Molecular Neurobiology最新文献

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Single-Cell Transcriptome Patterns of Transposable Elements in Alzheimer's Disease. 阿尔茨海默病转座因子的单细胞转录组模式。
IF 4.3 2区 医学
Molecular Neurobiology Pub Date : 2025-10-01 Epub Date: 2025-06-19 DOI: 10.1007/s12035-025-05140-9
Cali M McEntee, Thomas J LaRocca
{"title":"Single-Cell Transcriptome Patterns of Transposable Elements in Alzheimer's Disease.","authors":"Cali M McEntee, Thomas J LaRocca","doi":"10.1007/s12035-025-05140-9","DOIUrl":"10.1007/s12035-025-05140-9","url":null,"abstract":"<p><p>Growing evidence implicates transcripts from transposable elements (TEs) in the pathogenesis of Alzheimer's disease (AD). However, despite recent single-cell/nucleus RNA sequencing (sc/snRNA-seq) studies of AD, cell type-specific patterns in TE transcripts have not been reported. Therefore, we examined TE transcripts in snRNA-seq datasets based on prefrontal cortex samples from AD patients. We analyzed gene/TE expression in 143,951 cells and found that: (1) TE transcripts are broadly increased with AD in most brain cell types; (2) retrotransposon transcripts are most increased with AD pathology in excitatory neurons; and (3) TE loci are more transcriptionally accessible in AD, especially in neurons/excitatory neurons. We also confirmed our findings in complementary analyses of bulk RNA-seq data on AD. Together, our data provide novel insight into TE transcript dynamics across different cell types in the AD brain.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"13449-13460"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333523","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}
引用次数: 0
PGC-1α Expands Neural Precursor Pool and Facilitates Cognitive Recovery Within AD Hippocampus Through the Regulation of Mitochondrial Dynamics. PGC-1α通过线粒体动力学调节扩大AD海马神经前体池促进认知恢复
IF 4.3 2区 医学
Molecular Neurobiology Pub Date : 2025-10-01 Epub Date: 2025-06-20 DOI: 10.1007/s12035-025-05146-3
Yu-Xin Wang, Yi-Jie Wang, Wen Pan, Long-Fei Xu, Jia-Qing Wang, Hua Wang, Xin Qian, Cheng-Zhi Zou, Xu Zhu, Jia Wang
{"title":"PGC-1α Expands Neural Precursor Pool and Facilitates Cognitive Recovery Within AD Hippocampus Through the Regulation of Mitochondrial Dynamics.","authors":"Yu-Xin Wang, Yi-Jie Wang, Wen Pan, Long-Fei Xu, Jia-Qing Wang, Hua Wang, Xin Qian, Cheng-Zhi Zou, Xu Zhu, Jia Wang","doi":"10.1007/s12035-025-05146-3","DOIUrl":"10.1007/s12035-025-05146-3","url":null,"abstract":"<p><p>The dysfunction in learning and memory observed in Alzheimer's disease (AD) is strongly associated with impaired neurogenesis in the hippocampal region. As research on adult neurogenesis advances, it becomes increasingly crucial to identify potential targets for interventions aimed at enhancing endogenous neurogenesis and promoting functional recovery in AD patients. Our previous studies have demonstrated the potential of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) in mitigating the pathological abnormalities associated with AD. Serving as a ubiquitous metabolic regulator, PGC-1α is highly expressed in energy-demanding tissues, such as the hippocampus. However, the precise role and underlying mechanisms by which PGC-1α regulates neurogenesis within the AD-affected hippocampus remain to be fully elucidated. In this study, we induced PGC-1α overexpression by microinfusing AAV-Pgc-1α into the dentate gyrus (DG) of the hippocampus in APP/PS1 mice. Our findings indicate that PGC-1α effectively alleviates AD-related pathological abnormalities and behavioral dysfunction, including deficits in short-term habituation and spatial reference memory impairment. PGC-1α induces the activation of quiescent radial-glia like neural stem cells (NSCs) in the hippocampal DG region, giving rise to intermediate progenitor cells and neuroblasts that ultimately differentiate into mature neurons. By regulating mitochondrial dynamics-specifically promoting fusion while inhibiting fission-PGC-1α facilitates the expansion of precursor cell populations. Collectively, these findings highlight the significance of PGC-1α in maintaining NSC self-renewal, promoting neuronal lineage progression, and contributing to endogenous neurogenesis in AD. Elevating PGC-1α levels, either pharmacologically or through alternative approaches, may represent a promising therapeutic strategy for treating AD.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"13534-13556"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333521","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}
引用次数: 0
Single-Nucleus RNA Sequencing of HDAC6 Inhibition in Resolving Doxorubicin-Induced Cognitive Impairment. HDAC6抑制在解决阿霉素诱导的认知障碍中的单核RNA测序。
IF 4.3 2区 医学
Molecular Neurobiology Pub Date : 2025-10-01 Epub Date: 2025-06-21 DOI: 10.1007/s12035-025-05161-4
Vena K Martinez, Blake R McAlpin, Anand K Singh, Cobi J Heijnen, Rajasekaran Mahalingam
{"title":"Single-Nucleus RNA Sequencing of HDAC6 Inhibition in Resolving Doxorubicin-Induced Cognitive Impairment.","authors":"Vena K Martinez, Blake R McAlpin, Anand K Singh, Cobi J Heijnen, Rajasekaran Mahalingam","doi":"10.1007/s12035-025-05161-4","DOIUrl":"10.1007/s12035-025-05161-4","url":null,"abstract":"<p><p>Breast cancer is the most common cancer worldwide, accounting for 12.5% of all new cases. Doxorubicin, an effective treatment for breast cancer, is associated with chemotherapy-induced cognitive impairment (CICI), which affects up to 82% of survivors. Currently, no interventions for CICI have been approved by the US Food and Drug Administration. Histone deacetylase 6 (HDAC6) inhibition has been shown to improve cognitive function in neurodegenerative disease models, and we previously reported that the HDAC6 inhibitor ACY-1083 restored CICI-related cognitive dysfunction. Here, we used behavioral testing and single-nucleus transcriptomic analysis of the hippocampi of female mice to evaluate the efficacy of ACY-1083 in reversing doxorubicin-induced CICI. Our results from cognitive testing (the novel object placement recognition task as a test for working memory; the puzzle box test as a measure executive functioning) suggest that HDAC6 inhibition successfully reverses CICI. We also identified specific cell populations and gene expression patterns in oligodendrocytes, astrocytes, microglia, and dentate gyrus granule cells from the hippocampus. Doxorubicin treatment upregulated genes related to neurodegeneration, impaired synaptic function, and oxidative stress. Treatment with ACY-1083 reversed some of the doxorubicin-induced changes in gene expression and created a unique transcriptomic phenotype in treated mice that was not present in untreated control mice. This unique phenotype was characterized by increased expression of genes related to neurodevelopment, neurite outgrowth, and mitochondrial function. Therefore, HDAC6 inhibition may not only reverse gene expression caused by doxorubicin treatment but may also induce a unique gene expression that contributes to cognitive function restoration via homeostatic mechanisms. Because HDAC6 inhibitors have been used successfully in clinical trials focusing on tolerability and safety, we suggest that HDAC6 inhibition may be a realistic and effective intervention for reversing CICI in cancer survivors.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"13557-13575"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340270","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}
引用次数: 0
Xuebijing Promotes HMGB1-Mediated Autophagy to Alleviate Oxidative Stress and Inflammation in Heat Stroke-Induced Brain Damage. 血必净促进hmgb1介导的自噬减轻中暑脑损伤的氧化应激和炎症
IF 4.3 2区 医学
Molecular Neurobiology Pub Date : 2025-10-01 Epub Date: 2025-06-23 DOI: 10.1007/s12035-025-05120-z
Hongbo Li, Chunhe Li, Jun Li, Yongrui Liu, Minyong Wen, Lin Wang
{"title":"Xuebijing Promotes HMGB1-Mediated Autophagy to Alleviate Oxidative Stress and Inflammation in Heat Stroke-Induced Brain Damage.","authors":"Hongbo Li, Chunhe Li, Jun Li, Yongrui Liu, Minyong Wen, Lin Wang","doi":"10.1007/s12035-025-05120-z","DOIUrl":"10.1007/s12035-025-05120-z","url":null,"abstract":"<p><p>Heat stroke (HS) is a life-threatening condition with complex underlying mechanisms, posing challenges for pharmacological treatment. Xuebijing (XBJ) can effectively relieve HS-induced brain injury, but its molecular mechanism is not well-established. This study was conducted to investigate the mechanisms underlying the protective role of XBJ in HS-induced brain injury. HS-induced mice and cell models were established to elucidate the protective effects and underlying mechanisms of XBJ on HS-induced brain injury in vivo and in vitro. HMGB1 knockout (HMGB1<sup>-/-</sup>) mice and HMGB1 silencing in primary neuronal cells were used to study the effects of XBJ on HMGB1 in HS. Assessments included survival rate, neuronal damage score, and pathological changes. Various techniques such as Western blot, Transmission Electron Microscope (TEM), immunofluorescence staining, RT-qPCR, commercial kits, TUNEL assay, CCK-8, EdU, flow cytometry, and Co-IP assay were employed to assess autophagy, reactive oxygen species (ROS) levels, oxidative stress, inflammation, neuronal apoptosis, and protein complexes. Data revealed that XBJ ameliorated brain damage and neuron apoptosis in HS-exposed mice and promoted autophagy while inhibiting oxidative stress and inflammatory responses, both in vivo and in vitro. Additionally, XBJ alleviated neuronal brain damage, neuron apoptosis, oxidative stress, and inflammatory responses in HS via inducing autophagy. Furthermore, XBJ promoted the cytoplasmic translocation of HMGB1 from the nucleus and competed with Bcl-2 for binding to Beclin1. Moreover, HMGB1<sup>-/-</sup> mice and HMGB1 silencing in primary neuronal cells displayed reduced autophagy and enhanced inflammatory responses, both in vivo and in vitro. XBJ protects against HS-induced brain injury via a mechanism involving the autophagy-inflammation pathway mediated by HMGB1.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"13601-13615"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476053","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}
引用次数: 0
Huang Lian Jie Du Decoction Prevents Chronic Alcoholic Encephalopathy and Improves Gut Microbiota Imbalance in Mice. 黄连解毒汤预防小鼠慢性酒精性脑病及改善肠道菌群失衡。
IF 4.3 2区 医学
Molecular Neurobiology Pub Date : 2025-10-01 Epub Date: 2025-06-25 DOI: 10.1007/s12035-025-05151-6
Yun Chen, Lianyan Jiang, Yuan Zhang, Yuling Shen, Mao Li, Dongdong Yang, Bo Wang
{"title":"Huang Lian Jie Du Decoction Prevents Chronic Alcoholic Encephalopathy and Improves Gut Microbiota Imbalance in Mice.","authors":"Yun Chen, Lianyan Jiang, Yuan Zhang, Yuling Shen, Mao Li, Dongdong Yang, Bo Wang","doi":"10.1007/s12035-025-05151-6","DOIUrl":"10.1007/s12035-025-05151-6","url":null,"abstract":"<p><p>Huang Lian Jie Du Decoction (HLJDD) has anti-inflammatory, immunomodulatory, intestinal flora regulation, and anticoagulant effects, but the effects and mechanisms of HLJDD on chronic alcoholic encephalopathy (CAE) remain unclear. This study aimed to investigate the effect and mechanism of HLJDD to improve CAE. CAE mouse model was established, and the mice were treated with different doses of HLJDD according to the principle of randomized controlled trial. Open field test and Morris water maze were used to observe the locomotor and learning memory abilities of mice, hematoxylin-eosin (HE) staining was used to observe the pathological changes in prefrontal cortex and hippocampal CA1, toluidine blue staining was used to detect the neuronal survival in prefrontal cortex and hippocampal CA1, transmission electron microscopy was used to examine neuronal micropathology in prefrontal cortex and hippocampal CA1, and immunofluorescent staining and western blot were used to detect the expression of postsynaptic density protein 95 (PSD95) and synaptophysin (SYN) in hippocampal CA1. Moreover, the changes in gut microbiota were analyzed by 16S rRNA sequencing. The present study found that HLJDD improved the voluntary motor ability and learning memory ability of CAE mice, attenuated prefrontal cortex and hippocampal CA1 damage, and increased the expression of synaptic remodeling-related proteins PSD95 and SYN (P < 0.01), and HLJDD treatment affected the composition of gut microbiota in mice with CAE. HLJDD is an effective traditional Chinese medicine against CAE, and regulating its gut microbiota imbalance.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"13665-13677"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485125","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}
引用次数: 0
PDZD8 Dysregulation Mediates RVLM Neuronal Hyperexcitation Via Activation of Ca2+-Calpain-2 Signaling in Stress-Induced Hypertension. PDZD8失调通过激活Ca2+-Calpain-2信号介导应激性高血压RVLM神经元亢奋。
IF 4.3 2区 医学
Molecular Neurobiology Pub Date : 2025-10-01 Epub Date: 2025-05-26 DOI: 10.1007/s12035-025-05081-3
Tianfeng Liu, Linping Wang, Lei Tong, Zhangyan Ren, Bingjie Zhao, Haisheng Liu, Wen Lu, Haili Zhang, Shuai Zhang, Dongshu Du
{"title":"PDZD8 Dysregulation Mediates RVLM Neuronal Hyperexcitation Via Activation of Ca<sup>2+</sup>-Calpain-2 Signaling in Stress-Induced Hypertension.","authors":"Tianfeng Liu, Linping Wang, Lei Tong, Zhangyan Ren, Bingjie Zhao, Haisheng Liu, Wen Lu, Haili Zhang, Shuai Zhang, Dongshu Du","doi":"10.1007/s12035-025-05081-3","DOIUrl":"10.1007/s12035-025-05081-3","url":null,"abstract":"<p><p>Neuronal hyperexcitation in the rostral ventrolateral medulla (RVLM) is crucial in the pathogenesis of stress-induced hypertension (SIH). PDZD8 connects endoplasmic reticulum (ER) to mitochondria, and is involved in SIH through regulating RVLM neuronal mitochondrial physiological function. However, the underlying mechanisms of the PDZD8 dysregulation-mediated mitochondrial dysfunction of RVLM neurons, affecting neuronal excitability during SIH, are not fully clarified. An SIH rat model was established by administering intermittent electric foot shocks combined with noise exposure for 2 h twice daily over a period of 15 days. The impacts of PDZD8 on regulating RVLM neuronal ER stress, mitochondrial function, apoptosis, and blood pressure (BP) of SIH rats, along with the related signaling pathway, were explored through using in-vivo and in-vitro techniques like RVLM microinjection, Western blot, flow cytometry, and immunofluorescence. We demonstrated that the ratio of c-Fos-positive tyrosine hydroxylase (TH) neurons, renal sympathetic nerve activity (RSNA), plasma norepinephrine (NE) levels, BP, and heart rate (HR) increased in SIH rats. The activated neuronal ER stress, impaired mitochondrial function, and apoptosis were observed in the RVLM of SIH rats and PDZD8-deficient N2a cells. ER stress inhibitor (4-phenylbutyric acid, 4-PBA) administration effectively alleviated PDZD8 dysregulation-induced mitochondrial dysfunction and apoptosis. Mechanistically, PDZD8 negatively regulated Calpain-2 (CAPN2) expression through modulating cytoplasmic Ca<sup>2+</sup> levels. In vitro, CAPN2 inhibition rescued PDZD8 deficiency-induced ER stress, mitochondrial dysfunction, and apoptosis. In vivo, PDZD8 upregulation in the RVLM of SIH rats attenuated neuronal ER stress, mitochondrial dysfunction, and apoptosis, thus reducing RVLM neuronal excitability, RSNA, plasma NE, BP, and HR. These effects were blocked by CAPN2 overexpression. Overall, this study revealed that PDZD8 dysregulation induced RVLM neuronal ER stress, mitochondrial damage, and apoptosis by activating the Ca<sup>2+</sup>-CAPN2 axis, playing a crucial pathological role in SIH progression.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"12539-12558"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143092","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}
引用次数: 0
Trifluoperazine improves postoperative cognition by influencing astrocyte endfoot morphology and aquaporin-4 polarity. 三氟拉嗪通过影响星形胶质细胞终足形态和水通道蛋白-4极性改善术后认知。
IF 4.3 2区 医学
Molecular Neurobiology Pub Date : 2025-10-01 Epub Date: 2025-05-27 DOI: 10.1007/s12035-025-05072-4
Chunqu Chen, Binbin Zhu, Wenjun Luo, Angyang Cao, Weijian Zhou, Yifei Weng, Jianhua Wang
{"title":"Trifluoperazine improves postoperative cognition by influencing astrocyte endfoot morphology and aquaporin-4 polarity.","authors":"Chunqu Chen, Binbin Zhu, Wenjun Luo, Angyang Cao, Weijian Zhou, Yifei Weng, Jianhua Wang","doi":"10.1007/s12035-025-05072-4","DOIUrl":"10.1007/s12035-025-05072-4","url":null,"abstract":"<p><p>Postoperative cognitive dysfunction (POCD) represents a debilitating neurological complication associated with progressive cognitive deterioration and heightened dementia risk in surgical populations. Despite emerging evidence implicating glymphatic dysfunction in neuroinflammatory pathogenesis, perioperative dynamics of astrocytic endfoot architecture and aquaporin-4 (AQP4) polarization remain insufficiently characterized. Aged murine models were stratified into POCD phenotypes through standardized behavioral assessments. Transmission electron microscopy (TEM) quantified perioperative astrocytic endfoot morphology, while immunofluorescence and qPCR evaluated AQP4 expression/polarization. Mechanistic investigations employed trifluoperazine (TFP), a selective AQP4 polarity inhibitor, to delineate its therapeutic effects on glymphatic clearance, cognitive performance, and neuroinflammatory pathways. POCD-positive mice exhibited significant pathological swelling of terminal feet accompanied by AQP4 polarization disruption. TFP pretreatment significantly alleviated postoperative anxiety-like behaviors and cognitive deficits. Behavioral results demonstrated that the TFP 2 mg/kg group showed 1.4-fold and 2.4-fold increases the time spent in centerarea and the time spent in novel arm, respectively, compared to the surgery group (p < 0.05). This was accompanied by the restoration of AQP4 polarization and increased perivascular CSF tracer influx. At the molecular level, TFP upregulated synaptic plasticity regulators (compared to the surgery group, Snta1 expression increased 1.9-fold and Agrin expression increased 3.4-fold in the TFP group). Additionally, TFP suppressed pro-inflammatory cytokine levels (IL-6 expression decreased by 41.2%, and TNF-α expression decreased by 35.3%, p < 0.05). This study identifies impaired AQP4 polarization as a novel mechanism underlying perioperative glymphatic failure and neuroinflammation. Pharmacological preservation of AQP4 functionality via TFP emerges as a promising therapeutic strategy for POCD mitigation.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"12574-12587"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144160459","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}
引用次数: 0
Inhibition of Cathepsin B Ameliorates Murine Cognitive Dysfunction and Neuronal Damage in Ischemic Stroke by Inhibiting Mitochondrial Apoptosis and Drp1-Mediated Mitochondrial Fission. 抑制组织蛋白酶B通过抑制线粒体凋亡和drp1介导的线粒体分裂改善缺血性卒中小鼠认知功能障碍和神经元损伤
IF 4.3 2区 医学
Molecular Neurobiology Pub Date : 2025-10-01 Epub Date: 2025-05-30 DOI: 10.1007/s12035-025-05094-y
Hongyi Jia, Bingge Zhang, Xiao Han, Pei Yu, Bocheng Xiong, Tiansu Liu, Luchen Shan, Xifei Yang, Qinghua Hou
{"title":"Inhibition of Cathepsin B Ameliorates Murine Cognitive Dysfunction and Neuronal Damage in Ischemic Stroke by Inhibiting Mitochondrial Apoptosis and Drp1-Mediated Mitochondrial Fission.","authors":"Hongyi Jia, Bingge Zhang, Xiao Han, Pei Yu, Bocheng Xiong, Tiansu Liu, Luchen Shan, Xifei Yang, Qinghua Hou","doi":"10.1007/s12035-025-05094-y","DOIUrl":"10.1007/s12035-025-05094-y","url":null,"abstract":"<p><p>The surviving brain tissue undergoes secondary degeneration long after an ischemic stroke. Cathepsin B plays dual roles as both a scavenger and an executor. Using a mouse model of ischemic stroke, we specifically investigated the mechanism by which inhibiting Cathepsin B with CA074 methyl ester (CA-074Me) during the chronic phase of stroke exerts a protective effect. In the intervention group, CA-074Me (20 μg CA-074Me/1 μl DMSO) was stereotaxically injected in the right ventricle, and, 30 min later, the animals were subjected to develop transient middle cerebral artery occlusion and reperfusion (tMCAO/R) stroke model with modified Longa method. In the model group, 1 μl DMSO was given in the right ventricle instead and the sham-operated group received 1 μl DMSO in the right ventricle without arterial occlusion. We evaluated the effects of inhibition of Cathepsin B on the nervous system after tMCAO/R injury by combined use behavioral tests, neurological deficit scoring, Western blot and other pharmacological methods and explored the underlying mechanism. After tMCAO/R, sustained upregulation and activation of Cathepsin B was noticed in the ipsilateral hippocampus CA1 zone and CA-074Me ameliorated the parallel lysosome-mitochondria damage, decreased apoptosis, improved the cognitive dysfunction, but had no effects on levels of mouse anxiety or depression. Furthermore, CA-074Me reduced neuroinflammation, levels of oxidative stress and mitochondria fission. Inhibition of Cathepsin B alleviates mitochondrial abnormalities in the ipsilateral hippocampus CA1 zone 28 days after tMCAO/R by suppressing Drp-1mediated excessive mitochondrial fission. This, in turn, reduces neuronal apoptosis, ameliorates neuroinflammation, and mitigates oxidative stress and neuronal damage, indicating Cathepsin B may serve as a potential therapeutic target for remote secondary degeneration following acute ischemic stroke.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"12688-12704"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187401","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}
引用次数: 0
Panax Ginseng Protects Against Doxorubicin-Induced Testicular Injury in Male Rats by Modulating NF-κB/COX-2 and AR Pathways. 人参通过调节NF-κB/COX-2和AR通路对阿霉素致雄性大鼠睾丸损伤的保护作用
IF 4.3 2区 医学
Molecular Neurobiology Pub Date : 2025-10-01 Epub Date: 2025-06-02 DOI: 10.1007/s12035-025-05116-9
Yesim Yeni, Betul Cicek, Ahmet Hacimuftuoglu, Mustafa Ozkaraca, Behzad Mokhtare
{"title":"Panax Ginseng Protects Against Doxorubicin-Induced Testicular Injury in Male Rats by Modulating NF-κB/COX-2 and AR Pathways.","authors":"Yesim Yeni, Betul Cicek, Ahmet Hacimuftuoglu, Mustafa Ozkaraca, Behzad Mokhtare","doi":"10.1007/s12035-025-05116-9","DOIUrl":"10.1007/s12035-025-05116-9","url":null,"abstract":"<p><p>Panax ginseng (PG) is a medicinal plant used for many years to treat many diseases. The current study aimed to investigate the possible prophylactic and therapeutic effects of PG extract on doxorubicin (DOX)-induced testicular toxicity in rats. 32 adult male Sprague-Dawley rats (200-250 g) were used in the experiment. The experimental groups were designed as control (normal saline, intraperitoneal), DOX (18 mg/kg, intraperitoneal), PG (200 mg/kg, gavage), and PG + DOX (200 mg/kg, gavage). After treatment, serum levels of testosterone, interleukin-1β (IL-1β), glutathione (GSH), luteinizing hormone (LH), superoxide dismutase (SOD), lactate dehydrogenase (LDH), catalase (CAT), follicle stimulating hormone (FSH), tumor necrosis factor-α (TNF-α), and malondialdehyde (MDA) were measured. Then, gene expression, histopathological, and immunohistochemical analyses were performed on testicular tissues. Compared to DOX, treatment with PG + DOX showed a significant improvement in serum levels of FSH, testosterone, LH, TNF-α, IL-1β, MDA, SOD, LDH, GSH, and CAT. It was also observed that PG + DOX decreased nuclear factor-κB and cyclooxygenase-2 expression levels, increased androgen receptor expression, restored testicular histopathological structure, and significantly improved spermatogenesis. The results of the present study showed that PG may have an ameliorative effect against DOX-induced male reproductive toxicity, as DOX causes male reproductive toxicity. It can be concluded that PG is one of the effects that protect against DOX-induced testicular toxicity in rats by reducing lipid peroxidation and activating the antioxidant system. In light of this information, PG may be a useful agent to prevent the testicular toxicity observed in men receiving DOX treatment.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"12839-12850"},"PeriodicalIF":4.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199628","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}
引用次数: 0
Unraveling Predominantly Inattentive ADHD (ADHD-PI): Insights from Proteomic Analysis of the Striatum of Thyroid Hormone-Responsive Protein (THRSP)-Overexpressing Mice. 揭示显性注意力不集中多动症(ADHD- pi):来自甲状腺激素反应蛋白(THRSP)过表达小鼠纹状体蛋白质组学分析的见解。
IF 4.3 2区 医学
Molecular Neurobiology Pub Date : 2025-10-01 Epub Date: 2025-06-10 DOI: 10.1007/s12035-025-05031-z
Raly James Perez Custodio, Leandro Val Sayson, Ara Cho, Hyeryeon Jung, Darlene Mae Ortiz, Hyun Jun Lee, Emad Alyan, Edmund Wascher, Stephan Getzmann, Mikyung Kim, Kyeong-Man Kim, Eugene C Yi, Hee Jin Kim, Jae Hoon Cheong
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