Synapse最新文献

{"title":"The Selective 5HT_2A Receptor Agonist, 25CN-NBOH Exerts Excitatory and Inhibitory Cellular Actions on Mouse Medial Prefrontal Cortical Neurons.","authors":"Yang Wang, Jesper L Kristensen, Kristi A Kohlmeier","doi":"10.1002/syn.70014","DOIUrl":"10.1002/syn.70014","url":null,"abstract":"<p><p>Psychedelic compounds have gained renewed interest due to their rapid and long-lasting therapeutic effects on stress-related disorders. While the underlying mechanisms of therapeutic actions of psychedelic compounds are still unclear, these drugs are thought to modulate the activity of the serotonergic system, primarily through activating serotonin type 2A receptor (5-HT_2AR) and studies have focused on these actions in the medial prefrontal cortex (mPFC). 25CN-NBOH, a synthetic psychedelic compound with a high binding affinity for 5-HT_2ARs and anti-anxiety actions, has emerged as a valuable tool for investigating the physiological functions mediated by this receptor. This study aimed to investigate the electrophysiological effects of 25CN-NBOH on pyramidal mPFC neurons using whole-cell patch clamp recordings in mouse brain slices. We recorded synaptic events and action potential rates during acute and long-term exposure to two concentrations of 25CN-NBOH. Acute application of 10 µM 25CN-NBOH increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) that was reliant on activation of 5-HT_2AR, and which was not seen upon chronic exposure. A similar effect of 200 nM 25CN-NBOH was not noted. Surprisingly, both 10 µM and 200 nM 25CN-NBOH significantly suppressed the firing rate following acute as well as a longer-term exposure of 1 h. This suppression was independent of 5-HT_2AR activation but was mediated by M-current channels, as evidenced by the reversal of suppression with the M-current blocker XE-991. Our data suggest a complicated dual action of 25CN-NBOH in enhancing excitatory transmission while also reducing excitability. Our data contribute to knowledge regarding the cellular consequence of 5-HT_2AR agonism and contribute to widening our understanding of the potential mechanisms underlying the therapeutic actions of serotonergic psychedelics.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 2","pages":"e70014"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701562","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":"Cellular-Resolution and Bulk-Fluorescence Recordings of Calcium Activity Yield Reciprocal Readouts of In Vivo Drug Efficacy.","authors":"Seongsik Yun, Jones G Parker","doi":"10.1002/syn.70011","DOIUrl":"10.1002/syn.70011","url":null,"abstract":"<p><p>Genetically encoded fluorescent sensors of neural activity have become a mainstay of basic neuroscience. However, preclinical drug development has been slower to adopt these tools. Recently, we used miniature microscopes to record Ca²⁺ activity in D1 and D2 dopamine receptor-expressing spiny projection neurons (SPNs) in response to antipsychotic drugs or candidates. Despite the fact that most antipsychotics block D2 receptors, clinical efficacy was associated with the normalization of D1-SPN activity under hyperdopaminergic conditions. In this study, we re-processed these data to approximate a fiber photometry signal and asked whether the conclusions were the same. This re-evaluation is important because fiber photometry has several advantages over cellular-resolution imaging. Consistent with our previous finding that bulk and cellular-resolution imaging report distinct SPN Ca²⁺ dynamics, here the two data types suggested reciprocal effects of drug treatment on D1-SPN and D2-SPN Ca²⁺ activity. While amphetamine treatment increased D1-SPN and decreased D2-SPN Ca²⁺ event rates in cellular-resolution data, it increased the fluorescence of individual neurons but decreased their bulk fluorescence in both cell types. Analyzing detected bulk-fluorescence \"events\" yielded a closer correlation between the bulk and somatic Ca²⁺ fluorescence. However, it did not fully replicate the results of our previous cellular-resolution recordings following amphetamine or antipsychotic drug treatment. Our results highlight important distinctions between cellular-resolution and bulk measurements of in vivo Ca²⁺ activity. While experimenters using in vivo imaging to understand drug effects on neural activity should heed these distinctions, they should also utilize them to gain a more holistic view of drug action.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 2","pages":"e70011"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515713","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":"Ginkgo biloba Extract Improves Dendritic Spine Injury in Cerebellar Purkinje Cells Induced by MPTP in Mice by Regulating the PLK2-SPAR Pathway.","authors":"Yilin Lyu, Yumei Zhang","doi":"10.1002/syn.70013","DOIUrl":"https://doi.org/10.1002/syn.70013","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a common neurodegenerative disease, and, currently, there is no cure for patients with PD. Studies have shown that Ginkgo biloba extract (EGb) has good neuroprotective effects against PD. The cerebellum is widely involved in cognitive function and may be related to the regulation of static tremors in PD. However, research on the corresponding microstructures is limited. Purkinje cells (PCs) are the only efferent neurons present in the cerebellum, and dendritic spines in PCs are considered the key structures for transmitting neuronal excitatory signals. When neurons are activated, polo-like kinase 2 (PLK2) is expressed, leading to the degradation of spine-associated Rap guanosine triphosphatase activating protein (SPAR) and, ultimately, the loss of postsynaptic density protein 95 (PSD-95), causing changes in the morphology or quantity of dendritic spines. This raises the question of whether the neuroprotective effect of EGb involves the PLK2-SPAR pathway. In this study, we used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to establish a mouse model of dopamine neuronal injury. Golgi staining was performed to observe the dendritic spine changes. Immunohistochemistry was used to detect the expression of PLK2, SPAR, and PSD-95. The results showed that EGb improves MPTP-induced behavioral changes, dopamine neuronal injury, and dendritic spine damage in mice. In addition, EGb reversed the changes in PLK2, SPAR, and PSD-95 expressions caused by MPTP, revealing the potential mechanism by which EGb improves the condition of patients with PD.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 2","pages":"e70013"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606111","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":"Subanesthetic Ketamine Ameliorates Activity-Based Anorexia of Adult Mice.","authors":"Yiru Dong, Chiye Aoki","doi":"10.1002/syn.70005","DOIUrl":"10.1002/syn.70005","url":null,"abstract":"<p><strong>Objective: </strong>Anorexia nervosa (AN) is an eating disorder with the second highest mortality of all mental illnesses and high relapse rate, especially among adult females, yet with no accepted pharmacotherapy. A small number of studies have reported that adult females who struggled with severe and relapsing AN experienced sustained remission of the illness following ketamine infusions. Two other reports showed that 30 mg/kg IP ketamine can reduce vulnerability of adolescent mice to activity-based anorexia (ABA), an animal model of AN. However, no study has tested the efficacy of ketamine on adult ABA mice. This study aimed to fill this gap in knowledge.</p><p><strong>Methods: </strong>Forty-one female mice underwent three cycles of ABA (ABA1, ABA2, and ABA3) to assess relapse vulnerability in adulthood. Of them, 13 received ketamine injections (30 mg/kg, 3 doses) during ABA2 (KET) in adulthood to assess ketamine's acute effects during ABA2 and ketamine's potential for sustained efficacy during ABA3, 10-13 days later. The remaining 28 received vehicle or no injections during ABA2 (CON).</p><p><strong>Results: </strong>Severe weight loss (>20% of baseline) during ABA3 was observed for 89% of CON but only 69% of KET. Overall wheel running per day was significantly less for KET than CON (p < 0.01) throughout ABA2, including hours of food availability, and these reductions were sustained through ABA3. Food consumption was not altered significantly by ketamine.</p><p><strong>Discussion: </strong>These findings suggest that ketamine may reduce adult females' vulnerability to ABA and may protect women from AN relapse by reducing hyperactivity.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 1","pages":"e70005"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923265","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 Effect of Curcumin-Metavanadate in the Hippocampus of Aged Rats.","authors":"Sonia Irais Gonzalez-Cano, Ulises Peña-Rosas, Guadalupe Muñoz-Arenas, Diana Milena Torres-Cinfuentes, Samuel Treviño, Carolina Moran-Raya, Gonzalo Flores, Jorge Guevara, Alfonso Diaz","doi":"10.1002/syn.70008","DOIUrl":"https://doi.org/10.1002/syn.70008","url":null,"abstract":"<p><p>Brain aging is a multifactorial process that includes a reduction in the biological and metabolic activity of individuals. Oxidative stress and inflammatory processes are characteristic of brain aging. Given the current problems, the need arises to implement new therapeutic approaches. Polyoxidovanadates (POV), as well as curcumin, have stood out for their participation in a variety of biological activities. This work aimed to evaluate the coupling of metavanadate and curcumin (Cuma-MV) on learning, memory, redox balance, neuroinflammation, and cell death in the hippocampal region (CA1 and CA3) and dentate gyrus (DG) of aged rats. Rats 18 months old were administered a daily dose of curcumin (Cuma), sodium metavanadate (MV), or Cuma-MV for two months. The results demonstrated that administration of Cuma-MV for 60 days in aged rats improved short- and long-term recognition memory, decreased reactive oxygen species, and substantially improved lipoperoxidation in the hippocampus. Furthermore, the activity of superoxide dismutase and catalase increased in animals treated with Cuma-MV. It is important to highlight that the treatment with Cuma-MV exhibited a significantly greater effect than the treatments with MV or Cuma in all the parameters evaluated. Finally, we conclude that Cuma-MV represents a potential therapeutic option in the prevention and treatment of cognitive decline associated with aging.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 1","pages":"e70008"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923261","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":"Measuring Alcohol-Induced Striatal Dopamine Release in Healthy Humans With [¹¹C]-Raclopride: A Meta-Analysis.","authors":"Amir Kania, Natasha Porco, Fernando Caravaggio","doi":"10.1002/syn.70007","DOIUrl":"10.1002/syn.70007","url":null,"abstract":"<p><p>Alcohol consumption is known to affect dopamine (DA) release in the brain, with significant implications for understanding addiction and its neurobiological underpinnings. This meta-analysis examined the effects of acute alcohol administration on striatal DA release in healthy humans as measured with [¹¹C]-raclopride positron emission tomography (PET). Oral alcohol administration was associated with a significant reduction in [¹¹C]-raclopride binding potential (BP_ND) in the ventral striatum (Cohen's d = -0.76), indicative of increased DA release, particularly at lower blood alcohol concentration (BAC) levels (0.08 gm%; Z = 2.34, p = 0.02). That oral alcohol may increase DA release in the ventral striatum at lower doses, and decrease DA release at higher doses, warrants further investigation but appears consistent with other known biphasic, hermetic dose-response effects of alcohol. Additionally, larger effect-sizes in the ventral striatum were observed among those studies which sampled more males than females (Z = -2.08, p = 0.04). While oral alcohol administration was associated with reduced [¹¹C]-raclopride BP_ND in the caudate (Cohen's d = -0.39) and putamen (Cohen's d = -0.37), these findings in the dorsal striatum were more variable and less robust. Our analyses suggests that study design (i.e., counterbalanced versus fixed order) may moderate effect sizes observed in the putamen across studies (Z = -2.27, p = 0.02). By identifying gaps in the current literature and proposing directions for future research, this study hopes to inform the design of future PET studies aimed at quantifying alcohol-induced dopamine release in the striatum of humans.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 1","pages":"e70007"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898175","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":"Correction to \"[11C]PBB3 binding in Aβ(-) or Aβ(+) corticobasal syndrome\".","authors":"","doi":"10.1002/syn.70006","DOIUrl":"10.1002/syn.70006","url":null,"abstract":"","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 1","pages":"e70006"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898169","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":"Harnessing Miniscope Imaging in Freely Moving Animals to Unveil Migraine Pathophysiology and Validate Novel Therapeutic Strategies.","authors":"Caroline Degel, Kevin Zitelli, Jonathan Zapata, Jonathan Nassi, Paolo Botta","doi":"10.1002/syn.70001","DOIUrl":"10.1002/syn.70001","url":null,"abstract":"<p><p>Migraine is a debilitating neurological disorder that affects millions worldwide. Elucidating its underlying mechanisms is crucial for developing effective therapeutic interventions. In this editorial, we discuss the potential applications of one-photon miniscopes, which enable minimally invasive, high spatiotemporal resolution fluorescence imaging in freely moving animals. By providing real-time visualization of vascular dynamics and neuronal activity, these cutting-edge techniques can offer unique insights into migraine pathophysiology. We explore the significance of these applications in preclinical research with a case study demonstrating their potential to drive the development of novel therapeutic strategies for effective migraine management.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"78 6","pages":"e70001"},"PeriodicalIF":1.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682827","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":"ERK1/2 Regulates Epileptic Seizures by Modulating the DRP1‐Mediated Mitochondrial Dynamic","authors":"Ting Chen, Juan Yang, Yongsu Zheng, Xuejiao Zhou, Hao Huang, Haiqing Zhang, Zucai Xu","doi":"10.1002/syn.22309","DOIUrl":"https://doi.org/10.1002/syn.22309","url":null,"abstract":"After seizures, the hyperactivation of extracellular signal‐regulated kinases (ERK1/2) causes mitochondrial dysfunction. Through the guidance of dynamin‐related protein 1 (DRP1), ERK1/2 plays a role in the pathogenesis of several illnesses. Herein, we speculate that ERK1/2 affects mitochondrial division and participates in the pathogenesis of epilepsy by regulating the activity of DRP1. LiCl‐Pilocarpine was injected intraperitoneally to establish a rat model of status epilepticus (SE) for this study. Before SE induction, PD98059 and Mdivi‐1 were injected intraperitoneally. The number of seizures and the latency period before the onset of the first seizure were then monitored. The analysis of Western blot was also used to measure the phosphorylated and total ERK1/2 and DRP1 protein expression levels in the rat hippocampus. In addition, immunohistochemistry revealed the distribution of ERK1/2 and DRP1 in neurons of hippocampal CA1 and CA3. Both PD98059 and Mdivi‐1 reduced the susceptibility of rats to epileptic seizures, according to behavioral findings. By inhibiting ERK1/2 phosphorylation, the Western blot revealed that PD98059 indirectly reduced the phosphorylation of DRP1 at Ser616 (p‐DRP1‐Ser616). Eventually, the ERK1/2 and DRP1 were distributed in the cytoplasm of neurons by immunohistochemistry. Inhibition of ERK1/2 signaling pathways downregulates p‐DRP1‐Ser616 expression, which could inhibit DRP1‐mediated excessive mitochondrial fission and then regulate the pathogenesis of epilepsy.","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"19 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255018","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":"Calsyntenin-1 expression and function in brain tissue of lithium-pilocarpine rat seizure models.","authors":"Fu Zhou, Rong Hu, Yuzhu Wang, Xiaohui Wu, Xuan Chen, Zhiqin Xi, Kebin Zeng","doi":"10.1002/syn.22307","DOIUrl":"10.1002/syn.22307","url":null,"abstract":"<p><p>To present the expression of calsyntenin-1 (Clstn1) in the brain and investigate the potential mechanism of Clstn1 in lithium-pilocarpine rat seizure models. Thirty-five male SD adult rats were induced to have seizures by intraperitoneal injection of lithium chloride pilocarpine. Rats exhibiting spontaneous seizures were divided into the epilepsy (EP) group (n = 15), whereas those without seizures were divided into the control group (n = 14). Evaluate the expression of Clstn1 in the temporal lobe of two groups using Western blotting, immunohistochemistry, and immunofluorescence. Additionally, 55 male SD rats were subjected to status epilepticus (SE) using the same induction method. Rats experiencing seizures exceeding Racine's level 4 (n = 48) were randomly divided into three groups: SE, SE + control lentivirus (lentiviral vector expressing green fluorescent protein [LV-GFP]), and SE + Clstn1-targeted RNA interference lentivirus (LV-Clstn1-RNAi). The LV-GFP group served as a control for the lentiviral vector, whereas the LV-Clstn1-RNAi group received a lentivirus designed to silence Clstn1 expression. These lentiviral treatments were administered via hippocampal stereotactic injection 2 days after SE induction. Seven days after SE, Western blot analysis was performed to evaluate the expression of Clstn1 in the hippocampus and temporal lobe. Meanwhile, we observed the latency of spontaneous seizures and the frequency of spontaneous seizures within 8 weeks among the three groups. The expression of Clstn1 in the cortex and hippocampus of the EP group was significantly increased compared to the control group (p < .05). Immunohistochemistry and immunofluorescence showed that Clstn1 was widely distributed in the cerebral cortex and hippocampus of rats, and colocalization analysis revealed that it was mainly co expressed with neurons in the cytoplasm. Compared with the SE group (11.80 ± 2.17 days) and the SE + GFP group (12.40 ± 1.67 days), there was a statistically significant difference (p < .05) in the latency period of spontaneous seizures (15.14 ± 2.41 days) in the SE + Clstn1 + RNAi group rats. Compared with the SE group (4.60 ± 1.67 times) and the SE + GFP group (4.80 ± 2.05 times), the SE + Clstn1 + RNAi group (2.0 ± .89 times) showed a significant reduction in the frequency of spontaneous seizures within 2 weeks of chronic phase in rats (p < .05). Elevated Clstn1 expression in EP group suggests its role in EP onset. Targeting Clstn1 may be a potential therapeutic approach for EP management.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"78 5","pages":"e22307"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018680","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}