Sarah A Eisenstein, Ryan Bogdan, Latisha Love-Gregory, Nadia S Corral-Frías, Jonathan M Koller, Kevin J Black, Stephen M Moerlein, Joel S Perlmutter, Deanna M Barch, Tamara Hershey
{"title":"Prediction of striatal D2 receptor binding by DRD2/ANKK1 TaqIA allele status.","authors":"Sarah A Eisenstein, Ryan Bogdan, Latisha Love-Gregory, Nadia S Corral-Frías, Jonathan M Koller, Kevin J Black, Stephen M Moerlein, Joel S Perlmutter, Deanna M Barch, Tamara Hershey","doi":"10.1002/syn.21916","DOIUrl":"https://doi.org/10.1002/syn.21916","url":null,"abstract":"<p><p>In humans, the A1 (T) allele of the dopamine (DA) D2 receptor/ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1) TaqIA (rs1800497) single nucleotide polymorphism has been associated with reduced striatal DA D2/D3 receptor (D2/D3R) availability. However, radioligands used to estimate D2/D3R are displaceable by endogenous DA and are nonselective for D2R, leaving the relationship between TaqIA genotype and D2R specific binding uncertain. Using the positron emission tomography (PET) radioligand, (N-[(11) C]methyl)benperidol ([(11) C]NMB), which is highly selective for D2R over D3R and is not displaceable by endogenous DA, the current study examined whether DRD2/ANKK1 TaqIA genotype predicts D2R specific binding in two independent samples. Sample 1 (n = 39) was composed of obese and nonobese adults; sample 2 (n = 18) was composed of healthy controls, unmedicated individuals with schizophrenia, and siblings of individuals with schizophrenia. Across both samples, A1 allele carriers (A1+) had 5 to 12% less striatal D2R specific binding relative to individuals homozygous for the A2 allele (A1-), regardless of body mass index or diagnostic group. This reduction is comparable to previous PET studies of D2/D3R availability (10-14%). The pooled effect size for the difference in total striatal D2R binding between A1+ and A1- was large (0.84). In summary, in line with studies using displaceable D2/D3R radioligands, our results indicate that DRD2/ANKK1 TaqIA allele status predicts striatal D2R specific binding as measured by D2R-selective [(11) C]NMB. These findings support the hypothesis that DRD2/ANKK1 TaqIA allele status may modify D2R, perhaps conferring risk for certain disease states.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"418-31"},"PeriodicalIF":2.3,"publicationDate":"2016-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21916","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34531199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rajat Sandhir, Namita Mahajan, Arpit Mehrotra, Aanchal Aggarwal, Aditya Sunkaria
{"title":"4-hydroxy tempo improves mitochondrial and neurobehavioral deficits in experimental model of Huntington's disease.","authors":"Rajat Sandhir, Namita Mahajan, Arpit Mehrotra, Aanchal Aggarwal, Aditya Sunkaria","doi":"10.1002/syn.21793","DOIUrl":"https://doi.org/10.1002/syn.21793","url":null,"abstract":"<p><p>Mitochondrial dysfunctions have been implicated in the progression of Huntington's disease (HD). To date, several free radical scavengers have been tested in experimental HD, but only a few have shown promise. Although most antioxidants rapidly reduce ROS but in the process they are oxidized, which limits their ability to protect. Therefore, in the present study we employed a potent recycling antioxidant, 4-hydroxy tempo (4-HT), because it can reinstate its reduced state even after its oxidation during scavenging of ROS. Female Wistar rats were administered 3-nitropropionic acid (3-NP) and/or 4-HT for 21 days, after which animals were subjected to biochemical and behavioral assessments. Our results showed that 4-HT treatment significantly attenuated the 3-NP induced decrease in the activities of mitochondrial electron transport chain enzymes. In addition, 4-HT administration restored the increased nitrite and lipid peroxidation levels. Apart from this, 4-HT also attenuated the 3-NP induced decrease in superoxide dismutase and catalase activities. Further, 4-HT administration resulted in significant improvement in 3-NP induced cognitive and motor impairments. Taken together, the results of the study demonstrate that 4-HT is beneficial in 3-NP induced model of HD and thus could be a potential therapeutic agent in management of this disease.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"128-38"},"PeriodicalIF":2.3,"publicationDate":"2015-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21793","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32886402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bone marrow stromal cells transplantation combined with ultrashortwave therapy promotes functional recovery on spinal cord injury in rats.","authors":"Yan-Mei Yin, Yu Lu, Li-Xin Zhang, Guang-Ping Zhang, Zhi-Qiang Zhang","doi":"10.1002/syn.21802","DOIUrl":"https://doi.org/10.1002/syn.21802","url":null,"abstract":"<p><strong>Objective: </strong>This study investigated the effects of bone marrow stromal cells (BMSCs) transplantation combined with low dose ultrashortwave (USW) radiation on functional recovery from spinal cord injury (SCI) in rats. Female Sprague-Dawley rats (n = 64) were randomly divided into five groups: sham-operated, as well as control, USW, BMSCs, and BMSCs + USW that were subjected to spinal cord contusion. BMSCs were transplanted into rats in the BMSCs and BMSCs+USW groups, while those in the USW and BMSCs + USW were exposed to radiation; Basso-Beattie-Bresnahan (BBB) tests were performed before the operation and at 1-week intervals after SCI for 7 weeks. 7 weeks later, animals were assessed footprint pattern, motor evoked potential (MEP), histological features, and expression of the ED1 and glial fibrillary acidic protein (GFAP), markers of activated macrophages and astrocytes, respectively, in the lesion area. BBB scores were higher in the BMSCs + USW than in the BMSCs and control groups. The USW and BMSCs + USW groups had improved coordination compared to the BMSCs and control groups (P < 0.01 and P < 0.001, respectively, vs. control). BMSCs + USW rats had a lower ratio of lesion/cavity to spinal cord area than the other injured rats, and also had expression of GFAP in transplanted BMSCs. All treatment groups had lower ED1 expression and MEP latency than the controls (P < 0.01 and P < 0.001, respectively). The results indicate that BMSCs transplantation combined with USW radiation is more effective than either treatment alone in promoting functional recovery after SCI, possibly due to concomitant suppression of inflammation and spinal cord repair.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"139-47"},"PeriodicalIF":2.3,"publicationDate":"2015-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21802","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32985707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francisco García-Oscos, Oswaldo Torres-Ramírez, Lu Dinh, Luis Galindo-Charles, Elsy Arlene Pérez Padilla, Juan Carlos Pineda, Marco Atzori, Humberto Salgado
{"title":"Activation of 5-HT receptors inhibits GABAergic transmission by pre-and post-synaptic mechanisms in layer II/III of the juvenile rat auditory cortex.","authors":"Francisco García-Oscos, Oswaldo Torres-Ramírez, Lu Dinh, Luis Galindo-Charles, Elsy Arlene Pérez Padilla, Juan Carlos Pineda, Marco Atzori, Humberto Salgado","doi":"10.1002/syn.21794","DOIUrl":"https://doi.org/10.1002/syn.21794","url":null,"abstract":"<p><p>The specific mechanisms by which serotonin (5-HT) modulates synaptic transmission in the auditory cortex are still unknown. In this work, we used whole-cell recordings from layer II/III of pyramidal neurons in rat brain slices to characterize the influence of 5-HT on inhibitory synaptic activity in the auditory cortex after pharmacological blockade of excitatory glutamatergic transmission. We found that bath application of 5-HT (5 µM) reduced the frequency and amplitude of both spontaneous and miniature inhibitory postsynaptic currents (IPSCs), reduced the amplitude of evoked IPSCs, and enhanced facilitation of paired pulse ratio (PPR), suggesting presynaptic inhibition. To determine which the serotonin receptors were involved in this effect, we studied the influence of specific 5-HT receptor agonists and antagonists on ɣ-aminobutyric acid (GABA)ergic synaptic transmission. The inhibiting influence of 5-HT in the GABAergic synaptic activity was mimicked by using the selective agonists of the 5-HT1A and 5-HT2A receptors, 8(OH)-DPAT (10 µM) and DOI (10 µM), respectively; and it was prevented by their respective antagonists NAN-190 (1 µM) and ritanserin (1 μM). Furthermore, the application of the selective agonist of 5-HT1A receptors, 8-(OH)-DPAT (10 µM), produced PPR facilitation, while DOI application (5-HT2A agonist) did not change the PPR. Moreover, the 5-HT2A agonist reduced the amplitude of the IPSCs evoked by application of the selective GABA agonist, muscimol. These results suggest a presynaptic and postsynaptic reduction of GABAergic transmission mediated by 5-HT1A and 5-HT2A serotonergic receptors, respectively.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"115-27"},"PeriodicalIF":2.3,"publicationDate":"2015-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21794","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32886474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Philippe Huot, Tom H Johnston, Susan H Fox, Jonathan M Brotchie
{"title":"Pioglitazone may impair L-DOPA anti-parkinsonian efficacy in the MPTP-lesioned macaque: results of a pilot study.","authors":"Philippe Huot, Tom H Johnston, Susan H Fox, Jonathan M Brotchie","doi":"10.1002/syn.21801","DOIUrl":"https://doi.org/10.1002/syn.21801","url":null,"abstract":"In this pilot study, pioglitazone, an agonist of the peroxisome proliferator-activated receptor gamma (PPAR-γ) used in the treatment of diabetes mellitus, was administered to dyskinetic parkinsonian macaques. Pioglitazone alleviated L-DOPA-induced dyskinesia, but impaired L-DOPA anti-parkinsonian efficacy. These results suggest caution when administering pioglitazone to patients with advanced Parkinson's disease.","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"99-102"},"PeriodicalIF":2.3,"publicationDate":"2015-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21801","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32950193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guadalupe Muñoz-Arenas, Francisco Paz-Bermúdez, Ana Báez-Cordero, René Caballero-Florán, Brenda González-Hernández, Benjamín Florán, I Daniel Limón
{"title":"Cannabinoid CB1 receptors activation and coactivation with D2 receptors modulate GABAergic neurotransmission in the globus pallidus and increase motor asymmetry.","authors":"Guadalupe Muñoz-Arenas, Francisco Paz-Bermúdez, Ana Báez-Cordero, René Caballero-Florán, Brenda González-Hernández, Benjamín Florán, I Daniel Limón","doi":"10.1002/syn.21796","DOIUrl":"https://doi.org/10.1002/syn.21796","url":null,"abstract":"<p><p>The cannabinoid CB1 (CB1R) and dopaminergic D2 (D2R) receptors modify GABAergic transmission in the globus pallidus. Although dopaminergic denervation produces changes in the expression and supersensitization of these receptors, the consequences of these changes on GABAergic neurotransmission are unknown. The aim of this study was to show the effects of CB1R and D2R activation and coactivation on the uptake and release of [(3) H]GABA in the globus pallidus of hemiparkinsonian rats as well as their effects on motor behavior. The activation of CB1R blocked GABA uptake and decreased GABA release in the globus pallidus in the dopamine denervated side, whereas the co-activation of CB1R-D2R increased GABA release and had no effect on GABA uptake. A microinjection of the CB1R agonist ACEA into the globus pallidus ipsilaterally to a 6-OHDA lesion potentiated turning behavior that was induced by methamphetamine. However, a microinjection of the D2R agonist quinpirole did not modify this behavior, and a microinjection of a mixture of CB1R and D2R agonists significantly potentiated turning behavior. The behavioral effects produced after the activation of the CB1R and the co-activation of CB1R and D2R can be explained by increased GABAergic neurotransmission produced by a block of GABA uptake and an increase in the release of GABA in the globus pallidus, respectively.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"103-14"},"PeriodicalIF":2.3,"publicationDate":"2015-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21796","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32919637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of (+)-pentazocine on the antinociceptive effects of (-)-pentazocine in mice.","authors":"Tomohisa Mori, Junpei Ohya, Toshimasa Itoh, Yuya Ise, Masahiro Shibasaki, Tsutomu Suzuki","doi":"10.1002/syn.21799","DOIUrl":"https://doi.org/10.1002/syn.21799","url":null,"abstract":"<p><p>Previous studies have shown that sigma-1 receptor chaperone (Sig-1R) ligands can regulate pain-related behaviors, and Sig-1R itself can regulate μ-opioid receptor functions as well as signal transduction. Even though (±)-pentazocine has been used clinically for the treatment of pain through opioid receptors, (+)-pentazocine is known to be a selective Sig-1R agonist. To the best of our knowledge, there is no information available regarding the involvement of Sig-1R agonistic action in the antinociceptive effects of (±)-pentazocine. Therefore, the present study was designed to investigate the effects of (+)-pentazocine on the antinociceptive effects of (-)-pentazocine in mice. Both and (-)-pentazocine induced biphasic antinociceptive effects as measured by the warm-plate test. The early phase, but not the delayed phase, of the antinociceptive effects induced by (-)-pentazocine, which are mediated by the activation of μ-opioid receptors, were suppressed by pretreatment with (+)-pentazocine. These results suggest that the innate antinociceptive action of (±)-pentazocine could be marginally reduced by the effects of (+)-pentazocine, but (+)-pentazocine can suppress the antinociceptive effects of (-)-pentazocine at certain time points.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"166-71"},"PeriodicalIF":2.3,"publicationDate":"2015-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21799","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32952017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jussi Lehto, Mika M Hirvonen, Jarkko Johansson, Jukka Kemppainen, Pauliina Luoto, Tarja Naukkarinen, Vesa Oikonen, Eveliina Arponen, Juha Rouru, Jukka Sallinen, Harry Scheinin, Lauri Vuorilehto, Sjoerd J Finnema, Christer Halldin, Juha O Rinne, Mika Scheinin
{"title":"Validation of [(11) C]ORM-13070 as a PET tracer for alpha2c -adrenoceptors in the human brain.","authors":"Jussi Lehto, Mika M Hirvonen, Jarkko Johansson, Jukka Kemppainen, Pauliina Luoto, Tarja Naukkarinen, Vesa Oikonen, Eveliina Arponen, Juha Rouru, Jukka Sallinen, Harry Scheinin, Lauri Vuorilehto, Sjoerd J Finnema, Christer Halldin, Juha O Rinne, Mika Scheinin","doi":"10.1002/syn.21798","DOIUrl":"https://doi.org/10.1002/syn.21798","url":null,"abstract":"<p><p>This study explored the use of the α2C -adrenoceptor PET tracer [(11) C]ORM-13070 to monitor α2C -AR occupancy in the human brain. The subtype-nonselective α2 -AR antagonist atipamezole was administered to eight healthy volunteer subjects to determine its efficacy and potency (Emax and EC50 ) at inhibiting tracer uptake. We also explored whether the tracer could reveal changes in the synaptic concentrations of endogenous noradrenaline in the brain, in response to several pharmacological and sensory challenge conditions. We assessed occupancy from the bound-to-free ratio measured during 5-30 min post injection. Based on extrapolation of one-site binding, the maximal extent of inhibition of striatal [(11) C]ORM-13070 uptake (Emax ) achievable by atipamezole was 78% (95% CI 69-87%) in the caudate nucleus and 65% (53-77%) in the putamen. The EC50 estimates of atipamezole (1.6 and 2.5 ng/ml, respectively) were in agreement with the drug's affinity to α2C -ARs. These findings represent clear support for the use of [(11) C]ORM-13070 for monitoring drug occupancy of α2C -ARs in the living human brain. Three of the employed noradrenaline challenges were associated with small, approximately 10-16% average reductions in tracer uptake in the dorsal striatum (atomoxetine, ketamine, and the cold pressor test; P < 0.05 for all), but insulin-induced hypoglycemia did not affect tracer uptake. The tracer is suitable for studying central nervous system receptor occupancy by α2C -AR ligands in human subjects. [(11) C]ORM-13070 also holds potential as a tool for in vivo monitoring of synaptic concentrations of noradrenaline, but this remains to be further evaluated in future studies.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"172-81"},"PeriodicalIF":2.3,"publicationDate":"2015-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21798","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32924897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yong Wang, Qiao Jun Zhang, Hui Sheng Wang, Tao Wang, Jian Liu
{"title":"Genome-wide microarray analysis identifies a potential role for striatal retrograde endocannabinoid signaling in the pathogenesis of experimental L-DOPA-induced dyskinesia.","authors":"Yong Wang, Qiao Jun Zhang, Hui Sheng Wang, Tao Wang, Jian Liu","doi":"10.1002/syn.21740","DOIUrl":"https://doi.org/10.1002/syn.21740","url":null,"abstract":"<p><p>l-3,4-Dihydroxyphenylalanine (L-DOPA) is the most widely used drug for the treatment of Parkinson's disease. Unfortunately, chronic administration of this dopamine precursor causes L-DOPA-induced dyskinesia (LID), which is a debilitating complication whose pathogenesis remains unclear. In this study, we compared gene expression profiles of sensorimotor striatum tissue derived from LID and non-LID 6-hydroxydopamine-lesioned rats treated with L-DOPA. Total RNA was amplified, transcribed and hybridized to Agilent Whole Rat Genome Oligo Microarray chips. Quantitative real-time reverse transcription PCR was conducted to validate the microarray data. We detected 382 upregulated genes and 115 downregulated genes in LID rats when compared with that of non-LID subjects with Significance Analysis for Microarrays software. The differentially expressed genes were mainly associated with postsynaptic cell membranes, synapses, and neurotransmitter receptors. Gene Set Analysis (GSA) software was used to identify differentially expressed gene ontology (GO) categories and pathways. The GSA found that \"long-term depression\" and \"retrograde endocannabinoid signaling\" pathways were downregulated, whereas a set of lipid metabolism-related GO categories and pathways were upregulated in LID rats compared with non-LID controls. Our study provides further experimental evidence to support the direct correlation between abnormal striatal synaptic plasticity and the induction of LID, and it suggests that the dysfunction of the retrograde endocannabinoid signaling system, a lipid-based neuromodulatory system, and the relevant alteration of the related lipid metabolism processes might play an important role in the pathogenesis of LID.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"332-43"},"PeriodicalIF":2.3,"publicationDate":"2014-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21740","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40285989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ling Chen, Zhihua Wang, Bo Tang, Min Fang, Jie Li, Guojun Chen, Xuefeng Wang
{"title":"Altered expression of c-Abl in patients with epilepsy and in a rat model.","authors":"Ling Chen, Zhihua Wang, Bo Tang, Min Fang, Jie Li, Guojun Chen, Xuefeng Wang","doi":"10.1002/syn.21741","DOIUrl":"https://doi.org/10.1002/syn.21741","url":null,"abstract":"<p><p>c-Abl is an ubiquitous nonreceptor tyrosine kinase involved in signal transduction pathways that promote cytoskeleton remodeling and apoptosis. In brain, c-Abl plays important roles in neuronal development, neurogenesis, neuronal migration, neurite outgrowth, and synaptic plasticity. Neuronal death, gliosis and synaptic remodeling are thought to be involved in the development of epilepsy. Here we investigated the expression pattern and distribution of total and phosphorylated c-Abl in patients with temporal lobe epilepsy (TLE) and a rat model of epilepsy to explore the probable relationship between c-Abl expression and TLE. Double immunolabeling, Immunohistochemistry, and immunoblotting results showed that both total and phosphorylated c-Abl were upregulated in the temporal neocortex of 26 patients with TLE compared to nonepileptic controls. In the temporal neocortex of pilocarpine-treated rats, upregulation of total and phosphorylated c-Abl began 6 hours after seizures, with relatively high expression for 60 days. In the hippocampus of experimental rats, total unphosphorylated c-Abl elevated from 6 hours to 30 days after seizures, the expression then returned to normal levels at 60 days, while phosphorylated c-Abl increased along with the time and maintained at significant high levels for up to 60 days. These results indicate that c-Abl may play an important role in the development of TLE.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"306-16"},"PeriodicalIF":2.3,"publicationDate":"2014-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21741","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40304704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}