Synapse (New York, N.y.)最新文献

{"title":"Fluoxetine administration modulates the cytoskeletal microtubular system in the rat hippocampus.","authors":"Massimiliano Bianchi,&nbsp;Ajit J Shah,&nbsp;Kevin C F Fone,&nbsp;Alan R Atkins,&nbsp;Lee A Dawson,&nbsp;Christian A Heidbreder,&nbsp;Mark E Hows,&nbsp;Jim J Hagan,&nbsp;Charles A Marsden","doi":"10.1002/syn.20614","DOIUrl":"https://doi.org/10.1002/syn.20614","url":null,"abstract":"<p><p>A number of studies suggest that stressful conditions can induce structural alterations in the hippocampus and that antidepressant drugs may prevent such deficits. In particular, the selective serotonin reuptake inhibitor (SSRI) fluoxetine was more effective in modulating different neuronal plasticity phenomena and related molecules in rat hippocampus. Cytoskeletal microtubule dynamics are fundamental to dendrites and axons remodeling, leading to the hypothesis that fluoxetine may affect the microtubular system. However, despite reports of stress-induced alterations in microtubule dynamics by different stressors, only few studies investigated the in vivo effects of antidepressants on microtubules in specific rat brain regions. The present study investigated the dose-related (1, 5, or 10 mg/kg i.p.) effects of acute and chronic (21 days) treatments with fluoxetine on the ratio of hippocampal alpha-tubulin isoforms which is thought to reflect microtubule dynamics. Western Blot analysis was used to quantify alpha-tubulin isoforms, high-performance liquid chromatography and fluorescence detection was used to measure ex vivo monoamine metabolism. The results showed that acute fluoxetine increased the stable forms acetylated and detyrosinated alpha-tubulin. Conversely, chronic fluoxetine decreased acetylated alpha-tubulin, indicative of increased microtubule dynamics. The neuron-specific Delta2-Tubulin was increased by chronic fluoxetine indicating neuronal involvement in the observed cytoskeletal changes. Although acute and chronic fluoxetine similarly altered serotonin metabolism by inhibition of serotonin reuptake, this showed no apparent correlation to the cytoskeletal perturbations. Our findings demonstrate that fluoxetine administration modulates microtubule dynamics in rat hippocampus. The cytoskeletal effect exerted by fluoxetine may eventually culminate in promoting events of structural neuronal remodeling.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"359-64"},"PeriodicalIF":2.3,"publicationDate":"2009-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20614","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39988741","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":"Subchronic racemic gamma vinyl-GABA produces weight loss in Sprague Dawley and Zucker fatty rats.","authors":"Amy DeMarco,&nbsp;Reema M Dalal,&nbsp;Milan Kahanda,&nbsp;Uma Mullapudi,&nbsp;Jessica Pai,&nbsp;Crystie Hammel,&nbsp;Courtney N B Liebling,&nbsp;Vinal Patel,&nbsp;Jonathan D Brodie,&nbsp;Wynne K Schiffer,&nbsp;Stephen L Dewey,&nbsp;Stefanie D Aquilina","doi":"10.1002/syn.20555","DOIUrl":"https://doi.org/10.1002/syn.20555","url":null,"abstract":"<p><p>Given the growing obesity epidemic, pressure to develop an effective pharmacologic treatment is mounting. Following the completion of a randomized, double-blind, placebo controlled trial as well as two small open label trials, gamma vinyl-GABA (GVG) has been shown to be safe and effective for treating cocaine and/or methamphetamine dependence. In an extension of these findings, the present study examined whether GVG could produce weight loss in adolescent as well as genetically obese animals. Specifically, adolescent Sprague Dawley and adolescent and adult Zucker fatty rats received GVG at various doses (75-300 mg/kg, i.p., racemic) for treatment periods lasting no longer than 14 consecutive days. GVG produced significant weight loss in a dose dependent fashion in all groups. These effects were marked, as average decreases of 12-20% of original body weight were observed. These findings suggest that GVG may be useful as a treatment for obesity. Further, that these results occurred in genetically obese animals offers the possibility that GVG may even help manage severe obesity resulting from binge-eating, a disorder involving food consumption in a pattern similar to the compulsive drug-seeking behavior observed in cocaine and methamphetamine dependent subjects.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"870-2"},"PeriodicalIF":2.3,"publicationDate":"2008-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20555","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27611656","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":"Extracellular dopamine induces the oxidative toxicity of SH-SY5Y cells.","authors":"Yuhua Jiang,&nbsp;Lin Pei,&nbsp;Shupeng Li,&nbsp;Min Wang,&nbsp;Fang Liu","doi":"10.1002/syn.20554","DOIUrl":"https://doi.org/10.1002/syn.20554","url":null,"abstract":"<p><p>Dopamine-induced neuronal cytotoxicity has been proposed as a leading pathological mechanism underlying many neuronal degenerative disorders including Parkinson disease. Various hypotheses have been proposed including oxidative stress and dopamine (DA)-induced intracellular signal disorder via DA D1 and D2 receptors. The exact mechanism involved in this process is far from clear. In this study, employing a neuronal blastoma cell line, SH-SY5Y, we tried to elucidate the roles of these different suggested mechanisms in this pathological process. The results showed that DA induced cell toxicity in a dose- and time-dependent way. Selective D1 and D2 DA receptor antagonist could not block the cytotoxic effects, whereas reductive reagent ascorbic acid but not GSH could effectively rescue the cell death, suggesting that DA-induced cell toxicity was caused by an extracellular oxidative stress. This was further supported by the enhancing effects of DA transporter blocker, GBR, which could increase the cell death when pretreated. Finally, ascorbic acid could also protect SY5Y cells from DA-induced cellular apoptotic signal changes including PARP and P53. Our studies suggested that DA exerted its cytotoxic effects via an extracellular metabolism, whereas intracellular transportation could reduce its oxidative stress. Cytotoxicity effects induced by extracellular DA could be protected by reductive agents as ascorbic acid. These results help to broaden our understanding of the mechanisms of DA-induced cell death and may provide potentially therapeutical alternative for the neurodegenerative disorders.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"797-803"},"PeriodicalIF":2.3,"publicationDate":"2008-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20554","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27611788","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":"Aripiprazole and its human metabolite OPC14857 reduce, through a presynaptic mechanism, glutamate release in rat prefrontal cortex: possible relevance to neuroprotective interventions in schizophrenia.","authors":"Tsung-Tsair Yang,&nbsp;Su-Jane Wang","doi":"10.1002/syn.20548","DOIUrl":"https://doi.org/10.1002/syn.20548","url":null,"abstract":"<p><p>Aripiprazole is a novel atypical antipsychotic drug with neuroprotective properties. As excessive glutamate release is now considered to be part of the pathophysiology of schizophrenia, the objective of this study was to use an in vitro assay system to investigate the effect of aripiprazole and its human metabolite OPC14857 on the release of endogenous glutamate from isolated nerve terminals (synaptosomes), freshly prepared from rat prefrontal cortex. Both aripiprazole and OPC13857 potently inhibited 4-aminopyridine (4-AP)-evoked glutamate release in a concentration-dependent manner. Inhibition of glutamate release by aripiprazole and OPC13857 was associated with a reduction of 4AP-evoked Na+ influx and depolarization, as well as downstream elevation of cytoplasmic free calcium concentration mediated via N- and P/Q-type voltage-dependent Ca2+ channels (VDCCs). Release induced by direct Ca2+ entry with Ca2+ ionophore (ionomycin) was unaffected by aripiprazole or OPC13857, indicating that the inhibitory effect of aripiprazole or OPC13857 is not due to directly interfering with the release process at some point subsequent to Ca2+ influx. In addition, the dopamine D2 receptor antagonist haloperidol and the 5-HT 1A receptor antagonist WAY100635 all effectively blocked the aripiprazole or OPC13857-mediated inhibition of 4-AP-evoked glutamate release. Moreover, aripiprazole or OPC13857 modulation of 4-AP-evoked glutamate release appears to involve a protein kinase A (PKA) signaling cascade, insofar as pretreatment of synaptosomes with the PKA inhibitor H89 suppressed the inhibitory effect of aripiprazole or OPC13857. Together, these results suggest that aripiprazole and its human metabolite OPC14857 inhibit glutamate release from rat prefrontocortical nerve terminals, likely by the activation of dopamine D2 and 5-HT 1A receptors, which subsequently results in the reduction of nerve terminal excitability and downstream VDCC activation through a signaling cascade involving PKA. These actions of aripiprazole may contribute to its neuroprotective effect in excitotoxic injury.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"804-18"},"PeriodicalIF":2.3,"publicationDate":"2008-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20548","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27611789","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":"Phencyclidine and glutamate agonist LY379268 stimulate dopamine D2High receptors: D2 basis for schizophrenia.","authors":"Philip Seeman,&nbsp;Hong-Chang Guan","doi":"10.1002/syn.20561","DOIUrl":"https://doi.org/10.1002/syn.20561","url":null,"abstract":"<p><p>It has previously been reported that the glutamate ionotropic antagonist phencyclidine directly inhibits the release of prolactin in anterior pituitary cells in culture, suggesting that phencyclidine has a dopamine (DA)-like action on prolactin-releasing cells. It has also been reported that the glutamate metabotropic agonist LY379268 can stimulate the incorporation of [35S]GTP-gamma-S into DA D2Long receptors. The present study was done to examine whether such glutamatergic drugs had similar actions on the DA D2Short receptor. The present results show that phencyclidine, ketamine, and LY379268 also stimulated the incorporation of [35S]GTP-gamma-S into D2Short receptors. The proportion of D2Long and D2Short receptors existing in the high-affinity state were both markedly reduced by NaCl. While phencyclidine and LY379268 each stimulated the incorporation of GTP-gamma-S into D2Long and D2Short receptors, this stimulation was reduced by NaCl, with D2Short being much more sensitive than D2Long to the inhibition by NaCl. The binding of phencyclidine and LY379268 to D2High receptors in vivo was directly confirmed by the i.v. injection of phencyclidine and LY379268 in which 50% inhibited the binding of [3H]PHNO to the striatum ex vivo at 0.25 and 1.5 mg/kg, respectively. The results confirm that glutamate agonists and antagonists have a significant affinity for DA D2High receptors. The psychotogenic action of phencyclidine may stem from a combination or synergistic action of glutamate receptor antagonism and DA D2 agonism. In addition, the antipsychotic clinical action of LY379268 congeners such as LY404039 may be related to a combined or synergistic action of glutamate receptor stimulation together with a partial DA agonist action that reduces endogenous DA neurotransmission.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"819-28"},"PeriodicalIF":2.3,"publicationDate":"2008-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20561","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27611790","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":"Glutamate receptor subunits expression in memory-associated brain structures: regional variations and effects of aging.","authors":"Ping Liu,&nbsp;Paul F Smith,&nbsp;Cynthia L Darlington","doi":"10.1002/syn.20563","DOIUrl":"https://doi.org/10.1002/syn.20563","url":null,"abstract":"<p><p>We investigated regional variations and the effects of aging on the expression of the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) receptor subunits in several memory-associated structures using Western blotting. In young adult rats, NR1, NR2A, and GluR2 levels varied between the hippocampus and parahippocampal region and between the subregions of the hippocampus. When a comparison was made between young (4-month-old) and aged (24-month-old) rats, significant decreases in NR1 expression were found in the aged ventral hippocampus and the entorhinal and postrhinal cortices. There were significant decreases in NR2A expression in the aged parahippocampal region, but not in the hippocampus. The expression of the GluR2 subunit was significantly reduced in the ventral hippocampus and the postrhinal cortex. A dramatic decrease in NR1 and GluR2 expression was found in the aged CA2/3 and CA1, respectively, but there were no significant age-related changes in NR2A expression. All three subunits were expressed at a similar level in the two age groups in the prefrontal cortex. These results suggest differential expression and effects of aging on NMDA and AMPA receptor subunits in memory-associated brain structures.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"834-41"},"PeriodicalIF":2.3,"publicationDate":"2008-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20563","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27611194","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":"Elevated synaptophysin I in the prefrontal cortex of human chronic alcoholics.","authors":"Richard Henriksson,&nbsp;Alexander Kuzmin,&nbsp;Anna Okvist,&nbsp;Clive Harper,&nbsp;Donna Sheedy,&nbsp;Therese Garrick,&nbsp;Tatjana Yakovleva,&nbsp;Georgy Bakalkin","doi":"10.1002/syn.20559","DOIUrl":"https://doi.org/10.1002/syn.20559","url":null,"abstract":"<p><p>Convergent lines of evidence suggest potentiation of glutamatergic synapses after chronic ethanol exposure, and indicate that the presynaptic effect hereof is on modulators of synaptic strength rather than on executors of glutamate release. To address this hypothesis in the context of ethanol dependence in humans, we used semiquantitative immunoblotting to compare the immunoreactivities of synaptophysin I, syntaxin 1A, synaptosome-associated protein 25, and vesicle-associated membrane protein in the prefrontal and motor cortices between chronic alcoholics and control subjects. We found a region-specific elevation in synaptophysin I immunoreactivity in the prefrontal cortex of alcoholics, but detected no significant differences between the groups in the immunoreactivities of the other three proteins. Our findings are consistent with an effect of repeated ethanol exposure on modulators of synaptic strength but not on executors of glutamate release, and suggest a role for synaptophysin I in the enduring neuroplasticity in the prefrontal cortical glutamate circuitry that is associated with ethanol dependence.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"829-33"},"PeriodicalIF":2.3,"publicationDate":"2008-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20559","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27611787","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}

{"title":"Dopamine modulating drugs influence striatal (+)-[11C]DTBZ binding in rats: VMAT2 binding is sensitive to changes in vesicular dopamine concentration.","authors":"Junchao Tong,&nbsp;Alan A Wilson,&nbsp;Isabelle Boileau,&nbsp;Sylvain Houle,&nbsp;Stephen J Kish","doi":"10.1002/syn.20573","DOIUrl":"https://doi.org/10.1002/syn.20573","url":null,"abstract":"<p><p>Binding of (+)-[11C]DTBZ (dihydrotetrabenazine) to the striatal vesicular monoamine transporter (VMAT2) is widely considered to be a stable marker of dopamine neurone integrity. However, we now find that specific binding of a tracer dose of (+)-[11C]DTBZ is modestly increased in rat striatum following dopamine depletion with alpha-methyl-p-tyrosine (alpha-MPT, +14%) or d-amphetamine (d-AMPH, 20 mg/kg, +12%) and decreased following dopamine elevation with gamma-hydroxybutyrate (GHB, -16%) or levodopa (-20%). We suggest that in vivo (+)-[11C]DTBZ binding in imaging studies is subject to competition by vesicular dopamine and, in this respect, is not a \"stable\" dopamine biomarker as is generally assumed.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"873-6"},"PeriodicalIF":2.3,"publicationDate":"2008-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20573","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27611681","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":"Cocaine abuse and sensitization of striatal dopamine transmission: a critical review of the preclinical and clinical imaging literature.","authors":"Rajesh Narendran,&nbsp;Diana Martinez","doi":"10.1002/syn.20566","DOIUrl":"https://doi.org/10.1002/syn.20566","url":null,"abstract":"<p><p>Much effort has been devoted in the preclinical addiction literature to understanding the phenomenon of sensitization, an enhanced dopaminergic response in the nucleus accumbens that occurs after repeated exposure to psychostimulant drugs. Although sensitization has been reported in preclinical studies, studies of sensitization in humans measuring behavioral and physiological responses have been mixed and inconclusive. However, imaging studies with positron emission tomography (PET) and single photon emission computed tomography (SPECT) using a stimulant challenge to induce dopamine (DA) release provide a unique opportunity to probe DA transmission in cocaine dependent human subjects. In contrast to the basic science literature that predicted sensitization, three independent cohorts have shown a blunted DA response, or the opposite of sensitization, in human cocaine dependent subjects. This article reviews the methodological differences between the preclinical and clinical PET studies that have investigated DA sensitization in order to address the discrepancy between the human and animal literature.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"851-69"},"PeriodicalIF":2.3,"publicationDate":"2008-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20566","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27611680","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":"Chandelier cartridges in the prefrontal cortex are reduced in isolation reared rats.","authors":"Claire Bloomfield,&nbsp;Sarah J French,&nbsp;Declan N C Jones,&nbsp;Charlie Reavill,&nbsp;Eric Southam,&nbsp;Jackie Cilia,&nbsp;Susan Totterdell","doi":"10.1002/syn.20521","DOIUrl":"https://doi.org/10.1002/syn.20521","url":null,"abstract":"<p><p>Chandelier neurons are a subset of parvalbumin containing cortical interneurons characterised by their preferential targeting of the axon initial segments of pyramidal neurons. They have been the focus of recent interest after evidence that the arrays of boutons are reduced in the prefrontal cortex of schizophrenic patients, post mortem. Since one chandelier neuron may innervate the axon initial segments of several hundred pyramidal neurons, it is hypothesized that their special connectivity might facilitate synchronisation of cortical outputs and play a key role in working memory. Disruption in their function is therefore thought to play a potentially important role in cortically associated symptoms of schizophrenia. Using the isolation rearing animal model of schizophrenia, we examined immunolabelling for GABA-transporter 1, a marker of chandelier cartridges. We show that the numbers of arrays of chandelier axons are reduced by 36% in the ventral prelimbic cortex of isolation-reared rats, compared with their socially-housed litter mates. This mimics findings in the PFC of schizophrenic patients where GAT-1-positive cartridges are reduced by 40% and is the first study to demonstrate changes in chandelier cartridges in an animal model of schizophrenia.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"628-31"},"PeriodicalIF":2.3,"publicationDate":"2008-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20521","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27468946","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}