Neurochemistry international最新文献

{"title":"Stroke triggers dynamic m6A reprogramming of cerebral circular RNAs","authors":"Suresh L. Mehta ,&nbsp;Hadjer Namous ,&nbsp;Raghu Vemuganti","doi":"10.1016/j.neuint.2024.105802","DOIUrl":"10.1016/j.neuint.2024.105802","url":null,"abstract":"<div><p>We previously showed that stroke alters circular RNA (circRNA) expression profiles. Many circRNAs undergo epitranscriptomic modifications, particularly methylation of adenosine to form N⁶-methyladenosine (m⁶A). This modification significantly influences the circRNA metabolism and functionality. Hence, we currently evaluated if transient focal ischemia in adult C57BL/6J mice alters the m⁶A methylation of circRNAs. Changes in m⁶A were profiled in the peri-infarct cortex following immunoprecipitation coupled with microarrays. Correlation and gene ontology analyses were performed to understand the association of m⁶A changes with circRNA regulation and functional implications after stroke. Many circRNAs showed differential regulation (up or down) after stroke, and this change was highest at 24h of reperfusion. Notably, most circRNAs differentially regulated after stroke also exhibited temporal changes in m⁶A modification patterns. The majority of circRNAs that showed post-stroke differential m⁶A modifications were derived from protein-coding genes. Hyper-than hypomethylation of circRNAs was most prevalent after stroke. Gene ontology analysis of the host genes suggested that m⁶A-modified circRNAs might regulate functions such as synapse-related processes, indicating that m⁶A epitranscriptomic modification in circRNAs could potentially influence post-stroke synaptic pathophysiology.</p></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"178 ","pages":"Article 105802"},"PeriodicalIF":4.4,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544356","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":"Astrocyte-secreted lipocalin-2 elicits bioenergetic failure-induced neuronal death that is causally related to high fatality in a mouse model of hepatic encephalopathy","authors":"Ching-Yi Tsai,&nbsp;Chin-Lai Lee,&nbsp;Jacqueline C.C. Wu","doi":"10.1016/j.neuint.2024.105800","DOIUrl":"10.1016/j.neuint.2024.105800","url":null,"abstract":"<div><p>Hepatic encephalopathy (HE) is a neurological complication arising from acute liver failure with poor prognosis and high mortality; the underlying cellular mechanisms are still wanting. We previously found that neuronal death caused by mitochondrial dysfunction in rostral ventrolateral medulla (RVLM), which leads to baroreflex dysregulation, is related to high fatality in an animal model of HE. Lipocalin-2 (Lcn2) is a secreted glycoprotein mainly released by astrocytes in the brain. We noted the presence of Lcn2 receptor (Lcn2R) in RVLM neurons and a parallel increase of <em>Lcn2</em> gene in astrocytes purified from RVLM during experimental HE. Therefore, our guiding hypothesis is that Lcn2 secreted by reactive astrocytes in RVLM may underpin high fatality during HE by eliciting bioenergetic failure-induced neuronal death in this neural substrate. In this study, we first established the role of astrocyte-secreted Lcn2 in a liver toxin model of HE induced by azoxymethane (100 μg/g, ip) in C57BL/6 mice, followed by mechanistic studies in primary astrocyte and neuron cultures prepared from postnatal day 1 mouse pups. In animal study, immunoneutralization of Lcn2 reduced apoptotic cell death in RVLM, reversed defunct baroreflex-mediated vasomotor tone and prolonged survival during experimental HE. In our primary cell culture experiments, Lcn2 produced by cultured astrocytes and released into the astrocyte-conditioned medium significantly reduced cell viability of cultured neurons. Recombinant Lcn2 protein reduced cell viability, mitochondrial ATP (mitoATP) production, and pyruvate dehydrogenase (PDH) activity but enhanced the expression of pyruvate dehydrogenase kinase (PDK) 1, PDK3 and phospho-PDHA1 (inactive PDH) through MAPK/ERK pathway in cultured neurons, with all cellular actions reversed by Lcn2R knockdown. Our results suggest that astrocyte-secreted Lcn2 upregulates PDKs through MAPK/ERK pathway, which leads to reduced PDH activity and mitoATP production; the reinforced neuronal death in RVLM is causally related to baroreflex dysregulation that underlies high fatality associated with HE.</p></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"178 ","pages":"Article 105800"},"PeriodicalIF":4.4,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533188","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":"Combating Parkinson's disease with plant-derived polyphenols: Targeting oxidative stress and neuroinflammation","authors":"Reem M. Gahtani ,&nbsp;Shoaib Shoaib ,&nbsp;Umme Hani ,&nbsp;R. Jayachithra ,&nbsp;Mohammad N. Alomary ,&nbsp;Waseem Chauhan ,&nbsp;Roshan Jahan ,&nbsp;Saba Tufail ,&nbsp;Mohammad Azam Ansari","doi":"10.1016/j.neuint.2024.105798","DOIUrl":"10.1016/j.neuint.2024.105798","url":null,"abstract":"<div><p>Parkinson's disease (PD) is a devastating neurodegenerative disorder predominantly affecting the elderly, characterized by the loss of dopaminergic neurons in the substantia nigra. Reactive oxygen species (ROS) generation plays a central role in the pathogenesis of PD and other neurodegenerative diseases. An imbalance between cellular antioxidant activity and ROS production leads to oxidative stress, contributing to disease progression. Dopamine metabolism, mitochondrial dysfunction, and neuroinflammation in dopaminergic neurons have been implicated in the pathogenesis of Parkinson's disease. Consequently, there is a pressing need for therapeutic interventions capable of scavenging ROS. Current pharmacological approaches, such as L-dihydroxyphenylalanine (levodopa or L-DOPA) and other drugs, provide symptomatic relief but are limited by severe side effects. Researchers worldwide have been exploring alternative compounds with less toxicity to address the multifaceted challenges associated with Parkinson's disease. In recent years, plant-derived polyphenolic compounds have gained significant attention as potential therapeutic agents. These compounds exhibit neuroprotective effects by targeting pathophysiological responses, including oxidative stress and neuroinflammation, in Parkinson's disease. The objective of this review is to summarize the current understanding of the neuroprotective effects of various polyphenols in Parkinson's disease, focusing on their antioxidant and anti-inflammatory properties, and to discuss their potential as therapeutic candidates. This review highlights the progress made in elucidating the molecular mechanisms of action of these polyphenols, identifying potential therapeutic targets, and optimizing their delivery and bioavailability. Well-designed clinical trials are necessary to establish the efficacy and safety of polyphenol-based interventions in the management of Parkinson's disease.</p></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"178 ","pages":"Article 105798"},"PeriodicalIF":4.4,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475599","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":"Naringenin mitigates nanoparticulate-aluminium induced neuronal degeneration in brain cortex and hippocampus through downregulation of oxidative stress and neuroinflammation","authors":"Ravina Rai ,&nbsp;Pankaj Lal Kalar ,&nbsp;Deepali Jat ,&nbsp;Siddhartha Kumar Mishra","doi":"10.1016/j.neuint.2024.105799","DOIUrl":"10.1016/j.neuint.2024.105799","url":null,"abstract":"<div><p>Alumunium usage and toxicity has been a global concern especially an increased use of nanoparticulated aluminum (Al-NPs) products from the environment and the workplace. Al degrades in to nanoparticulate form in the environment due to the routine process of bioremediation in human body. Al-NPs toxicity plays key role in the pathophysiology of neurodegeneration which is characterised by the development of neurofibrillary tangles and neuritic plaques which correlates to the Alzheimer's disease. This study evaluated the Al-NPs induced neurodegeneration and causative behavioral alterations due to oxidative stress, inflammation, DNA damage, β-amyloid aggregation, and histopathological changes in mice. Furthermore, the preventive effect of naringenin (NAR) as a potent neuroprotective flavonoid against Al-NPs induced neurodegeneration was assessed. Al-NPs were synthesized and examined using FTIR, XRD, TEM, and particle size analyzer. Mice were orally administered with Al-NPs (6 mg/kg b.w.) followed by NAR treatment (10 mg/kg b.w. per day) for 66 days. The spatial working memory was determined by novel object recognition, T-maze, Y-maze, and Morris Water Maze tests. We measured nitric oxide, advanced oxidation of protein products, protein carbonylation, lipid peroxidation, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, reduced glutathione, oxidised glutathione, and acetylcholine esterase, as well as cytokines analysis, immunohistochemistry, and DNA damage. Al-NPs significantly reduced the learning memory power, increased oxidative stress, reduced antioxidant enzymatic activity, increased DNA damage, altered the levels of cytokines, and increased β-amyloid aggregation in the cortex and hippocampus regions of the mice brain. These neurobehavioral impairments, neuronal oxidative stress, and histopathological alterations were significantly attenuated by NAR supplementation. In conclusion, Al-NPs may be potent neurotoxic upon exposure and that NAR could serve as a potential preventive measure in the treatment and management of neuronal degeneration.</p></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"178 ","pages":"Article 105799"},"PeriodicalIF":4.4,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475600","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":"Interweaving the Numerical harmonic symmetry principles of the K+ Pore ion channel momentum","authors":"Yuval Ben-Abu","doi":"10.1016/j.neuint.2024.105797","DOIUrl":"10.1016/j.neuint.2024.105797","url":null,"abstract":"<div><p>K+ channels exist in all living systems. They allow a selective transition to the K+ ion, which enables the activity of various vital tissues such as muscle cells, neurons, and even bacteria and plants. Despite the mechanism variation in the gating process of K+ channels in different tissues, the selectivity for the K+ ion is preserved and the electrochemical cascade is maintained in these tissues. The electrochemical gradient of the K+ ion is very close to the diffusion rate of K+ ions in bulk water. On the molecular level, how does a K+ ion move across the ion conduction pathway? There are many molecular models that describe and answer this question, however, this is rarely described on the macro level. Here, a physical model can serve as a very good basis for enabling a deeper understanding of the K+ ion for ion transport. Classical physical energy and linear and angular momentum laws can provide a good explanation as to how and what happens to K+ ions when they pass through an ion conduction pathway. This model describes the passage of the ion even before it enters the ion conduction path until the last ion at the end exits. The simulation described here is fascinating and depicts the state of the ion at the farthest end released at almost the same speed as the first ion initially, while all the other ions remain almost at rest. How does this occur? What happens if we change the size or mass of the ion? In this work, I describe this principle and the related problems that could be studied.</p></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"178 ","pages":"Article 105797"},"PeriodicalIF":4.4,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465142","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":"Anticonvulsant and anxiolytic-like potential of the essential oil from the Ocimum basilicum Linn leaves and its major constituent estragole on adult zebrafish (Danio rerio)","authors":"Francisco Lucas A. Batista ,&nbsp;Sandra Maria B. de Araújo ,&nbsp;Daniela Braga de Sousa ,&nbsp;Francisco Bastos C. Sobrinho ,&nbsp;Maria Gabriely de Lima Silva ,&nbsp;Maria Rayane C. de Oliveira ,&nbsp;Roger Henrique S. da Costa ,&nbsp;Lindaiane Bezerra Rodrigues ,&nbsp;Franciglauber Silva Bezerra ,&nbsp;Djane Ventura de Azevedo ,&nbsp;Antônio Eufrásio Vieira-Neto ,&nbsp;Francisco Ernani A. Magalhães ,&nbsp;Irwin Rose Alencar de Menezes","doi":"10.1016/j.neuint.2024.105796","DOIUrl":"10.1016/j.neuint.2024.105796","url":null,"abstract":"<div><p>The Ocimum species present active compounds with the potential to develop drugs for treating chronic disease conditions, such as anxiety and seizures. The present study aims to investigate the anticonvulsant and anxiolytic-like effect of the essential oil from <em>O. basilicum</em> Linn (OEFOb) leaves and its major constituent estragole (ES) <em>in vivo</em> on adult zebrafish (aZF) and <em>in silico</em>. The aZF were treated with OEFOb or ES or vehicle and submitted to the tests of toxicity, open-field, anxiety, and convulsion and validated the interactions of the estragole on the involvement of GABAergic and serotonergic receptors by molecular docking assay. The results showed that the oral administration of OEFOb and ES did not have a toxic effect on the aZF and showed anxiolytic-like effects with the involvement of GABA_A, 5-HT₁, 5-HT_2A/2C and 5-HT_3A/3B as well on anxiety induced by alcohol withdrawal. The OEFOb and ES showed anticonvulsant potential attenuating the seizures induced by pentylenetetrazole (PTZ) by modulation of the GABA_A system. Both anxiolytic and anticonvulsant effects were corroborated by the potential of the interaction of ES by <em>in silico</em> assay. These study samples demonstrate the pharmacological evidence and potential for using these compounds to develop new anxiolytic and anticonvulsant drugs.</p></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"178 ","pages":"Article 105796"},"PeriodicalIF":4.4,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465141","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":"p53 lysine-lactylated modification contributes to lipopolysaccharide-induced proinflammatory activation in BV2 cell under hypoxic conditions","authors":"Xuechao Fei ,&nbsp;Lu Chen ,&nbsp;Jiayue Gao ,&nbsp;Xiufang Jiang ,&nbsp;Wen Sun ,&nbsp;Xiang Cheng ,&nbsp;Tong Zhao ,&nbsp;Ming Zhao ,&nbsp;Lingling Zhu","doi":"10.1016/j.neuint.2024.105794","DOIUrl":"10.1016/j.neuint.2024.105794","url":null,"abstract":"<div><p>p53 has diversity functions in regulation of transcription, cell proliferation, cancer metastasis, etc. Recent studies have shown that p53 and nuclear factor-κB (NF-κB) co-regulate proinflammatory responses in macrophages. However, the role of p53 lysine lactylation (p53Kla) in mediating proinflammatory phenotypes in microglia under hypoxic conditions remains unclear. In the current study, we investigated the proinflammatory activation exacerbated by hypoxia and the levels of p53Kla in microglial cells. BV2 cells, an immortalized mouse microglia cell line, were divided into control, lipopolysaccharide (LPS)-induced, hypoxia (Hy), and LPS-Hy groups. The protein expression levels of p53 and p53Kla and the activation of microglia were compared among the four groups. Sodium oxamate and mutant p53 plasmids were transfected into BV2 cells to detect the effect of p53Kla on microglial proinflammatory activation. LPS-Hy stimulation significantly upregulated p53Kla levels in both the nucleus and the cytoplasm of BV2 cells. In contrast, the p53 protein levels were downregulated. LPS-Hy stimulation upregulated phosphorylated p65 protein levels in nuclear and activated the NF-κB pathway in BV2 cells, resulting in increased expression of pro-inflammatory cytokines (iNOS, IL6, IL1β, TNFα), enhanced cell viability, and concomitantly, increased cytotoxicity. In conclusion, p53 lysine-lactylated modification contributes to LPS-induced proinflammatory activation in BV2 cells under hypoxia through NF-κB pathway and inhibition of lactate production may alleviate neuroinflammatory injury.</p></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"178 ","pages":"Article 105794"},"PeriodicalIF":4.4,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141439950","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":"Intermittent fasting induced cerebral ischemic tolerance altered gut microbiome and increased levels of short-chain fatty acids to a beneficial phenotype","authors":"Bharath Chelluboina ,&nbsp;Tony Cho ,&nbsp;Jin-Soo Park ,&nbsp;Suresh L. Mehta ,&nbsp;Saivenkateshkomal Bathula ,&nbsp;Soomin Jeong ,&nbsp;Raghu Vemuganti","doi":"10.1016/j.neuint.2024.105795","DOIUrl":"10.1016/j.neuint.2024.105795","url":null,"abstract":"<div><p>Preconditioning-induced cerebral ischemic tolerance is known to be a beneficial adaptation to protect the brain in an unavoidable event of stroke. We currently demonstrate that a short bout (6 weeks) of intermittent fasting (IF; 15 h fast/day) induces similar ischemic tolerance to that of a longer bout (12 weeks) in adult C57BL/6 male mice subjected to transient middle cerebral artery occlusion (MCAO). In addition, the 6 weeks IF regimen induced ischemic tolerance irrespective of age (3 months or 24 months) and sex. Mice subjected to transient MCAO following IF showed improved motor function recovery (rotarod and beam walk tests) between days 1 and 14 of reperfusion and smaller infarcts (T2-MRI) on day 1 of reperfusion compared with age/sex matched ad libitum (AL) controls. Diet influences the gut microbiome composition and stroke is known to promote gut bacterial dysbiosis. We presently show that IF promotes a beneficial phenotype of gut microbiome following transient MCAO compared with AL cohort. Furthermore, post-stroke levels of short-chain fatty acids (SCFAs), which are known to be neuroprotective, are higher in the fecal samples of the IF cohort compared with the AL cohort. Thus, our studies indicate the efficacy of IF in protecting the brain after stroke, irrespective of age and sex, probably by altering gut microbiome and SCFA production.</p></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"178 ","pages":"Article 105795"},"PeriodicalIF":4.4,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141439949","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":"A2AR antagonists triggered the AMPK/m-TOR autophagic pathway to reverse the calcium-dependent cell damage in 6-OHDA induced model of PD","authors":"Tuithung Sophronea,&nbsp;Saurabh Agrawal,&nbsp;Namrata Kumari,&nbsp;Jyoti Mishra,&nbsp;Vaishali Walecha,&nbsp;Pratibha Mehta Luthra","doi":"10.1016/j.neuint.2024.105793","DOIUrl":"10.1016/j.neuint.2024.105793","url":null,"abstract":"<div><p>Calcium dyshomeostasis, oxidative stress, autophagy and apoptosis are the pathogenesis of selective dopaminergic neuronal loss in Parkinson's disease (PD). Earlier, we reported that A_2A R modulates IP₃-dependent intracellular Ca²⁺ signalling via PKA. Moreover, A_2A R antagonist has been reported to reduce oxidative stress and apoptosis in PD models, however intracellular Ca²⁺ ([Ca²⁺]_i) dependent autophagy regulation in the 6-OHDA model of PD has not been explored. In the present study, we investigated the A_2A R antagonists mediated neuroprotective effects in 6-OHDA-induced primary midbrain neuronal (PMN) cells and unilateral lesioned rat model of PD. 6-OHDA-induced oxidative stress (ROS and superoxide) and [Ca²⁺]_i was measured using Fluo4AM, DCFDA and DHE dye respectively. Furthermore, autophagy was assessed by Western blot of p-m-TOR/mTOR, p-AMPK/AMPK, LC3I/II, Beclin and β-actin. Apoptosis was measured by Annexin V-APC-PI detection and Western blot of Bcl₂, Bax, caspase3 and β-actin. Dopamine levels were measured by Dopamine ELISA kit and Western blot of tyrosine hydroxylase. Our results suggest that 6-OHDA-induced PMN cell death occurred due to the interruption of [Ca²⁺]_i homeostasis, accompanied by activation of autophagy and apoptosis. A_2A R antagonists prevented 6-OHDA-induced neuronal cell death by decreasing [Ca²⁺]_i overload and oxidative stress. In addition, we found that A_2A R antagonists upregulated mTOR phosphorylation and downregulated AMPK phosphorylation thereby reducing autophagy and apoptosis both in 6-OHDA induced PMN cells and 6-OHDA unilateral lesioned rat model. In conclusion, A_2A R antagonists alleviated 6-OHDA toxicity by modulating [Ca²⁺]_i signalling to inhibit autophagy mediated by the AMPK/mTOR pathway.</p></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"178 ","pages":"Article 105793"},"PeriodicalIF":4.4,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141329977","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":"Exposure to lipid mixture induces intracellular lipid droplet formation and impairs mitochondrial functions in astrocytes","authors":"Yi-Chen Li,&nbsp;Jing-Ting Fu,&nbsp;Shun-Fen Tzeng","doi":"10.1016/j.neuint.2024.105792","DOIUrl":"10.1016/j.neuint.2024.105792","url":null,"abstract":"<div><p>Astrocytes, the predominant glial cells in the central nervous system (CNS), play diverse roles including metabolic support for neurons, provision of neurotrophic factors, facilitation of synaptic neurotransmitter uptake, regulation of ion balance, and involvement in synaptic formation. The accumulation of lipids has been noted in various neurological conditions, yet the response of astrocytes to lipid-rich environments remains unclear. In this study, primary astrocytes isolated from the neonatal rat cortex were exposed to a lipid mixture (LM) comprising cholesterol and various fatty acids to explore their reaction. Our results showed that astrocyte viability remained unchanged following 24 h of 5% or 10% LM treatment. However, exposure to LM for 96 h resulted in reduced cell viability. In addition, LM treatment led to the accumulation of lipid droplets (LDs) in astrocytes, with LD size increasing over prolonged exposure periods. Following 24 h of LM treatment and then 48 h in fresh medium, a significant reduction in intracellular LD size was observed in cultures treated with 5% LM, while no change occurred in cultures exposed to 10% LM. Yet, exposure to 10% LM for 24 h significantly increased the expression of the cholesterol efflux regulatory protein/ATP-binding cassette transporter (ABCA1) gene, responsible for intracellular cholesterol efflux, resulting in reduced cholesterol content within astrocytes. Moreover, LM exposure led to decreased mitochondrial membrane potential (MMP) and increased levels of mature apoptosis-inducing factor (AIF). The smaller LDs were observed to co-localize with microtubule-associated protein 1A/1 B light chain 3 B (LC3) and lysosomal-associated membrane protein-1 (LAMP-1) in LM-treated astrocytes, coinciding with lysosomal acidification. These results indicate that the continuous buildup of LDs in astrocytes residing in lipid-enriched environments may be attributed to disruptions caused by LM in mitochondrial and lysosomal functions. Such disruptions could potentially impede the supportive role of astrocytes in neuronal function.</p></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"178 ","pages":"Article 105792"},"PeriodicalIF":4.2,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141329978","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}