Synapse最新文献

{"title":"Synaptic dysfunction in schizophrenia.","authors":"Emre Mısır,&nbsp;Güvem Gümüş Akay","doi":"10.1002/syn.22276","DOIUrl":"https://doi.org/10.1002/syn.22276","url":null,"abstract":"<p><p>Schizophrenia is a chronic disease presented with psychotic symptoms, negative symptoms, impairment in the reward system, and widespread neurocognitive deterioration. Disruption of synaptic connections in neural circuits is responsible for the disease's development and progression. Because deterioration in synaptic connections results in the impaired effective processing of information. Although structural impairments of the synapse, such as a decrease in dendritic spine density, have been shown in previous studies, functional impairments have also been revealed with the development of genetic and molecular analysis methods. In addition to abnormalities in protein complexes regulating exocytosis in the presynaptic region and impaired vesicle release, especially, changes in proteins related to postsynaptic signaling have been reported. In particular, impairments in postsynaptic density elements, glutamate receptors, and ion channels have been shown. At the same time, effects on cellular adhesion molecular structures such as neurexin, neuroligin, and cadherin family proteins were detected. Of course, the confusing effect of antipsychotic use in schizophrenia research should also be considered. Although antipsychotics have positive and negative effects on synapses, studies indicate synaptic deterioration in schizophrenia independent of drug use. In this review, the deterioration in synapse structure and function and the effects of antipsychotics on the synapse in schizophrenia will be discussed.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 5","pages":"e22276"},"PeriodicalIF":2.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9796807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationships of in vivo brain norepinephrine transporter and age, BMI, and gender.","authors":"Sheida Koohsari, Faranak Ebrahimian Sadabad, Brian Pittman, Jean-Dominque Gallezot, Richard E Carson, Christopher H van Dyck, Chiang-Shan R Li, Marc N Potenza, David Matuskey","doi":"10.1002/syn.22279","DOIUrl":"10.1002/syn.22279","url":null,"abstract":"<p><p>Previous research reported an age-related decline in brain norepinephrine transporter (NET) using (S, S)-[11C]O-methylreboxetine ([11C]MRB) as a radiotracer. Studies with the same tracer have been mixed in regard to differences related to body mass index (BMI). Here, we investigated potential age-, BMI-, and gender-related differences in brain NET availability using [11C]MRB, the most selective available radiotracer. Forty-three healthy participants (20 females, 23 males; age range 18-49 years), including 12 individuals with normal/lean weight, 15 with overweight, and 16 with obesity were scanned with [11C]MRB using a positron emission tomography (PET) high-resolution research tomograph (HRRT). We evaluated binding potential (BP_ND ) in brain regions with high NET availability using multilinear reference tissue model 2 (MRTM2) with the occipital cortex as a reference region. Brain regions were delineated with a defined anatomic template applied to subjects' structural MR scans. We found a negative association between age and NET availability in the locus coeruleus, raphe nucleus, and hypothalamus, with a 17%, 19%, and 14% decrease per decade, respectively, in each region. No gender or BMI relationships with NET availability were observed. Our findings suggest an age-related decline, but no BMI- or gender-related differences, in NET availability in healthy adults.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 5","pages":"e22279"},"PeriodicalIF":1.6,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10416616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10039040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Date palm spathe extract reverses chronic stress-induced changes in dendritic arborization in the amygdala and impairment of hippocampal long-term potentiation.","authors":"Mohammadmehdi Hadipour,&nbsp;Gholam Hossein Meftahi,&nbsp;Gila Pirzad Jahromi","doi":"10.1002/syn.22278","DOIUrl":"https://doi.org/10.1002/syn.22278","url":null,"abstract":"<p><p>Chronic restraint stress induces anxiety-like behaviors and emotional abnormalities via an alteration of synaptic remodeling in the amygdala and the hippocampus. Given that the date palm spathe has been shown to have neuroprotective effects on different experimental models, this study aimed to address whether the date palm spathe extract (hydroalcoholic extract of date palm spathe [HEDPP]) can reduce chronic restraint stress-induced behavioral, electrophysiological, and morphological changes in the rat model. Thirty-two male Wistar rats (weight 200-220 g) were randomly divided into control, stress, HEDPP, and stress + HEDPP for 14 days. Animals were submitted to restraint stress for 2 h per day for 14 consecutive days. The animals of the HEDPP and stress + HEDPP groups were supplemented with HEDPP (125 mg/kg) during these 14 days, 30 min before being placed in the restraint stress tube. We used passive avoidance, open-field test, and field potential recording to assess emotional memory, anxiety-like behavioral and long-term potentiation in the CA1 region of the hippocampus, respectively. Moreover, Golgi-Cox staining was used to investigate the amygdala neuron dendritic arborization. Results showed that stress induction was associated with behavioral changes (anxiety-like behavioral and emotional memory impairment), and the administration of HEDPP effectively normalized these deficits. HEDPP remarkably amplified the slope and amplitude of mean-field excitatory postsynaptic potentials (fEPSPs) in the CA1 area of the hippocampus in stressed rats. Chronic restraint stress significantly decreased the dendritic arborization in the central and basolateral nucleus of the amygdala neuron. HEDPP suppressed this stress effect in the central nucleus of the amygdala. Our findings indicated that HEDPP administration improves stress-induced learning impairment and memory and anxiety-like behaviors by preventing adverse effects on synaptic plasticity in the hippocampus and amygdala.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 5","pages":"e22278"},"PeriodicalIF":2.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9800235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Information","authors":"","doi":"10.1002/syn.22240","DOIUrl":"https://doi.org/10.1002/syn.22240","url":null,"abstract":"","PeriodicalId":22131,"journal":{"name":"Synapse","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2023-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44613815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective mechanism of human umbilical cord mesenchymal stem cell-derived extracellular vesicles improving the phenotype polarization of microglia via the PI3K/AKT/Nrf2 pathway in vascular dementia.","authors":"Pengwei Wang,&nbsp;Tingting Yi,&nbsp;Senlin Mao,&nbsp;Mingjie Li","doi":"10.1002/syn.22268","DOIUrl":"https://doi.org/10.1002/syn.22268","url":null,"abstract":"<p><p>Vascular dementia (VaD) is a prevalent cause of dementia after Alzheimer's disease. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUCMSC-Evs) are critical for VaD treatment. We explored the mechanism of hUCMSC-Evs in VaD. VaD rat model was established by bilateral common carotid artery ligation and hUCMSC-Evs were extracted. VaD rats were injected with Evs through the tail vein. Rat neurological scores, neural behaviors, memory and learning abilities, brain tissue pathological changes, and neurological impairment were evaluated by Zea-Longa method, Morris water maze tests, HE staining, and ELISA (through acetylcholine [ACH] and dopamine [DA] assessment). Microglia M1/M2 polarization was detected by immunofluorescence staining. Pro-/anti-inflammatory factor levels in brain tissue homogenate, oxidative stress-related indicators, and p-PI3K, PI3K, p-AKT, AKT, and Nrf2 protein levels were determined by ELISA, kits, and Western blot. VaD rats were jointly treated with PI3K phosphorylation inhibitor Ly294002 and hUCMSC-Evs. VaD rats manifested increased neurological function injury scores, decreased cognitive function and learning ability, abnormal brain structure, obvious inflammatory infiltration, diminished ACH and DA levels, increased microglial cells and M1-polarized cells, M1/M2 polarization ratio, inflammation, and oxidative stress. hUCMSC-Evs alleviated the neurological damage of VaD rats, inhibited M1 polarization, inflammation, and oxidative stress of microglial cells in brain tissues of VaD rats, and activated the PI3K/AKT/Nrf2 pathway. Ly294002 partially averted the effects of hUCMSC-Evs on microglial polarization, inflammation, and oxidative stress. Briefly, hUCMSC-Evs activated the PI3K/AKT/Nrf2 pathway and inhibited microglial M1 polarization, inflammation, and oxidative stress, thus protecting VaD rat nerve functions.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 4","pages":"e22268"},"PeriodicalIF":2.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9518410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[¹¹ C]PBB3 binding in Aβ(-) or Aβ(+) corticobasal syndrome.","authors":"Zsolt Cselényi,&nbsp;Johan Wallin,&nbsp;Jonathan Tjerkoski,&nbsp;Björn Bloth,&nbsp;Samuel Svensson,&nbsp;Inger Nennesmo,&nbsp;Dan Sunnemark,&nbsp;Vesna Jelic,&nbsp;Lars Farde,&nbsp;Per Svenningsson","doi":"10.1002/syn.22269","DOIUrl":"https://doi.org/10.1002/syn.22269","url":null,"abstract":"<p><p>Corticobasal syndrome (CBS) is associated with 4-repeat tauopathy and/or Alzheimer's disease pathologies. To examine tau and amyloid-β (Aβ) deposits in CBS patients using positron emission tomography (PET). Eight CBS patients and three healthy individuals lacking amyloid pathology underwent PET with [¹¹ C]PBB3 for tau imaging, and [¹¹ C]AZD2184 for Aβ. Subcortical and cortical binding of [¹¹ C]PBB3 was compared between Aβ(-) and Aβ(+) CBS patients and reference group. Postmortem analysis was done in one CBS patient. Three CBS patients were considered Aβ(+). Total binding was higher in all patients compared to the reference group. Similar regional binding profiles of [¹¹ C]PBB3 in Aβ(+) and Aβ(-) CBS patients were found. Elevated [¹¹ C]PBB3 binding in pallidum was observed in all CBS patients. Cortical [¹¹ C]PBB3 binding was higher in Aβ(+) compared to Aβ(-) patients. Postmortem analysis of a CBS patient revealed corticobasal degeneration neuropathology and [¹¹ C]PBB3 autofluorescence in some tau-positive structures. [¹¹ C]PBB3 is elevated in CBS patients with binding in relevant areas capturing some, but not all, 4-repeat tauopathy in CBS.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 4","pages":"e22269"},"PeriodicalIF":2.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9506874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upregulation of SLITRK5 in patients with epilepsy and in a rat model.","authors":"Yan Liu,&nbsp;Linming Zhang,&nbsp;Mingda Ai,&nbsp;Di Xia,&nbsp;Hongyu Chen,&nbsp;Ruijing Pang,&nbsp;Rong Mei,&nbsp;Lianmei Zhong,&nbsp;Ling Chen","doi":"10.1002/syn.22266","DOIUrl":"10.1002/syn.22266","url":null,"abstract":"<p><p>SLIT and NTRK-like protein-5 (SLITRK5) is one of the six members of SLITRK protein family, which is widely expressed in central nervous system (CNS). In brain, SLITRK5 plays important roles in neurite outgrowth, dendritic branching, neuron differentiation, synaptogenesis, and signal transmission of neurons. Epilepsy is a common, chronic neurological disorder characterized by recurrent spontaneous seizures. The pathophysiological mechanism of epilepsy remains unclear. Neuronal apoptosis, abnormal nerve excitatory transmission, and synaptic remodeling are thought to be involved in the development of epilepsy. To explore whether there is a potential relationship between SLITRK5 and epilepsy, we investigated the expression and distribution of SLITRK5 in patients with temporal lobe epilepsy (TLE) and a rat model of epilepsy. We collected cerebral cortex samples from patients with drug-refractory temporal lobe epilepsy, and a rat model of epilepsy induced by lithium chloride/pilocarpine was established. The ways of immunohistochemistry, double-immunofluorescence labeling and western blot have been used in our study to research the expression and distribution of SLITRK5 in the temporal lobe epilepsy patients and epilepsy animal model. All of the results have shown that SLITRK5 is mainly localized in the cell cytoplasm of neurons both in patients with TLE and in epilepsy model. In addition, compared with nonepileptic controls, the expression of SLITRK5 was upregulated in the temporal neocortex of TLE patients. And both in the temporal neocortex and hippocampus of pilocarpine-induced epilepsy rats, the expression of SLITRK5 was increased at 24 h after status epilepticus (SE), with a relatively high level within 30 days, and reached the peak on the 7th day after SE. Our preliminary results revealed that SLITRK5 may have a potential relationship with epilepsy, which may be a foundation for the further study of the underlying mechanism between SLITRK5 and epilepsy and the therapeutic targets of antiepileptic drugs.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 4","pages":"e22266"},"PeriodicalIF":2.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10069646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neonatal olfactory bulbectomy induces anxiety-related behavior and modifies dopaminergic receptor expression in post-pubertal rats.","authors":"Gonzalo Flores,&nbsp;María de Jesús Gómez-Villalobos,&nbsp;Tommaso Iannitti,&nbsp;Julio César Morales-Medina","doi":"10.1002/syn.22272","DOIUrl":"https://doi.org/10.1002/syn.22272","url":null,"abstract":"<p><p>Olfaction is a complex physiological process producing effects in the central nervous system (CNS) and implicated in emotional processes. Indeed, the olfactory bulbs (OB) send projections to various CNS regions including the nucleus accumbens (NAcc) and caudate-putamen (CPu). Both the NAcc and CPu receive important dopaminergic input. Emerging evidence suggests that dopamine (DA) is related to anxiety-related behaviors. Therefore, we aimed to investigate the consequences of neonatal olfactory bulbectomy (nOBX) to anxiety-related behavior as assayed in the elevated plus maze (EPM) as well as the expression of dopaminergic receptors (D1-like, D2-like, and D3) in the NAcc and CPu at pre- and post-pubertal ages in the rat. The results show that nOBX increased the number of entries in the open arm of the EPM post-pubertally, suggesting an anxiolytic-related effect. nOBX increased the D2-like binding in the NAcc shell and D3 binding in the NAcc core pre-pubertally. At post-pubertal ages, the D3 binding was reduced at the olfactory tubercle and islands of Calleja in nOBX rats. Alterations in the DA receptor expression may be one mechanism responsible for the observed behavioral modifications in nOBX rats.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 4","pages":"e22272"},"PeriodicalIF":2.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9516392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The increase of Nrf2 m6A modification induced by FTO downregulation promotes hippocampal neuron injury and aggravates the progression of epilepsy in a rat model.","authors":"Mao-Qiang Tian,&nbsp;Juan Li,&nbsp;Xiao-Mei Shu,&nbsp;Chang-Hui Lang,&nbsp;Jing Chen,&nbsp;Long-Ying Peng,&nbsp;Wen-Ting Lei,&nbsp;Chang-Jian Yang","doi":"10.1002/syn.22270","DOIUrl":"https://doi.org/10.1002/syn.22270","url":null,"abstract":"<p><p>Epilepsy is a common chronic neurological disorder characterized by widespread neuronal death. The purpose of this study was to investigate the role of nuclear factor erythroid 2-related factor 2 (Nrf2) m6A methylation in epilepsy. To create epileptic models, the rats were given Lithium chloride and pilocarpine, and isolated primary rat hippocampal neurons were cultured in an Mg2⁺ -free medium. The frequency of seizures was recorded in the epilepsy group of rats. The functional tests included TUNEL, MTT, and flow cytometry. Mechanistically, RNA degradation assay, RNA immunoprecipitation, and methylated RNA immunoprecipitation were performed. In epileptic models, Nrf2 and fat mass and obesity-associated (FTO) levels were downregulated, whereas YT521-B homology (YTH) domain family protein 2 (YTHDF2) was upregulated. Additionally, in epileptic models, there was a rise in the m6A methylation level of Nrf2 mRNA. Overexpressing FTO increased cell viability and reduced apoptosis, but Nrf2 interference reversed these effects. Meanwhile, FTO overexpression decreased the m6A methylation of Nrf2 mRNA. Moreover, YTHDF2 bound to Nrf2 mRNA and decreased its stability. Furthermore, FTO overexpression reduced seizure frequency in rats and inhibited hippocampal neuron apoptosis via lowering the m6A methylation level of Nrf2 mRNA. Overexpressing FTO reduced m6A methylation of Nrf2 mRNA, increased cell viability, suppressed apoptosis, and slowed the progression of epileptic diseases, which is linked to YTHDF2 binding to m6A-modified Nrf2 and promoting its degradation, as well as downregulating Nrf2 expression in hippocampal neurons.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 4","pages":"e22270"},"PeriodicalIF":2.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9518968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic resveratrol administration reduces oxidative stress and brain cell loss and improves memory of recognition in old rats.","authors":"Daniel Juarez,&nbsp;Ivan Arteaga,&nbsp;Haisha Cortes,&nbsp;Ruben Vazquez-Roque,&nbsp;Gustavo Lopez-Lopez,&nbsp;Gonzalo Flores,&nbsp;Samuel Treviño,&nbsp;Jorge Guevara,&nbsp;Alfonso Diaz","doi":"10.1002/syn.22271","DOIUrl":"https://doi.org/10.1002/syn.22271","url":null,"abstract":"<p><p>The cognitive functions of people over 60 years of age have been diminished, due to the structural and functional changes that the brain has during aging. The most evident changes are at the behavioral and cognitive level, with decreased learning capacity, recognition memory, and motor incoordination. The use of exogenous antioxidants has been implemented as a potential pharmacological option to delay the onset of brain aging by attenuating oxidative stress and neurodegeneration. Resveratrol (RSVL) is a polyphenol present in various foods, such as red fruits, and drinks, such as red wine. This compound has shown great antioxidant capacity due to its chemical structure. In this study, we evaluated the effect of chronic RSVL treatment on oxidative stress and cell loss in the prefrontal cortex, hippocampus, and cerebellum of 20-month-old rats, as well as its impact on recognition memory and motor behavior. Rats treated with RSVL showed an improvement in locomotor activity and in short- and long-term recognition memory. Likewise, the concentration of reactive oxygen species and lipid peroxidation decreased significantly in the group with RSVL, coupled with an improvement in the activity of the antioxidant system. Finally, with the help of hematoxylin and eosin staining, it was shown that chronic treatment with RSVL prevented cell loss in the brain regions studied. Our results demonstrate the antioxidant and neuroprotective capacity of RSVL when administered chronically. This strengthens the proposal that RSVL could be an important pharmacological option to reduce the incidence of neurodegenerative diseases that affect older adults.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 4","pages":"e22271"},"PeriodicalIF":2.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9567809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}