Molecular Neurobiology最新文献

{"title":"Retraction Note to: Anthocyanins Improve Hippocampus-Dependent Memory Function and Prevent Neurodegeneration via JNK/Akt/GSK3β Signaling in LPS-Treated Adult Mice.","authors":"Muhammad Sohail Khan, Tahir Ali, Min Woo Kim, Myeung Hoon Jo, Jong Il Chung, Myeong Ok Kim","doi":"10.1007/s12035-025-05156-1","DOIUrl":"https://doi.org/10.1007/s12035-025-05156-1","url":null,"abstract":"","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310209","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":"Deciphering the Antidepressant Potential of Piper betle L. Essential Oil and Its Inclusion Complex: Network Pharmacology and Experimental Insights.","authors":"Sejuti Ray Chowdhury, Sourav Ghosh, Biswajit Basu, Amartya Sen, Abhishek Digar, Arindom Halder, Bhupendra Prajapati","doi":"10.1007/s12035-025-05117-8","DOIUrl":"https://doi.org/10.1007/s12035-025-05117-8","url":null,"abstract":"<p><p>This study evaluates the antidepressant effects of Piper betle L. leaf essential oil (PBEO) and its inclusion complex (PBECD) in mice whilst exploring potential mechanisms. Gas chromatography-mass spectroscopy (GC-MS) identified PBEO's compounds, and β-cyclodextrins were used to enhance stability and bioavailability by forming PBECD. Characterization was performed using various analytical techniques. ADME pharmacokinetics, network pharmacology, and molecular docking predicted active compounds, antidepressant targets, and signalling pathways. The Chronic Unpredictable Mild Stress (CUMS) model was used to validate findings, with fluoxetine (20 mg/kg) as the standard. Mice received PBEO and PBECD at 50 mg/kg and 100 mg/kg doses. Behavioural tests, including the open field, sucrose preference, Y-maze, and forced swim tests, assessed antidepressant effects. Toxicity was evaluated during dosing. Serum levels of IL-1β and TNF-α were measured using ELISA, whilst biochemical markers such as glutathione (GSH) and malondialdehyde (MDA) were analysed. ADME and network pharmacology identified six active components targeting 244 depression-related proteins, primarily in the MAPK signalling pathway. Molecular docking confirmed strong binding affinities between the ligands and the obtained proteins from network pharmacology. In vivo results showed PBEO and PBECD reduced depressive behaviours, with PBECD demonstrating superior effects. PBECD (100 mg/kg) significantly reduced immobility time by 42.5% in the forced swim test, increased sucrose preference by 36.8%, and improved Y-maze alternation by 31.7% compared to the control group. Serum levels of IL-1β and TNF-α decreased by 48.3% and 41.2% respectively, whilst GSH levels rose by 35.6% and MDA levels dropped by 39.4%, indicating reduced oxidative stress and inflammation. Modulating MAPK signalling, PBECD emerges as a promising candidate for antidepressant activity than PBEO in preclinical findings, as its complexation with cyclodextrin improves the oils' stability, solubility, and bioavailability, resulting in enhanced efficacy.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310208","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":"Neuroprotective Effect of Salvianolic Acid C in Neonatal Rats Following Hypoxic-ischemic Brain Damage.","authors":"Chunfang Dai, Xiaohuan Li, Zhifang Dong, Boqing Xu, Xi Lai, Jianrui Wei, Dahong Long, Dandan Hu","doi":"10.1007/s12035-025-05030-0","DOIUrl":"https://doi.org/10.1007/s12035-025-05030-0","url":null,"abstract":"<p><p>Neonatal hypoxia-ischemia (HI) is a significant cause of lasting disabilities and death in newborns. Salvianolic acid C (SAC), a phenolic compound extracted from Salvia miltiorrhiza, exhibits neuroprotection. However, it is currently uncertain if SAC displays a neuroprotective impact against neonatal hypoxic-ischemic brain damage (HIBD), and if it does, what mechanism is involved. Here, our study found SAC administration (15 mg/kg/day, i.p.) improved muscle strength, motor function, and spatial memory impairment in rats with HIBD. The amelioration of these behaviors was attributed to a notable suppression of neuron loss by SAC in the CA1 and CA3 hippocampal zones. Moreover, oxidative stress analysis revealed SAC enhanced anti-oxidants production while reducing pro-oxidants production. Western blot assays revealed SAC downregulated the levels of phospho-c-Jun N-terminal kinase (p-JNK) and jun proto-oncogene (c-JUN). ELISA measurements further showed SAC effectively diminished pro-inflammatory factors, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). Collectively, these results suggest SAC exhibits a potential neuroprotective impact by attenuating neuronal injury through inhibiting oxidative stress, JNK pathway activation, and inflammation, thereupon then polishes up motor and cognitive deficits caused by HI in the neonatal rats, indicating SAC may be a promising treatment for neonatal hypoxic-ischemic encephalopathy (HIE).</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302510","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":"Serotonergic Regulation of Photic Signaling of Ascorbate in the Rat Thalamus.","authors":"Hiroyuki Miyamoto, Kozo Hamada","doi":"10.1007/s12035-025-05132-9","DOIUrl":"https://doi.org/10.1007/s12035-025-05132-9","url":null,"abstract":"<p><p>Ascorbate, a potent reducing agent highly concentrated in the brain, prevents neuronal oxidative damage and functions as a neuromodulator. Disrupted ascorbate homeostasis has been linked to neurological disorders, including Alzheimer's disease. However, the in vivo mechanisms regulating brain ascorbate levels remain largely unexplored. Here, we demonstrate that serotonin and photic signaling jointly modulate extracellular ascorbate levels in the rat brain. Using in vivo microdialysis, we observed circadian rhythms in both serotonin metabolites and ascorbate levels in the thalamus of freely moving rats. Ascorbate exhibited marked photosensitivity, decreasing under light exposure and recovering in darkness. Serotonin depletion disrupted these circadian rhythms and abolished ascorbate's photosensitivity. These findings suggest that brain ascorbate dynamics are regulated by both serotonergic activity and environmental light, highlighting a novel interplay between neural signaling and redox systems in the thalamus.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302511","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":"Altered Lipid Homeostasis in Mutant FUS^R521H Astrocytes from HiPSCs.","authors":"Yingli Zhu, Katrien Neyrinck, Thibaut Burg, Yoke Chin Chai, Fatemeharefeh Nami, Karan Ahuja, Johannes V Swinnen, Ludo Van Den Bosch, Catherine Verfaillie","doi":"10.1007/s12035-025-05127-6","DOIUrl":"https://doi.org/10.1007/s12035-025-05127-6","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron loss, leading to paralysis and death. Mutations in the fused in sarcoma (FUS) gene cause early-onset ALS with rapid disease progression. Although motor neuron degeneration is central to ALS, recent studies highlight a significant role for dysfunctional glial cells, particularly astrocytes, in disease progression. In this study, we generated astrocytes from FUS^R521H mutant and isogenic human induced pluripotent stem cells (hiPSCs) by inducible overexpressing SOX9. Lipidomic analysis revealed marked glycerophospholipid deficiencies in FUS^R521H mutant astrocytes, especially reduced phosphatidylcholine (PC) and phosphatidylinositol (PI) levels. This reduction in PC was also observed in FUS^R521H mutant oligodendroglial progenitors and motor neurons, suggesting a potential dysregulation of glycerophospholipid metabolism across multiple central nervous system (CNS) cell types in FUS-ALS. These observations highlight the need for further investigation into lipid dysregulation and its relevance to FUS-ALS pathogenesis.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294115","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 in the Rostral Ventromedial Medulla Mediate Synaptic Pruning via the C1q/C3-CR3 Signaling Pathway-A Mechanism for the Chronic Orofacial Pain.","authors":"Xilu Huang, Jie Zeng, Zhanwei Hu, Yujia Wu, Guangyan Zhang, Chao Zhang, Cong Yu, Min Song","doi":"10.1007/s12035-025-05109-8","DOIUrl":"https://doi.org/10.1007/s12035-025-05109-8","url":null,"abstract":"<p><p>The mechanism of chronic orofacial pain was investigated by examining the interaction between activated microglia, C1q, and neurons in the rostral ventromedial medulla (RVM) of rats with orofacial pain caused by temporomandibular joint injection of complete Freund's adjuvant (CFA). The results demonstrated that the pain threshold in the CFA group exhibited a continuous decline, reaching its lowest point on the third day. During the modeling process, administered daily stereotactic injections of ANX-005 and minocycline into the RVM, which resulted in a notable recovery in the rats' pain threshold and a significant increase in C1q/C3 and microglia in the RVM of CFA rats. The application of ANX-005 or minocycline resulted in a reduction in the expression of C1q/C3 and microglia. Notably, the expression of excitatory presynaptic membrane markers reduced, and the length and density of dendritic spines decreased on neurons in the RVM. Additionally, C1q was abundantly localized on excitatory presynaptic membranes and expressed in microglial lysosomes. Treatment with ANX-005 or minocycline resulted in a reduced number of immunofluorescence colocalizations and an elevated dendritic spine density. These findings indicate that initial orofacial pain induced by CFA and microglia in the RVM are involved in the pruning of excitatory presynaptic membranes through the complement C1q/C3-CR3 signaling pathway. This process results in a reduction in the proportion of excitatory synapses and a disruption in the physiological balance between RVM descending facilitation and descending inhibition. This leads to the predominance of descending facilitation in pain transmission in the RVM, which in turn facilitates the chronification of orofacial pain.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285507","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":"Polyphenols and Exercise in Mitochondrial Biogenesis: Focus on Age-Related CNS Disorders.","authors":"Junbiao Tu","doi":"10.1007/s12035-025-05121-y","DOIUrl":"https://doi.org/10.1007/s12035-025-05121-y","url":null,"abstract":"<p><p>Age-related central nervous system (CNS) disorders, including neurodegenerative diseases, represent a growing global health burden. Mitochondrial dysfunction is a recognized hallmark in the pathogenesis of these conditions, emphasizing the critical importance of maintaining neuronal energy homeostasis and cellular integrity. Mitochondrial biogenesis, the dynamic process of generating new, functional mitochondria, is paramount for neuronal health and resilience against age-related decline. This review investigates the therapeutic potential of physical activity and polyphenols in modulating mitochondrial biogenesis and offering neuroprotection within the context of age-related CNS disorders. We explore how regular exercise profoundly impacts the brain by enhancing synaptic plasticity, promoting neurogenesis via neurotrophic factors like BDNF, and stimulating mitochondrial biogenesis through pathways such as PGC-1alpha activation. These adaptations collectively improve cognitive function and bolster neuronal resistance to damage. Concurrently, polyphenols, known for their antioxidant and anti-inflammatory properties, demonstrate significant neuroprotective effects. They are capable of crossing the blood-brain barrier and influencing key neuronal signaling pathways, directly stimulating mitochondrial biogenesis, and mitigating oxidative stress, thereby supporting neuronal survival. By synthesizing current evidence, this review highlights the complementary and potentially synergistic roles of exercise and polyphenols in preserving mitochondrial health and function in the CNS. The combined impact of these interventions offers a promising non-pharmacological strategy to combat age-related neurodegeneration. Future research should focus on optimizing exercise protocols and polyphenol interventions in human trials to maximize their neurotherapeutic benefits for CNS disorders.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285508","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":"Prediction of Post-Stroke Cognitive Impairment Based on Iron Metabolism Parameters: Results From A Prospective Study.","authors":"Chunxiao Wei, Panpan Zhao, Weijie Zhai, Meng Zhao, Li Sun","doi":"10.1007/s12035-025-05142-7","DOIUrl":"https://doi.org/10.1007/s12035-025-05142-7","url":null,"abstract":"<p><p>Disruption of iron homeostasis is associated with the pathogenesis of neurological disorders. This study aims to elucidate the correlation between serum iron metabolism profiles and the occurrence of post-stroke cognitive impairment (PSCI). Acute ischemic stroke (AIS) patients (n = 500) were enrolled, and serum iron metabolism parameters were collected at baseline. Cognitive abilities, including global cognition, episodic memory, language proficiency, attention, and executive function, were successfully assessed in participants six months after the AIS event (n = 224, mean age = 62). Multivariate logistic regression analysis was employed to screen for iron metabolism indicators influencing PSCI. A general linear model was used to analyze the correlation between total iron-binding capacity (TIBC) and overall cognitive function as well as performance in various cognitive domains. Additionally, we constructed a nomogram model to predict PSCI risk and validated its performance. The results revealed that the TIBC levels were significantly lower in the PSCI group. Elevated TIBC levels may represent a potential protective factor against PSCI development (OR = 0.940, 95% CI = 0.894-0.989, p = 0.018). Furthermore, higher serum TIBC levels were associated with better overall cognitive function, episodic memory, and language proficiency. The nomogram model constructed using age, gender, education level, National Institutes of Health Stroke Scale (NIHSS) score, and TIBC variables demonstrated good predictive performance for PSCI risk (AUC = 0.761, 95%CI = 0.696-0.825). In conclusion, serum TIBC is a potential biomarker for PSCI and is closely associated with cognitive ability.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294116","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":"Amelioration of Chemotherapy Induced Neuropathic Pain using Novel Nicotinic Acid Derivatives with possible HCN channel binding ability.","authors":"Akash Saini, Shiwani Sharma, Priyanka Rana, Bhawna Khanna, Tanzeer Kaur, Neelima Dhingra","doi":"10.1007/s12035-025-05088-w","DOIUrl":"https://doi.org/10.1007/s12035-025-05088-w","url":null,"abstract":"<p><p>One of the major debilitating side effects of cancer chemotherapy is neuropathic pain, which results from abnormal neural signaling and significantly diminishes patients' quality of life. Paclitaxel (PT), a widely used chemotherapeutic agent, induces peripheral nerve degeneration, leading to the development of painful neuropathy. In this study, PT was used to establish a mouse model of chemotherapy-induced peripheral neuropathy. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a key role in regulating neuronal pacemaker activity. The HCN current (I_h) promotes repetitive firing in nociceptive neurons, contributing to neuropathic pain. We synthesized a series of novel compounds and investigated their molecular interactions with HCN1 using docking studies based on a homology model of the channel's open pore. Pharmacokinetic predictions were subsequently performed to identify potential HCN1 inhibitors. Among the synthesized compounds, 3'-4'-dimethylphenyl pyridine-3-carboxylate (NDAK-6) showed strong binding affinity for HCN1. In vitro cell viability assays using the SH-SY5Y cell line revealed that NDAK-6 exhibited lower cytotoxicity than ivabradine, a known HCN inhibitor. NDAK-6 was further evaluated in vivo in the PT-induced neuropathic pain model, where it significantly reduced pain-like behaviors, including thermal hyperalgesia and mechanical allodynia. Moreover, it attenuated the expression of inflammatory markers TNF-α, NF-κB, p53, and PKC-δ in the thalamus, as well as NF-κB and p53 in dorsal root ganglion (DRG) neurons. These findings suggest that NDAK-6 may be a promising therapeutic candidate for chemotherapy-induced neuropathic pain.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275419","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":"bFGF Knockdown Inhibits mTOR Signaling by Suppressing Caveolin-1 and Aggravates Cognitive Damage After Arterial Ischemic Brain Injury in Juvenile Rats.","authors":"Qiongyi Pang, Yudan Wu, Tianyu Jin, Dalin Xing, Tong Zhang, Fengxia Tu","doi":"10.1007/s12035-025-05108-9","DOIUrl":"https://doi.org/10.1007/s12035-025-05108-9","url":null,"abstract":"<p><p>Pediatric arterial ischemic stroke (AIS) is the leading cause of stroke in children and approximately two-thirds of affected patients experience permanent neurological sequelae. Although basic fibroblast growth factor (bFGF) has positive effects on neural development, axon regeneration, and synaptic reconstruction, its effects in AIS remain unclear. Here, we examined the role of bFGF in post-ischemic cognitive function in juvenile rats. Behavioral assessments using the Morris water maze and the three-chamber test revealed that bFGF knockdown impairs spatial learning, memory, and social interactions. Golgi staining and electron microscopy demonstrated that bFGF knockdown disrupts neuronal axon morphology and synaptic ultrastructure. In the hippocampus of AIS rats, bFGF deficiency significantly reduced PSD95 and synapsin I protein levels. Moreover, bFGF knockdown decreased autophagy and apoptosis markers while increasing necrosis indicators. Mechanistically, loss of bFGF inhibited phosphorylation of mammalian target of rapamycin (mTOR), a process regulated by fibroblast growth factor receptor 1 (FGFR1). We further show that bFGF interacts with FGFR1 and caveolin-1 (Cav1), a membrane scaffold protein; knockdown of Cav1 in the hippocampus similarly attenuated mTOR signaling. Collectively, our results suggest that bFGF deficiency suppresses Cav1, thereby inhibiting mTOR signaling and exacerbating cognitive deficits after AIS in juvenile rats. These findings provide insight into the molecular mechanisms underlying pediatric AIS.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275420","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}