Neurochemistry international最新文献

{"title":"Role of PI3Kγ in the polarization, migration, and phagocytosis of microglia","authors":"Xinghua Liang ,&nbsp;Yuan Hu ,&nbsp;Xinyue Li ,&nbsp;Xi Xu ,&nbsp;Zhonglan Chen ,&nbsp;Yalin Han ,&nbsp;Yingying Han ,&nbsp;Guangping Lang","doi":"10.1016/j.neuint.2024.105917","DOIUrl":"10.1016/j.neuint.2024.105917","url":null,"abstract":"<div><div>Phosphoinositide 3-kinase γ (PI3Kγ) is a signaling protein that is constitutively expressed in immune competent cells and plays a crucial role in cell proliferation, apoptosis, migration, deformation, and immunology. Several studies have shown that high expression of PI3Kγ can inhibit the occurrence of inflammation in microglia while also regulating the polarization of microglia to inhibit inflammation and enhance microglial migration and phagocytosis. It is well known that the regulation of microglial polarization, migration, and phagocytosis is key to the treatment of most neurodegenerative diseases. Therefore, in this article, we review the important regulatory role of PI3Kγ in microglia to provide a basis for the treatment of neurodegenerative diseases.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"182 ","pages":"Article 105917"},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826549","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}

{"title":"Hydrogen restores central tryptophan and metabolite levels and maintains mitochondrial homeostasis to protect rats from chronic mild unpredictable stress damage","authors":"Jiaxin Li ,&nbsp;Gaimei Hao ,&nbsp;Yupeng Yan ,&nbsp;Ming Li ,&nbsp;Gaifen Li ,&nbsp;Zhengmin Lu ,&nbsp;Zhibo Sun ,&nbsp;Yanjing Chen ,&nbsp;Haixia Liu ,&nbsp;Yukun Zhao ,&nbsp;Meng Wu ,&nbsp;Xiangxin Bao ,&nbsp;Yong Wang ,&nbsp;Yubo Li","doi":"10.1016/j.neuint.2024.105914","DOIUrl":"10.1016/j.neuint.2024.105914","url":null,"abstract":"<div><h3>Background and purpose</h3><div>The field of hydrogen medicine has garnered extensive attention since Professor Ohsawa established that low concentrations of hydrogen (2%–4%) exert antioxidant effects. The present study aimed to evaluate the therapeutic effect of molecular hydrogen in a CUMS rat model.</div></div><div><h3>Methods</h3><div>A total of 40 SD rats were randomly divided into a control group, a model group, a hydrogen group, and a positive drug group. Four weeks post-modeling, hydrogen inhalation and other treatments were administered. Behavioral, biochemical, and immunohistochemical evaluations were performed after treatment.</div></div><div><h3>Results</h3><div>Hydrogen inhalation alleviated depressive behavior and hippocampal neuronal damage in CUMS rats, as well as restored the levels of neurotransmitters, inflammatory factors, and oxidative stress. Moreover, it maintained mitochondrial homeostasis and up-regulated the expression of PGC-1α, PINK1, and Parkin.</div></div><div><h3>Conclusions</h3><div>The results collectively indicated that hydrogen significantly attenuated CUMS-induced depressive-like behavior and monoamine neurotransmitter deficiency, as well as protected the brain from oxidative stress and inflammatory damage and effectively preserved mitochondrial homeostasis.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"182 ","pages":"Article 105914"},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799034","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}

{"title":"Leptin deficiency leads to nerve degeneration and impairs axon remyelination by inducing Schwann cell apoptosis and demyelination in type 2 diabetic peripheral neuropathy in rats","authors":"Yuan-Shuo Hsueh ,&nbsp;Szu-Han Chen ,&nbsp;Wan-Ling Tseng ,&nbsp;Sheng-Che Lin ,&nbsp;De-Quan Chen ,&nbsp;Chih-Chung Huang ,&nbsp;Yuan-Yu Hsueh","doi":"10.1016/j.neuint.2024.105908","DOIUrl":"10.1016/j.neuint.2024.105908","url":null,"abstract":"<div><div>Diabetic peripheral neuropathy, characterized by symptoms such as paresthesia, neuropathic pain, and potential lower limb amputation, poses significant clinical management challenges. Recent studies suggest that chronic hyperglycemia-induced Schwann cells (SCs) apoptosis contributes to neurodegeneration and impaired nerve regeneration, but the detailed mechanisms are still unknown. Our study investigated a mixed-sex type 2 diabetes mellitus (T2DM) rat model using leptin knockout (KO) to simulate obesity and diabetes-related conditions. Through extensive assessments, including mechanical allodynia, electrophysiology, and microcirculation analyses, along with myelin degradation studies in KO versus wild-type rats, we focused on apoptosis, autophagy, and SCs dedifferentiation in the sciatic nerve and examined nerve regeneration in KO rats. KO rats exhibited notable reductions in mechanical withdrawal force, prolonged latency, decreased compound muscle action potential (CMAP) amplitude, reduced microcirculation, myelin sheath damage, and increases in apoptosis, autophagy, and SCs dedifferentiation. Moreover, leptin KO was found to impair peripheral nerve regeneration postinjury, as indicated by reduced muscle weight, lower CMAP amplitude, extended latency, and decreased remyelination and SCs density. These findings underscore the effectiveness of the T2DM rat model in clarifying the impact of leptin KO on SCs apoptosis, dedifferentiation, and demyelination, providing valuable insights into new therapeutic avenues for treating T2DM-induced peripheral neuropathy.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"182 ","pages":"Article 105908"},"PeriodicalIF":4.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745657","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}

{"title":"Striatum-enriched protein, arginase 2 localizes to medium spiny neurons and controls striatal metabolic profile","authors":"Martyna Nalepa ,&nbsp;Beata Toczyłowska ,&nbsp;Aleksandra Owczarek ,&nbsp;Aleksandra Skweres ,&nbsp;Elżbieta Ziemińska ,&nbsp;Michał Węgrzynowicz","doi":"10.1016/j.neuint.2024.105907","DOIUrl":"10.1016/j.neuint.2024.105907","url":null,"abstract":"<div><div>Arginase 2 (Arg2) is the predominant arginase isoenzyme in the brain, however its distribution appears to be limited to selected, region-specific subpopulations of cells. Although striatum is highly enriched with Arg2, precise localization and function of striatal Arg2 have never been studied. Here, we confirm that Arg2 is the only arginase isoenzyme in the striatum, and, using genetic model of total Arg2 loss, we show that Arg2 in this region is fully responsible for arginase catalytic activity, and its loss doesn't induce compensatory activation of Arg1. We exhibit that Arg2 is present in medium spiny neurons (MSNs), striatum-specific projecting neurons, where it localizes in soma and neuronal processes, and is absent in astrocytes or microglia. Finally, analysis of NMR spectroscopy-measured metabolic profiles of striata of Arg2-null mice enabled to recognize two metabolites (NADH and malonic acid) to be significantly altered compared to control animals. Multivariate comparison of the data using orthogonal projections to latent structures discriminant analysis, allowed for discrimination between control and Arg2-null mice and identified metabolites that contributed the most to this between-group dissimilarity. Our study reveals for the first time the localization of Arg2 in MSNs and demonstrates significant role of this enzyme in regulating striatal metabolism. These findings may be especially interesting in the context of Huntington's disease (HD), a disorder that specifically affects MSNs and in which, with the use of mouse models, the onset of pathological phenotypes was recently shown to be preceded by progressive impairment of striatal Arg2, a phenomenon of an unknown significance for disease pathogenesis.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"182 ","pages":"Article 105907"},"PeriodicalIF":4.4,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accelerated senescence exacerbates α-synucleinopathy in senescence-accelerated prone 8 mice via persistent neuroinflammation","authors":"Hiroshi Sakiyama ,&nbsp;Kousuke Baba ,&nbsp;Yasuyoshi Kimura ,&nbsp;Kotaro Ogawa ,&nbsp;Ujiakira Nishiike ,&nbsp;Hideki Hayakawa ,&nbsp;Miki Yoshida ,&nbsp;Cesar Aguirre ,&nbsp;Kensuke Ikenaka ,&nbsp;Seiichi Nagano ,&nbsp;Hideki Mochizuki","doi":"10.1016/j.neuint.2024.105906","DOIUrl":"10.1016/j.neuint.2024.105906","url":null,"abstract":"<div><div>Parkinson's disease (PD) is characterized by the formation of α-synuclein (α-syn) aggregates, which lead to dopaminergic neuronal degeneration. The incidence of PD increases with age, and senescence is considered to be a major risk factor for PD. In this study, we evaluated the effect of senescence on PD pathology using α-synuclein preformed fibrils (PFF) injection model in senescence-accelerated mice. We injected PFF into the substantia nigra (SN) of senescence-accelerated prone 8 (SAMP8) mice and senescence-accelerated resistant 1 (SAMR1) mice. At 24 weeks after injection of saline or PFF, we found that SAMP8 mice injected with PFF exhibited robust Lewy pathology and exacerbated degeneration of dopaminergic neurons in the SN compared to PFF-injected SAMR1 mice. We further observed an increase in the number of Iba1-positive cells in the brains of PFF-injected SAMP8 mice. RNA sequencing revealed that several genes related to neuroinflammation were upregulated in the brains of PFF-injected SAMP8 mice compared to SAMR1 mice. Inflammatory chemokine <em>C</em>C-chemokine ligand 21 (CCL21) was upregulated in PFF-injected SAMP8 mice and expressed in the glial cells of these mice. Our research indicates that accelerated senescence leads to persistent neuroinflammation, which plays an important role in the exacerbation of α-synucleinopathy.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"182 ","pages":"Article 105906"},"PeriodicalIF":4.4,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142705326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcium balance through mutual orchestrated inter-organelle communication: A pleiotropic target for combating Alzheimer's disease","authors":"Muhammad Kamal Hossain ,&nbsp;Han Jung Chae","doi":"10.1016/j.neuint.2024.105905","DOIUrl":"10.1016/j.neuint.2024.105905","url":null,"abstract":"<div><div>Dysfunctional intraneuronal organelles in Alzheimer's Disease (AD) propel aberrant calcium handling, triggering molecular miscommunication within organelles such as mitochondria, endoplasmic reticulum, and lysosomes. This disruption in organelle function not only impairs cellular homeostasis but also exacerbates neurodegenerative processes involving the accumulation of amyloid-β (Aβ) and hyperphosphorylated tau, amplifying the disease's vicious cycle. In this review, the concept of Mutual Orchestrated Inter-organelle Communication (MOIC) proposes potential therapeutic avenues for restoring Ca²⁺ homeostasis in AD, offering a theoretical framework for developing disease-modifying treatments. The intricate nature of AD necessitates a shift towards combination therapies targeting MOIC-associated pathways, presenting a more effective approach than monotherapy.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"182 ","pages":"Article 105905"},"PeriodicalIF":4.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective effects of nutraceuticals and natural products in traumatic brain injury","authors":"K.M. Bhargavi ,&nbsp;Niya Gowthami ,&nbsp;G.K. Chetan ,&nbsp;M.M. Srinivas Bharath","doi":"10.1016/j.neuint.2024.105904","DOIUrl":"10.1016/j.neuint.2024.105904","url":null,"abstract":"<div><div>Traumatic Brain Injury (TBI) is a global healthcare concern with considerable mortality and morbidity. Early diagnosis and timely treatment are critical for optimal clinical prognosis in TBI patients. Injury to the brain tissue following TBI is categorized into primary and secondary injury events, with the former being acute, while the latter evolves over a long period. Although surgical intervention is effective to treat primary injury, secondary injury events that could contribute to long term neurological deterioration, cognitive impairment and neurodegeneration do not have appropriate pharmacotherapy. To address this lacuna, studies based on modern medicine to explore novel drugs in TBI have met with limited success. This has led to focussed efforts to assess natural products capable of targeting multiple pathways in TBI. Complex natural mixtures and isolated phytochemicals capable of targeting redox mechanisms, neuroinflammation, mitochondrial dysfunction, cell death pathways and other specific targets etc. have been characterized. However, the field has met with certain limitations and challenges with inadequate clinical studies and trials being the most important concern. The current review provides an overview of the dietary factors, nutraceuticals, natural extracts, and phytochemicals that could be potentially applied in neuroprotection, TBI therapy and long-term management of cognitive symptoms and other neurological deficits.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"182 ","pages":"Article 105904"},"PeriodicalIF":4.4,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646555","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}

{"title":"Polygonatum sibiricum polysaccharides: A promising strategy in the treatment of neurodegenerative disease","authors":"Xue Jiang ,&nbsp;Yumei Wang ,&nbsp;Zhaochen Lin ,&nbsp;Chao Li ,&nbsp;Qian Wang ,&nbsp;Junyan Zhang ,&nbsp;Xiuhua Liu ,&nbsp;Ziye Li ,&nbsp;Chao Cui","doi":"10.1016/j.neuint.2024.105902","DOIUrl":"10.1016/j.neuint.2024.105902","url":null,"abstract":"<div><div>Neurodegenerative diseases (NDDs), as a neurological disorder characterised by neuronal degeneration and death, are a serious threat to human health and have long attracted attention due to their complex pathogenesis and the ineffectiveness of therapeutic drugs. Existing studies have shown that <em>Polygonatum Sibiricum</em> polysaccharides (PSP) have immunoregulatory, antioxidant, anti-inflammatory and other pharmacological effects, and their neuroprotective effects have been demonstrated in several scientific studies. This paper reviews the main pharmacological effects and mechanisms of PSP in the protection and treatment of NDDs, to provide a reference for the clinical application and basic research of PSP in NDDs.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"181 ","pages":"Article 105902"},"PeriodicalIF":4.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611479","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}

{"title":"The wnt/pyruvate kinase, muscle axis plays an essential role in the differentiation of mouse neuroblastoma cells","authors":"Cheng Lei ,&nbsp;Jiaqi Wang ,&nbsp;Xiaoyu Zhang ,&nbsp;Xuemin Ge ,&nbsp;Wei Zhao ,&nbsp;Xinrong Li ,&nbsp;Wei Jiang ,&nbsp;Mingyu Ma ,&nbsp;Zhenhai Wang ,&nbsp;Shanshan Sun ,&nbsp;Qingfei Kong ,&nbsp;Hulun Li ,&nbsp;Lili Mu ,&nbsp;Jinghua Wang","doi":"10.1016/j.neuint.2024.105901","DOIUrl":"10.1016/j.neuint.2024.105901","url":null,"abstract":"<div><div>Neuronal differentiation and neurite growth are essential processes in nervous system development and are regulated by several factors. Although all-trans retinoic acid (ATRA) has been shown to mediate the differentiation of mouse neuroblastoma cells via the activation of several pathways, including Wnt/β-catenin signaling, the mechanism remains unclear. The pyruvate kinase, muscle (PKM) plays an important role in the glycolysis of neuroblastoma cells and regulates the Wnt signaling pathway in various cancer cells. In this study, we hypothesized that the Wnt/PKM axis regulates the differentiation of neuroblastoma cells (Neuro-2a and N1E-115). To test this hypothesis, we used inhibitors and activators of the Wnt/β-catenin and glycolytic pathways in ATRA-induced differentiated Neuro-2a and N1E-115 cells and established cell lines with silenced or a mutant replacement of Pkm. Western blot and qPCR showed that ATRA treatment activated the Wnt signaling pathway and inhibited PKM-mediated glycolysis. The oxygen consumption rate (indicating oxidative phosphorylation) significantly increased, whereas the extracellular acidification rate (indicating glycolysis) significantly decreased during differentiation; these effects were reversed upon PKM inhibition. The Wnt inhibitor ICG-001 and PKM activator ML-265 inhibited ATRA-induced Neuro-2a and N1E-115 differentiation, whereas RNA interference-mediated Pkm silencing promoted Neuro-2a and N1E-115 differentiation, which was reversed by PKM overexpression. Treatment with the Wnt activator kenpaullone promoted Neuro-2a and N1E-115 differentiation, which was reversed by ML-265 administration. These results indicate that Wnt/β-catenin signaling promotes Neuro-2a and N1E-115 differentiation by inhibiting PKM-mediated glycolysis during ATRA-induced differentiation. These findings may provide a new theoretical basis for the role of glycolysis in nerve differentiation.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"181 ","pages":"Article 105901"},"PeriodicalIF":4.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611483","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}

{"title":"The developing mouse dopaminergic system: Cortical-subcortical shift in D1/D2 receptor balance and increasing regional differentiation","authors":"Ingvild E. Bjerke ,&nbsp;Harry Carey ,&nbsp;Jan G. Bjaalie ,&nbsp;Trygve B. Leergaard ,&nbsp;Jee Hyun Kim","doi":"10.1016/j.neuint.2024.105899","DOIUrl":"10.1016/j.neuint.2024.105899","url":null,"abstract":"<div><div>The dopaminergic system of the brain is involved in complex cognitive functioning and undergoes extensive reorganization during development. Yet, these changes are poorly characterized. We have quantified the density of dopamine 1- and 2-receptor (D1 and D2) positive cells across the forebrain of male and female mice at five developmental stages using validated transgenic mice expressing green fluorescent protein in cells producing D1 or D2 mRNA. After analyzing &gt;4,500 coronal brain images, a cortico-subcortical shift in D1/D2 balance was discovered, with increasing D1 dominance in cortical regions as a maturational pattern that occurs earlier in females. We describe postnatal trajectories of D1 and D2 cell densities across major brain regions and observe increasing regional differentiation of D1 densities through development. Our results provide the most comprehensive overview of the developing dopaminergic system to date, and an empirical foundation for further experimental and computational investigations of dopaminergic signaling.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"182 ","pages":"Article 105899"},"PeriodicalIF":4.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}