Neuropharmacology最新文献

{"title":"Ferroptosis and cognitive impairment: Unraveling the link and potential therapeutic targets","authors":"Soudabeh Naderi ,&nbsp;Fariba Khodagholi ,&nbsp;Mahyar Janahmadi ,&nbsp;Fereshteh Motamedi ,&nbsp;Abolfazl Torabi ,&nbsp;Zehra Batool ,&nbsp;Mahshad Fadaeimoghadam Heydarabadi ,&nbsp;Hamid Gholami Pourbadie","doi":"10.1016/j.neuropharm.2024.110210","DOIUrl":"10.1016/j.neuropharm.2024.110210","url":null,"abstract":"<div><div>Neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases, share key characteristics, notably cognitive impairment and significant cell death in specific brain regions. Cognition, a complex mental process allowing individuals to perceive time and place, is disrupted in these conditions. This consistent disruption suggests the possibility of a shared underlying mechanism across all neurodegenerative diseases. One potential common factor is the activation of pathways leading to cell death. Despite significant progress in understanding cell death pathways, no definitive treatments have emerged. This has shifted focus towards less-explored mechanisms like ferroptosis, which holds potential due to its involvement in oxidative stress and iron metabolism. Unlike apoptosis or necrosis, ferroptosis offers a novel therapeutic avenue due to its distinct biochemical and genetic underpinnings, making it a promising target in neurodegenerative disease treatment. Ferroptosis is distinguished from other cellular death mechanisms, by distinctive characteristics such as an imbalance of iron hemostasis, peroxidation of lipids in the plasma membrane, and dysregulated glutathione metabolism. In this review, we discuss the potential role of ferroptosis in cognitive impairment. We then summarize the evidence linking ferroptosis biomarkers to cognitive impairment brought on by neurodegeneration while highlighting recent advancements in our understanding of the molecular and genetic mechanisms behind the condition. Finally, we discuss the prospective therapeutic implications of targeting ferroptosis for the treatment of cognitive abnormalities associated with neurodegeneration, including natural and synthetic substances that suppress ferroptosis via a variety of mechanisms. Promising therapeutic candidates, including antioxidants and iron chelators, are being explored to inhibit ferroptosis and mitigate cognitive decline.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"263 ","pages":"Article 110210"},"PeriodicalIF":4.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific changes in voluntary alcohol consumption and nucleus accumbens synaptic plasticity in C57BL/6J mice exposed to neonatal maternal separation","authors":"Giuseppe Talani ,&nbsp;Francesca Biggio ,&nbsp;Maria Cristina Mostallino ,&nbsp;Elisabetta Batzu ,&nbsp;Giovanni Biggio ,&nbsp;Enrico Sanna","doi":"10.1016/j.neuropharm.2024.110212","DOIUrl":"10.1016/j.neuropharm.2024.110212","url":null,"abstract":"<div><div>The long-term influence of early-life stress on brain neurophysiology has been extensively investigated using different animal models. Among these, repeated maternal separation (RMS) in rodents is one of the most commonly adopted. In this study, we elucidated the long-lasting effects of exposure to postnatal RMS in C57BL/6J adult mice on voluntary alcohol consumption and nucleus accumbens (NAc) neurophysiology. Mice were separated from their dam for 360 min daily from postnatal day 2 (PND2) to PND17, and experiments were then performed in adult (PND60) animals. In addition, as recent evidence showed that circulating estrogens may play a protective role against stress effects on brain function, including the organization and activation of neuronal structures, we also evaluated the effect of a single injection of β-estradiol 3-benzoate (EB) at PND2, which is known to disrupt male sex differentiation, in male RMS mice. The RMS exposure was associated with an increased voluntary alcohol consumption and preference in male mice, but not in female mice or male mice treated with a single injection of EB. Patch clamp experiments conducted in NAc medium spiny neurons (MSNs) revealed that excitatory but not inhibitory synaptic transmission and long-term plasticity of glutamatergic synapses were significantly impaired in male but not in female mice exposed to the RMS protocol. This effect was again prevented in RMS male mice treated with EB. Our findings strengthen the idea of a sex-dependent influence of early-life stress on long-lasting modifications in synaptic transmission and plasticity in brain areas involved in goal-directed behavior and alcohol intake.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"262 ","pages":"Article 110212"},"PeriodicalIF":4.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adenosine regulates depressive behavior in mice with chronic social defeat stress through gut microbiota","authors":"Yao Huang ,&nbsp;Yue You ,&nbsp;Wei Wang ,&nbsp;Yuan-Hao Chen ,&nbsp;Hao Zhang ,&nbsp;Qu-Peng Li ,&nbsp;Le Liu ,&nbsp;Kun Tong ,&nbsp;Nan Sun ,&nbsp;Jing-Ru Hao ,&nbsp;Can Gao","doi":"10.1016/j.neuropharm.2024.110209","DOIUrl":"10.1016/j.neuropharm.2024.110209","url":null,"abstract":"<div><div>Major depressive disorder (MDD) is recognized as the most prevalent affective disorder worldwide. Metagenomic studies increasingly support a critical role for dysbiosis of gut microbiota in the development of depression. Previous studies have demonstrated that adenosine alleviates gut dysbiosis, suggesting that elevating adenosine levels could be a novel intervention for MDD; however, the mechanisms underlying this effect remain unclear. This study utilized 16S rRNA gene sequencing, fecal microbiota transplantation (FMT) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to test the hypothesis that increased adenosine alleviates depressive behaviors in male mice subjected to chronic social defeat stress (CSDS) through alterations to gut microbiota. The data showed that depression-susceptible (SUS) mice exhibited gut dysbiosis, and FMT from SUS mice increased depression-like behaviors in healthy recipients. In SUS mice, adenosine supplementation ameliorated both depression-like behaviors and abnormalities in gut microbiota, and co-administration of probiotics and adenosine not only mitigated depression-like behaviors but also enhanced gut barrier integrity. By including 83 depressed adolescents and 67 healthy controls, this study found that the level of short-chain fatty acids (SCFAs) in the depression group was reduced, this finding parallels reductions seen in SUS mice and in recipient mice after FMT from SUS donors. Conversely, supplementation with either adenosine or probiotics led increased SCFAs concentrations in the serum of SUS mice. These findings suggest that adenosine may alleviate depression-like behaviors in CSDS mice by modulating the gut microbiota. This effect is likely associated with increased serum SCFAs, metabolites produced by the gut microbiota, following adenosine supplementation.</div><div>This article is part of the Special Issue on \"Personality Disorders\".</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"262 ","pages":"Article 110209"},"PeriodicalIF":4.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Humanin attenuates metabolic, toxic, and traumatic neuropathic pain in mice by protecting against oxidative stress and increasing inflammatory cytokine","authors":"Batuhan Bilgin ,&nbsp;Munevver Gizem Hekim ,&nbsp;Ferah Bulut ,&nbsp;Muhammed Mirac Kelestemur ,&nbsp;Muhammed Adam ,&nbsp;Sibel Ozcan ,&nbsp;Sinan Canpolat ,&nbsp;Ahmet Ayar ,&nbsp;Mete Ozcan","doi":"10.1016/j.neuropharm.2024.110207","DOIUrl":"10.1016/j.neuropharm.2024.110207","url":null,"abstract":"<div><div>Neuropathic pain is associated with diverse etiologies, including sciatica, diabetes, and the use of chemotherapeutic agents. Despite the varied origins, mitochondrial dysfunction, oxidative stress, and inflammatory cytokines are recognized as key contributing factors in both the initiation and maintenance of neuropathic pain. The effects of the mitochondrial-derived peptide humanin on neuropathic pain, however, remain unclear, despite its demonstrated influence on these mechanisms in numerous disease models. This study aimed to evaluate the effects of humanin on pain behavior in murine models of metabolic (streptozotocin/STZ), toxic (oxaliplatin/OXA), traumatic (sciatic nerve cuffing/cuff), and neuropathic pain. A secondary objective was to assess whether humanin modulates oxidative damage and inflammatory cytokine levels in these neuropathic pain models.</div><div>Humanin (4 mg/kg) was administered intraperitoneally (i.p.) to BALB/c male mice with induced neuropathic pain over a period of 15 days, with pain thresholds assessed using hot plate, cold plate, and Von Frey tests. Serum levels of antioxidant enzymes, oxidative stress markers, and inflammatory/anti-inflammatory cytokines were measured via enzyme-linked immunosorbent assay (ELISA).</div><div>In neuropathic pain-induced mice, humanin administration resulted in a statistically significant increase in pain threshold values in the STZ + Humanin, OXA + Humanin, and cuff + Humanin groups compared to their respective control groups (P &lt; 0.05) over 15 days. Furthermore, humanin treatment significantly elevated antioxidant enzyme levels and anti-inflammatory cytokine concentrations, while reducing oxidative stress markers and pro-inflammatory cytokine levels compared to control groups (P &lt; 0.01).</div><div>These findings suggest that humanin exhibits therapeutic potential in the treatment of neuropathic pain induced by STZ, OXA, and cuff models. The ability of humanin to mitigate neuropathic pain through the suppression of oxidative stress and inflammatory cytokines indicates its promise as a novel therapeutic strategy.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"263 ","pages":"Article 110207"},"PeriodicalIF":4.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asiatic acid alleviates subarachnoid hemorrhage-induced brain injury in rats by inhibiting ferroptosis of neurons via targeting acyl-coenzyme a oxidase 1","authors":"Yukun Hu ,&nbsp;Jingyu Gu ,&nbsp;Xin Jin ,&nbsp;Xiaoxiao Wu ,&nbsp;Haiying Li ,&nbsp;Lei Bai ,&nbsp;Jiang Wu ,&nbsp;Xiang Li Sr.","doi":"10.1016/j.neuropharm.2024.110208","DOIUrl":"10.1016/j.neuropharm.2024.110208","url":null,"abstract":"<div><div>The occurrence of subarachnoid hemorrhage (SAH) can lead to brain injury, which is a fatal condition with limited effective clinical intervention strategies. The naturally occurring component Asiatic acid (AA), found in the tropical plant <em>Centella asiatica</em>, has been reported to possess neuroprotective properties. The objective of this study was to evaluate the neuroprotective effect of AA following SAH and investigate its potential mechanisms. The SAH model was established in male Sprague-Dawley (SD) rats through intravascular perforation, following a standardized protocol. The administration of AA was performed via gavage following SAH. A lentiviral vector was constructed and utilized for the knockdown of Acyl Coenzyme A Oxidase 1 (ACOX1) Firstly, AA treatment effectively improves brain neurological deficit, neuronal damage, and iron deposition induced by SAH. Furthermore, it has been demonstrated that AA directly interacts with ACOX1, which exhibits decreased expression in neurons following SAH. Additionally, our study reveals AA can reverse SAH-induced reduction in ACOX1 expression, concurrently ameliorating neuronal ferroptosis. This improvement is evidenced by reduced lipid peroxidation, including mitigated GSH depletion, decreased MDA production, and increased GPX4 content and activity. Also, AA enhances mitochondrial constriction while alleviating cristae disruption induced by SAH, providing crucial insights into its neuroprotective effects against neuronal ferroptosis in SAH. Moreover, when ACOX1 is knocked down, the neuroprotective effects of AA are weakened. Collectively, this study elucidated the neuroprotective effect of AA by inhibiting neuronal cell ferroptosis through targeting ACOX1. These findings suggest that AA holds promise as a potential therapeutic candidate for ameliorating SAH-induced brain injury.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"262 ","pages":"Article 110208"},"PeriodicalIF":4.6,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglia phagocytosis of PNNs mediates PV-positive interneuron dysfunction and associated gamma oscillations in neuroinflammation-induced cognitive impairment in mice","authors":"Kai Liu ,&nbsp;Yu-zhu Gao ,&nbsp;Xin-miao Wu ,&nbsp;Xiao-yi Hu ,&nbsp;Cui-na Shi ,&nbsp;Qiu-li He ,&nbsp;Hai-peng Wu ,&nbsp;Hao Yao ,&nbsp;Da-qing Ma ,&nbsp;Jian-jun Yang ,&nbsp;Mu-huo Ji","doi":"10.1016/j.neuropharm.2024.110205","DOIUrl":"10.1016/j.neuropharm.2024.110205","url":null,"abstract":"<div><div>Neuroinflammation, characterized by activation of glial cells, plays a critical role in central nervous system disorders. However, the precise mechanisms of neuroinflammation contributing to cognitive impairment remain elusive. Perineuronal nets (PNNs) are extracellular matrixes that envelop the cell bodies and dendrites of parvalbumin (PV)-positive interneurons and may be mediated by apolipoprotein E <em>(ApoE</em>) gene. To investigate whether disruption of PNNs associated with <em>ApoE</em> is implicated in neuroinflammation-induced cognitive impairment, we established a neuroinflammation model by administering lipopolysaccharides (LPS) at 0.5 mg/kg for 7 consecutive days. Cognitive function was assessed using the open field, Y-maze, and novel object recognition tests, and neural oscillations were also recorded. Furthermore, differentially expressed genes in microglia within the hippocampus were identified through single-cell RNA sequencing analysis. Overexpression of hyaluronan and proteoglycan link protein 1 (<em>Hapln1</em>) and <em>ApoE</em> knockdown were carried out through adeno-associated virus (AAV) injection to C57BL/6J mice and CX3CR1-CreERT2 mice, respectively. It was found that LPS-induced neuroinflammation impaired cognitive function by reducing PNNs and PV-positive interneurons’ outputs, as well as disrupting gamma (γ) oscillations in the hippocampal CA1. Overexpression of <em>Hapln1</em> was able to restore PV-positive interneurons and γ oscillations, ultimately alleviating the cognitive impairment. Mechanistically, LPS-triggered microglial activation leads to the phagocytosis of PNNs, a process influenced by <em>ApoE</em>. Notably, prevention of PNNs engulfment through targeting microglial <em>ApoE</em> in the CA1 improved cognitive impairment. Collectively, our study suggested that microglial phagocytosis of PNNs plays a key role in neuroinflammation-induced cognitive impairment, which is probably mediated by the <em>ApoE</em>.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"262 ","pages":"Article 110205"},"PeriodicalIF":4.6,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psilocybin reduces grooming in the SAPAP3 knockout mouse model of compulsive behaviour","authors":"James J. Gattuso ,&nbsp;Carey Wilson ,&nbsp;Anthony J. Hannan ,&nbsp;Thibault Renoir","doi":"10.1016/j.neuropharm.2024.110202","DOIUrl":"10.1016/j.neuropharm.2024.110202","url":null,"abstract":"<div><div>Psilocybin is a serotonergic psychedelic compound which shows promise for treating compulsive behaviours. This is particularly pertinent as compulsive disorders require research into new pharmacological treatment options as the current frontline treatments such as selective serotonin reuptake inhibitors, require chronic administration, have significant side effects, and leave almost half of the clinical population refractory to treatment.</div><div>In this study, we investigated psilocybin administration in male and female SAPAP3 knockout (KO) mice, a well-validated mouse model of obsessive compulsive and related disorders. We assessed the effects of acute psilocybin (1 mg/kg, intraperitoneal) administration on head twitch and locomotor behaviour as well as anxiety- and compulsive-like behaviours at multiple time-points (1, 3 and 8 days post-injection).</div><div>While psilocybin did not have any effect on anxiety-like behaviours, we revealed that acute psilocybin administration led to enduring reductions in compulsive behaviour in male SAPAP3 KO mice and reduced grooming behaviour in female wild-type (WT) and SAPAP3 KO mice. We also found that psilocybin increased locomotion in WT littermates but not in SAPAP3 KO mice, suggesting <em>in vivo</em> serotonergic dysfunctions in KO animals. On the other hand, the typical head-twitch response following acute psilocybin (confirming its hallucinogenic-like effect at this dose) was observed in both genotypes.</div><div>Our novel findings suggest that acute psilocybin may have potential to reduce compulsive-like behaviours (up to 1 week after a single injection). Our study can inform future research directions as well as supporting the utility of psilocybin as a novel treatment option for compulsive disorders.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"262 ","pages":"Article 110202"},"PeriodicalIF":4.6,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARM1 deficiency induced depressive-like behavior via AMPKα/p-eEF2 axis to synapse dysfunction","authors":"Weifen Li ,&nbsp;Wenhui Zhu ,&nbsp;Junhao Chen ,&nbsp;Tahir Ali ,&nbsp;Shupeng Li","doi":"10.1016/j.neuropharm.2024.110206","DOIUrl":"10.1016/j.neuropharm.2024.110206","url":null,"abstract":"<div><div>Sterile Alpha and TIR Motif Containing 1 (SARM1) are proteins implicated in various neurological processes; however, their role in depression remains unexplored. This study investigated the contribution of SARM1 to depressive-like behaviors in a chronic stress-induced depression model and SARM1 knockout (KO) mice. Depressive-like behaviors were assessed using a battery of behavioral tests, including the Open Field Test (OFT), the Forced Swim Test (FST), the Sucrose Preference Test (SPT), and the Tail Suspension Test (TST). Mitochondrial energy metabolism alteration, cytokine level changes, and other related molecular signaling protein expression were evaluated using ELISA and western blotting techniques to investigate the underlying mechanisms. Behavioral assessments (OFT, FST, SPT, TST) revealed depressive-like phenotypes in SARM1 KO mice, accompanied by altered mitochondrial energy metabolism (NAD+, ATP) in the cortex. Intriguingly, SARM1 depletion led to peripheral inflammation, as evidenced by elevated cytokine levels in plasma but not in brain regions (cortex). In addition, we found dysregulated energy metabolism, AMPK signaling, and synaptic plasticity in the cortex of SARM1 KO mice. Notably, AICAR (Acadesine), an AMPK activator, ameliorated depressive-like behaviors and synaptic dysfunction, while Compound C, an AMPK inhibitor, reversed these effects. Additionally, NH125, an eEF2 kinase inhibitor, improved depressive-like behaviors in SARM1 KO mice. These findings demonstrate that SARM1 is critical in regulating depressive-like behaviours through the AMPKα/p-eEF2 signaling pathway. Targeting AMPK signaling and synaptic function may offer novel therapeutic avenues for depression.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"262 ","pages":"Article 110206"},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hippocampal SENP3 mediates chronic stress-induced depression-like behaviors by impairing the CREB-BDNF signaling","authors":"Zhiwei Gao ,&nbsp;Jie Peng ,&nbsp;Yi Zhang ,&nbsp;Zhuo Chen ,&nbsp;Rongrong Song ,&nbsp;Ze Song ,&nbsp;Qijie Feng ,&nbsp;Micona Sun ,&nbsp;Haojie Zhu ,&nbsp;Xu Lu ,&nbsp;Rongrong Yang ,&nbsp;Chao Huang","doi":"10.1016/j.neuropharm.2024.110203","DOIUrl":"10.1016/j.neuropharm.2024.110203","url":null,"abstract":"<div><div>Impaired signaling between cyclic adenosine monophosphate response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the hippocampus is generally considered to be the cause of depression. The mechanisms underlying the impairment of CREB-BDNF signaling under stress conditions are largely unclear. Small ubiquitin-like modifier (SUMO) specific peptidase 3 (SENP3) is a molecule that can regulate SUMOylation of target proteins related to synaptic plasticity. Its dynamic changes have been reported to be associated with neuronal damage in various models of central nervous disorders such as cerebral ischemia and traumatic brain injury. However, its role in depression is completely unknown. This problem was addressed in the present study. Our results showed that chronic unpredictable stress (CUS) triggered a specific increase in SENP3 expression in the hippocampus of non-stressed mice. Overexpression of SENP3 in the hippocampus of non-stressed mice elicited depression-like behaviors in the tail suspension test, forced swimming test, and sucrose preference test, accompanied by impairment of the CREB-BDNF signaling cascade in the hippocampus. Conversely, genetic silencing of SENP3 in the hippocampus suppressed the development of depression-like behaviors. Furthermore, infusion of SENP3-shRNA into the hippocampus failed to suppress CUS-induced depression-like behaviors when mice received genetic silencing CREB or BDNF in the hippocampus or inhibition of the BDNF receptor by K252a. Taken together, these results suggest that abnormally elevated SENP3 in the hippocampus leads to the development of depression-like behavior by impairing the CREB-BDNF signaling cascade. SENP3 in the hippocampus could be a promising target for the development of new antidepressants.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"262 ","pages":"Article 110203"},"PeriodicalIF":4.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxytocin alleviates high-fat diet-induced anxiety by decreasing glutamatergic synaptic transmission in the ventral dentate gyrus in adolescent mice","authors":"Xi Cao ,&nbsp;Qiyuan Wang ,&nbsp;Lina Zhang ,&nbsp;Huichao Sun ,&nbsp;Gang Xu ,&nbsp;Xiao Chen ,&nbsp;Zhihong Wu ,&nbsp;Huibao Liu ,&nbsp;Gaole Yuan ,&nbsp;Jian Wu ,&nbsp;Tao Liu","doi":"10.1016/j.neuropharm.2024.110201","DOIUrl":"10.1016/j.neuropharm.2024.110201","url":null,"abstract":"<div><div>A high-fat diet (HFD)-induced obesity is associated with mental disorders in adolescence. However, the mechanisms underlying these associations remain unclear. In this study, we hypothesized that synaptic remodeling occurs in the ventral hippocampus (vHP) of obese mice. To investigate this, we established a postnatal model of HFD-induced obesity in mice and observed increased body weight, elevated plasma luteinizing hormone and testosterone levels, premature puberty, and enhanced anxiety-like behavior in male subjects. We also examined the effect of HFD on the c-Fos protein expression in the ventral dentate gyrus (vDG) and explored the influence of intracerebroventricular (i.c.v) oxytocin injections on HFD-induced anxiety. Our results indicated an increase in c-Fos-positive cells in the vDG following HFD consumption. Additionally, we recorded the spontaneous synaptic activity of miniature excitatory postsynaptic currents (mEPSCs) in the vDG. Notably, HFD resulted in an elevated mEPSC frequency without affecting mEPSC amplitude. Subsequently, investigations demonstrated that i.c.v oxytocin injections reversed anxiety-like behavior induced by HFD. Moreover, the application of oxytocin in a bath solution reduced the mEPSC frequency in the vDG. These findings suggest that postnatal HFD intake induces synaptic dysfunction in the vDG, associated with the hyperactivity of vDG neurons, potentially contributing to the anxiety-like behavior in juvenile obesity.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"262 ","pages":"Article 110201"},"PeriodicalIF":4.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}