Molecular and Cellular Neuroscience最新文献

Exosome-based therapeutic approach for spinal cord injury: A review. 基于外泌体的脊髓损伤治疗方法综述。

IF 2.4 3区医学

Molecular and Cellular Neuroscience Pub Date : 2025-09-25 DOI: 10.1016/j.mcn.2025.104048

Shuai Bai, Rong Rong Qiang, Rui Yang Liu, De Jie Kang, Yan Ling Yang

{"title":"Exosome-based therapeutic approach for spinal cord injury: A review.","authors":"Shuai Bai, Rong Rong Qiang, Rui Yang Liu, De Jie Kang, Yan Ling Yang","doi":"10.1016/j.mcn.2025.104048","DOIUrl":"https://doi.org/10.1016/j.mcn.2025.104048","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is a devastating neurological condition associated with high rates of disability and mortality, placing substantial burdens on patients, families, and healthcare systems. Current treatment strategies, including surgical decompression, pharmacological intervention, and rehabilitation, offer only limited functional recovery. Exosomes, extracellular vesicles with a double-membrane structure, range in diameter from 30 to 150 nm (nm) and play a key role in intercellular communication by transporting proteins, lipids, and nucleic acids. Recent studies have highlighted their potential as natural nanocarriers for the treatment of neurodegenerative disorders. Due to their low immunogenicity and multifunctional reparative properties, exosomes have shown considerable efficacy in promoting neurological recovery following SCI. They exert therapeutic effects through multiple mechanisms, including modulation of the inflammatory response, promoting axonal regeneration and angiogenesis, and inhibiting apoptosis. This review summarizes the pathophysiological mechanisms underlying SCI and elucidates the therapeutic roles of exosomes and exosomal microRNAs (exo-miR) in SCI repair. Furthermore, it discusses current challenges and prospects for the clinical translation of exosome-based therapies, aiming to provide valuable insights for future research and clinical applications.</p>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":" ","pages":"104048"},"PeriodicalIF":2.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chronic functional deficits following a single closed head injury in mice are prevented by minocycline and N-acetyl cysteine. 二甲胺四环素和n -乙酰半胱氨酸可预防小鼠单一闭合性头部损伤后的慢性功能缺陷。

IF 2.4 3区医学

Molecular and Cellular Neuroscience Pub Date : 2025-09-23 DOI: 10.1016/j.mcn.2025.104049

Siobhán C Lawless, Craig Kelley, Elena Nikulina, Ufaq Tahir, Ashmeet Kaur, Juan Marcos Alarcon, Peter J Bergold

{"title":"Chronic functional deficits following a single closed head injury in mice are prevented by minocycline and N-acetyl cysteine.","authors":"Siobhán C Lawless, Craig Kelley, Elena Nikulina, Ufaq Tahir, Ashmeet Kaur, Juan Marcos Alarcon, Peter J Bergold","doi":"10.1016/j.mcn.2025.104049","DOIUrl":"10.1016/j.mcn.2025.104049","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) can produce chronic limb coordination and gait deficits that are associated with ongoing white matter damage. In rodent TBI models, chronic motor deficits may be obscured by aging or motor compensation. In addition, there are no treatments for TBI. The murine closed head injury (CHI) model produces diffuse, chronic white matter injury that may underlie chronic white matter dysfunction and motor deficits. Evoked compound action potentials (CAP) assess corpus callosum function from 3 to 180-days post injury (DPI). CHI acutely decreases total CAP amplitudes that recover by 90 DPI and increase further at 180 DPI. Total CAP amplitude changes are blocked by dosing of minocycline and N-acetylcysteine beginning 12 h post-injury (MN12). Injured or sham mice have similar times to traverse or number of foot faults on beam walk. DeepLabCut™ markerless limb tracking provides limb positions used to develop novel assays to assess beam walk and simple/complex wheel. Absition analysis integrates the duration and extent of foot faults during beam walk. Injured mice develop absition deficits at 90 DPI that worsen at 180 DPI suggesting a chronic and progressive decline. Chronic absition deficits are blocked by MN12 treatment. Speed typically assesses performance on simple/complex wheel. Novel limb coordination assays show that at 180 DPI, injured mice decrease coordination that significantly correlates with increased total CAP amplitude. MN12 alleviates chronic corpus callosum dysfunction and motor deficits suggesting a strong efficacy to treat TBI. DeepLabCut™ limb tracking reveals chronic deficits and motor compensation not seen with standard outcomes.</p>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":" ","pages":"104049"},"PeriodicalIF":2.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Covalent inhibitors in Parkinson's disease: Molecular targeting strategies for neuroprotective intervention 帕金森病的共价抑制剂：神经保护干预的分子靶向策略。

IF 2.4 3区医学

Molecular and Cellular Neuroscience Pub Date : 2025-09-09 DOI: 10.1016/j.mcn.2025.104037

Devadharuna Mohan , Raghul Venkatesan , Amarjith Thiyyar Kandy , Santhoshkumar Muthu , Saravanan Jayaram , Rajinikanth Baskaran , Palanisamy Pethappachetty , Divakar Selvaraj

{"title":"Covalent inhibitors in Parkinson's disease: Molecular targeting strategies for neuroprotective intervention","authors":"Devadharuna Mohan , Raghul Venkatesan , Amarjith Thiyyar Kandy , Santhoshkumar Muthu , Saravanan Jayaram , Rajinikanth Baskaran , Palanisamy Pethappachetty , Divakar Selvaraj","doi":"10.1016/j.mcn.2025.104037","DOIUrl":"10.1016/j.mcn.2025.104037","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by dopaminergic neuronal loss, protein aggregation, and neuroinflammation. Current symptomatic therapies have not demonstrated disease-modifying effects. Covalent inhibitors represent a promising multifactorial therapeutic approach due to their ability to form irreversible and specific bonds with target proteins. This narrative review incorporates recent experimental and computational findings on emerging covalent inhibitors that target key molecular mechanisms implicated in PD. This includes α-synuclein aggregation, LRRK2 kinase hyperactivity, monoamine oxidase B (MAO-B) dysfunction, glutathione S-transferase Pi 1 (GSTP1)-mediated oxidative stress, and modulation of the Nrf2 signaling pathway. We discuss structure-guided drug design strategies, warhead chemistry, and unique inhibition modalities that contribute to improved pharmacological profiles and neuroprotective potential. In addition to classical covalent inhibition, the review explores emerging targeted covalent degrader strategies that expand therapeutic possibilities by promoting selective protein degradation rather than mere functional suppression. Furthermore, recent preclinical advances and clinical translation challenges are evaluated, positioning covalent approaches as leading candidates for targeted and sustained PD interventions. Lastly, we address developmental obstacles, such as enhancing selectivity and blood-brain barrier penetration while minimizing off-target effects, highlighting the role of activity-based protein profiling, covalent PROTACs, and bifunctional covalent degraders as next-generation strategies to optimize therapeutic efficacy in PD treatment.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"135 ","pages":"Article 104037"},"PeriodicalIF":2.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic modifiers of epilepsy: A narrative review 癫痫的遗传修饰因子：一个叙述性的回顾。

IF 2.4 3区医学

Molecular and Cellular Neuroscience Pub Date : 2025-09-05 DOI: 10.1016/j.mcn.2025.104038

Saliha Rizvi , Syed Tasleem Raza , Farzana Mahdi

{"title":"Genetic modifiers of epilepsy: A narrative review","authors":"Saliha Rizvi , Syed Tasleem Raza , Farzana Mahdi","doi":"10.1016/j.mcn.2025.104038","DOIUrl":"10.1016/j.mcn.2025.104038","url":null,"abstract":"<div><div>Epilepsy is a neurological disorder that shows strong genetic control on the timing and onset of symptoms and drug response variability. Some epilepsy syndromes have clear monogenic mutations but genes with control on the phenotype and severity of the disorder and drug sensitivity are present in the whole genetic profile. Genetic modifiers are not the cause of epilepsy but control significant networks such as synaptic plasticity and ion channels and neurodevelopment and neuroinflammation and therefore the reason why two individuals with the same primary mutations have different clinical courses. The review comprehensively examines the genetics of epilepsy to outline standard and minority genetic determinants and to distinguish between single-genetic and poly-genetic causes. It examines genetic modifiers and the mechanism by which they act and the control they exert on drug resistance and seizure risk and development of epilepsy and cognitive and behavioral problems. Alongside it explains how GWAS data with the help of epigenetics to identify significant modifying genes with control on neurotransmission and the immune response and metabolic pathways and ion channel regulation such as <em>SCN1A</em> and <em>KCNQ2</em>. The major functional mechanisms of genetic modifiers and the control they exert on network excitability and the control on the blood-brain barrier and neurodevelopmental pathways has been emphasized and explained in specific sections. The final section in this overview discusses the future possibility with precision medicine through genetic modifier-directed treatments and new drug development strategies and will develop tailored epilepsy treatment strategies.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"135 ","pages":"Article 104038"},"PeriodicalIF":2.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stable apelin-13 analogues promote cell proliferation, differentiation and protect inflammation induced cell death 稳定的apelin-13类似物促进细胞增殖、分化和保护炎症诱导的细胞死亡。

IF 2.4 3区医学

Molecular and Cellular Neuroscience Pub Date : 2025-09-04 DOI: 10.1016/j.mcn.2025.104036

Priya Sharma , Mary Erazo Bastidas , Usman Ali , Shivadas Sivasubramaniam , Vadivel Parthsarathy

{"title":"Stable apelin-13 analogues promote cell proliferation, differentiation and protect inflammation induced cell death","authors":"Priya Sharma , Mary Erazo Bastidas , Usman Ali , Shivadas Sivasubramaniam , Vadivel Parthsarathy","doi":"10.1016/j.mcn.2025.104036","DOIUrl":"10.1016/j.mcn.2025.104036","url":null,"abstract":"<div><div>Emerging evidence indicates that apelin, an adipokine, plays a critical role in numerous biological functions and may hold potential for therapeutic applications; however, its efficacy is constrained by rapid plasma degradation. Thus, the search for novel apelin analogues with reduced susceptibility to plasma degradation is ongoing. We have previously shown novel modified apelin-13 analogues, providing exciting opportunities for potential therapeutic development against Alzheimer's disease. In this study we explored novel insights into the neuroprotective effects of stable fatty acid modified (Lys8GluPAL) apelin-13-amide and amidated apelin-13 amide in mitigating cellular damage in SH-SY5Y neuroblastoma cells exposed to palmitic acid (PA) and lipopolysaccharide-induced (LPS) stress. Both apelin-13 analogues were found to modulate ER stress response and reduce oxidative stress by suppressing PA- and LPS-induced ROS production (36 % and 42 % reductions in GSH/GSG (<em>p</em> < 0.005). The peptides attenuated apoptosis by reducing caspase 3/7 activity and restoring bcl2 expression (<em>p</em> < 0.05) in cells treated with PA and LPS. They also downregulated pro-apoptotic genes, protected neurites from stress-induced damage, and promoted neurite outgrowth. The observed protective effects could be due to activation of the AMPK pathway, a critical regulator of cellular energy homeostasis and survival. These findings provide insight into novel, enzymatically stable apelin-13 analogues and highlight their potential to be developed as therapeutic agents against neuroinflammation and neurodegenerative disease, including Alzheimer's disease.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"135 ","pages":"Article 104036"},"PeriodicalIF":2.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modulation of Nrf-2/HO-1/HIF-1α/TFAM pathways by Arbutin in rat model of cerebral ischemic stroke. 熊果苷对大鼠脑缺血模型中Nrf-2/HO-1/HIF-1α/TFAM通路的调节作用

IF 2.4 3区医学

Molecular and Cellular Neuroscience Pub Date : 2025-09-01 Epub Date: 2025-08-05 DOI: 10.1016/j.mcn.2025.104034

Pinki Balhara, Sunil Sharma, Neeru Vasudeva, Neelam Rani, Sapna Grewal, Deepak Deepak, Babu Lal Jangir

{"title":"Modulation of Nrf-2/HO-1/HIF-1α/TFAM pathways by Arbutin in rat model of cerebral ischemic stroke.","authors":"Pinki Balhara, Sunil Sharma, Neeru Vasudeva, Neelam Rani, Sapna Grewal, Deepak Deepak, Babu Lal Jangir","doi":"10.1016/j.mcn.2025.104034","DOIUrl":"10.1016/j.mcn.2025.104034","url":null,"abstract":"<p><p>Ischemic stroke (IS) reduces the blood flow to the brain regions that trigger oxidative stress-induced biochemical, behavioural, molecular, and cellular impairments. Current treatment strategies are limited due to their narrow therapeutic window as, there is an urgent need to identify alternative therapeutic strategies in clinical settings to promote beneficial outcomes in stroke patients. Current study, focused on the neuro-protective potential of Arbutin (AR) in ischemic brain injury via modulation in Nrf-2/HO-1/HIF-1α/TFAM pathway. MCAO surgery was performed for 90 min, followed by reperfusion on male wistar rats, and the drug was administered intra-peritoneally. Animals were then sacrificed to estimate infarct volume, brain edema, BBB permeability, oxidative stress, inflammation, mitochondrial dysfunction, gene expression along with behavioural and morphological studies at different time intervals, i.e., 24 h and 21 days post-stroke. The results revealed that AR treatment improved neurological functions by maintaining BBB integrity and reducing edema, infarct volume, oxidative stress, and neuro-inflammation. It also improved the mitochondrial functions by increasing the gene expression of HIF-1α and TFAM along with reducing caspase-3 activation and iNOS gene expression through enhancing Nrf-2/HO-1 expression that supports the antioxidant activity of AR. Further, strong binding affinity of AR with the Nrf2 as revealed by the docking studies, reinforces our finding especially given the lack of prior target specific investigations exploring the detailed patho-mechanism of IS. Overall, AR exerts neuro-protective effect by modulating the Nrf-2/HO-1/HIF-1/TFAM pathways leading to improved mitochondrial functions, enhanced neurological outcomes, and increased neuronal survival which underscore its potential to as a therapeutic candidate for the treatment of IS.</p>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":" ","pages":"104034"},"PeriodicalIF":2.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144789578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neuroprotective effect of the peroxisome proliferator-activated receptor γ agonist lobeglitazone following intracerebral hemorrhage in rats. 过氧化物酶体增殖物激活受体γ激动剂洛贝列酮对脑出血大鼠的神经保护作用。

IF 2.4 3区医学

Molecular and Cellular Neuroscience Pub Date : 2025-09-01 Epub Date: 2025-07-10 DOI: 10.1016/j.mcn.2025.104030

Tae Jung Kim, Young-Ju Kim, Soo-Hyun Park, Youngjoon Kim, Sang-Bae Ko

{"title":"Neuroprotective effect of the peroxisome proliferator-activated receptor γ agonist lobeglitazone following intracerebral hemorrhage in rats.","authors":"Tae Jung Kim, Young-Ju Kim, Soo-Hyun Park, Youngjoon Kim, Sang-Bae Ko","doi":"10.1016/j.mcn.2025.104030","DOIUrl":"10.1016/j.mcn.2025.104030","url":null,"abstract":"<p><p>Lobeglitazone, an oral antidiabetic medication, acts as a peroxisome proliferator-activated receptor γ (PPARγ) agonist and demonstrates neuroprotective effects. This study investigated beneficial effects and mechanisms of lobeglitazone treatment in an experimental intracerebral hemorrhage (ICH) rat model. ICH was induced in the left striatum of Sprague-Dawley rats by administration of 0.6 units of collagenase type IV. Rats with ICH were assigned randomly to three treatment groups: (1) control group, (2) lobeglitazone 2 mg/kg, and (3) lobeglitazone 4 mg/kg (N = 6, in each group). Medications were administered orally for 3 days following ICH. Outcomes were measured based on brain edema on the third day after ICH. Behavioral outcomes were evaluated on days 1, 3, 6, and 13 following ICH utilizing the modified neurological severity score (mNSS). On the third day after ICH, inflammatory cytokines were evaluated using western blotting, and inflammatory cells were examined through immunohistochemistry. Administration of lobeglitazone at a dosage of 4 mg/kg reduced brain edema significantly (15 %) in comparison to the control and 2 mg/kg (7 %) groups. Moreover, lobeglitazone administration at a dosage of 4 mg/kg suppressed infiltration of macrophages and neutrophils in perihematomal areas. Expression of several inflammatory cytokines, including interleukin-1 beta (IL-1b), extracellular signal-regulated kinase (ERK), and cyclooxygenase-2 (COX2) were also reduced. Regarding functional outcomes, a high dose of lobeglitazone (4 mg/kg) improved the mNSS significantly on days 3 and 13 after ICH. The results suggest that lobeglitazone, a PPARγ agonist, has potential neuroprotective effects on ICH by modulating brain edema and brain inflammation via IL-1β-ERK-COX-2 pathway inhibition.</p>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":" ","pages":"104030"},"PeriodicalIF":2.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Eprosartan alleviates the traumatic brain injury-induced multi-organ dysfunction syndrome in mice via AT1R/SNS/HMGB1 blockade and PDL-1 modulation 依普沙坦通过阻断AT1R/SNS/HMGB1和调节PDL-1减轻小鼠外伤性脑损伤多器官功能障碍综合征。

IF 2.4 3区医学

Molecular and Cellular Neuroscience Pub Date : 2025-08-29 DOI: 10.1016/j.mcn.2025.104035

Manisha Thakur , Sunil Sharma , Neeru Vasudeva , Paras Saini , Deepika Lather , Deepak Deepak

{"title":"Eprosartan alleviates the traumatic brain injury-induced multi-organ dysfunction syndrome in mice via AT1R/SNS/HMGB1 blockade and PDL-1 modulation","authors":"Manisha Thakur , Sunil Sharma , Neeru Vasudeva , Paras Saini , Deepika Lather , Deepak Deepak","doi":"10.1016/j.mcn.2025.104035","DOIUrl":"10.1016/j.mcn.2025.104035","url":null,"abstract":"<div><div>Traumatic brain injury is not constrained only to the brain but delayed secondary events disturb the end organ functioning via intense response of three homeostatic mechanisms such as sympathetic activity, inflammation, and immunosuppression. Current study involved weight drop model to induce TBI in Swiss albino mice. Eprosartan was administered orally after 30–45 min post injury to mice in 0.35 mg/kg and 0.7 mg/kg doses. Mice were tested for neurobehavioral alterations and multiple organs, including brain, heart, lungs, liver, and kidney were excised for further edema, biochemical, inflammatory, catecholamine, gene expression and histopathological estimations at both acute and chronic phases of injury. Results highlighted that Epro improved neurobehavioral performance, maintained the BBB and lung integrity. It also ameliorated the oxidative stress as well as docking studies exhibited strong binding affinity of Epro for HMGB1 and PDL-1, that further supported by low tissue HMGB1 and serum IL-6 and TNF-α cytokines levels which halted the systemic hyperinflammation. Moreover, Epro treatment successfully restored the cardiac, hepatic and kidney function through stabilized serum biomarkers with declined plasma noradrenaline levels that subsides the sympathetic storm. Considerably, a bizarre cellular morphology was displayed by the organs in acute phase of injury whereas Epro reversed the morphological changes at chronic stage. Also, epro encouraged the PD-1/PDL-1 and IL-10 gene expression in the tissues that regulates immune response. Thus, it is concluded that Epro exerts its organ protective effect against MODS via AT<sub>1</sub>/SNS pathway inhibition.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"135 ","pages":"Article 104035"},"PeriodicalIF":2.4,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Knockout of indoleamine 2,3-dioxygenase 1 gene expression improves depressive and anxiety-like phenotypes in a murine model of mild traumatic brain injury 敲除吲哚胺2,3-双加氧酶1基因表达可改善轻度创伤性脑损伤小鼠模型的抑郁和焦虑样表型。

IF 2.4 3区医学

Molecular and Cellular Neuroscience Pub Date : 2025-08-05 DOI: 10.1016/j.mcn.2025.104033

João Luís Vieira Monteiro de Barros , Caroline Amaral Machado , Ricardo Tadeu de Carvalho , Bruna da Silva Oliveira , Ingrid dos Santos Freitas , Lorena Taveira Nogueira , Giovana Cougo Ferreira , Heliana de Barros Fernandes , Brener Cunha Carvalho , Vivian Vasconcelos Costa , Antônio Lúcio Teixeira , Aline Silva de Miranda

{"title":"Knockout of indoleamine 2,3-dioxygenase 1 gene expression improves depressive and anxiety-like phenotypes in a murine model of mild traumatic brain injury","authors":"João Luís Vieira Monteiro de Barros , Caroline Amaral Machado , Ricardo Tadeu de Carvalho , Bruna da Silva Oliveira , Ingrid dos Santos Freitas , Lorena Taveira Nogueira , Giovana Cougo Ferreira , Heliana de Barros Fernandes , Brener Cunha Carvalho , Vivian Vasconcelos Costa , Antônio Lúcio Teixeira , Aline Silva de Miranda","doi":"10.1016/j.mcn.2025.104033","DOIUrl":"10.1016/j.mcn.2025.104033","url":null,"abstract":"<div><h3>Background</h3><div>Indoleamine 2,3-dioxygenase (IDO) modulates the kynurenine pathway and may influence post-mild traumatic brain injury (mTBI) outcomes. This study tested whether IDO knockout (IDO-KO) mice exhibit distinct behavioral profiles and neurotrophic factor levels after a mTBI.</div></div><div><h3>Methods</h3><div>Male C57BL/6 WT and IDO-KO mice (10–12 weeks) underwent weight-drop-induced mTBI or sham procedures. Anxiety- and depression-like behaviors were assessed 72 h later via elevated plus maze and forced swim tests, respectively. Neurotrophic factors BDNF, NGF, NT3 and GDNF levels were measured by ELISA in the ipsilateral and contralateral prefrontal cortex and hippocampus.</div></div><div><h3>Results</h3><div>WT mice exhibited increased anxiety- and depressive-like behaviors post-mTBI, whereas IDO-KO mice did not show these behaviors. In parallel, mTBI increased BDNF levels in the ipsilateral hippocampus that were more pronounced in IDO-KO compared to WT. IDO-KO mice also exhibited a different pattern of NGF and GDNF compared to WT after mTBI.</div></div><div><h3>Conclusion</h3><div>IDO deficiency prevented mTBI-induced anxiety- and depressive-like behaviors and altered neurotrophic factor levels regionally. These findings implicate IDO in post-mTBI behavioral and neurotrophic responses, warranting further study of kynurenine pathway metabolites and downstream signaling to clarify the mechanism underlying the role of IDO in mTBI outcomes.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"134 ","pages":"Article 104033"},"PeriodicalIF":2.4,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The glymphatic and meningeal lymphatic systems may converge, connecting traumatic brain injury progression with chronic traumatic encephalopathy onset 淋巴系统和脑膜淋巴系统可能会聚，将创伤性脑损伤的进展与慢性创伤性脑病的发病联系起来

IF 2.6 3区医学

Molecular and Cellular Neuroscience Pub Date : 2025-07-23 DOI: 10.1016/j.mcn.2025.104031

Randy Bent Barker , Eda Karakaya , Didem Baran , Adviye Ergul , Kaan Yagmurlu , Mehmet Albayram , Onder Albayram

{"title":"The glymphatic and meningeal lymphatic systems may converge, connecting traumatic brain injury progression with chronic traumatic encephalopathy onset","authors":"Randy Bent Barker , Eda Karakaya , Didem Baran , Adviye Ergul , Kaan Yagmurlu , Mehmet Albayram , Onder Albayram","doi":"10.1016/j.mcn.2025.104031","DOIUrl":"10.1016/j.mcn.2025.104031","url":null,"abstract":"<div><div>Chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disease marked by perivascular deposition of hyperphosphorylated tau (P-tau), is strongly linked to repetitive concussive traumatic brain injuries (TBIs). Emerging evidence implicates disruptions in the clearance of interstitial fluid (ISF) and cerebrospinal fluid (CSF) from the brain—specifically within the glymphatic and meningeal lymphatic systems—as a pivotal driver of disease onset and progression. TBI disrupts glymphatic ISF–CSF exchange, compromising the clearance of pathogenic proteins—including P-tau, TDP-43, and inflammatory mediators—while promoting perivascular accumulation and neuroinflammation. Simultaneously, meningeal lymphatic dysfunction impedes CSF drainage and sustains neuroimmune activation, further amplifying glymphatic failure. Developmental trajectories of these systems suggest age-dependent susceptibilities to injury, potentially shaping both acute outcomes and long-term neurodegenerative risk. Species-specific differences between rodents and humans in brain fluid clearance pathways add translational complexity, emphasizing the need for refined models. This review reconceptualizes CTE as a disorder driven by disrupted brain fluid clearance, highlighting the convergent roles of glymphatic and meningeal lymphatic dysfunction in linking TBI to chronic neurodegeneration and identifying therapeutic targets to restore clearance and resilience.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"134 ","pages":"Article 104031"},"PeriodicalIF":2.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0