Molecular Neurobiology最新文献

{"title":"Galactose Impairs Motor Performance and Cerebellar Signaling in Young Male Wistar Rats.","authors":"Bruna Klippel Ferreira, Thiago Paz-Simões, Thairine Neves Melo, Patricia Felix Rolo Gonçalves, Regina Celia Cussa Kubrusly, Ricardo Augusto de Melo Reis, Gilda Angela Neves, Gustavo Costa Ferreira, Patricia Fernanda Schuck","doi":"10.1007/s12035-024-04684-6","DOIUrl":"10.1007/s12035-024-04684-6","url":null,"abstract":"<p><p>Galactosemias are a group of inborn errors of galactose metabolism that causes different motor symptoms such as ataxia, tremor, and fine motor dysfunction. The objective was to investigate the cerebellar damage caused by an acute galactose administration. Thirty-day-old male and female Wistar rats were used. Animals were randomized into the following groups: I) galactose group, receiving a single subcutaneous administration of galactose; II) control group, receiving the vehicle solution under the same conditions. One, 3 or 24 h after administration, the animals were evaluated in the Rotarod test. A lower motor performance was observed in male rats 3 h after a galactose administration. This effect was not seen in females or with galactose exposure for 1 or 24 h. The activities of acetylcholinesterase and choline acetyltransferase were found unaltered in the cerebellum of males 3 h after galactose injection. We also found lower TH levels in cerebellar hemispheres and higher TH levels in cerebellar vermis 3 h after galactose administration in male rats, without differences in MAO-A or MAO-B activities. Galactose administration resulted in lower p-CREB(Ser¹³³) and GAD67 levels in cerebellar hemispheres, without altering these parameters in cerebellar vermis of male rats. Finally, a decrease in TrkB-FL immunocontent (but not of TrkB-T levels) was observed in male cerebellar hemispheres. The absence of neurochemical alterations 1 h or 24 h after galactose administration indicates a transient effect for this hexose. The signs and symptoms of galactosemic patients underscore the need to study galactose effects in males and females and in various brain areas. Our findings enhance the understanding of therapeutic mechanisms of catecholaminergic drugs, which are proposed as a potential therapy for galactosemia.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7542-7556"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255952","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":"Role of Probiotics in Depression: Connecting Dots of Gut-Brain-Axis Through Hypothalamic-Pituitary Adrenal Axis and Tryptophan/Kynurenic Pathway involving Indoleamine-2,3-dioxygenase.","authors":"Sneha Tiwari, Vijay Paramanik","doi":"10.1007/s12035-025-04708-9","DOIUrl":"10.1007/s12035-025-04708-9","url":null,"abstract":"<p><p>Depression is one of the most disabling mental disorders worldwide and characterized by symptoms including worthlessness, anhedonia, sleep, and appetite disturbances. Recently, studies have suggested that tryptophan (Trp) metabolism plays a key role in depressed mood through serotonin and kynurenine pathway involving enzyme tryptophan 5-monooxygenase (TPH) and indoleamine-2,3-dioxygenase (IDO) respectively. Moreover, during neuroinflammation, IDO is activated by proinflammatory cytokines and affects neurogenesis, cognition, disturbed hypothalamic-pituitary-adrenal (HPA) axis, and gut homeostasis by altering the gut bacteria and its metabolites like Trp derivatives. Furthermore, over the decades, researchers have focused on understanding communication between the human microbiome, especially gut microbiota, and mental health, called gut-brain-axis (GBA), particularly through Trp metabolism. Supplementation of probiotics in depression has gained attention from researchers and clinicians. However, there is limited information about probiotics supplementation on depression involving enzyme IDO and kynurenine pathway metabolites. This review discussed the potential role of probiotics in depression through the tryptophan/kynurenine pathway.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7230-7241"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059626","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":"Nandrolone Abuse Prior to Head Trauma Mitigates Endoplasmic Reticulum Stress, Mitochondrial Bioenergetic Deficits, and Markers of Neurodegeneration.","authors":"Marcelo S Rodolphi, Nathan R Strogulski, Afonso Kopczynski, Monia Sartor, Gabriela Soares, Vitoria G de Oliveira, Lucia Vinade, Chariston Dal-Belo, Juliana V Portela, Cesar A Geller, Marco A De Bastiani, Jijo S Justus, Luiz Osorio C Portela, Douglas H Smith, Luis V Portela","doi":"10.1007/s12035-024-04488-8","DOIUrl":"10.1007/s12035-024-04488-8","url":null,"abstract":"<p><p>The abuse of synthetic steroids, such as nandrolone decanoate (ND), is often associated with violent behavior, increasing the risk of traumatic brain injury (TBI). After a TBI, proteins like APP, β-amyloid peptide-42 (Aβ42), and phosphorylated tau (pTau) accumulate and trigger endoplasmic reticulum (ER) stress associated with an unfolded protein response (UPR). The involvement of mitochondrial bioenergetics in this context remains unexplored. We interrogate whether the abuse of ND before TBI alters the responses of ER stress and mitochondrial bioenergetics in connection with neurodegeneration and memory processing in mice. Male CF1 adult mice were administered ND (15 mg/kg) or vehicle (VEH) s.c. for 19 days, coinciding with the peak day of aggressive behavior, and then underwent cortical controlled impact (CCI) or sham surgery. Spatial memory was assessed through the Morris water maze task (MWM) post-TBI. In synaptosome preparations, i) we challenged mitochondrial complexes (I, II, and V) in a respirometry assay, employing metabolic substrates, an uncoupler, and inhibitors; and ii) assessed molecular biomarkers through Western blot. TBI significantly increased APP, Aβ42, and pTau^Ser396 levels, along with ER-stress proteins, GRP78, ATF6, and CHOP, implying it primed apoptotic signaling. Concurrently, TBI reduced mitochondrial Ca²⁺ efflux in exchange with Na⁺, disturbed the formation/dissipation of membrane potential, increased H₂O₂ production, decreased biogenesis (PGC-1⍺ and TOM20), and ATP biosynthesis coupled with oxygen consumption. Unexpectedly, ND abuse before TBI attenuated the elevations in APP, Aβ42, and pTau^Ser396, accompanied by a decrease in GRP78, ATF6, and CHOP levels, and partial normalization of mitochondrial-related endpoints. A principal component analysis revealed a key hierarchical signature featuring mitochondrial Ca²⁺ efflux, CHOP, GRP78, TOM20, H₂O₂, and bioenergetic efficiency as a unique variable (PC1) able to explain the memory deficits caused by TBI, as well as the preservation of memory fitness induced by prior ND abuse.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"6951-6967"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308081","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":"LDL Exposure Disrupts Mitochondrial Function and Dynamics in a Hippocampal Neuronal Cell Line.","authors":"Hémelin Resende Farias, Jessica Marques Obelar Ramos, Caroline Tainá Griesang, Lucas Santos, Osmar Vieira Ramires Junior, Debora Guerini Souza, Fernanda Silva Ferreira, Sabrina Somacal, Leo Anderson Meira Martins, Diogo Onofre Gomes de Souza, José Cláudio Fonseca Moreira, Angela T S Wyse, Fátima Theresinha Costa Rodrigues Guma, Jade de Oliveira","doi":"10.1007/s12035-024-04476-y","DOIUrl":"10.1007/s12035-024-04476-y","url":null,"abstract":"<p><p>Hypercholesterolemia has been associated with cognitive dysfunction and neurodegenerative diseases. Moreover, this metabolic condition disrupts the blood-brain barrier, allowing low-density lipoprotein (LDL) to enter the central nervous system. Thus, we investigated the effects of LDL exposure on mitochondrial function in a mouse hippocampal neuronal cell line (HT-22). HT-22 cells were exposed to human LDL (50 and 300 μg/mL) for 24 h. After this, intracellular lipid droplet (LD) content, cell viability, cell death, and mitochondrial parameters were assessed. We found that the higher LDL concentration increases LD content compared with control. Both concentrations increased the number of Annexin V-positive cells, indicating apoptosis. Moreover, in mitochondrial parameters, the LDL exposure on hippocampal neuronal cell line leads to a decrease in mitochondrial complexes I and II activities in both concentrations tested and a reduction in Mitotracker™ Red fluorescence and Mitotracker™ Red and Mitotracker™ Green ratio in the higher concentration, indicating mitochondrial impairment. The LDL incubation induces mitochondrial superoxide production and decreases superoxide dismutase activity in the lower concentration in HT-22 cells. Finally, LDL exposure increases the expression of genes associated with mitochondrial fusion (OPA1 and mitofusin 2) in the lower concentration. In conclusion, our findings suggest that LDL exposure induces mitochondrial dysfunction and modulates mitochondrial dynamics in the hippocampal neuronal cells.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"6939-6950"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291492","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":"Research Progress in the Molecular Mechanism of NLRP3 Inflammasome in Alzheimer's Disease and Regulation by Natural Plant Products.","authors":"Runru Zu, Hao Lu, Wanting Liu, Simai Shao, Jiayao Zheng, Xiran Ying, Yangang Zhou, Zhonghua Li, Wang Wang, Dejuan Li, Quekun Peng, Huifen Ma, Zhenqiang Zhang, Yiran Sun","doi":"10.1007/s12035-025-04715-w","DOIUrl":"10.1007/s12035-025-04715-w","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a prominent neurodegenerative disorder affecting the central nervous system in the elderly. Current understanding of AD primarily centers on the gradual decline in cognitive and memory functions, believed to be influenced by factors including mitochondrial dysfunction, β-amyloid aggregation, and neuroinflammation. Emerging research indicates that neuroinflammation plays a significant role in the development of AD, with the inflammasome potentially mediating inflammatory responses that contribute to neurodegeneration. Recent studies in AD pathology have identified a novel form of inflammasome referred to as NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. Pathological alterations closely associated with NLRP3 inflammasome activation have been observed in the brain tissues of AD patients, transgenic mice, and in vitro neurocyte models. Numerous studies have demonstrated the potent neuroprotective properties of natural plant products (NPPs) against NLRP3 inflammasome-mediated AD pathology. This review provides a comprehensive examination of the NLRP3 inflammasome, its involvement in AD pathology, and the mechanisms underlying the therapeutic effects of NPP targeting the NLRP3 inflammasome.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7296-7312"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059624","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":"Assessing the Causal Relationships Between Lipid Species and Stroke by Using Mendelian Randomization.","authors":"Shi-Qi Wang, Hao Zhang, Xiao-Shan Hui, Qi Zhang, Rubing Chen, Fei Xie","doi":"10.1007/s12035-025-04697-9","DOIUrl":"10.1007/s12035-025-04697-9","url":null,"abstract":"<p><p>Circulating lipids and changes in lipid profiles have long been associated with the development of stroke but causal relationships remain unclear.In this study, we aimed to assess the causal relationships between lipid species and multiple stroke phenotypes to inform stroke prevention and treatment strategies. We conducted a two-sample Mendelian randomization analysis using data from genome-wide association studies. The primary method for causal assessment was inverse variance weighting (IVW), complemented by the MR-Egger, weighted median, and weighted mode methods. Sensitivity analyses, based on MR-Egger, MR-PRESSO, and Cochran's Q statistics, were also applied to reinforce the results. In total, potential causality was observed for 133 pairs of lipids with stroke types(P < 0.05). After multiple testing correction (PFDR < 0.05), potential causal associations remained for 10 pairs of lipids, including specific sterol esters and phosphatidylcholines, with various stroke subtypes. The findings demonstrate the significant role that genetically determined lipid profiles may play in the pathogenesis of stroke. Further research is needed to establish whether these biomarkers can be used for stroke prevention or treatment.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7174-7182"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040253","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":"The Effects of miR-22-3p on Differentiation of Human Dental Pulp Stem Cells into Neural Progenitor-Like Cells.","authors":"Muhammad Tehsil Gul, Muhammad Nasir Khan Khattak, Rizwan Qaisar, Manju Nidagodu Jayakumar, A B Rani Samsudin, Amir Ali Khan","doi":"10.1007/s12035-025-04702-1","DOIUrl":"10.1007/s12035-025-04702-1","url":null,"abstract":"<p><p>Stem cell treatment shows promise in treating conditions such as neurodegenerative disorders and spinal injuries, but its effectiveness is hampered by cell death and apoptosis. Improving the differentiation of MSCs into neural cells could enhance their therapeutic potential. The role of miR-22-3p in human dental pulp stem cells (HDPSCs), a superior alternative to treat neurodegenerative disorders, and its molecular mechanisms during neural differentiation remain elusive. Therefore, we investigated the miR-22-3p transfections during HDPSC differentiation into neural progenitor-like cells (NPCs) and elucidated the molecular processes through transcriptomic analysis. HDPSCs were differentiated into NPCs after transfection with a miR-22-3p mimic and inhibitor; the differentiation process was assessed by cell viability and expression of Nestin protein. mRNA sequencing on days 1, 3, and 7 of the differentiation process identified several differentially expressed genes (DEGs). Cytoscape and functional enrichment analysis pinpointed central hub genes among the DEGs and uniquely expressed genes. miR-22-3p mimic hindered HDPSC differentiation by reducing proliferation and increasing apoptosis. It downregulated genes linked to extracellular matrix, synaptic and vesicle functions, lipid metabolism, JAK-STAT, and cell cycle pathways across all days while activating proteasome and digestion pathways. In contrast, miR-22-3p inhibition boosts NPC proliferation and elevates Nestin neural marker protein expression. Altogether, miR-22-3p disrupts synapse functioning and lipid metabolism pathways, resulting in apoptosis and death. Conversely, inhibiting miR-22-3p enhances neural differentiation and proliferation of HDPSCs, suggesting its potential application in generating a greater quantity of NPCs and neurons.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7445-7468"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123383","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":"The Nerve-Induced Adipose Stem Cells Promote Nerve Repair in Stress Urinary Incontinence by Regulating Schwann Cell Repair Phenotype Conversion Through Activation of the Notch Pathway.","authors":"Ming Liu, Youyi Lu, Fengze Sun, Yongwei Li, Jitao Wu, Qingsong Zou","doi":"10.1007/s12035-025-04704-z","DOIUrl":"10.1007/s12035-025-04704-z","url":null,"abstract":"<p><p>Stress urinary incontinence (SUI) currently lacks effective treatment options, and the restoration of neurological function remains a major challenge, with unmet clinical needs. Research has indicated that adipose-derived stem cells (ADSCs) can be induced to differentiate into neural-induced adipose-derived stem cells (NI-ADSCs) under specific inductive conditions, exhibiting excellent neuroregenerative capabilities. ADSCs were obtained from female SD rats and induced into NI-ADSCs. In vitro, NI-ADSCs were co-cultured with Schwann cells (SCs) to investigate their effects on SC proliferation and repair phenotype transition and further explore its underlying mechanism. In vivo, a rat model of SUI was established using a bilateral pudendal nerve transection method. NI-ADSCs were injected into the urethral sphincter to evaluate their effects on urodynamics, muscle angiogenesis, and neural repair in SUI rats, while also exploring the mechanisms of neural repair. This study used EGF, FGF, and B27 to induce ADSCs into NI-ADSCs expressing neural induction markers (MAP, Nestin, and PAX6). In vitro experiments found no significant difference in the proliferation of L6 and RSC96 between NI-ADSCs and ADSCs (p > 0.05). However, when co-cultured with NI-ADSCs, SCs showed upregulated expression of repair-related phenotypic markers (BDNF, GDNF, and GFAP). In this phenotypic transformation process, the expression of Notch-related pathway proteins (Notch1, NICD, and Hes1) was increased, and the use of DAPT (a Notch pathway inhibitor) could suppress the SC repair phenotype transformation. In vivo, experiments revealed that intraurethral injection of NI-ADSCs significantly promoted the expression of neural marker (S100β) and demyelination markers (GFAP) and urodynamic recovery in SUI rats, while DAPT inhibited its neural repair effect. In summary, our study demonstrates that NI-ADSCs can promote nerve regeneration by promoting and maintaining the repair-related phenotype of SCs. The underlying mechanism may be related to the activation of the Notch signaling pathway.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7330-7344"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066751","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":"Microglial NLRP3 Inflammasomes in Alzheimer's Disease Pathogenesis: From Interaction with Autophagy/Mitophagy to Therapeutics.","authors":"Gunel Ayyubova, Leelavathi N Madhu","doi":"10.1007/s12035-025-04758-z","DOIUrl":"10.1007/s12035-025-04758-z","url":null,"abstract":"<p><p>The nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, discovered 20 years ago, is crucial in controlling innate immune reactions in Alzheimer's disease (AD). By initiating the release of inflammatory molecules (including caspases, IL-1β, and IL-18), the excessively activated inflammasome complex in microglia leads to chronic inflammation and neuronal death, resulting in the progression of cognitive deficiencies. Even though the involvement of NLRP3 has been implicated in neuroinflammation and widely explored in several studies, there are plenty of controversies regarding its precise roles and activation mechanisms in AD. Another prominent feature of AD is impairment in microglial autophagy, which can be either the cause or the consequence of NLRP3 activation and contributes to the aggregation of misfolded proteins and aberrant chronic inflammatory state seen in the disease course. Studies also demonstrate that intracellular buildup of dysfunctional and damaged mitochondria due to defective mitophagy enhances inflammasome activation, further suggesting that restoration of impaired autophagy and mitophagy can effectively suppress it, thereby reducing inflammation and protecting microglia and neurons. This review is primarily focused on the role of NLRP3 inflammasome in the etiopathology of AD, its interactions with microglial autophagy/mitophagy, and the latest developments in NLRP3 inflammasome-targeted therapeutic interventions being implicated for AD treatment.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7124-7143"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414300","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":"Potential Ameliorating Effects of Fluvoxamine in a Rat Model of Endotoxin-Induced Neuroinflammation: Molecular Aspects Through SIRT-1/GPX-4 and HMGB-1 Signaling.","authors":"Muhammet Yusuf Tepebaşı, Halil Aşcı, Pınar Aslan Koşar, Emine Nur Dinçer, Esma Selçuk, Öznur Kolay, İbrahim Hüseynov","doi":"10.1007/s12035-025-04764-1","DOIUrl":"10.1007/s12035-025-04764-1","url":null,"abstract":"<p><p>Research on the tissue-protective effects of fluvoxamine (FLV), a selective serotonin reuptake inhibitor, rapidly expands. This study explores FLV's potential to protect against lipopolysaccharide (LPS)-induced neuroinflammation, a key factor in systemic inflammation-related neuronal damage. Four equal groups of thirty-two female Wistar Albino rats were created: FLV, LPS-FLV (50 mg/kg intraperitoneal), LPS (5 mg/kg intraperitoneal), and control. Both drugs were given in one dose on the same day. Tissues from the brain cortex, cerebellum, and hippocampus were taken for histopathology, immunohistochemistry, biochemistry, and genetic analysis. In the LPS group, histological examinations revealed hyperemia, edema, mild degeneration, neuronal death, and modest gliosis. Additionally, while apelin and total antioxidant status levels were reduced, greater levels of oxidative stress index, glial fibrillary acidic protein (GFAP), mammalian target of rapamycin (mTOR), and total oxidant status were noted. FLV treatment reversed all these findings. Genetic analyses revealed that LPS decreased sirtuin-1 (SIRT-1) and glutathione peroxidase 4 (GPX-4) while increasing high mobility group box protein 1 (HMGB-1). FLV treatment reversed all these parameters, and a significant result was obtained only with GPX-4. In this study, FLV treatment was shown to have anti-inflammatory and neuroprotective effects through various mechanisms on the brain cortex, cerebellum, and hippocampus tissues in addition to its antidepressant effects.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7892-7902"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425587","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}