyses were used to determine TGF-β1 effect on FOS mRNA and protein expression levels as well as FosB subcellular localization. Transient silencing of FosB protein was used to determine its role in cell proliferation, migration, and invasion. Our data show that FOS mRNA and proteins were differentially expressed in human prostate epithelial (RWPE-1) and prostate cancer cell lines (LNCaP, DU145, and PC3). TGF-β1 induced the expression of FosB at both the mRNA and protein levels in DU145 and PC3 cells, whereas cFos and Fra1 were unaffected. Immunofluorescence analysis showed an increase in the accumulation of FosB protein in the nucleus of PC3 cells after treatment with exogenous TGF-β1. Selective knockdown of endogenous FosB by specific siRNA did not have any effect on cell proliferation in PC3 and DU145 cells. However, basal and TGF-β1- and EGF-induced cell migration was significantly reduced in DU145 and PC3 cells lacking endogenous FosB. TGF-β1- and EGF-induced cell invasion were also significantly

  1. TGF-β Effects on Prostate Cancer Cell Migration and Invasion Require FosB

    PubMed Central

    Barrett, Cachétne S.X.; Millena, Ana C.; Khan, Shafiq A.

    2017-01-01

    BACKGROUND Activator Protein-1 (AP-1) family (cJun, JunB, JunD, cFos, FosB, Fra1, and Fra2) plays a central role in the transcriptional regulation of many genes that are associated with cell proliferation, differentiation, migration, metastasis, and survival. Many oncogenic signaling pathways converge at the AP-1 transcription complex. Transforming growth factor beta (TGF-β) is a multifunctional regulatory cytokine that regulates many aspects of cellular function, including cellular proliferation, differentiation, migration, apoptosis, adhesion, angiogenesis, immune surveillance, and survival. METHODS This study investigated, the role of FOS proteins in TGF-β signaling in prostate cancer cell proliferation, migration, and invasion. Steady state expression levels of FOS mRNA and proteins were determined using RT-PCR and western blotting analyses. DU145 and PC3 prostate cancer cells were exposed to TGF-β1 at varying time and dosage, RT-PCR, western blot, and immunofluorescence analyses were used to determine TGF-β1 effect on FOS mRNA and protein expression levels as well as FosB subcellular localization. Transient silencing of FosB protein was used to determine its role in cell proliferation, migration, and invasion. RESULTS Our data show that FOS mRNA and proteins were differentially expressed in human prostate epithelial (RWPE-1) and prostate cancer cell lines (LNCaP, DU145, and PC3). TGF-β1 induced the expression of FosB at both the mRNA and protein levels in DU145 and PC3 cells, whereas cFos and Fra1 were unaffected. Immunofluorescence analysis showed an increase in the accumulation of FosB protein in the nucleus of PC3 cells after treatment with exogenous TGF-β1. Selective knockdown of endogenous FosB by specific siRNA did not have any effect on cell proliferation in PC3 and DU145 cells. However, basal and TGF-β1- and EGF-induced cell migration was significantly reduced in DU145 and PC3 cells lacking endogenous FosB. TGF-β1- and EGF-induced cell invasion

  2. c-fos-like immunoreactivity in the cat's neuraxis following moderate hypoxia or hypercapnia.

    PubMed

    Larnicol, N; Wallois, F; Berquin, P; Gros, F; Rose, D

    1994-01-01

    The overall pattern of c-fos immunoreactivity was studied in the brainstem and spinal cord of cats subjected to moderate hypoxia or hypercapnia. In control cats (normoxic, normocapnic), c-fos was expressed mainly in pontine and periaqueductal grey but not in brainstem structures engaged in respiratory control nor in the spinal cord. Both hypoxia and hypercapnia induced c-fos expression in the parabrachial area (pneumotaxic center). In the retrotrapezoid nucleus, a structure involved in respiratory rhythmogenesis and chemoreception, immunoreactivity was detected in hypoxic but not in hypercapnic cats. Neurons in the nucleus raphe pallidus preferentially expressed c-fos in response to hypercapnia. Labelled neurons were concentrated in the dorsal and gelatinosus subnuclei of the solitary tract following hypoxia and hypercapnia, respectively. Our data suggest that some neurons that express c-fos in hypoxic or hypercapnic cats may be involved in coordination of cardiovascular and respiratory function.

  3. Influence of Pre-reproductive Maternal Enrichment on Coping Response to Stress and Expression of c-Fos and Glucocorticoid Receptors in Adolescent Offspring.

    PubMed

    Cutuli, Debora; Berretta, Erica; Pasqualini, Greta; De Bartolo, Paola; Caporali, Paola; Laricchiuta, Daniela; Sampedro-Piquero, Patricia; Gelfo, Francesca; Pesoli, Matteo; Foti, Francesca; Begega, Azucena; Petrosini, Laura

    2017-01-01

    Environmental enrichment (EE) is an experimental setting broadly used for investigating the effects of complex social, cognitive, and sensorimotor stimulations on brain structure and function. Recent studies point out that parental EE experience, even occurring in the pre-reproductive phase, affects neural development and behavioral trajectories of the offspring. In the present study we investigated the influences of pre-reproductive EE of female rats on maternal behavior and adolescent male offspring's coping response to an inescapable stressful situation after chronic social isolation. For this purpose female Wistar rats were housed from weaning to breeding age in enriched or standard environments. Subsequently, all females were mated and housed in standard conditions until offspring weaning. On the first post partum day (ppd 1), mother-pup interactions in undisturbed conditions were recorded. Further, after weaning the male pups were reared for 2 weeks under social isolation or in standard conditions, and then submitted or not to a single-session Forced Swim Test (FST). Offspring's neuronal activation and plastic changes were identified by immunohistochemistry for c-Fos and glucocorticoid receptors (GRs), and assessed by using stereological analysis. The biochemical correlates were measured in the hippocampus, amygdala and cingulate cortex, structures involved in hypothalamic-pituitary-adrenocortical axis regulation. Enriched dams exhibited increased Crouching levels in comparison to standard reared dams. In the offspring of both kinds of dams, social isolation reduced body weight, decreased Immobility, and increased Swimming during FST. Moreover, isolated offspring of enriched dams exhibited higher levels of Climbing in comparison to controls. Interestingly, in the amygdala of both isolated and control offspring of enriched dams we found a lower number of c-Fos immunopositive cells in response to FST and a higher number of GRs in comparison to the offspring of

  4. A Signaling Network Controlling Androgenic Repression of c-Fos Protein in Prostate Adenocarcinoma Cells*

    PubMed Central

    Shankar, Eswar; Song, Kyung; Corum, Sarah L.; Bane, Kara L.; Wang, Hui; Kao, Hung-Ying; Danielpour, David

    2016-01-01

    The transcription factor c-Fos controls many important cellular processes, including cell growth and apoptosis. c-Fos expression is rapidly elevated in the prostate upon castration-mediated androgen withdrawal through an undefined mechanism. Here we show that androgens (5α-dihydrotestosterone and R1881) suppress c-Fos protein and mRNA expression induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) or EGF in human prostate cancer (PCa) cell lines. Such suppression transpires through a transcriptional mechanism, predominantly at the proximal serum response element of the c-fos promoter. We show that androgen signaling suppresses TPA-induced c-Fos expression through repressing a PKC/MEK/ERK/ELK-1 signaling pathway. Moreover, our results support the hypothesis that p38MAPK, PI3K, and PKCδ are involved in the androgenic regulation of c-Fos through controlling MEK/ERK. Stable silencing of c-Fos and PKCδ with shRNAs suggests that R1881 promotes cell death induced by low-dose TPA through a mechanism that is dependent on both PKCδ and loss of c-Fos expression. Reciprocally, loss of either PKCδ or c-Fos activates p38MAPK while suppressing the activation of ERK1/2. We also provide the first demonstration that R1881 permits cell death induced by low-dose TPA in the LNCaP androgen-dependent PCa cell line and that TPA-induced cell death is independent of exogenous androgen in the castration-resistant variants of LNCaP, C4-2 and C4-2B. Acquisition of androgen-independent killing by TPA correlates with activation of p38MAPK, suppression of ERK1/2, and loss of c-Fos. These results provide new insights into androgenic control of c-Fos and use of PKC inhibitors in PCa therapy. PMID:26786102

  5. Dimerumic acid inhibits SW620 cell invasion by attenuating H₂O₂-mediated MMP-7 expression via JNK/C-Jun and ERK/C-Fos activation in an AP-1-dependent manner.

    PubMed

    Ho, Bing-Ying; Wu, Yao-Ming; Chang, King-Jen; Pan, Tzu-Ming

    2011-01-01

    Reactive oxygen species (ROS) such as hydrogen peroxide (H₂O₂) in the tumor microenvironment play important roles in tumor invasion and metastasis. Recently, ROS have been reported to cause a significant increase in the production and expression of matrix metalloproteinase (MMP)-7, which is closely correlated with metastatic colorectal cancer. The present study was undertaken to evaluate the scavenging activity of dimerumic acid (DMA) for H₂O₂ isolated from Monascus-fermented rice to investigate the inhibitory effects of DMA on the invasive potential of SW620 human colon cancer cells, and to explore the mechanisms underlying both these phenomena. Our results showed that increased MMP-7 expression due to H₂O₂ exposure was mediated by activation of mitogen-activated protein kinases (MAPKs) such as Jun N-terminal kinase (JNK), extracellular-regulated kinase (ERK), and p38 kinase. DMA pretreatment suppressed activation of H₂O₂-mediated MAPK pathways and cell invasion. Moreover, H₂O₂-triggered MMP-7 production was demonstrated via JNK/c-Jun and ERK/c-Fos activation in an activating protein 1 (AP-1)-dependent manner. Taken together, these results suggest that DMA suppresses H₂O₂-induced cell invasion by inhibiting AP-1-mediated MMP-7 gene transcription via the JNK/c-Jun and ERK/c-Fos signaling pathways in SW620 human colon cancer cells. Our data suggest that DMA may be useful in minimizing the development of colorectal metastasis. In the future, DMA supplementation may be a beneficial antioxidant to enhance surgical outcomes.

  6. The Effects of Pre-emptive Administration of Ketamine and norBNI on Pain Behavior, c-Fos, and Prodynorphin Protein Expression in the Rat Spinal Cord after Formalin-induced Pain Is Modulated by the DREAM Protein

    PubMed Central

    Suppian, Rapeah; Ismail, Zalina

    2013-01-01

    Background We investigated the effects of pre-emptive administration of ketamine and norBNI on pain behavior and the expression of DREAM, c-Fos, and prodynorphin proteins on the ipsilateral side of the rat spinal cord at 2 and 4 hours after formalin injection. Methods Eighty-four male Sprague Dawley rats were divided into 4 major groups consisting of control rats (C) (n = 12), rats given only formalin injections (F) (n = 24), and rats treated with pre-emptive administration of either ketamine (K+F) (n = 24) or norBNI (N+F) (n = 24). The non-control groups were further divided into subgroups consisting of rats that were sacrificed at 2 and 4 hours (n = 12 for each group) after formalin injection. Pain behavior was recorded for 1 hour. After 2 and 4 hours, the rats were sacrificed and the spinal cords (L4-L5 sections) were removed for immunohistochemistry and Western blot analysis. Results The pain behavior response was reduced in the K+F group compared to the other groups during the second phase of the formalin pain response. We detected an increase in the nuclear DREAM protein level in the K+F group at 2 and 4 hours and a transient decrease in the N+F group at 2 hours; however, it increased at 4 hours after injection. Fos-like immunoreactivity (FLI) and Prodynorphin-like immunoreactivity (PLI) neurons decreased in the K+F group but increased in the N+F group at 2 hours after injection. While FLI decreased, PLI increased in all groups at 4 hours after injection. Conclusions We suggest that NMDA and kappa opioid receptors can modulate DREAM protein expression, which can affect pain behavior and protein transcriptional processes at 2 hours and bring about either harmful or protective effects at 4 hours after formalin injection. PMID:23861999

  7. Functional role of the N-terminal domain of ΔFosB in response to stress and drugs of abuse.

    PubMed

    Ohnishi, Y N; Ohnishi, Y H; Vialou, V; Mouzon, E; LaPlant, Q; Nishi, A; Nestler, E J

    2015-01-22

    Previous work has implicated the transcription factor, ΔFosB, acting in the nucleus accumbens, in mediating the pro-rewarding effects of drugs of abuse such as cocaine as well as in mediating resilience to chronic social stress. However, the transgenic and viral gene transfer models used to establish these ΔFosB phenotypes express, in addition to ΔFosB, an alternative translation product of ΔFosB mRNA, termed Δ2ΔFosB, which lacks the N-terminal 78 aa present in ΔFosB. To study the possible contribution of Δ2ΔFosB to these drug and stress phenotypes, we prepared a viral vector that overexpresses a point mutant form of ΔFosB mRNA which cannot undergo alternative translation as well as a vector that overexpresses Δ2ΔFosB alone. Our results show that the mutant form of ΔFosB, when overexpressed in the nucleus accumbens, reproduces the enhancement of reward and of resilience seen with our earlier models, with no effects seen for Δ2ΔFosB. Overexpression of full length FosB, the other major product of the FosB gene, also has no effect. These findings confirm the unique role of ΔFosB in the nucleus accumbens in controlling responses to drugs of abuse and stress.

  8. Cadmium induces phosphorylation and stabilization of c-Fos in HK-2 renal proximal tubular cells

    SciTech Connect

    Iwatsuki, Mamiko; Inageda, Kiyoshi; Matsuoka, Masato

    2011-03-15

    We examined the effects of cadmium chloride (CdCl{sub 2}) exposure on the expression and phosphorylation status of members of the Fos family, components of the activator protein-1 transcription factor, in HK-2 human renal proximal tubular cells. Following the exposure to CdCl{sub 2}, the expression of c-fos, fosB, fra-1, and fra-2 increased markedly, with different magnitudes and time courses. The levels of Fos family proteins (c-Fos, FosB, Fra-1, and Fra-2) also increased in response to CdCl{sub 2} exposure. Although the elevation of c-fos transcripts was transient, c-Fos protein levels increased progressively with lower electrophoretic mobility, suggesting stabilization of c-Fos through post-translational modifications. Consistently, we observed phosphorylation of c-Fos at Ser362 and Ser374 in HK-2 cells treated with CdCl{sub 2}. Phosphorylated forms of mitogen-activated protein kinases (MAPKs)-including extracellular signal-regulated protein kinase (ERK), c-Jun NH{sub 2}-terminal kinase, and p38-increased after CdCl{sub 2} exposure, whereas treatment with the MAPK/ERK kinase inhibitor U0126 and the p38 inhibitor SB203580 suppressed the accumulation and phosphorylation of c-Fos. We mutated Ser362 to alanine (S362A), Ser374 to alanine (S374A), and both residues to alanines (S362A/S374A) to inhibit potential phosphorylation of c-Fos at these sites. S374A or double S362A/S374A mutations reduced c-Fos level markedly, but S362A mutation did not. On the other hand, S362A/S374A mutations induced a more pronounced reduction in c-Fos DNA-binding activity than S374A mutation. These results suggest that while Ser374 phosphorylation seems to play a role in c-Fos stabilization, phosphorylation at two C-terminal serine residues is required for the transcriptional activation of c-Fos in HK-2 cells treated with CdCl{sub 2}.

  9. Influence of Pre-reproductive Maternal Enrichment on Coping Response to Stress and Expression of c-Fos and Glucocorticoid Receptors in Adolescent Offspring

    PubMed Central

    Cutuli, Debora; Berretta, Erica; Pasqualini, Greta; De Bartolo, Paola; Caporali, Paola; Laricchiuta, Daniela; Sampedro-Piquero, Patricia; Gelfo, Francesca; Pesoli, Matteo; Foti, Francesca; Begega, Azucena; Petrosini, Laura

    2017-01-01

    Environmental enrichment (EE) is an experimental setting broadly used for investigating the effects of complex social, cognitive, and sensorimotor stimulations on brain structure and function. Recent studies point out that parental EE experience, even occurring in the pre-reproductive phase, affects neural development and behavioral trajectories of the offspring. In the present study we investigated the influences of pre-reproductive EE of female rats on maternal behavior and adolescent male offspring's coping response to an inescapable stressful situation after chronic social isolation. For this purpose female Wistar rats were housed from weaning to breeding age in enriched or standard environments. Subsequently, all females were mated and housed in standard conditions until offspring weaning. On the first post partum day (ppd 1), mother-pup interactions in undisturbed conditions were recorded. Further, after weaning the male pups were reared for 2 weeks under social isolation or in standard conditions, and then submitted or not to a single-session Forced Swim Test (FST). Offspring's neuronal activation and plastic changes were identified by immunohistochemistry for c-Fos and glucocorticoid receptors (GRs), and assessed by using stereological analysis. The biochemical correlates were measured in the hippocampus, amygdala and cingulate cortex, structures involved in hypothalamic-pituitary-adrenocortical axis regulation. Enriched dams exhibited increased Crouching levels in comparison to standard reared dams. In the offspring of both kinds of dams, social isolation reduced body weight, decreased Immobility, and increased Swimming during FST. Moreover, isolated offspring of enriched dams exhibited higher levels of Climbing in comparison to controls. Interestingly, in the amygdala of both isolated and control offspring of enriched dams we found a lower number of c-Fos immunopositive cells in response to FST and a higher number of GRs in comparison to the offspring of

  10. Widespread Fosfomycin Resistance in Gram-Negative Bacteria Attributable to the Chromosomal fosA Gene

    PubMed Central

    Ito, Ryota; Tomich, Adam D.; Callaghan, Jake D.; McElheny, Christi L.; Mettus, Roberta T.; Sluis-Cremer, Nicolas

    2017-01-01

    ABSTRACT Fosfomycin is a decades-old antibiotic which is being revisited because of its perceived activity against many extensively drug-resistant Gram-negative pathogens. FosA proteins are Mn2+ and K+-dependent glutathione S-transferases which confer fosfomycin resistance in Gram-negative bacteria by conjugation of glutathione to the antibiotic. Plasmid-borne fosA variants have been reported in fosfomycin-resistant Escherichia coli strains. However, the prevalence and distribution of fosA in other Gram-negative bacteria are not known. We systematically surveyed the presence of fosA in Gram-negative bacteria in over 18,000 published genomes from 18 Gram-negative species and investigated their contribution to fosfomycin resistance. We show that FosA homologues are present in the majority of genomes in some species (e.g., Klebsiella spp., Enterobacter spp., Serratia marcescens, and Pseudomonas aeruginosa), whereas they are largely absent in others (e.g., E. coli, Acinetobacter baumannii, and Burkholderia cepacia). FosA proteins in different bacterial pathogens are highly divergent, but key amino acid residues in the active site are conserved. Chromosomal fosA genes conferred high-level fosfomycin resistance when expressed in E. coli, and deletion of chromosomal fosA in S. marcescens eliminated fosfomycin resistance. Our results indicate that FosA is encoded by clinically relevant Gram-negative species and contributes to intrinsic fosfomycin resistance. PMID:28851843

  11. Age-associated changes in basal c-fos transcription factor binding activity in rat hearts.

    PubMed

    Tsou, H; Azhar, G; Lu, X G; Kovacs, S; Peacocke, M; Wei, J Y

    1996-12-15

    The early response proto-oncogene c-fos is expressed at very low levels in the mammalian heart at baseline. To further investigate the mechanism of altered c-fos expression with age, we studied in the basal state the binding of five transcription proteins to their cognate sites in the c-fos promoter/enhancer region, in adult and old F344 rats. Our results show a reduced binding of E2F and AP1 proteins to the c-fos promoter in aging hearts. The major calcium/cyclic AMP response element (CRE) and SP1 binding was unchanged. The only increase seen with age was in the serum response element (SRE) binding proteins. SRE is the point of convergence of different signal transduction pathways (via MAP kinases and the Rho family of GTPases) at the c-fos promoter. Increased SRE binding may reflect a compensation for a decreased binding of other transcription proteins to the c-fos promoter, alteration in the phosphorylation status of SRF, or a change in the ternary complex factors Elk 1 or SAP 1. Other possibilities include defects in the signal transduction pathways with aging, which combine to produce an overall negative balance in the function of the c-fos promoter despite the increased SRE binding activity. Both in vitro and in vivo experiments have shown decreased c-fos expression with age. This may be due partly to alterations in the basal levels of transcription factor binding.

  12. Expression of c-Fos protein in medial septum/diagonal band of Broca and CA3 region, associated with the temporary inactivation of the supramammillary area.

    PubMed

    Aranda, Lourdes

    2016-07-01

    The supramammillary (SuM) area is part of the diencephalic nuclei comprising the mammillary bodies, and is a key structure in the memory and spatial learning processes. It is a critical region in the modulation/generation of hippocampal theta rhythm. In addition, many papers have recently shown a clear involvement of this structure in the processes of spatial learning and memory in animal models, although it is still not known how it modulates spatial navigation and response emotional. The aim of the present research was to study the effect of the temporary inactivation of the SuM area on synaptic plasticity of crucial structures in the formation of spatial memory and emotional response. Sprague-Dawley rats were asigned in three groups: a control group where the animals were not subjected to any treatment, and two groups where the rats received microinjections of tetrodotoxin (TTX) in the SuM area (5ng diluted in 0.5μl of saline) or saline (0.5μl). The microinjections were administered 90min before the perfusion. Later, cellular activity in medial septum/diagonal band of Broca (MS/DBB) and CA3 region of the dorsal hippocampus was assessed, by measuring the immediate early gene c-fos. The results show a clear hiperactivity cellular in medial septum/diagonal band of Broca and a clear hypoactivity cellular in the CA3 region of the hippocampus when there was a functional inactivation of the SuM area. It suggests that the SuM area seems to be part of the connection and information input pathways to CA3 region of the hippocampal formation, key for proper functioning in spatial memory and emotional response.

  13. Serotonin2C receptor stimulation inhibits cocaine-induced Fos expression and DARPP-32 phosphorylation in the rat striatum independently of dopamine outflow.

    PubMed

    Devroye, Céline; Cathala, Adeline; Maitre, Marlène; Piazza, Pier Vincenzo; Abrous, Djoher Nora; Revest, Jean-Michel; Spampinato, Umberto

    2015-02-01

    The serotonin(2C) receptor (5-HT(2C)R) is known to control dopamine (DA) neuron function by modulating DA neuronal firing and DA exocytosis at terminals. Recent studies assessing the influence of 5-HT(2C)Rs on cocaine-induced neurochemical and behavioral responses have shown that 5-HT2CRs can also modulate mesoaccumbens DA pathway activity at post-synaptic level, by controlling DA transmission in the nucleus accumbens (NAc), independently of DA release itself. A similar mechanism has been proposed to occur at the level of the nigrostriatal DA system. Here, using in vivo microdialysis in freely moving rats and molecular approaches, we assessed this hypothesis by studying the influence of the 5-HT(2C)R agonist Ro 60-0175 on cocaine-induced responses in the striatum. The intraperitoneal (i.p.) administration of 1 mg/kg Ro 60-0175 had no effect on the increase in striatal DA outflow induced by cocaine (15 mg/kg, i.p.). Conversely, Ro 60-0175 inhibited cocaine-induced Fos immunoreactivity and phosphorylation of the DA and c-AMP regulated phosphoprotein of Mr 32 kDa (DARPP-32) at threonine 75 residue in the striatum. Finally, the suppressant effect of Ro 60-0175 on cocaine-induced DARPP-32 phosphorylation was reversed by the selective 5-HT(2C)R antagonist SB 242084 (0.5 mg/kg, i.p.). In keeping with the key role of DARPP-32 in DA neurotransmission, our results demonstrate that 5-HT(2C)Rs are capable of modulating nigrostriatal DA pathway activity at post-synaptic level, by specifically controlling DA signaling in the striatum.

  14. Effects of the fatty acid amide hydrolase inhibitor URB597 on the sleep-wake cycle, c-Fos expression and dopamine levels of the rat.

    PubMed

    Murillo-Rodríguez, Eric; Vázquez, Edgar; Millán-Aldaco, Diana; Palomero-Rivero, Marcela; Drucker-Colin, René

    2007-05-07

    Our group has described previously that the endogenous cannabinoid anandamide induces sleep. The hydrolysis of this lipid involves the activity of the fatty acid amide hydrolase (FAAH), which additionally catalyzes the degradation of the satiety factor oleoylethanolamide and the analgesic-inducing lipid palmitoylethanolamide. It has been demonstrated that the inhibition of the FAAH by URB597 increases levels of anandamide, oleoylethanolamide and palmitoylethanolamide in the brain of rats. In order to determinate the physiological properties of the FAAH inhibition on the sleep modulation, we report the pharmacological effects on the sleep-wake cycle of the rat after i.c.v. administrations of URB597, oleoylethanolamide or palmitoylethanolamide (10, 20 microg/5 microl). Separate unilateral i.c.v. injections of 3 compounds during the lights-on period, increased wakefulness and decreased slow wave (SW) sleep in rats in a dose-dependent fashion. We additionally found out that, compared to controls, c-Fos immunoreactivity in hypothalamus and dorsal raphe nucleus was increased in rats that received URB597, oleoylethanolamide or palmitoylethanolamide (10, 20 microg/5 microl, i.c.v.). Next, we found that after an injection of the compounds, levels of dopamine were increased whereas extracellular levels of levodopa (l-DOPA) were decreased. These findings indicate that that inhibition of the FAAH, via URB597, modulates waking. These effects were mimicked separately by the administration of oleoylethanolamide or palmitoylethanolamide. The alertness induced by the compounds tested here activated wake-promoting brain regions and they also induced the release of dopamine. Our results suggest that FAAH activity as well as two molecules that are catalyzed by this enzyme, oleoylethanolamide and palmitoylethanolamide, participate in the regulation of the waking state. Alternative approaches to treat sleep disorders such as excessive somnolence might consider the use of the URB597

  15. TGF alpha and v-fos cooperation in transgenic mouse epidermis induces aberrant keratinocyte differentiation and stable, autonomous papillomas.

    PubMed

    Wang, X J; Greenhalgh, D A; Lu, X R; Bickenbach, J R; Roop, D R

    1995-01-19

    To assess the synergistic effect of growth and transcription factor deregulation on carcinogenesis in vivo, mating experiments were performed between transgenic mice expressing human TGF alpha or v-fos exclusively in the epidermis by means of a human keratin K1-based targeting vector (HK1.fos, HK1.TGF alpha and HK1.fos/alpha). While HK1.TGF alpha mice exhibited mild epidermal hyperplasia resulting in a wrinkled appearance, this hyperplasia was significantly increased in HK1.fos/alpha mice which also exhibited a novel opalescent and peeling skin phenotype. HK1.fos/alpha keratinocyte differentiation was considerably deregulated with cornified cells appearing in the granular layer, granular cells in the spinous layer and a sixfold increase in BrdU labeling over normal. In addition, hyperplastic HK1.fos/alpha epidermis exhibited aberrant loricrin, filaggrin and novel K13 expression associated with v-fos expression. Unlike adult HK1.TGF alpha controls, hyperplasia persisted in HK1.fos/alpha adults which also rapidly developed autonomous squamous cell papillomas. These results demonstrate that v-fos and TGF alpha over-expression can cooperate to reprogram keratinocyte differentiation and elicit the early stages of neoplasia. Moreover, TGF alpha over-expression appeared to play an early, initiating role in HK1.fos/alpha papilloma etiology, and a promotion role in the accelerated appearance of v-fos wound-associated preneoplastic phenotypes. However, the stable persistence of HK1.fos/alpha papillomas for up to 12 months, suggests that additional events are required for malignant conversion.

  16. Experience-Dependent Induction of Hippocampal ΔFosB Controls Learning.

    PubMed

    Eagle, Andrew L; Gajewski, Paula A; Yang, Miyoung; Kechner, Megan E; Al Masraf, Basma S; Kennedy, Pamela J; Wang, Hongbing; Mazei-Robison, Michelle S; Robison, Alfred J

    2015-10-07

    The hippocampus (HPC) is known to play an important role in learning, a process dependent on synaptic plasticity; however, the molecular mechanisms underlying this are poorly understood. ΔFosB is a transcription factor that is induced throughout the brain by chronic exposure to drugs, stress, and variety of other stimuli and regulates synaptic plasticity and behavior in other brain regions, including the nucleus accumbens. We show here that ΔFosB is also induced in HPC CA1 and DG subfields by spatial learning and novel environmental exposure. The goal of the current study was to examine the role of ΔFosB in hippocampal-dependent learning and memory and the structural plasticity of HPC synapses. Using viral-mediated gene transfer to silence ΔFosB transcriptional activity by expressing ΔJunD (a negative modulator of ΔFosB transcriptional function) or to overexpress ΔFosB, we demonstrate that HPC ΔFosB regulates learning and memory. Specifically, ΔJunD expression in HPC impaired learning and memory on a battery of hippocampal-dependent tasks in mice. Similarly, general ΔFosB overexpression also impaired learning. ΔJunD expression in HPC did not affect anxiety or natural reward, but ΔFosB overexpression induced anxiogenic behaviors, suggesting that ΔFosB may mediate attentional gating in addition to learning. Finally, we found that overexpression of ΔFosB increases immature dendritic spines on CA1 pyramidal cells, whereas ΔJunD reduced the number of immature and mature spine types, indicating that ΔFosB may exert its behavioral effects through modulation of HPC synaptic function. Together, these results suggest collectively that ΔFosB plays a significant role in HPC cellular morphology and HPC-dependent learning and memory. Consolidation of our explicit memories occurs within the hippocampus, and it is in this brain region that the molecular and cellular processes of learning have been most closely studied. We know that connections between hippocampal

  17. cAMP and in vivo hypoxia induce tob, ifr1, and fos expression in erythroid cells of the chick embryo.

    PubMed

    Dragon, Stefanie; Offenhäuser, Nina; Baumann, Rosemarie

    2002-04-01

    During avian embryonic development, terminal erythroid differentiation occurs in the circulation. Some of the key events, such as the induction of erythroid 2,3-bisphosphoglycerate (2,3-BPG), carbonic anhydrase (CAII), and pyrimidine 5'-nucleotidase (P5N) synthesis are oxygen dependent (Baumann R, Haller EA, Schöning U, and Weber M, Dev Biol 116: 548-551, 1986; Dragon S and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 280: R870-R878, 2001; Dragon S, Carey C, Martin K, and Baumann R, J Exp Biol 202: 2787-2795, 1999; Dragon S, Glombitza S, Götz R, and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 271: R982-R989, 1996; Dragon S, Hille R, Götz R, and Baumann R, Blood 91: 3052-3058, 1998; Million D, Zillner P, and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 261: R1188-R1196, 1991) in an indirect way: hypoxia stimulates the release of norepinephrine (NE)/adenosine into the circulation (Dragon et al., J Exp Biol 202: 2787-2795, 1999; Dragon et al., Am J Physiol Regulatory Integrative Comp Physiol 271: R982-R989, 1996). This leads via erythroid beta-adrenergic/adenosine A(2) receptor activation to a cAMP signal inducing several proteins in a transcription-dependent manner (Dragon et al., Am J Physiol Regulatory Integrative Comp Physiol 271: R982-R989, 1996; Dragon et al., Blood 91: 3052-3058, 1998; Glombitza S, Dragon S, Berghammer M, Pannermayr M, and Baumann R, Am J Physiol Regulatory Integrative Comp Physiol 271: R973-R981, 1996). To understand how the cAMP-dependent processes are initiated, we screened an erythroid cDNA library for cAMP-regulated genes. We detected three genes that were strongly upregulated (>5-fold) by cAMP in definitive and primitive red blood cells. They are homologous to the mammalian Tob, Ifr1, and Fos proteins. In addition, the genes are induced in the intact embryo during short-term hypoxia. Because the genes are regulators of proliferation and differentiation in other cell types, we suggest that c

  18. Differential induction of c-Fos and phosphorylated ERK by a noxious stimulus after peripheral nerve injury.

    PubMed

    Tabata, Mitsuyasu; Terayama, Ryuji; Maruhama, Kotaro; Iida, Seiji; Sugimoto, Tomosada

    2017-10-02

    In this study, we compared induction of c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) in the spinal dorsal horn after peripheral nerve injury. We examined the spinal dorsal horn for noxious heat-induced c-Fos and p-ERK protein-like immunoreactive (c-Fos- and p-ERK-IR) neuron profiles after tibial nerve injury. The effect of administration of a MEK 1/2 inhibitor (PD98059) on noxious heat-induced c-Fos expression was also examined after tibial nerve injury. A large number of c-Fos- and p-ERK-IR neuron profiles were induced by noxious heat stimulation to the hindpaw in sham-operated animals. A marked reduction in the number of c-Fos- and p-ERK-IR neuron profiles was observed in the medial 1/3 (tibial territory) of the dorsal horn at 3 and 7 days after nerve injury. Although c-Fos-IR neuron profiles had reappeared by 14 days after injury, the number of p-ERK-IR neuron profiles remained decreased in the tibial territory of the superficial dorsal horn. Double immunofluorescence labeling for c-Fos and p-ERK induced by noxious heat stimulation to the hindpaw at different time points revealed that a large number of c-Fos-IR, but not p-ERK-IR, neuron profiles were distributed in the tibial territory after injury. Although administration of a MEK 1/2 inhibitor to the spinal cord suppressed noxious heat-induced c-Fos expression in the peroneal territory, this treatment did not alter c-Fos induction in the tibial territory after nerve injury. ERK phosphorylation may be involved in c-Fos induction in normal nociceptive responses, but not in exaggerated c-Fos induction after nerve injury.

  19. Protooncogene c-fos Involvement in the Molecular Mechanism of Rat Brain Sexual Differentiation.

    PubMed

    Giannakopoulou, M; Bozas, E; Philippidis, H; Stylianopoulou, F

    2001-06-01

    Brain sexual differentiation is mediated through testosterone, which acts during the perinatal period in the form of both 5alpha-dihydrotestosterone and estradiol. In order to gain insight into the molecular mechanisms involved, we studied induction of c-fos, an index of functional neuronal activation, in the 2-day-old female rat brain after injection of a masculinizing dose of testosterone. Administration of testosterone resulted in induction of c-fos gene expression in the hypothalamus, as determined by Northern analysis. Following immunocytochemistry, we demonstrated an increase in the number of Fos-positive nuclei in the median and medial preoptic nucleus, the medial preoptic area extending to the lateral preoptic area, and the peri- and paraventricular area. In an effort to see whether testosterone acted as 5alpha-dihydrotestosterone or as estradiol, we injected either steroid and looked at fos induction. Estradiol mimicked the effect of testosterone, while 5alpha-dihydrotestosterone was without effect. Furthermore, injection of an estrogen receptor blocker, clomiphene, together with testosterone, abolished the testosterone-induced increase in Fos-positive nuclei, thus confirming the finding that testosterone induces c-fos by acting through estrogen receptors. Electrophoretic mobility shift assays showed that nuclear extracts from 2-day-old female hypothalamus contain a protein, most probably the estrogen receptor, which binds specifically to oligodeoxynucleotides with the sequence of either vitERE, the consensus estrogen-responsive element (ERE) found in the vittelogenin gene, or fosERE, the ERE found in the 3'-untranslated region of the mouse c-fos gene. This suggests that the effect of testosterone-derived estradiol on c-fos expression is a direct one, mediated by binding of estrogen receptors to an ERE in the c-fos gene-regulatory regions.

  20. Differential activation of c-Fos in the paraventricular nuclei of the hypothalamus and thalamus following myocardial infarction in rats

    PubMed Central

    Tae, Hyun-Jin; Park, Seung Min; Cho, Jeong Hwi; Kim, In Hye; Ahn, Ji Hyeon; Park, Joon Ha; Won, Moo-Ho; Chen, Bai Hui; Shin, Bich-Na; Shin, Myoung Cheol; Lee, Choong Hyun; Hong, Seongkweon; Lee, Jae-Chul; Cho, Jun Hwi

    2016-01-01

    Proto-oncogene c-Fos (c-Fos) is frequently used to detect a pathogenesis in central nervous system disorders. The present study examined changes in the immunoreactivity of c-Fos in the paraventricular nucleus of the hypothalamus (PVNH) and paraventricular nucleus of the thalamus (PVNT) following myocardial infarction (MI) in rats. Infarction in the left ventricle was examined by Masson's trichrome staining. Neuronal degeneration was monitored for 56 days after MI using crystal violet and Fluoro-Jade B histofluorescence staining. Changes in the immunoreactivity of c-Fos were determined using immunohistochemistry for c-Fos. The average infarct size of the left ventricle circumference was ~44% subsequent to MI. Neuronal degeneration was not detected in PVNH and PVNT following MI. c-Fos immunoreactive (+) cells were infrequently observed in the nuclei of the sham-group. However, the number of c-Fos+ cells was increased in the nuclei following MI and peaked in the PVNH and PVNT at 3 and 14 days, respectively. The number of c-Fos+ cells were comparable with the sham group at 56 days after MI. Therefore, MI may induce c-Fos immunoreactivity in PVNH and PVNT, this increase of c-Fos expression levels may be associated with the stress that occurs in the brain following MI. PMID:27601012

  1. Fos family protein degradation by the proteasome.

    PubMed

    Gomard, Tiphanie; Jariel-Encontre, Isabelle; Basbous, Jihane; Bossis, Guillaume; Moquet-Torcy, Gabriel; Mocquet-Torcy, Gabriel; Piechaczyk, Marc

    2008-10-01

    c-Fos proto-oncoprotein defines a family of closely related transcription factors (Fos proteins) also comprising Fra-1, Fra-2, FosB and DeltaFosB, the latter two proteins being generated by alternative splicing. Through the regulation of many genes, most of them still unidentified, they regulate major functions from the cell level up to the whole organism. Thus they are involved in the control of proliferation, differentiation and apoptosis, as well as in the control of responses to stresses, and they play important roles in organogenesis, immune responses and control of cognitive functions, among others. Fos proteins are intrinsically unstable. We have studied how two of them, c-Fos and Fra-1, are degraded. Departing from the classical scenario where unstable key cell regulators are hydrolysed by the proteasome after polyubiquitination, we showed that the bulk of c-Fos and Fra-1 can be broken down independently of any prior ubiquitination. Certain conserved structural domains suggest that similar mechanisms may also apply to Fra-2 and FosB. Computer search indicates that certain motifs shared by the Fos proteins and putatively responsible for instability are found in no other protein, suggesting the existence of degradation mechanisms specific for this protein family. Under particular signalling conditions, others have shown that a part of cytoplasmic c-Fos requires ubiquitination for fast turnover. This poses the question of the multiplicity of degradation pathways that apply to proteins depending on their intracellular localization.

  2. Paired-housing selectively facilitates within-session extinction of avoidance behavior, and increases c-Fos expression in the medial prefrontal cortex, in anxiety vulnerable Wistar-Kyoto rats.

    PubMed

    Smith, Ian M; Pang, Kevin C H; Servatius, Richard J; Jiao, Xilu; Beck, Kevin D

    2016-10-01

    The perseveration of avoidance behavior, even in the absence of once threatening stimuli, is a key feature of anxiety and related psychiatric conditions. This phenomenon can be observed in the Wistar-Kyoto (WKY) rat which, in comparison to outbred controls, demonstrates impaired extinction of avoidance behavior. Also characteristic of the WKY rat is abnormalities of the neurocircuitry and neuroplasticity of the medial prefrontal cortex (mPFC). One means of reducing physiological responses to anxiety, and conditioned fear, in social species is the presence of a conspecific animal. The current study investigates whether or not pair-housed WKY rats would show facilitated extinction of avoidance in comparison to individual-housed WKY rats, and whether or not pair-housing influences mPFC activation during lever-press avoidance. Male WKY rats were assigned to individual-housed and pair-housed conditions. Rats were trained in lever-press avoidance. Each session of lever-press avoidance consisted of 20 trials, where pressing a lever in response to a warning tone prevented foot-shocks. Rats received 12 acquisition sessions over 4weeks; followed by 6 extinction sessions over 2weeks, where foot-shocks ceased to be delivered. Brains were harvested 90min after trials 1 and 10 of extinction sessions 1 and 6, and mPFC sections underwent c-Fos staining as a measure of activation. Pair-housed rats showed facilitated lever-press avoidance extinction rates, but the main cause for this overall difference was a selective facilitation of within-session extinction. Similar to individual-housed rats, pair-housed rats continued to avoid during trial 1 of extinction even when the avoidance responding had been significantly reduced by the end of the previous session. Pair-housed rats sacrificed on trial 1 showed greater c-Fos expression in the anterior cingulate cortex and prelimbic cortex subregions of the mPFC compared individual-housed rats sacrificed on trial 1. This data shows pair

  3. Evaluate the Antigenotoxicity and Anticancer Role of β-Sitosterol by Determining Oxidative DNA Damage and the Expression of Phosphorylated Mitogen-activated Protein Kinases’, C-fos, C-jun, and Endothelial Growth Factor Receptor

    PubMed Central

    Sharmila, Ramalingam; Sindhu, Ganapathy

    2017-01-01

    reduced the elevated expression of p-p38 MAPK, p-JNK, p-ERK, c-fos and c-jun in carcinogen induced rats, which suggest that β-sitosterol might protect renal tissue from neoplastic transformation. The interaction of β-sitosterol with the ATP binding site of ERK-2 by molecular docking studies also validates the inhibitory effect of β-sitosterol on ERK-2. The results of the present study reveal that β-sitosterol inhibit oncogenic MAPK signaling, to abrogate hyper cell proliferation, angiogenesis, and to induce apoptosis thereby prevent DEN and Fe-NTA induced renal carcinogenesis. Thus,β-sitosterol that modulates signal transduction pathways and their downstream events may serve as a potential cancer chemopreventive and therapeutic agent. Abbreviation used: AP-1: Activator protein-1,DEPC: Diethyl pyrocarbonate,EDTA: Ethylenediaminetetraacetic acid,EGFR: Endothelial growth factor receptor,ERK: Extracellular-signal regulating kinase,Fe-NTA: Ferric nitrilotriacetate,GAPDH: Glyceraldehyde-3-phosphate dehydrogenase,HBSS: Hank's balanced salt solution,JNK: c-Jun N-terminal kinase,MAPK: Mitogen-activated protein kinase,DEN: N-diethylnitrosamine,RCC: Renal cell carcinoma,SDS-PAGE: Sodium dodecyl sulfate polyacrylamide gel electrophoresis PMID:28216890

  4. Soft coral-derived lemnalol alleviates monosodium urate-induced gouty arthritis in rats by inhibiting leukocyte infiltration and iNOS, COX-2 and c-Fos protein expression.

    PubMed

    Lee, Hsin-Pai; Huang, Shi-Ying; Lin, Yen-You; Wang, Hui-Min; Jean, Yen-Hsuan; Wu, Shu-Fen; Duh, Chang-Yih; Wen, Zhi-Hong

    2013-01-10

    An acute gout attack manifests in the joint as dramatic inflammation. To date, the clinical use of medicinal agents has typically led to undesirable side effects. Numerous efforts have failed to create an effective and safe agent for the treatment of gout. Lemnalol-an extract from Formosan soft coral-has documented anti-inflammatory and anti-nociceptive properties. In the present study, we attempt to examine the therapeutic effects of lemnalol on intra-articular monosodium urate (MSU)-induced gouty arthritis in rats. In the present study, we found that treatment with lemnalol (intramuscular [im]), but not colchicine (oral [po]), significantly attenuated MUS-induced mechanical allodynia, paw edema and knee swelling. Histomorphometric and immunohistochemistry analysis revealed that MSU-induced inflammatory cell infiltration, as well as the elevated expression of c-Fos and pro-inflammatory proteins (inducible nitric oxide synthase and cyclooxygenase-2) observed in synovial tissue, were significantly inhibited by treatment with lemnalol. We conclude that lemnalol may be a promising candidate for the development of a new treatment for gout and other acute neutrophil-driven inflammatory diseases.

  5. Soft Coral-Derived Lemnalol Alleviates Monosodium Urate-Induced Gouty Arthritis in Rats by Inhibiting Leukocyte Infiltration and iNOS, COX-2 and c-Fos Protein Expression

    PubMed Central

    Lee, Hsin-Pai; Huang, Shi-Ying; Lin, Yen-You; Wang, Hui-Min; Jean, Yen-Hsuan; Wu, Shu-Fen; Duh, Chang-Yih; Wen, Zhi-Hong

    2013-01-01

    An acute gout attack manifests in the joint as dramatic inflammation. To date, the clinical use of medicinal agents has typically led to undesirable side effects. Numerous efforts have failed to create an effective and safe agent for the treatment of gout. Lemnalol—an extract from Formosan soft coral—has documented anti-inflammatory and anti-nociceptive properties. In the present study, we attempt to examine the therapeutic effects of lemnalol on intra-articular monosodium urate (MSU)-induced gouty arthritis in rats. In the present study, we found that treatment with lemnalol (intramuscular [im]), but not colchicine (oral [po]), significantly attenuated MUS-induced mechanical allodynia, paw edema and knee swelling. Histomorphometric and immunohistochemistry analysis revealed that MSU-induced inflammatory cell infiltration, as well as the elevated expression of c-Fos and pro-inflammatory proteins (inducible nitric oxide synthase and cyclooxygenase-2) observed in synovial tissue, were significantly inhibited by treatment with lemnalol. We conclude that lemnalol may be a promising candidate for the development of a new treatment for gout and other acute neutrophil-driven inflammatory diseases. PMID:23306170

  6. Smov Fos/rd Initial Operations

    NASA Astrophysics Data System (ADS)

    Fitch, John

    1994-01-01

    This proposal will be used to take a dark exposure and a CAL lamp exposure to verify the science data interfaces and the proper functioning of the FOS. This must be preceeded by verification that the FOS ION gauge pressure reading is less than 1E-5 Torr. This activity must also be accomplished before any other use of the HV with the FOS RED detector.

  7. Fos immunohistochemical determination of brainstem neuronal activation in the muskrat after nasal stimulation.

    PubMed

    McCulloch, P F; Panneton, W M

    1997-06-01

    Stimulation of the nasal passages of muskrats with either ammonia vapours or retrogradely-flowing water produced cardiorespiratory responses (an immediate 62% decrease in heart rate, 29% increase in mean arterial blood pressure, and sustained expiratory apnoea). We used the immunohistological detection of Fos, the protein product of the c-fos gene, as a marker of neuronal activation to help elucidate the brainstem circuitry of this cardiorespiratory response. After repeated ammonia stimulation of the nasal passages, increased Fos expression was detected within the spinal trigeminal nucleus (ventral laminae I and II of the medullary dorsal horn, ventral paratrigeminal nucleus, and spinal trigeminal nucleus interpolaris), an area just ventromedial to the medullary dorsal horn, the caudal dorsal reticular formation and the area of the A5 catecholamine group compared to control animals. Repeated water stimulation of the nasal passages produced increased Fos expression only in the A5 catecholamine group. There was an increase in the number of Fos-positive cells in the ammonia group in the ventral laminae I and II of the medullary dorsal horn and the ventral paratrigeminal nuclei compared with the water group. We conclude that ammonia stimulation of the nasal passages produces a different pattern of neuronal activation within the brainstem compared with water stimulation. We also conclude that Fos immunohistochemistry is a good technique to determine functional afferent somatotopy, but that immunohistochemical detection of Fos is not a good technique to identify the medullary neurons responsible for the efferent aspects of an intermittently produced cardiorespiratory reflex.

  8. Striatal overexpression of ΔFosB reproduces chronic levodopa-induced involuntary movements

    PubMed Central

    Cao, Xuebing; Yasuda, Toru; Uthayathas, Subramaniam; Watts, Ray L.; Mouradian, M. Maral; Mochizuki, Hideki; Papa, Stella M.

    2010-01-01

    Long-term dopamine replacement therapy in Parkinson’s disease leads to the development of disabling involuntary movements named dyskinesias that are related to adaptive changes in striatal signaling pathways. The chronic transcription factor ΔFosB, which is overexpressed in striatal neurons after chronic dopaminergic drug exposure, is suspected to mediate these adaptive changes. Here, we sought to demonstrate the ability of ΔFosB to lead directly to the abnormal motor responses associated with chronic dopaminergic therapy. Using rAAV viral vectors, high levels of ΔFosB expression were induced in the striatum of dopamine-denervated rats naïve of chronic drug administration. Transgenic ΔFosB overexpression reproduced the entire spectrum of altered motor behaviors in response to acute levodopa tests, including different types of abnormal involuntary movements and hypersensitivity of rotational responses that are typically associated with chronic levodopa treatment. JunD, the usual protein partner of ΔFosB binding to AP-1 sites of genes, remained unchanged in rats with high ΔFosB expression induced by viral vectors. These findings demonstrate that the increase of striatal ΔFosB in the evolution of chronically treated Parkinson’s disease may be a trigger for the development of abnormal responsiveness to dopamine and the emergence of involuntary movements. PMID:20505100

  9. An Indirect Action Contributes to C-Fos Induction in Paraventricular Hypothalamic Nucleus by Neuropeptide Y

    PubMed Central

    Fan, Shengjie; Dakshinamoorthy, Janani; Kim, Eun Ran; Xu, Yong; Huang, Cheng; Tong, Qingchun

    2016-01-01

    Neuropeptide Y (NPY) is a well-established orexigenic peptide and hypothalamic paraventricular nucleus (PVH) is one major brain site that mediates the orexigenic action of NPY. NPY induces abundant expression of C-Fos, an indicator for neuronal activation, in the PVH, which has been used extensively to examine the underlying NPY orexigenic neural pathways. However, PVH C-Fos induction is in discordance with the abundant expression of NPY receptors, a group of inhibitory Gi protein coupled receptors in the PVH, and with the overall role of PVH neurons in feeding inhibition, suggesting a mechanism of indirect action. Here we showed that the ability of NPY on C-Fos induction in the PVH was blunted in conditions of insulin deficiency and fasting, a condition associated with a high level of NPY and a low level of insulin. Moreover, insulin insufficiency blunted C-Fos induction in the PVH by fasting-induced re-feeding, and insulin and NPY induced c-Fos induction in the same group of PVH neurons. Finally, NPY produced normal C-Fos induction in the PVH with disruption of GABA-A receptors. Thus, our results revealed that PVH C-Fos induction by NPY is mediated by an indirect action, which is at least partially mediated by insulin action, but not GABA-A receptors. PMID:26813148

  10. The Role of ΔFosB in the Medial Preoptic Area: Differential Effects of Mating and Cocaine History

    PubMed Central

    McHenry, Jenna A.; Robison, Christopher L.; Bell, Genevieve A.; Bolaños-Guzmán, Carlos A.; Vialou, Vincent V.; Nestler, Eric J.; Hull, Elaine M.

    2016-01-01

    The transcription factor deltaFosB (ΔFosB) is induced in the nucleus accumbens (NAc) by repeated exposure to drugs of abuse and natural rewards. Less is known about its role in other brain areas. Here, we compared the effects of mating versus cocaine history on induction of ΔFosB in the medial preoptic area (MPOA), an integral site for reproductive behavior, and in the NAc. ΔFosB immunoreactivity (ir) was increased in the MPOA of previously naïve and experienced male rats that mated the day before euthanasia, compared to unmated controls and experienced males with recent mating abstinence. Western immunoblots confirmed that the 35–37-kDa isoform of ΔFosB was increased more in recently mated males. Conversely, previous plus recent cocaine did not increase ΔFosB-ir in the MPOA, despite an increase in the NAc. Next, a viral vector expressing ΔFosB, its dominant negative antagonist ΔJunD, or green fluorescent protein (GFP) control, were microinjected bilaterally into the MPOA. ΔFosB overexpression impaired copulation and promoted female-directed aggression, compared to ΔJunD and control males. These data suggest that ΔFosB in the mPOA is expressed in an experience-dependent manner and affects systems that coordinate mating and aggression. PMID:27657309

  11. Differential induction of FosB isoforms throughout the brain by fluoxetine and chronic stress.

    PubMed

    Vialou, Vincent; Thibault, Mackenzie; Kaska, Sophia; Cooper, Sarah; Gajewski, Paula; Eagle, Andrew; Mazei-Robison, Michelle; Nestler, Eric J; Robison, A J

    2015-12-01

    Major depressive disorder is thought to arise in part from dysfunction of the brain's "reward circuitry", consisting of the mesolimbic dopamine system and the glutamatergic and neuromodulatory inputs onto this system. Both chronic stress and antidepressant treatment regulate gene transcription in many of the brain regions that make up these circuits, but the exact nature of the transcription factors and target genes involved in these processes remain unclear. Here, we demonstrate induction of the FosB family of transcription factors in ∼25 distinct regions of adult mouse brain, including many parts of the reward circuitry, by chronic exposure to the antidepressant fluoxetine. We further uncover specific patterns of FosB gene product expression (i.e., differential expression of full-length FosB, ΔFosB, and Δ2ΔFosB) in brain regions associated with depression--the nucleus accumbens (NAc), prefrontal cortex (PFC), and hippocampus--in response to chronic fluoxetine treatment, and contrast these patterns with differential induction of FosB isoforms in the chronic social defeat stress model of depression with and without fluoxetine treatment. We find that chronic fluoxetine, in contrast to stress, causes induction of the unstable full-length FosB isoform in the NAc, PFC, and hippocampus even 24 h following the final injection, indicating that these brain regions may undergo chronic activation when fluoxetine is on board, even in the absence of stress. We also find that only the stable ΔFosB isoform correlates with behavioral responses to stress. These data suggest that NAc, PFC, and hippocampus may present useful targets for directed intervention in mood disorders (ie, brain stimulation or gene therapy), and that determining the gene targets of FosB-mediated transcription in these brain regions in response to fluoxetine may yield novel inroads for pharmaceutical intervention in depressive disorders.

  12. Differential induction of FosB isoforms throughout the brain by fluoxetine and chronic stress

    PubMed Central

    Vialou, Vincent; Thibault, Mackenzie; Kaska, Sophia; Gajewski, Paula; Eagle, Andrew; Mazei-Robison, Michelle; Nestler, Eric J.; Robison, A.J.

    2015-01-01

    Major depressive disorder is thought to arise in part from dysfunction of the brain's “reward circuitry,” consisting of the mesolimbic dopamine system and the glutamatergic and neuromodulatory inputs onto this system. Both chronic stress and antidepressant treatment regulate gene transcription in many of the brain regions that make up these circuits, but the exact nature of the transcription factors and target genes involved in these processes remain unclear. Here, we demonstrate induction of the FosB family of transcription factors in ∼25 distinct regions of adult mouse brain, including many parts of the reward circuitry, by chronic exposure to the antidepressant fluoxetine. We further uncover specific patterns of FosB gene product expression (i.e., differential expression of full-length FosB, ΔFosB, and Δ2ΔFosB) in brain regions associated with depression – the nucleus accumbens (NAc), prefrontal cortex (PFC), and hippocampus – in response to chronic fluoxetine treatment, and contrast these patterns with differential induction of FosB isoforms in the chronic social defeat stress model of depression with and without fluoxetine treatment. We find that chronic fluoxetine, in contrast to stress, causes induction of the unstable full-length FosB isoform in the NAc, PFC, and hippocampus even 24 hours following the final injection, indicating that these brain regions may undergo chronic activation when fluoxetine is on board, even in the absence of stress. We also find that only the stable ΔFosB isoform correlates with behavioral responses to stress. These data suggest that NAc, PFC, and hippocampus may present useful targets for directed intervention in mood disorders (ie, brain stimulation or gene therapy), and that determining the gene targets of FosB-mediated transcription in these brain regions in response to fluoxetine may yield novel inroads for pharmaceutical intervention in depressive disorders. PMID:26164345

  13. A novel molluscan Fos gene with immune defense function identified in the Hong Kong oyster, Crassostrea hongkongensis.

    PubMed

    Qu, Fufa; Xiang, Zhiming; Wang, Fuxuan; Zhang, Yang; Tong, Ying; Li, Jun; Zhang, Yuehuan; Yu, Ziniu

    2015-07-01

    The transcription factor Fos is a member of one of the best-studied AP-1 sub-families and has been implicated in a wide variety of biological processes, including the regulation of apoptosis, immune responses and cytokine production. In this report, a novel mollusk Fos (referred to as ChFos) gene was cloned and characterized from the Hong Kong oyster, Crassostrea hongkongensis. The deduced ChFos protein sequence comprised 333 amino acids and shared significant homology with invertebrate homologs. Phylogenetic analysis revealed that ChFos clusters with Fos from Crassostrea gigas and Crassostrea ariakensis. Quantitative real-time PCR analysis revealed that ChFos mRNA was broadly expressed in all tested tissues and during different stages of the oyster's embryonic and larval development. In addition, the expression of ChFos mRNA was significantly up-regulated under challenge with microorganisms (Vibrio alginolyticus, Staphylococcus haemolyticus and Saccharomyces cerevisiae) and pathogen-associated molecular patterns (PAMPs: LPS, PGN and polyI:C). Moreover, fluorescence microscopy showed that ChFos protein is localized in the nucleus in HEK293T cells. Reporter assays suggested that ChFos may act as an efficient transcription activator in the regulation of AP-1-responsive gene expression through interaction with ChJun. Overall, this study presents the first experimental evidence of the presence and functional characteristics of Fos in mollusks, which reveals its involvement in host protection against immune challenge in the oyster. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. A mechanism of AP-1 suppression through interaction of c-Fos with lamin A/C

    PubMed Central

    Ivorra, Carmen; Kubicek, Markus; González, José M.; Sanz-González, Silvia M.; Álvarez-Barrientos, Alberto; O'Connor, José-Enrique; Burke, Brian; Andrés, Vicente

    2006-01-01

    AP-1 (Activating Protein 1) transcription factor activity is tightly regulated at multiple levels, including dimer formation (i.e., Fos/Jun). Here we show that the intermediate filament protein lamin A/C suppresses AP-1 function through direct interaction with c-Fos, and that both proteins can interact and colocalize at the nuclear envelope (NE) in mammalian cells. Perinuclear localization of c-Fos is absent in Lmna-null cells but can be restored by lamin A overexpression. In vitro, preincubation of c-Fos with lamin A prior to the addition of c-Jun inhibits AP-1 DNA-binding activity. In vivo, overexpression of lamin A reduces the formation of c-Fos/c-Jun heterodimers, and suppresses AP-1 DNA-binding and transcriptional activity. Notably, c-Fos colocalizes with lamin A/C at the NE in starvation-synchronized quiescent cells lacking detectable AP-1 DNA binding. In contrast, serum-induced AP-1 DNA-binding activity coincides with abundant nucleoplasmic c-Fos expression without changes in lamin A/C localization. We also found that Lmna-null cells display enhanced proliferation. In contrast, lamin A overexpression causes growth arrest, and ectopic c-Fos partially overcomes lamin A/C-induced cell cycle alterations. We propose lamin A/C-mediated c-Fos sequestration at the NE as a novel mechanism of transcriptional and cell cycle control. PMID:16452503

  15. [Immunocytochemical localization of c-fos protein in termite brains following flying behavior].

    PubMed

    Su, Xiao Hong; Xi, Geng Si; Zhang, Min

    2005-02-01

    The expression of c-fos protein was examined in the brain of reproduction termite (Reticulitermes aculabialis) with immunocytochemical localization method. The results showed c-fos protein immunoreactivity was found in the procerebrum, deutocerebrum and tritocerebrum of termites at all stages. At last instar nymph and after flying stage, c-fos immunoreactivity of procerebrum was weak, but the female and male termites displayed significantly increased the number of c-fos labeled cells in the protocerebrum at flying stage. On the other hand, previous studies have demonstrated neural cells of procerebrum could strongly secrete FSH (Follicle Stimulating Hormone) and LH (Luteinizing Hormone) which maintained libido and stimulated mating flight. This meaned that c-fos expression of procerebrum involved in hormone regulation in sexual behavior,as have been shown in mammal. In conclusion, we demonstrated here for the first time that c-fos expression of procerebrum of termites involved in sexual behavior. These resulats provided a new morphological proof that neural activation of procerebrum participated in the regulation of sexual behavior of termites.

  16. Involvement of FOS-mediated miR-181b/miR-21 signalling in the progression of malignant gliomas.

    PubMed

    Tao, Tao; Wang, Yingyi; Luo, Hui; Yao, Lei; Wang, Lin; Wang, Jiajia; Yan, Wei; Zhang, Junxia; Wang, Huibo; Shi, Yan; Yin, Yu; Jiang, Tao; Kang, Chunsheng; Liu, Ning; You, Yongping

    2013-09-01

    Recently, a group of microRNAs (miRNAs) were shown to be dysregulated in gliomas, and involved in glioma development. However, the effect of miRNA-miRNA functional networks on gliomas is poorly understood. In this study, we identified that FBJ murine osteosarcoma viral oncogene homolog (FOS)-mediated miR-181b/miR-21 signalling was critical for glioma progression. Using microarrays and quantitative RT-PCR (qRT-PCR), we found increased FOS in high grade gliomas. FOS depletion (via FOS-shRNA), inhibited invasion and promoted apoptosis in glioma cells. Using microarrays, combined with Pearson correlation analysis, we found FOS positively correlated with miR-21 expression. Reduction of FOS inhibited miR-21 expression by binding to the miR-21 promoter using luciferase reporter assays. Introduction of miR-21 abrogated FOS knockdown-induced cell invasion and apoptosis. Moreover, bioinformatics and luciferase reporter assays showed that miR-181b modulated FOS expression by directly targeting the binding site within the 3'UTR. Expression of FOS with a FOS cDNA lacking 3'UTR overrided miR-181b-induced miR-21 expression and cell function. Finally, immunohistochemistry (IHC) and in situ hybridisation (ISH) analysis revealed a significant correlation in miR-181b, FOS and miR-21 expression in nude mouse tumour xenograft and human glioma tissues. To our knowledge, it is the first time to demonstrate that miR-181b/FOS/miR-21 signalling plays a critical role in the progression of gliomas, providing important clues for understanding the key roles of transcription factor mediated miRNA-miRNA functional network in the regulation of gliomas.

  17. Widespread Fosfomycin Resistance in Gram-Negative Bacteria Attributable to the Chromosomal fosA Gene.

    PubMed

    Ito, Ryota; Mustapha, Mustapha M; Tomich, Adam D; Callaghan, Jake D; McElheny, Christi L; Mettus, Roberta T; Shanks, Robert M Q; Sluis-Cremer, Nicolas; Doi, Yohei

    2017-08-29

    Fosfomycin is a decades-old antibiotic which is being revisited because of its perceived activity against many extensively drug-resistant Gram-negative pathogens. FosA proteins are Mn(2+) and K(+)-dependent glutathione S-transferases which confer fosfomycin resistance in Gram-negative bacteria by conjugation of glutathione to the antibiotic. Plasmid-borne fosA variants have been reported in fosfomycin-resistant Escherichia coli strains. However, the prevalence and distribution of fosA in other Gram-negative bacteria are not known. We systematically surveyed the presence of fosA in Gram-negative bacteria in over 18,000 published genomes from 18 Gram-negative species and investigated their contribution to fosfomycin resistance. We show that FosA homologues are present in the majority of genomes in some species (e.g., Klebsiella spp., Enterobacter spp., Serratia marcescens, and Pseudomonas aeruginosa), whereas they are largely absent in others (e.g., E. coli, Acinetobacter baumannii, and Burkholderia cepacia). FosA proteins in different bacterial pathogens are highly divergent, but key amino acid residues in the active site are conserved. Chromosomal fosA genes conferred high-level fosfomycin resistance when expressed in E. coli, and deletion of chromosomal fosA in S. marcescens eliminated fosfomycin resistance. Our results indicate that FosA is encoded by clinically relevant Gram-negative species and contributes to intrinsic fosfomycin resistance.IMPORTANCE There is a critical need to identify alternate approaches to treat infections caused by extensively drug-resistant (XDR) Gram-negative bacteria. Fosfomycin is an old antibiotic which is routinely used for the treatment of urinary tract infections, although there is substantial interest in expanding its use to systemic infections caused by XDR Gram-negative bacteria. In this study, we show that fosA genes, which encode dimeric Mn(2+)- and K(+)-dependent glutathione S-transferase, are widely distributed in the

  18. Centralization of noxious stimulus-induced analgesia (NSIA) is related to activity at inhibitory synapses in the spinal cord.

    PubMed

    Tambeli, Claudia H; Levine, Jon D; Gear, Robert W

    2009-06-01

    The duration of noxious stimulus-induced antinociception (NSIA) has been shown to outlast the pain stimulus that elicited it, however, the mechanism that determines the duration of analgesia is unknown. We evaluated the role of spinal excitatory and inhibitory receptors (NMDA, mGluR(5), mu-opioid, GABA(A), and GABA(B)), previously implicated in NSIA initiation, in its maintenance. As in our previous studies, the supraspinal trigeminal jaw-opening reflex (JOR) in the rat was used for nociceptive testing because of its remoteness from the region of drug application, the lumbar spinal cord. NSIA was reversed by antagonists for two inhibitory receptors (GABA(B) and mu-opioid) but not by antagonists for either of the two excitatory receptors (NMDA and mGluR(5)), indicating that NSIA is maintained by ongoing activity at inhibitory synapses in the spinal cord. Furthermore, spinal administration of the GABA(B) agonist baclofen mimicked NSIA in that it could be blocked by prior injection of the mu-opioid receptor antagonist H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP) in nucleus accumbens. CTAP also blocked baclofen antinociception when administered in the spinal cord. We conclude that analgesia induced by noxious stimulation is maintained by activity in spinal inhibitory receptors.

  19. In vivo stimulus-induced vasodilation occurs without IP3 receptor activation and may precede astrocytic calcium increase

    PubMed Central

    Nizar, Krystal; Uhlirova, Hana; Tian, Peifang; Saisan, Payam A.; Cheng, Qun; Reznichenko, Lidia; Weldy, Kimberly L.; Steed, Tyler C.; Sridhar, Vishnu B.; MacDonald, Christopher L.; Cui, Jianxia; Gratiy, Sergey L.; Sakadžić, Sava; Boas, David A.; Beka, Thomas I.; Einevoll, Gaute T.; Chen, Ju; Masliah, Eliezer; Dale, Anders M.; Silva, Gabriel A.; Devor, Anna

    2013-01-01

    Calcium-dependent release of vasoactive gliotransmitters is widely assumed to trigger vasodilation associated with rapid increases in neuronal activity. Inconsistent with this hypothesis, intact stimulus-induced vasodilation was observed in inositol 1,4,5-triphosphate (IP3) type-2 receptor (R2) knockout (KO) mice, in which the primary mechanism of astrocytic calcium increase – the release of calcium from intracellular stores following activation of an IP3-dependent pathway – is lacking. Further, our results in wild type (WT) mice indicate that in vivo onset of astrocytic calcium increase in response to sensory stimulus could be considerably delayed relative to the simultaneously measured onset of arteriolar dilation. Delayed calcium increases in WT mice were observed in both astrocytic cell bodies and perivascular endfeet. Thus, astrocytes may not play a role in the initiation of blood flow response, at least not via calcium-dependent mechanisms. Moreover, an increase in astrocytic intracellular calcium was not required for normal vasodilation in the IP3R2-KO animals. PMID:23658179

  20. Selective uptake and degradation of c-Fos and v-Fos by rat liver lysosomes.

    PubMed

    Aniento, F; Papavassiliou, A G; Knecht, E; Roche, E

    1996-07-15

    The transcription factor c-Fos is a short-lived protein and calpains and ubiquitin-dependent systems have been proposed to be involved in its degradation. In this report, we consider a lysosomal degradation pathway for c-Fos. Using a cell-free assay, we have found that freshly isolated lysosomes can take up and degrade c-Fos with high efficiency. v-Fos, the oncogenic counterpart of c-Fos, can also be taken up by lysosomes, yet the amount of incorporated protein is much lower. c-Fos uptake is independent of its phosphorylation state but it appears to be regulated by dimerization with differentially phosphorylated forms of c-Jun, while v-Fos escapes this regulation. Moreover, we show that c-Fos is immunologically detected in lysosomes isolated from the liver of rats treated with the protease inhibitor leupeptin. Altogether, these results suggest that lysosomes can also participate in the selective degradation of c-Fos in rat liver.

  1. Two oncogenes, v-fos and v-ras, cooperate to convert normal keratinocytes to squamous cell carcinoma

    SciTech Connect

    Greenhalgh, D.A.; Welty, D.J.; Player, A.; Yuspa, S.H. )

    1990-01-01

    Previous studies have been implicated the ras{sup Ha} oncogene in the initiation of skin carcinogenesis and the fos oncogene in malignant progression of premalignant skin cell lines. To determine if these two oncogenes are sufficient to convert normal keratinocytes to cancer cells, freshly isolated mouse keratinocytes were coinfected with replication-defective ({psi}-2) v-ras{sup Ha} and v-fos viruses in culture. When tested in nude mice within several days of infection, v-fos/v-ras{sup Ha}-coinfected keratinocytes produced squamous cell carcinomas. Introduction of v-fos alone resulted in normal or hyperplastic skin, whereas v-ras{sup Ha} alone produced squamous papillomas. These results indicate that two oncogenes are sufficient to produce the malignant phenotype in epidermal cells. Furthermore, they clearly link the fos oncogene with malignant conversion. Since fos acts as a transcriptional regulator of other genes, malignant conversion may be an indirect consequence of the overexpression of the fos-encoded protein leading to a change in the expression of fos-controlled cellular genes.

  2. Activation of cFos in ovine fetal corticotropin-releasing hormone neurons at the time of parturition.

    PubMed

    Hoffman, G E; McDonald, T; Shedwick, R; Nathanielsz, P W

    1991-12-01

    The ovine fetal pituitary adrenal axis plays an important role in parturition. While lesions of the paraventricular nucleus (PVN) in the fetal sheep delay parturition, suggesting that the PVN is necessary for the processes that lead up to parturition, evidence for stimulation of PVN neurons at time of delivery/labor is lacking. The present study tested the hypothesis that activation (evidenced by expression of the oncogene product cFos) of a specific population of PVN neurons containing CRH accompanies labor in sheep. Monitoring of uterine electromyogram activity determined the onset of labor. The brains of nine fetuses (removed by ceasarian section under anesthesia at gestational ages of 125-145 days) and four newborn sheep were perfused and stained for cFos and CRH. Before labor, less than 5% of fetal paraventricular CRH neurons expressed cFos. Verification that the CRH neurons could express cFos when adequately stimulated was made by exposing an additional group of four preterm animals (125 days gestational age) to hypoxemia; the six untreated fetuses served as controls. Activation of the CRH neurons by hypoxemia produced a rapid induction of cFos in CRH neurons, with approximately 50% of the cells strongly expressing cFos protein 1 h after exposure to hypoxia. At the time uterine contractions were first detected, 70% of CRH neurons expressed cFos, and cFos immunoreactivity persisted until just after birth. cFos staining declined rapidly, reaching prelabor levels in some animals by 2-3 h after birth. These data are consistent with the hypothesis that in addition to their potential role in the processes that initiate parturition over several days before birth, fetal CRH neurons are stimulated during labor, and termination of stimulation probably occurs rapidly after delivery.

  3. Effect of acute and chronic bilateral visual deafferentation on c-Fos immunoreactivity in the visual system of adult rats.

    PubMed

    Wiedmann, Rhea; Rosahl, Steffen K; Brinker, Thomas; Samii, Madjid; Nakamura, Makoto

    2013-09-01

    In our study we examined acute and chronic changes in c-Fos expression patterns in the visual system of the rat after complete visual deafferentation. In 20 male Lewis rats, the retro-bulbar part of the optic nerve was sectioned bilaterally. Ten animals underwent c-Fos immunohistochemistry after 3 days and 10 animals after 3 weeks examining time-dependent changes. The control group consisted of 10 animals, which did not undergo any surgical manipulation. c-Fos expression in the rat visual system experienced significant changes after acute and chronic bilateral complete visual deafferentation. Acute decrease in c-Fos level was observed in the ventral lateral geniculate nucleus, intergeniculate leaflet, superficial gray layer of the superior colliculus and layers IV and V of the primary visual cortex. After chronic deafferentation, c-Fos expression was also found to be decreased in the optic and deep layers of the superior colliculus and layer VI of the primary visual cortex. No change in c-Fos expression was observed in the dorsal lateral geniculate nucleus and layers I, II and III of the primary visual cortex. This work shows that secondary complete blindness does not lead to uniform decrease in c-Fos levels in all subcortical and cortical brain regions related to vision. These findings provide important information concerning expression of the immediate-early gene product c-Fos in secondary blind rodent models. It may further serve as a relevant baseline finding when electrical stimulation of the visual system is performed, aiding the assessment of visual neuroprosthesis using c-Fos as a functional mapping tool when evaluating different stimulus parameters in blind rodent models.

  4. Persistent c-fos induction by nicotine in developing rat brain regions: interaction with hypoxia.

    PubMed

    Trauth, J A; Seidler, F J; McCook, E C; Slotkin, T A

    1999-01-01

    Prenatal nicotine exposure evokes postnatal CN