Synapse (New York, N.y.)最新文献

{"title":"Amyloid imaging in aged and young macaques with [11C]PIB and [18F]FDDNP.","authors":"Akihiro Noda,&nbsp;Yoshihiro Murakami,&nbsp;Shingo Nishiyama,&nbsp;Dai Fukumoto,&nbsp;Sosuke Miyoshi,&nbsp;Hideo Tsukada,&nbsp;Shintaro Nishimura","doi":"10.1002/syn.20508","DOIUrl":"https://doi.org/10.1002/syn.20508","url":null,"abstract":"<p><p>[11C]PIB and [18F]FDDNP were examined on five aged and five young adult male rhesus macaques using positron emission tomography. Both tracers showed increased accumulation in the striatum, thalamus, cingulate and pons in the aged group. Compared to [11C]PIB, [18F]FDDNP showed higher accumulation in the cortical regions of aged animals as well as young animals. Although [18F]FDDNP may have possible usefulness for imaging, including other proteins, [11C]PIB may be better for amyloid imaging owing to lower non-specific binding.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"472-5"},"PeriodicalIF":2.3,"publicationDate":"2008-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20508","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27340650","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":"Voltage-dependence of the human dopamine D2 receptor.","authors":"Kristoffer Sahlholm,&nbsp;Johanna Nilsson,&nbsp;Daniel Marcellino,&nbsp;Kjell Fuxe,&nbsp;Peter Arhem","doi":"10.1002/syn.20509","DOIUrl":"https://doi.org/10.1002/syn.20509","url":null,"abstract":"<p><p>The dopamine D2 receptor plays a critical role in activity-dependent synaptic plasticity in the striatum, and regulates the transitions between different states of electrical activity. The D2 receptor is the main target for antipsychotics, and its affinity towards dopamine has been shown to be increased in psychotic patients. Recently, voltage-sensitivity has been reported for the ligand binding and G protein-coupling properties of some neurotransmitter receptors, raising the question whether the D2 receptor is also regulated by voltage. Our present electrophysiology data from Xenopus oocytes indicate that the D2 receptor is indeed voltage-sensitive. Comparing concentration-response relationships for the activation of G protein-coupled inward rectifier potassium (GIRK) channels via D2 receptor stimulation by quinpirole or dopamine at -80 and at +40 mV revealed rightward shifts upon depolarisation of nearly tenfold, for both agonists. Our results are likely to bear relevance to the function of the D2 receptor in gating synaptic input and in regulating plasticity.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"476-80"},"PeriodicalIF":2.3,"publicationDate":"2008-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20509","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27340651","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":"Small effect of dopamine release and no effect of dopamine depletion on [18F]fallypride binding in healthy humans.","authors":"Vanessa L Cropley,&nbsp;Robert B Innis,&nbsp;Pradeep J Nathan,&nbsp;Amira K Brown,&nbsp;Janet L Sangare,&nbsp;Alicja Lerner,&nbsp;Yong Hoon Ryu,&nbsp;Kelly E Sprague,&nbsp;Victor W Pike,&nbsp;Masahiro Fujita","doi":"10.1002/syn.20506","DOIUrl":"https://doi.org/10.1002/syn.20506","url":null,"abstract":"<p><p>Molecular imaging has been used to estimate both drug-induced and tonic dopamine release in the striatum and most recently extrastriatal areas of healthy humans. However, to date, studies of drug-induced and tonic dopamine release have not been performed in the same subjects. This study performed positron emission tomography (PET) with [18F]fallypride in healthy subjects to assess (1) the reproducibility of [18F]fallypride and (2) both D-amphetamine-induced and alpha-methyl-p-tyrosine (AMPT)-induced changes in dopamin release on [(18)F]fallypride binding in striatal and extrastriatal areas. Subjects underwent [18F]fallypride PET studies at baseline and following oral D-amphetamine administration (0.5 mg/kg) and oral AMPT administration (3 g/70 kg/day over 44 h). Binding potential (BP) (BP(ND)) of [18F]fallypride was calculated in striatal and extrastriatal areas using a reference region method. Percent change in regional BP(ND) was computed and correlated with change in cognition and mood. Test-retest variability of [18F]fallypride was low in both striatal and extrastriatal regions. D-Amphetamine significantly decreased BP(ND) by 8-14% in striatal subdivisions, caudate, putamen, substantia nigra, medial orbitofrontal cortex, and medial temporal cortex. Correlation between change in BP(ND) and verbal fluency was seen in the thalamus and substantia nigra. In contrast, depletion of endogenous dopamine with AMPT did not effect [18F]fallypride BP(ND) in both striatum and extrastriatal regions. These findings indicate that [18F]fallypride is useful for measuring amphetamine-induced dopamine release, but may be unreliable for estimating tonic dopamine levels, in striatum and extrastriatal regions of healthy humans.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"399-408"},"PeriodicalIF":2.3,"publicationDate":"2008-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20506","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27339547","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":"Recovery of bipedal locomotion in bonnet macaques after spinal cord injury: footprint analysis.","authors":"R Suresh Babu,&nbsp;A Namasivayam","doi":"10.1002/syn.20513","DOIUrl":"https://doi.org/10.1002/syn.20513","url":null,"abstract":"<p><p>Analysis of the recovery of gait after spinal cord injury has been widely demonstrated in rat and cat models using different behavioral tests and scoring systems. The present investigation was aimed to quantitatively analyze the degree of functional recovery in bipedal locomotion of bonnet macaques after inflicting spinal cord hemisection lesion. To measure the degree of locomotor recovery, we recorded four gait variables, viz., tip of opposite foot (TOF), print length (PL), toe spread (TS), and intermediary toes (IT) using a footprint analyzing technique. Monkeys were trained preoperatively to perform the monopedal hop or bipedal locomotion on runways. Footprints of trained monkeys were recorded using the nontoxic ink and white paper before and after surgery. Surgical hemisection was induced unilaterally in the right side of spinal cord at T12-L1 level of trained monkeys. In hemiplegic monkeys, initially there was a substantial decrease in TOF and PL variables of the paretic limb, which then gradually increased for longer duration and reached the near presurgical values by the 7th and 5th postoperative month, respectively. In contrast to TOF and PL, the recovery of TS and IT variables was quicker, which dramatically increased at first and then slowly recovered to levels not significantly different from the corresponding preoperative values by the 4th postoperative month. The nonparetic limb has also showed mild alterations in all footprint variables but reached the normal values much faster compared to the paretic limb. The alterations in footprint variables of hemiplegic monkeys were examined for a postoperative period of up to 1 year. The findings of this study suggest that the mechanisms underlying locomotor recovery of lesioned macaques may be correlated to the mature function of spinal pattern generator for locomotion under the impact of residual descending and afferent connections. Further, this study also indicates the functional contribution of progressive strengthening of undamaged nerve fibers through a collateral sprouts/synaptic plasticity formed in partially lesioned cord of macaques.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"432-47"},"PeriodicalIF":2.3,"publicationDate":"2008-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20513","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27339549","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":"Memory reconsolidation of cocaine-associated context requires nitric oxide signaling.","authors":"Yossef Itzhak,&nbsp;Karen L Anderson","doi":"10.1002/syn.20446","DOIUrl":"https://doi.org/10.1002/syn.20446","url":null,"abstract":"<p><p>Recent studies suggest that long-term memory (LTM) is labile because retrieval of such memories may undergo a reconsolidation process which is vulnerable to disruption. Nitric oxide (NO) is a retrograde messenger involved in synaptic plasticity and LTM. In the present study the role of NO in reconsolidation of LTM of cocaine-associate context was investigated in wild type (WT) and neuronal nitric oxide synthase (nNOS) deficient mice (knockout; KO). LTM of cocaine-associated context was established in both WT and nNOS KO mice by conditioned place preference learning. Subsequently, the retrieval of place preference in WT mice was challenged by either saline or the selective nNOS inhibitor 7-nitroindazole, and retrieval of place preference in KO mice was challenged by either saline or the NO-donor molsidomine. Results suggest that in the absence of nNOS activity, particularly during the reconsolidation phase, LTM of cocaine-associated context is extinguished.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"1002-5"},"PeriodicalIF":2.3,"publicationDate":"2007-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20446","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40961094","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":"Treatment of Parkinson disease with C17.2 neural stem cells overexpressing NURR1 with a recombined republic-deficit adenovirus containing the NURR1 gene.","authors":"Qing-Jun Li,&nbsp;Ya-Mei Tang,&nbsp;Jun Liu,&nbsp;Dao-You Zhou,&nbsp;Xiang-Pen Li,&nbsp;Song-Hua Xiao,&nbsp;Dong-Xing Jian,&nbsp;Yi-Gang Xing","doi":"10.1002/syn.20449","DOIUrl":"https://doi.org/10.1002/syn.20449","url":null,"abstract":"<p><p>To study the potential benefit of the NURR1 gene in Parkinson's disease (PD), we constructed a recombinant republic-deficit adenovirus containing the NURR1 gene (Ad-NURR1) and expressed it in transplanted neural stem cells (NSC). Ad-NURR1 was constructed, and NURR1 mRNA and protein expression were identified by in situ hybridization and western blot analysis, respectively. The identified NURR1 protein could directly or indirectly induce NSC differentiation into neurons. To identify a potential therapeutic use for the transfected NSCs, cells were transplanted into 6-hydroxydopamine lesioned rats. Histopathological and behavioral alterations were evaluated via immunohistochemistry and the ration test, respectively, in rats transplanted with NSCs with or without the Ad-NURR1 adenovirus. The Ad-NURR1 construct effectively expressed the NURR1 protein, which could directly or indirectly induce NSC differentiation into neurons. Both histopathological and behavioral alterations were seen in rats treated with NSCs with or without the Ad-NURR1 construct, although in the case of the latter, the benefits were more robust. These results suggest a potential therapeutic benefit for Ad-NURR1-expressing cells in the treatment of PD. The Ad-NURR1 modification induced NSC differentiation and therefore represents a potential therapy for PD.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"971-7"},"PeriodicalIF":2.3,"publicationDate":"2007-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20449","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40981907","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":"The number of dopaminergic cells is increased in the olfactory bulb of monkeys chronically exposed to MPTP.","authors":"Silvia Belzunegui,&nbsp;Waldy San Sebastián,&nbsp;Pablo Garrido-Gil,&nbsp;Amaya Izal-Azcárate,&nbsp;Marianne Vázquez-Claverie,&nbsp;Berta López,&nbsp;Irene Marcilla,&nbsp;José Luis Lanciego,&nbsp;Maria Rosario Luquin","doi":"10.1002/syn.20451","DOIUrl":"https://doi.org/10.1002/syn.20451","url":null,"abstract":"<p><p>We investigated the impact of the nigrostriatal lesion on the olfactory tyrosine hydroxylase-immunoreactive (TH-ir) cells in monkeys. The majority of these TH-ir cells appeared in the glomerular layer of the olfactory bulb and many were immature but functional dopaminergic neurons. In parkinsonian monkeys the number of olfactory dopaminergic neurons increased up to 100% as compared to controls, but their phenotype did not change. This increased TH-ir cell population might be a direct consequence of the nigral cell loss and contribute to the hyposmia reported by Parkinson's disease patients.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"1006-12"},"PeriodicalIF":2.3,"publicationDate":"2007-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20451","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40961095","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":"Behavioral and histopathological consequences of paraquat intoxication in mice: effects of alpha-synuclein over-expression.","authors":"P O Fernagut, C B Hutson, S M Fleming, N A Tetreaut, J Salcedo, E Masliah, M F Chesselet","doi":"10.1002/syn.20456","DOIUrl":"10.1002/syn.20456","url":null,"abstract":"<p><p>Genetic variability in the alpha-synuclein gene and long-term exposure to the pesticide paraquat constitute possible risk factors for sporadic Parkinson's disease. The goal of the present study was to further characterize the effects of paraquat in mice as a model of Parkinson's disease and to determine whether it acted synergistically with alpha-synuclein over-expression to cause nigrostriatal cell death or dysfunction. Paraquat (10 mg/kg i.p.) was administered once a week for 3 weeks to mice over-expressing human alpha-synuclein under the Thy1 promoter and their wild-type littermates. The effect of paraquat on catecholaminergic neurons was reminiscent of that of Parkinson's disease, with preferential loss of dopaminergic neurons in the ventral tier of the substantia nigra pars compacta and loss of tyrosine hydroxylase staining in the locus coeruleus. alpha-Synuclein over-expression did not increase paraquat-induced cell loss, and paraquat did not worsen the behavioral deficits observed in the transgenic mice. However, paraquat markedly increased proteinase-K-resistant alpha-synuclein aggregates in substantia nigra of the transgenic mice. The data further validate the use of paraquat to model Parkinson's disease in mice and show that although paraquat and alpha-synuclein over-expression act synergistically to increase protein aggregation in vivo, this interaction does not result in short-term neuroprotection or increased vulnerability of nigrostriatal neurons.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"991-1001"},"PeriodicalIF":0.0,"publicationDate":"2007-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3097512/pdf/nihms294482.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40981909","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":"Neurophysiological actions of methylphenidate in the primary somatosensory cortex.","authors":"Candice Drouin,&nbsp;Dorothy Wang,&nbsp;Barry D Waterhouse","doi":"10.1002/syn.20454","DOIUrl":"https://doi.org/10.1002/syn.20454","url":null,"abstract":"<p><p>As a catecholamine reuptake blocker, methylphenidate (MPH) enhances noradrenergic transmission and is likely to influence norepinephrine actions in sensory systems. To characterize neurophysiological actions of MPH in the primary somatosensory (SI) cortex, we recorded basal and whisker deflection-evoked discharge of infragranular sensory cortical neurons, before and after intraperitoneal administrations of saline and MPH (5 mg/kg) in halothane-anesthetized rats. MPH had two types of actions on sensory-evoked neuronal responses in the SI cortex, depending on the initial amplitude of the sensory response. When the whisker deflection induced a small excitatory response under control conditions, MPH significantly increased the amplitude of the response by approximately 40%. When the whisker stimulation induced a large excitatory response under control conditions, MPH did not significantly alter the amplitude of the response, but significantly decreased the duration and the peak latency of the response, so that the response was more focused. These neurophysiological actions of MPH may underlie some of the beneficial effects of the drug on sensory processing and attention.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"985-90"},"PeriodicalIF":2.3,"publicationDate":"2007-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20454","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40960743","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":"Antiparkinson therapeutic potencies correlate with their affinities at dopamine D2(High) receptors.","authors":"Philip Seeman","doi":"10.1002/syn.20453","DOIUrl":"https://doi.org/10.1002/syn.20453","url":null,"abstract":"<p><p>To determine whether antiparkinson dopamine agonists preferentially act on the high-affinity or the low-affinity states of dopamine D1 and D2 receptors, the agonist potencies were obtained by competition against [(3)H]SCH23390 for D1(High) and D1(Low), and against [(3)H]domperidone for D2(High) and D2(Low). N-propylnorapomorphine and cabergoline were the most potent at D2(High), with dissociation constants of 0.18 and 0.36 nM, respectively. Other agonists had D2(High)K(i) values of 0.52 nM for quinagolide, 0.6 nM for (+)PHNO, 0.9 for bromocriptine, 1.8 nM for apomorphine, 2.4 nM for pergolide, 3 nM for quinpirole, and 6.2 nM for lergotrile. There was a clear correlation between the K(i) values at D2(High) and their therapeutic concentrations in the plasma water, as derived from the known concentrations after correction for the fraction bound to the human plasma proteins. The data suggest that D2(High) is the primary and common target for the antiparkinson action of dopamine agonists. Bromocriptine, cabergoline, lergotrile, pergolide, and pramipexole had no affinity for D1(High), consistent with the clinical observations that the D2-selective bromocriptine and pramipexole elicit low levels of dyskinesia.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"1013-8"},"PeriodicalIF":2.3,"publicationDate":"2007-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20453","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40960976","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}