Synapse最新文献

{"title":"Triptolide injection reduces Alzheimer's disease-like pathology in mice.","authors":"Rui Mao,&nbsp;Shihao Xu,&nbsp;Guangwen Sun,&nbsp;Yingying Yu,&nbsp;Zhiyi Zuo,&nbsp;Yuanyuan Wang,&nbsp;Kun Yang,&nbsp;Zhen Zhang,&nbsp;Wenqiong Yang","doi":"10.1002/syn.22261","DOIUrl":"https://doi.org/10.1002/syn.22261","url":null,"abstract":"<p><p>Triptolide is an epoxidized diterpene lactone isolated from Tripterygium wilfordii. Studies have shown that triptolide exerts organ-protective effects. However, it remains unknown whether triptolide improves Alzheimer's disease (AD)-like presentations. Thirty healthy 8-week-old male C57BL/6J mice were randomly divided into control (n = 10), model (n = 10), and triptolide (n = 10) groups. Amyloid-β (Aβ)42 was injected bilaterally into the ventricles of mice in the model group. Triptolide was injected intraperitoneally daily after injecting Aβ42 (a total of 30 days) in the triptolide group. Learning and memory were tested using the Morris water maze test. The deposition of Aβ42 in the hippocampus was detected using immunohistochemical staining. In the hippocampus, three synaptic-associated proteins-gephyrin, collybistin, and GABRA₁ -were detected by western blotting. Furthermore, we used ELISA to detect proinflammatory cytokines, including TNF-α and IL-1β, in the blood and hippocampus. Moreover, superoxide dismutase (SOD), malondialdehyde (MDA), and GSH levels were measured using the corresponding kits. We found that triptolide improved spatial learning and memory in AD-like mice. Additionally, triptolide maintained the expression of gephyrin, collybistin, and GABRA₁ and reduced Aβ in these mice. Additionally, triptolide reduced the expression of inflammatory cytokines and decreased oxidative damage in AD-like mice. Our study suggests that triptolide attenuates AD-like changes in the mouse brain.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 3","pages":"e22261"},"PeriodicalIF":2.3,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9617308","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":"Insulin decreases epileptiform activity in rat layer 5/6 prefrontal cortex in vitro.","authors":"N Villalobos,&nbsp;E Ramírez-Sánchez,&nbsp;A Mondragón-García,&nbsp;J Garduño,&nbsp;D Castillo-Rolón,&nbsp;S Trujeque-Ramos,&nbsp;S Hernández-López","doi":"10.1002/syn.22263","DOIUrl":"https://doi.org/10.1002/syn.22263","url":null,"abstract":"<p><p>Accumulating evidence indicates that insulin-mediated signaling in the brain may play important roles in regulating neuronal function. Alterations to insulin signaling are associated with the development of neurological disorders including Alzheimer's disease and Parkinson's disease. Also, hyperglycemia and insulin resistance have been associated with seizure activity and brain injury. In recent work, we found that insulin increased inhibitory GABA_A -mediated tonic currents in the prefrontal cortex (PFC). In this work, we used local field potential recordings and calcium imaging to investigate the effect of insulin on seizure-like activity in PFC slices. Seizure-like events (SLEs) were induced by perfusing the slices with magnesium-free artificial cerebrospinal fluid (ACSF) containing the proconvulsive compound 4-aminopyridine (4-AP). We found that insulin decreased the frequency, amplitude, and duration of SLEs as well as the synchronic activity of PFC neurons evoked by 4-AP. These insulin effects were mediated by the PI3K/Akt signaling pathway and mimicked by gaboxadol (THIP), a δ GABA_A receptor agonist. The effect of insulin on the number of SLEs was partially blocked by L-655,708, an inverse agonist with high selectivity for GABA_A receptors containing the α5 subunit. Our results suggest that insulin reduces neuronal excitability by an increase of GABAergic tonic currents. The physiological relevance of these findings is discussed.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 3","pages":"e22263"},"PeriodicalIF":2.3,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9268434","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":"Spinophilin-dependent regulation of GluN2B-containing NMDAR-dependent calcium influx, GluN2B surface expression, and cleaved caspase expression.","authors":"Asma B Salek, Emily T Claeboe, Ruchi Bansal, Nicolas F Berbari, Anthony J Baucum","doi":"10.1002/syn.22264","DOIUrl":"10.1002/syn.22264","url":null,"abstract":"<p><p>N-methyl-d-aspartate receptors (NMDARs) are calcium-permeable ion channels that are ubiquitously expressed within the glutamatergic postsynaptic density. Phosphorylation of NMDAR subunits defines receptor conductance and surface localization, two alterations that can modulate overall channel activity. Modulation of NMDAR phosphorylation by kinases and phosphatases regulates the amount of calcium entering the cell and subsequent activation of calcium-dependent processes. The dendritic spine enriched protein, spinophilin, is the major synaptic protein phosphatase 1 (PP1) targeting protein. Depending on the substrate, spinophilin can act as either a PP1 targeting protein, to permit substrate dephosphorylation, or a PP1 inhibitory protein, to enhance substrate phosphorylation. Spinophilin limits NMDAR function in a PP1-dependent manner. Specifically, we have previously shown that spinophilin sequesters PP1 away from the GluN2B subunit of the NMDAR, which results in increased phosphorylation of Ser-1284 on GluN2B. However, how spinophilin modifies NMDAR function is unclear. Herein, we utilize a Neuro2A cell line to detail that Ser-1284 phosphorylation increases calcium influx via GluN2B-containing NMDARs. Moreover, overexpression of spinophilin decreases GluN2B-containing NMDAR activity by decreasing its surface expression, an effect that is independent of Ser-1284 phosphorylation. In hippocampal neurons isolated from spinophilin knockout animals, there is an increase in cleaved caspase-3 levels, a marker of calcium-associated apoptosis, compared with wildtype mice. Taken together, our data demonstrate that spinophilin regulates GluN2B containing NMDAR phosphorylation, channel function, and trafficking and that loss of spinophilin enhances neuronal cleaved caspase-3 expression.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 3","pages":"e22264"},"PeriodicalIF":1.6,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9842645","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":"Abnormal [¹⁸ F]NIFENE binding in transgenic 5xFAD mouse model of Alzheimer's disease: In vivo PET/CT imaging studies of α4β2* nicotinic acetylcholinergic receptors and in vitro correlations with Aβ plaques.","authors":"Christopher Liang, Grace A Nguyen, Tram B Danh, Anoopraj K Sandhu, Lusine L Melkonyan, Amina U Syed, Jogeshwar Mukherjee","doi":"10.1002/syn.22265","DOIUrl":"10.1002/syn.22265","url":null,"abstract":"<p><p>Since cholinergic dysfunction has been implicated in Alzheimer's disease (AD), the effects of Aβ plaques on nicotinic acetylcholine receptors (nAChRs) α4β2* subtype were studied using the transgenic 5xFAD mouse model of AD. Using the PET radiotracer [¹⁸ F]nifene for α4β2* nAChRs, in vitro autoradiography and in vivo PET/CT studies in 5xFAD mice were carried out and compared with wild-type (C57BL/6) mice. Ratios of [¹⁸ F]nifene binding in brain regions versus cerebellum (CB) in 5xFAD mice brains were for thalamus (TH) = 17, hippocampus-subiculum = 7, frontal cortex (FC) = 5.5, and striatum = 4.7. [¹²⁵ I]IBETA and immunohistochemistry (IHC) in 5xFAD brain slices confirmed Aβ plaques. Nicotine and acetylcholine displaced [¹⁸ F]nifene in 5xFAD mice (IC₅₀ nicotine = 31-73 nM; ACh = 38-83 nM) and C57BL/6 (IC₅₀ nicotine = 16-18 nM; ACh = 34-55 nM). Average [¹⁸ F]nifene SUVR (CB as reference) in 5xFAD mice was significantly higher in FC = 3.04 compared to C57BL/6 mice FC = 1.92 (p = .001), whereas TH difference between 5xFAD mice (SUVR = 2.58) and C57BL/6 mice (SUVR = 2.38) was not significant. Nicotine-induced dissociation half life (t_1/2 ) of [¹⁸ F]nifene for TH were 37 min for 5xFAD mice and 26 min for C57BL/6 mice. Dissociation half life  for FC in C57BL/6 mice was 77 min , while no dissociation of [¹⁸ F]nifene occurred in the medial prefrontal cortex (mFC) of 5xFAD mice. Coregistration of [¹⁸ F]nifene PET with MR suggested that the mPFC, and anterior cingulate (AC) regions exhibited high uptake in 5xFAD mice compared to C57BL/6 mice. Ex vivo [¹⁸ F]nifene and in vitro [¹²⁵ I]IBETA Aβ plaque autoradiography after in vivo PET/CT scan of 5xFAD mouse brain were moderately correlated (r² = 0.68). In conclusion, 5xFAD mice showed increased non-displaceable [¹⁸ F]nifene binding in mPFC.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 3","pages":"e22265"},"PeriodicalIF":1.6,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10148164/pdf/nihms-1890633.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9735223","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":"Adolescence as a critical period for nandrolone-induced muscular strength in relation to abuse liability, alone and in conjunction with morphine, using accumbal dopamine efflux in freely moving rats.","authors":"Hiroki Kawashima,&nbsp;Yuri Aono,&nbsp;Shigeki Shimba,&nbsp;John L Waddington,&nbsp;Tadashi Saigusa","doi":"10.1002/syn.22262","DOIUrl":"https://doi.org/10.1002/syn.22262","url":null,"abstract":"<p><p>Nandrolone, an anabolic androgenic steroid, is included in the prohibited list of the World Anti-Doping Agency. Drugs of abuse activate brain dopamine neurons and nandrolone has been suspected of inducing dependence. Accordingly, possible critical periods for the effects of nandrolone on muscular strength and dopaminergic activity have been investigated, including the effects of chronically administered nandrolone alone and on morphine-induced increases in dopamine efflux in the nucleus accumbens. Six- or 10-week-old male Sprague-Dawley rats were used. Treatment with nandrolone was initiated in adolescent (6-week-old) and young adult (10-week-old) rats. Nandrolone (5.0 mg/kg s.c.) or sesame oil vehicle was given once daily, on six consecutive days per week, for 3 weeks and then once per day for 4 consecutive days. Nandrolone enhanced the developmental increase in grip strength of 6- but not 10-week-old rats, without altering the developmental increase in body weight of either age group. Using in vivo microdialysis in freely moving 6-week-old rats given nandrolone for 4 weeks, basal accumbal dopamine efflux was unaltered, while the increase in dopamine efflux induced by acute administration of morphine (1.0 mg/kg s.c.) was reduced. The present study provides in vivo evidence that adolescence constitutes a critical period during which repeated administration of nandrolone enhances increases in muscular strength without influencing increases in body weight. Though repeated administration of nandrolone during this period of adolescence did not stimulate in vivo mesolimbic dopaminergic activity, it disrupted stimulation by an opioid, the drug class that is most commonly coabused with nandrolone.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 3","pages":"e22262"},"PeriodicalIF":2.3,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9617312","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.22238","DOIUrl":"https://doi.org/10.1002/syn.22238","url":null,"abstract":"","PeriodicalId":22131,"journal":{"name":"Synapse","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43432650","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":"Cover Image, Volume 77, Issue 3","authors":"","doi":"10.1002/syn.22267","DOIUrl":"https://doi.org/10.1002/syn.22267","url":null,"abstract":"The cover image is based on the Research Article <i>Abnormal [¹⁸F]NIFENE binding in transgenic 5xFAD mouse model of Alzheimer's disease: In vivo PET/CT imaging studies of α4β2* nicotinic acetylcholinergic receptors and in vitro correlations with Aβ plaques</i> by Christopher Liang et al., https://doi.org/10.1002/syn.22265.","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"466 ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138505600","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":"Tactile stimulation improves cognition, motor, and anxiety-like behaviors and attenuates the Alzheimer's disease pathology in adult APP^{NL-G-F/NL-G-F} mice.","authors":"Shakhawat R Hossain,&nbsp;Hadil Karem,&nbsp;Zahra Jafari,&nbsp;Bryan E Kolb,&nbsp;Majid H Mohajerani","doi":"10.1002/syn.22257","DOIUrl":"https://doi.org/10.1002/syn.22257","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is one of the largest health crises in the world. There are limited pharmaceutical interventions to treat AD, however, and most of the treatment options are not for cure or prevention, but rather to slow down the progression of the disease. The aim of this study was to examine the effect of tactile stimulation (TS) on AD-like symptoms and pathology in APP^{NL-G-F/NL-G-F} mice, a mouse model of AD. The results show that TS reduces the AD-like symptoms on tests of cognition, motor, and anxiety-like behaviors and these improvements in behavior are associated with reduced AD pathology in APP mice. Thus, TS appears to be a promising noninvasive strategy for slowing the onset of dementia in aging animals.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 2","pages":"e22257"},"PeriodicalIF":2.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10625702","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":"Calorie restriction, but not Roux-en-Y gastric bypass surgery, increases [³ H] PK11195 binding in a rat model of obesity.","authors":"John Hamilton,&nbsp;Cynthia Nguyen,&nbsp;Margaret McAvoy,&nbsp;Nicole Roeder,&nbsp;Brittany Richardson,&nbsp;Teresa Quattrin,&nbsp;Andras Hajnal,&nbsp;Panayotis K Thanos","doi":"10.1002/syn.22258","DOIUrl":"https://doi.org/10.1002/syn.22258","url":null,"abstract":"<p><p>Roux-en-Y gastric bypass surgery (RYGB) remains an effective weight-loss method used to treat obesity. While it is successful in combating obesity, there are many lingering questions related to the changes in the brain following RYGB surgery, one of them being its effects on neuroinflammation. While it is known that chronic high-fat diet (HFD) contributes to obesity and neuroinflammation, it remains to be understood whether bariatric surgery can ameliorate diet-induced inflammatory responses. To examine this, rats were assigned to either a normal diet (ND) or a HFD for 8 weeks. Rats fed a HFD were split into the following groups: sham surgery with ad libitum access to HFD (sham-HF); sham surgery with calorie-restricted HFD (sham-FR); RYGB surgery with ad libitum access to HFD (RYGB). Following sham or RYGB surgeries, rats were maintained on their diets for 9 weeks before being euthanized. [³ H] PK11195 autoradiography was then performed on fresh-frozen brain tissue in order to measure activated microglia. Sham-FR rats showed increased [³ H] PK11195 binding in the amygdala (63%), perirhinal (60%), and ectorhinal cortex (53%) compared with the ND rats. Obese rats who had the RYGB surgery did not show this increased inflammatory effect. Since the sham-FR and RYGB rats were fed the same amount of HFD, the surgery itself seems responsible for this attenuation in [³ H] PK11195 binding. We speculate that calorie restriction following obese conditions may be seen as a stressor and contribute to inflammation in the brain. Further research is needed to verify this mechanism.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 2","pages":"e22258"},"PeriodicalIF":2.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10617687","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":"In the parvocellular part of paraventricular nucleus, glutamatergic and GABAergic neurons mediate cardiovascular responses to AngII.","authors":"Ali Rastegarmanesh,&nbsp;Bahar Rostami,&nbsp;Ali Nasimi,&nbsp;Masoumeh Hatam","doi":"10.1002/syn.22259","DOIUrl":"https://doi.org/10.1002/syn.22259","url":null,"abstract":"<p><p>Angiotensinergic, GABAergic, and glutamatergic neurons are present in the parvocellular region of the paraventricular nucleus (PVNp). It has been shown that microinjection of AngII into the PVNp increases arterial pressure (AP) and heart rate (HR). The presence of synapses between the angiotensinergic, GABAergic, and glutamatergic neurons has been shown in the PVNp. In this study, we investigated the possible interaction between these three systems of the PVNp for control of AP and HR. All drugs were bilaterally (100 nl/side) microinjected into the PVNp of urethane-anesthetized rats, and AP and HR were recorded continuously. Microinjection of AngII into the PVNp produced pressor and tachycardia responses. Pretreatment of PVNp with AP5 or CNQX, glutamatergic NMDA and AMPA receptors antagonists, attenuated the responses to AngII. Pretreatment of PVNp with bicuculline greatly attenuated the pressor and tachycardia responses to AngII. In conclusion, this study provides the first evidence that pressor and tachycardia responses to microinjection of AngII into the PVNp are partly mediated by both NMDA and non-NMDA receptors of glutamate. Activation of glutamatergic neurons by AngII stimulates the sympathoexcitatory neurons. We also showed that the responses to AngII were strongly mediated by GABA_A receptors, probably through activation of GABAergic neurons, which in turn inhibit sympathoinhibitory neurons.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"77 2","pages":"e22259"},"PeriodicalIF":2.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10617666","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}