Neuroscience Letters最新文献

{"title":"Synergistic anxiolytic-like effect of CPPG and harmaline in non-stressed and acute restraint stress (ARS) mice","authors":"Nazahnin Hasan-Kareem ,&nbsp;Sakineh Alijanpour ,&nbsp;Mohammad-Reza Zarrindast ,&nbsp;Fatemeh Khakpai","doi":"10.1016/j.neulet.2025.138157","DOIUrl":"10.1016/j.neulet.2025.138157","url":null,"abstract":"<div><div>Many studies revealed the role of metabotropic glutamate receptors (mGluRs) and harmaline in the modulation of anxiety-related behaviors. This study aimed to determine a possible interaction between harmaline and group III mGluR on the modulation of anxiety-correlated behaviors. The left lateral ventricle of male mice was unilaterally cannulated. Acute restraint stress (ARS) was induced by movement restraint for 4 h. Anxiety-like behaviors were measured using an elevated plus maze. The results showed that induction of ARS during 4 h reduced the percentage of time spent in open arms (%OAT) and percentage of entries to open arms (%OAE) without changing locomotor activity, indicating anxiogenic-like responses. Intraperitoneal (i.p.) administration of harmaline (2 mg/kg) increased %OAT in non-stressed and ARS mice, presenting anxiolytic-like responses. Intracerebroventricular (i.c.v.) infusion of CPPG (potent group III mGlu antagonist, 70 µg/mouse) induced anxiolytic-like behavior due to the augmentation of %OAT in non-stressed and ARS mice. Co-treatment of CPPG (70 µg/mouse, i.c.v.) along with harmaline (1 mg/kg, i.p) induced an anxiolytic-like effect. I.c.v. infusion of L-AP4 (selective group III mGlu agonist) or co-administration of it along harmaline had no significant effect on anxiety-like behaviors both in non-stressed and ARS mice. When harmaline and CPPG were co-administrated, CPPG potentiated the anxiolytic-like behavior induced by harmaline in non-stressed and ARS mice. The results revealed a synergistic effect between CPPG and harmaline on the induction of anxiolytic-like effect in non-stressed and ARS mice. Our results indicated an interaction between harmaline and group III mGluR on the modulation of anxiety-like responses in non-stressed and ARS mice.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"850 ","pages":"Article 138157"},"PeriodicalIF":2.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403162","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":"Downregulation of STAT1 improved learning and memory impairments in aging mice","authors":"Xiao Li ,&nbsp;Yao Xu ,&nbsp;Ting Li ,&nbsp;Bocheng Xiong ,&nbsp;Xifei Yang ,&nbsp;Yan Feng","doi":"10.1016/j.neulet.2025.138155","DOIUrl":"10.1016/j.neulet.2025.138155","url":null,"abstract":"<div><div>Cognitive impairment is a typical hallmark of aging in mice and humans. Here, we reported that downregulation of STAT1 improved learning and memory impairments in aging mice by enhancing the expression of synaptic protein and inhibiting the expression of inflammatory factors. Proteomic analysis revealed 139 differentially expressed proteins (DEPs) in the hippocampus of downregulated-STAT1 aging mice, compared with aging control mice. Functional classification of DEPs indicated that these mainly involved in inflammation, autophagy, synapse, mitochondria and apoptosis. The ClueGo analysis uncovered that the Wiki pathway of these DEPs were involved in proteasome degradation, IL-6 signaling pathway, signaling of hepatocyte growth factor receptor and so on. Taken together, downregulation of STAT1 may delay aging with multiple mechanisms.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"850 ","pages":"Article 138155"},"PeriodicalIF":2.5,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388075","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":"Dendritic phenotype and proliferation potency in the hippocampal dentate gyrus of the Ts66Yah model of Down syndrome","authors":"Marco Emili ,&nbsp;Fiorenza Stagni ,&nbsp;Sandra Guidi ,&nbsp;Carla Russo ,&nbsp;Claire Chevalier ,&nbsp;Arnaud Duchon ,&nbsp;Yann Herault ,&nbsp;Renata Bartesaghi","doi":"10.1016/j.neulet.2025.138156","DOIUrl":"10.1016/j.neulet.2025.138156","url":null,"abstract":"<div><div>The Ts65Dn mouse is the most widely used model of Down syndrome (DS), although, in addition to the triplication of 90 genes homologous to Human Chromosome 21 (Hsa21) genes, it bears the triplication of 46 extra genes. To clarify the latter’s impact, the Ts66Yah model has been created from the Ts65Dn mouse by exploiting CRISPR/Cas9 technology for extra gene deletion. It has been found that, similar to the Ts65Dn model, the Ts66Yah model exhibits impairment in hippocampus-dependent learning and memory and age-related hippocampal deterioration, with no increased activity. We examine here the dendritic development of the hippocampal granule neurons and the proliferation potency of granule cell precursors in Ts66Yah mice because these phenotypes are impaired in Ts65Dn mice and individuals with DS starting from early life stages and are thought to underpin cognitive impairment. In Ts66Yah mice aged 15 days and those aged three months, we found no reduction in dendritic arborization, dendritic spine density, proliferation potency, or total number of granule cells, suggesting that other mechanisms may underpin the behavioral impairment found in the Ts66Yah model in adulthood. Thus, the Ts66Yah model is unsuitable to study these neurodevelopmental alterations, although it may be useful to study other DS-related phenotypes.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"850 ","pages":"Article 138156"},"PeriodicalIF":2.5,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391336","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":"Effects of kratom alkaloids on mesolimbic dopamine release","authors":"James P. Manus ,&nbsp;Rebecca C. Crenshaw ,&nbsp;Lindsay C. Ringer ,&nbsp;Shelby A. Towers ,&nbsp;Nick B. Paige ,&nbsp;Francisco Leon ,&nbsp;Christopher R. McCurdy ,&nbsp;Deranda B. Lester","doi":"10.1016/j.neulet.2025.138153","DOIUrl":"10.1016/j.neulet.2025.138153","url":null,"abstract":"<div><div>Kratom is derived from the leaves of a plant (<em>Mitragyna speciosa</em>) native to Southeast Asia that has been consumed for its complex stimulant-like effects at low doses, opiate-like effects at high doses, to treat mood related issues like anxiety or depression, or to help ameliorate opioid withdrawal symptoms. However, the neural mechanisms of its major psychoactive alkaloids, mitragynine (MG) and 7-hydroxymitragynine (7-HMG), are still not clear. Given that the effects of kratom are often compared to drugs with abuse liabilities, the current study examined the effects of MG and 7-HMG on reward-related neurotransmission. Fixed potential amperometry was used to quantify stimulation-evoked phasic dopamine release in the nucleus accumbens (NAc) of anesthetized male and female mice before and after MG (1, 15, or 30 mg/kg i.p.), 7-HMG (0.5, 1, or 2 mg/kg i.p.), or vehicle. MG reduced dopamine release over the recording period (90 min) in a dose dependent manner, and the low dose of MG significantly increased dopamine autoreceptor functioning in males. Both sexes responded similarly to 7-HMG with the low dose of 7-HMG increasing dopamine release while the high dose decreased dopamine release. 7-HMG did not alter dopamine autoreceptor functioning for either sex. Neither MG nor 7-HMG altered the clearance rate of stimulation-evoked dopamine. Findings suggest that these kratom alkaloids do alter dopamine functioning, although potentially not in a way consistent with classic drugs of abuse. Further investigation of the neural mechanisms of kratom’s alkaloids will provide crucial and urgent insight into their therapeutic uses or potential abuse liability.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"850 ","pages":"Article 138153"},"PeriodicalIF":2.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382873","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":"Impact of fatty acids on glutamate-related gene expression in the hippocampus: Focus on lauric acid","authors":"Laura Romero-Muñoz ,&nbsp;Ana Belén Sanz-Martos ,&nbsp;Nuria Del Olmo ,&nbsp;Beatriz Merino ,&nbsp;Mariano Ruiz-Gayo ,&nbsp;Victoria Cano","doi":"10.1016/j.neulet.2025.138152","DOIUrl":"10.1016/j.neulet.2025.138152","url":null,"abstract":"<div><div>Excessive dietary fat consumption has been linked to impairments in synaptic plasticity in the hippocampus (HIP), a brain region crucial for learning and memory that relies on balanced glutamatergic neurotransmission. This study investigates the acute effects of three fatty acids (FAs)—lauric acid (LA), palmitic acid (PA), and oleic acid (OA)—on glutamate (GLU)-related gene expression in the HIP of male and female young mice. Hippocampal slices were treated with FAs, and mRNA levels of genes involved in GLU transport, GLU-glutamine (GLN) cycling, and GLU receptor subunit encoding were quantified using RT-PCR. FA treatment reduced mRNA levels of enzymes involved in the conversion of GLU to GLN (glutamine synthetase; GS), GABA (glutamate decarboxylase 1; GAD67), and α-ketoglutarate (glutamate pyruvate transaminase 2; AAT2). Additionally, the expression of glutamine transporters (SNAT1, SNAT2, SNAT3), the astrocytic GLU transporter GLT-1, and the NMDA receptor subunit NMDA2a was also reduced. These effects were most pronounced with LA. Notably, while the HIP showed similar sensitivity to fatty acids across sexes, overall gene expression levels were lower in females. These findings highlight the acute susceptibility of hippocampal GLU-related pathways to FA exposure, particularly LA, suggesting potential risks of high-LA diets on cognitive function. Further research is needed to explore the long-term consequences of dietary fat on hippocampal health and its sex-specific effects.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"850 ","pages":"Article 138152"},"PeriodicalIF":2.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377468","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":"Deletion of β-arrestin 2 in mice affects kappa opioid receptor-mediated behaviors depending on sex, ovariectomy status, and behavioral endpoints","authors":"Peng Huang,&nbsp;Conrad K. Ho,&nbsp;Kathryn Bland,&nbsp;Lee-Yuan Liu-Chen","doi":"10.1016/j.neulet.2025.138154","DOIUrl":"10.1016/j.neulet.2025.138154","url":null,"abstract":"<div><div>We previously demonstrated that in a mouse line expressing a kappa opioid receptor (KOR) mutant with all the four phosphorylation sites mutated to alanines (K4A) the selective KOR agonist U50,488H (U50)-induced anti-scratching tolerance was attenuated in males and conditioned place aversion (CPA) was reduced in females, without affecting acute U50-induced anti-scratching effect and hypo-locomotion (Huang et al, 2022, Neuropharmacology). KOR phosphorylation deficiency in K4A mice would lead to little recruitment of β-arrestin2 (arrb2) and hence greatly reduced arrb2-mediated KOR regulation, downstream signaling and behaviors. Herein we examined effects of arrb2 deletion in mice on KOR-mediated behaviors in arrb2 knockout (arrb2(-/-)) mice vs wildtype (WT) mice. We found that arrb2 deletion enhanced anti-scratching effects produced by acute U50 in males, but not in females. Intriguingly, in ovariectomized (OVX) but not sham-operated females, arrb2 deletion increased U50-induced anti-scratching effect, similar to males. Furthermore, OVX enhanced U50-induced anti-scratching effects specifically in arrb2(-/-) females, but not in WT females. Thus, ovarian hormones-related modulations may obscure the phenotype associated with arrb2(-/-) to promote the KOR-mediated anti-scratching signaling in females, while OVX unmasked it. In contrast, arrb2 deletion did not affect U50-induced CPA and had no effects on anti-scratching tolerance to repeated U50 in either male or female mice. The findings in arrb2(-/-) mice revealed both similarities and differences compared to our previous results in K4A mice. Overall, the effects of arrb2 deletion on KOR-mediated behaviors depended on specific behavioral endpoints, sex, and OVX status.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"850 ","pages":"Article 138154"},"PeriodicalIF":2.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382871","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":"Age-dependent increase in apoptosis is associated with dysregulation of miR-92a/Akt/mTOR and NF-κB signaling pathways in male rats","authors":"Roya Naderi ,&nbsp;Rahil Salimi ,&nbsp;Abbas Jafari ,&nbsp;Nasrin Mehranfard","doi":"10.1016/j.neulet.2025.138115","DOIUrl":"10.1016/j.neulet.2025.138115","url":null,"abstract":"<div><div>Brain aging is the leading risk factor for most neurodegenerative diseases and has been linked with high rates of neuron loss. Thus, identifying molecular mechanisms underlying neuron loss and pharmacological modulation may be of great importance for slowing or preventing age-related diseases. Herein, we investigated the roles of miR-92a, Akt, mTOR, and NF-κB in age-associated apoptosis in the hippocampus (a critical structure involved in brain aging) of male rats alone and in combination with prazosin. Twenty-four male Wistar rats were grouped into young control (3-month-old), aged (18-month-old), and aged + prazosin groups (n = 8 for each). Prazosin (1 mg/kg; i.p.) was administered for 4 weeks to aged rats. Apoptosis was detected by TUNEL staining. Western blot for Akt, mTOR, and NF-κB was conducted. miR-92a gene expression was performed by using RT-PCR. The results indicated a marked enhancement of apoptosis in the aging hippocampus. We also detected substantial up-regulation of NF-κB as well as substantial down-regulation of phosphorylated-Akt and mTOR in the aging hippocampus. Moreover, miR-92a gene expression was markedly reduced in the aging hippocampus. Treatment with prazosin significantly suppressed apoptosis and reversed miR-92a gene expression, as well as Akt, mTOR, and NF-κB protein expressions in the aging hippocampus. Considering the NF-κB regulatory role on miRNAs, our results suggest that NF-κB may be a negative transcriptional regulator of miR-92a, which in turn could regulate the Akt/mTOR signaling. In this regard, NF-κB upregulation may mediate the downregulation of miR-92a/Akt/mTOR axis, and thereby contribute to age-related neurodegeneration. This may provide a novel treatment target for delaying or preventing age-related problems.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"848 ","pages":"Article 138115"},"PeriodicalIF":2.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971705","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":"Extracellular baskets in inner hair cells and perineuronal nets in auditory nerves: Changes in noise-induced hearing loss rats","authors":"So Young Kim ,&nbsp;Jong Chan Jeon ,&nbsp;Bohyeon Park ,&nbsp;Do Eun Kim","doi":"10.1016/j.neulet.2025.138147","DOIUrl":"10.1016/j.neulet.2025.138147","url":null,"abstract":"<div><h3>Background</h3><div>The extracellular baskets of cochlear inner hair cell (IhC) ribbon synapses have been suggested to regulate synaptic coupling. This study aimed to investigate the expression of components of the extracellular baskets of the IhCs, chondroitin sulfate proteoglycans (CSPGs) and a hyaluronan and proteoglycan link protein 1 (HAPLN1) in the cochlea and auditory nerve. In addition, changes in CSPGs and HAPLN1 in noise-injured cochleae were examined.</div></div><div><h3>Methods</h3><div>The expression of CSPGs, including aggrecan (ACAN), brevican (BCAN), neurocan (NCAN), and HAPLN1, was evaluated in the cochleae of 2-month-old Sprague–Dawley (SD) rats. The expression of CSPGs and HAPLN1 in cochleae and auditory nerves was compared to that in 3-month-old noise-exposed SD rats during the developmental period. The cochlear immunohistochemistry (IHC) and cochlear whole mount immunofluorescence studies were conducted for ACAN, BCAN, NCAN, and HAPLN1. To examine the large ganglial cells in auditory nerves, IHC was conducted for parvalbumin (PV), glutamate decarboxylase 67 (GAD67), postsynaptic density protein 95 (PSD95), and glial fibrillary acidic protein (GFAP). In situ hybridization was performed for BCAN.</div></div><div><h3>Results</h3><div>ACAN, BCAN, and HAPLN1 expression was detected in the IhCs and was decreased tendency in noise-injured cochleae. In the spiral ganglial cell (SGC) region, ACAN and NCAN were expressed without the expression of BCAN. In auditory nerves, large ganglionic cells (LGCs) are encased with perineuronal nets (PNNs), which express PV, GAD67, and PSD95. The mRNA expression of BCAN was noted in SGCs and glial cells of auditory nerves.</div></div><div><h3>Conclusions</h3><div>The extracellular baskets of IhCs revealed the expression of CSPGs and HAPLN1, which was attenuated in noise-exposed cochleae. In auditory nerves, PV-positive LGCs with inhibitory synapses presented PNNs. The protein expression of BCAN was restricted to the extracellular baskets of IhC but not to the SGC region. However, the mRNA expression of BCAN in SGCs was not affected.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"850 ","pages":"Article 138147"},"PeriodicalIF":2.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374401","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":"Alterations in iron levels in the locus coeruleus of a transgenic Alzheimer’s disease rat model","authors":"Kayla Aishwarya Bhagaloo ,&nbsp;Lei Yu ,&nbsp;Elizabeth A. West ,&nbsp;Daniel J. Chandler ,&nbsp;Natalia Shcherbik","doi":"10.1016/j.neulet.2025.138151","DOIUrl":"10.1016/j.neulet.2025.138151","url":null,"abstract":"<div><div>Iron is essential for brain function, acting as a cofactor for enzymes involved in neurotransmitter synthesis and metabolism. However, dysregulated iron homeostasis is increasingly linked to neurodegenerative diseases, including Alzheimer’s disease (AD). The locus coeruleus (LC), a norepinephrine-producing brainstem nucleus, is among the earliest regions affected in AD, yet its iron dynamics remain poorly understood. This study presents the first comprehensive analysis of iron content in the LC by combining a transgenic AD rat model, precise anatomical isolation, and Inductively Coupled Plasma Mass Spectrometry for high-sensitivity metal quantification. This approach enabled the profiling of iron and zinc concentrations in the LC, uncovering novel insights into iron dysregulation in AD. We observed a significant genotype-specific increase in LC iron levels in TgF344-AD rats compared to wild-type controls. Notably, our findings reveal distinct iron alterations in TgF344-AD rats, suggesting a previously unrecognized role for iron homeostasis in LC dysfunction. These results provide new perspectives on iron dysregulation in AD pathology and its potential as a therapeutic target.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"850 ","pages":"Article 138151"},"PeriodicalIF":2.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372659","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":"Nasal mucosal mesenchymal stem cells promote repair of sciatic nerve injury in rats by modulating the inflammatory microenvironment","authors":"Yushi Tang ,&nbsp;Yilu Li ,&nbsp;Wenhui Yang ,&nbsp;Zhenxing Tao ,&nbsp;Wentao Shi ,&nbsp;Mengyuan Yu ,&nbsp;Bai Xu ,&nbsp;Xiaojie Lu","doi":"10.1016/j.neulet.2024.138112","DOIUrl":"10.1016/j.neulet.2024.138112","url":null,"abstract":"<div><div>Sciatic nerve injury (SNI) represents the most prevalent form of peripheral nerve damage, resulting in the rapid activation of macrophages into the M1 phenotype following injury. This activation induces an inflammatory microenvironment that negatively impacts nerve regeneration. Ectodermal mesenchymal stem cells (EMSCs), isolated from nasal mucosa, possess the capacity for multidirectional differentiation and exhibit immunomodulatory effects. Modulating macrophage polarization to create a favorable environment for nerve repair may represent a potential approach to facilitate nerve recovery. This investigation sought to explore the effects of EMSCs transplantation on macrophage polarization and nerve regeneration in SNI, as well as to identify the underlying mechanisms. An <em>in vivo</em> SNI model was established, and behavioral and histological analyses demonstrated that EMSCs transplantation facilitated nerve function recovery. Furthermore, immunofluorescence and Western blot assays revealed an increase in M2 macrophage presence and the secretion of anti-inflammatory cytokines following EMSCs transplantation, thereby promoting nerve regeneration. <em>In vitro</em>, EMSCs were found to enhance M2 macrophage polarization and the production of anti-inflammatory factors. Additionally, it was confirmed that EMSCs regulate macrophage polarization through the PI3K/AKT/NF-κB signaling pathway, thereby fostering an optimal inflammatory environment for nerve regeneration.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"848 ","pages":"Article 138112"},"PeriodicalIF":2.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915437","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}