Synapse最新文献

{"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}

{"title":"High Impact AMPAkines Induce a Gq-Protein Coupled Endoplasmic Calcium Release in Cortical Neurons: A Possible Mechanism for Explaining the Toxicity of High Impact AMPAkines.","authors":"Daniel P Radin, Sheng Zhong, Rok Cerne, Jeffrey M Witkin, Arnold Lippa","doi":"10.1002/syn.22310","DOIUrl":"10.1002/syn.22310","url":null,"abstract":"<p><p>α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) positive allosteric modulators (AMPAkines) have a multitude of promising therapeutic properties. The pharmaceutical development of high impact AMPAkines has, however, been limited by the appearance of calcium-dependent neuronal toxicity and convulsions in vivo. Such toxicity is not observed at exceptionally high concentrations of low impact AMPAkines. Because most AMPAR are somewhat impermeable to calcium, the current study sought to examine the extent to which different mechanisms contribute to the rise in intracellular calcium in the presence of high impact ampakines. In the presence of AMPA alone, cytosolic calcium elevation is shown to be sodium-dependent. In the presence of high impact AMPAkines such as cyclothiazide (CTZ) or CX614, however, AMPAR potentiation also activates an additional mechanism that induces calcium release from endoplasmic reticular (ER) stores. The pathway that connects AMPAR to the ER system involves a Gq-protein, phospholipase C_β-mediated inositol triphosphate (InsP3) formation, and ultimately stimulation of InsP3-receptors located on the ER. The same linkage was not observed using high concentrations of the low impact AMPAkines, CX516 (Ampalex), and CX717. We also demonstrate that CX614 produces neuronal hyper-excitability at therapeutic doses, whereas the newer generation low impact AMPAkine CX1739 is safe at exceedingly high doses. Although earlier studies have demonstrated a functional linkage between AMPAR and G-proteins, this report demonstrates that in the presence of high impact AMPAkines, AMPAR also couple to a Gq-protein, which triggers a secondary calcium release from the ER and provides insight into the disparate actions of high and low impact AMPAkines.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"78 5","pages":"e22310"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142295903","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":"microRNA-125b-5p alleviated CCI-induced neuropathic pain and modulated neuroinflammation via targeting SOX11.","authors":"Liping Wang, Bei Wang, Xia Geng, Xiaona Guo, Tingting Wang, Jingjing Xu, Linkai Jiang, Haining Zhen","doi":"10.1002/syn.22306","DOIUrl":"10.1002/syn.22306","url":null,"abstract":"<p><strong>Background: </strong>Increasing evidence demonstrated the involvement of microRNAs (miRNAs) in the onset and development of neuropathic pain (NP). Exploring the molecular mechanism underlying NP and identifying key molecules could provide potential targets for the therapy of NP. The function and mechanism of miR-125b-5p in regulating NP have been studied, aiming to find a potential therapeutic target for NP.</p><p><strong>Methods: </strong>NP rat models were established by the chronic constriction injury (CCI) method. The paw withdrawal threshold and paw withdrawal latency were assessed to evaluate the establishment and recovery of rats. Highly aggressive proliferating immortalized (HAPI) micoglia cell, a rat microglia cell line, was treated with lipopolysaccharide (LPS). The M1/M2 polarization and inflammation were evaluated by enzyme-linked immunosorbent assay and western blotting.</p><p><strong>Results: </strong>Decreasing miR-125b-5p and increasing SOX11 were observed in CCI rats and LPS-induced HAPI cells. Overexpressing miR-125b-5p alleviated mechanical allodynia and thermal hyperalgesia and suppressed inflammation in CCI rats. LPS induced M1 polarization and inflammation of HAPI cells, which was attenuated by miR-125b-5p overexpression. miR-125-5p negatively regulated the expression of SOX11 in CCI rats and LPS-induced HAPI cells. Overexpressing SOX11 reversed the protective effects of miR-125b-5p on mechanical pain in CCI rats and the polarization and inflammation in HAPI cells, which was considered the mechanism underlying miR-125b-5p.</p><p><strong>Conclusion: </strong>miR-125b-5p showed a protective effect on NP by regulating inflammation and polarization of microglia via negatively modulating SOX11.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"78 5","pages":"e22306"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971846","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":"Inhibitory modulation of action potentials in crayfish motor axons by fluoxetine.","authors":"Selene Wang, Si Seng Lam, Anisah Aguilar, Stephanie Anakwe, Katherine Barahona, Hani Haider, Olivia Hunyadi, Kaahini Jain, Derek Kolodziejski, Anindita Lal, Man Li, Frank MacKenzie, John Miller, Oliviero Nardin, Emily Nguyen, Jaii Pappu, Melissa Rodriguez, Jen-Wei Lin","doi":"10.1002/syn.22304","DOIUrl":"10.1002/syn.22304","url":null,"abstract":"<p><p>The goal of this report is to explore how K2P channels modulate axonal excitability by using the crayfish ventral superficial flexor preparation. This preparation allows for simultaneous recording of motor nerve extracellular action potentials (eAP) and intracellular excitatory junctional potential (EJP) from a muscle fiber. Previous pharmacological studies have demonstrated the presence of K2P-like channels in crayfish. Fluoxetine (50 µM) was used to block K2P channels in this study. The blocker caused a gradual decline, and eventually complete block, of motor axon action potentials. At an intermediate stage of the block, when the peak-to-peak amplitude of eAP decreased to ∼60%-80% of the control value, the amplitude of the initial positive component of eAP declined at a faster rate than that of the negative peak representing sodium influx. Furthermore, the second positive peak following this sodium influx, which corresponds to the after-hyperpolarizing phase of intracellularly recorded action potentials (iAP), became larger during the intermediate stage of eAP block. Finally, EJP recorded simultaneously with eAP showed no change in amplitude, but did show a significant increase in synaptic delay. These changes in eAP shape and EJP delay are interpreted as the consequence of depolarized resting membrane potential after K2P channel block. In addition to providing insights to possible functions of K2P channels in unmyelinated axons, results presented here also serve as an example of how changes in eAP shape contain information that can be used to infer alterations in intracellular events. This type of eAP-iAP cross-inference is valuable for gaining mechanistic insights here and may also be applicable to other model systems.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"78 4","pages":"e22304"},"PeriodicalIF":1.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421035","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}