Neuroscience Letters最新文献

{"title":"Repeated human cranial bone-derived mesenchymal stem cell transplantation improved electrophysiological recovery in a spinal cord injury rat model","authors":"Yuyo Maeda ,&nbsp;Takafumi Mitsuhara ,&nbsp;Masaaki Takeda ,&nbsp;Misaki Okamoto ,&nbsp;Takashi Otsuka ,&nbsp;Takeshi Hara ,&nbsp;Masashi Kuwabara ,&nbsp;Nobutaka Horie","doi":"10.1016/j.neulet.2024.138031","DOIUrl":"10.1016/j.neulet.2024.138031","url":null,"abstract":"<div><div>Mesenchymal stem cell (MSC)-based therapy has been applied in several clinical trials of spinal cord injury (SCI). We have successfully established MSCs from human cranial bone and developed a longitudinal neuromonitoring technique for rodents. In addition to single transplantation, the potential of multiple transplantations has been suggested as a new therapeutic strategy. However, there are no reports on the electrophysiological effects of multiple MSC transplantations in SCI using transcranial electrical stimulation motor-evoked potentials (tcMEPs). Here, we aimed to elucidate the efficacy and mechanism of action of multiple MSC transplantations using tcMEPs. After establishing a weight-drop-induced SCI rat model, we performed repeated intravenous transplantation of human cranial bone-derived MSCs (hcMSCs) on days 1 and 3 post-SCI. Motor function and tcMEP recovery were evaluated 6 weeks post-transplantation. Tissue repair post-SCI was assessed using immunostaining for myelin and neurons in the injured posterior cord. Repeated hcMSC transplantation significantly improved motor function and electrophysiological recovery compared to single transplantation and control treatment. Repeated hcMSC transplantation promoted electrophysiological functional recovery by exerting a protective effect on the functional structure of pyramidal tract axons. Thus, acute-phase repeated transplantation could be a novel and effective therapeutic strategy for the clinical application of MSCs in SCI.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"844 ","pages":"Article 138031"},"PeriodicalIF":2.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BAK ameliorated cerebral infarction/ischemia–reperfusion injury by activating AMPK/Nrf2 to inhibit TXNIP/NLRP3/caspase-1 axis","authors":"Yue-Wei Xu ,&nbsp;Chang-Heng Yao ,&nbsp;Xiao-Ming Gao ,&nbsp;Li Wang ,&nbsp;Meng-Xiang Zhang ,&nbsp;Xiao-Dan Yang ,&nbsp;Jing Li ,&nbsp;Wen-Ling Dai ,&nbsp;Man-Qin Yang ,&nbsp;Ming Cai","doi":"10.1016/j.neulet.2024.138037","DOIUrl":"10.1016/j.neulet.2024.138037","url":null,"abstract":"<div><h3>Background</h3><div>Cerebral ischemia/reperfusion (I/R) injury is a serious vascular disease with extremely high mortality and disability rate. Bakuchiol (BAK) was found in leaves and seeds of <em>Psoralea corylifolia</em> Linn and has been shown to decrease inflammation and reduce oxidative stress, while the mechanism of BAK in ameliorating cerebral I/R injury remains unclear.</div></div><div><h3>Methods</h3><div>Middle cerebral artery occlusion reperfusion (MACO/R) was used to establish mouse model. The protective effect of BAK in MCAO/R mices was detected by performing neurological deficit testing, TTC staining, and H&amp;E staining. Oxygen/glucose deprivation and reperfusion (OGD/R) was used to stimulate SH-SY5Y cells <em>in vitro</em>. Protein expression was detected by western blotting, gene expression was detected by quantitative real-time polymerase chain reaction and apoptosis was detected by immunofluorescence.</div></div><div><h3>Results</h3><div>Our study indicated that BAK protected ischemia–reperfusion injury in MACO/R mice, and upregulated superoxide dismutase (SOD) and the catalase (CAT) enzyme activity. BAK also inhibited the expression of TNF-α, IL-1β, IL-6, and IL-18 and suppressed apoptosis and pyroptosis both in MACO/R mice and in OGD/R SH-SY5Y cells. Further results showed that BAK could suppress TXNIP, ASC, NLRP3, and caspase-1 mRNA levels to reverse assembly of inflammasome. And BAK could also upregulate the expression of phosphorylated AMP-activated protein kinase (AMPK) and nuclear factor erythroid 2-related factor (Nrf2). In addition, Nrf2 inhibitor ML385 reversed the BAK induced reduction of TXNIP, ASC, NLRP3, and the AMPK inhibitor also abolished BAK’ the effect on the regulation of Nrf2, TXNIP, ASC, NLRP3, caspase-1, and pro-inflammatory cytokines. In conclusion, BAK, found in leaves and seeds of <em>Psoralea corylifolia</em> Linn, could ameliorated cerebral I/R injury through activating AMPK/Nrf2 to inhibit NLRP3 inflammasome, which might present new therapeutic strategy for cerebral I/R injury.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"844 ","pages":"Article 138037"},"PeriodicalIF":2.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered miR-10a gene expression in peripheral blood mononuclear cells correlates with frequency of T regulatory cells and cytokine profile in multiple sclerosis patients","authors":"Shiva Alipour ,&nbsp;Ali Aghebati-Maleki ,&nbsp;Mohammad Reza Sadeghi ,&nbsp;Mohammad Sadegh Soltani-Zangbar ,&nbsp;Ali Khakpour ,&nbsp;Leili Aghebati-Maleki","doi":"10.1016/j.neulet.2024.138036","DOIUrl":"10.1016/j.neulet.2024.138036","url":null,"abstract":"<div><div>A critical component in triggering and progressing autoimmune multiple sclerosis (MS) is the deregulation of immune responses, including dysfunction of T regulatory cells (Tregs), critical participants in the pathogenetic context of inflammation. It has been found that miRNAs have a crucial role in the induction of MS because dysregulation of miRNAs can result in defects in immunological tolerance. In this investigation, we examined the miR-10a contribution to MS disorder by comparing the altered expression of miR-10a in peripheral blood mononuclear cells (PBMCs) of 40 MS patients to 40 healthy controls. Additionally, we examined Tregs’ frequency in MS patients in compare with healthy controls. We evaluated the secreted levels of anti-inflammatory cytokines, such as IL-10 and TGF-B, in the serum of MS patients and their expression level in healthy controls’ and patients’ peripheral blood mononuclear cells (PBMCs). Then, we assessed the correlation between miR-10a expression with Treg frequency and levels of anti-inflammatory cytokines in serum. PBMCs from MS patients had downregulated expression of miR-10a, and a substantial correlation was found between this expression and a reduction in Treg cells’ frequency and the secreted anti-inflammatory cytokines associated with Tregs’ diminished functionality. In summary, our research demonstrated a strong correlation between Tregs’ frequency, lower levels of cytokines linked to Treg function, and lower expression of miR-10a in PBMCs. So, the alteration of miR-10a can be utilized as a probable therapeutic target for the prevention and management of MS disorder. However, further examination is requisite before this strategy become practical for use in the clinical setting.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"844 ","pages":"Article 138036"},"PeriodicalIF":2.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of ligustrazine on energy metabolism in migraine rats based on mitochondria-inflammation pathway","authors":"Yicheng Wang ,&nbsp;Yongli Wang ,&nbsp;Guangxin Yue ,&nbsp;Jingjing Lin ,&nbsp;Xueying Liu ,&nbsp;Liwei Wang ,&nbsp;Yonglie Zhao","doi":"10.1016/j.neulet.2024.138035","DOIUrl":"10.1016/j.neulet.2024.138035","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the effects of Ligustrazine (Lig) on nitroglycerin-induced migraine and explore the mechanism through the mitochondria-inflammation pathway.</div></div><div><h3>Methods</h3><div>Rats were divided into control, model, Lig(50 mg/kg) + Erastin, Lig(100 mg/kg), Lig(50 mg/kg), and Zolmitriptan groups. Nitroglycerin (NTG) was administered through injection to trigger a migraine. The following parameters were measured: mechanical pain threshold, mitochondrial morphology, levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), Adenosine triphosphate (ATP), and Nitric oxide (NO). The neuronal nitric oxide synthase (nNOS), transient receptor potential A1 (TRPA1), interleukin 1 beta (IL-1β), nuclear factor-kappaB (NF-κB), and calcitonin gene-related peptide (CGRP) were detected by Western blotting and immunohistochemistry.</div></div><div><h3>Results</h3><div>Compared with the model group, the Lig(100 mg/kg) and Lig(50 mg/kg) groups increased mechanical pain threshold as well as improved abnormal mitochondrial morphology. Moreover, compared with the model group, the Lig(100 mg/kg) and Lig(50 mg/kg) groups demonstrated reduced levels of ROS, and NO, and increased MMP, and ATP. Lig(100 mg/kg) and Lig(50 mg/kg) groups reduced inflammation and oxidative stress by inhibiting certain gene expressions. When Erastin was injected, the effectiveness of Lig decreased, indicating that Lig’s therapeutic effect was related to the extent of mPTP opening.</div></div><div><h3>Conclusion</h3><div>The mitochondria-inflammation pathway plays a critical role in regulating migraine. Lig exerts anti-migraine effects primarily by modulating the mitochondria-inflammation pathway providing a novel perspective on migraine research that is beneficial for its clinical application.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"844 ","pages":"Article 138035"},"PeriodicalIF":2.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel voltage-dependent Cl− channels in striatal medium spiny neurons are unrelated to ClC-1 or other known Ca2+-induced Cl− channel/transporter types","authors":"Viktor Yarotskyy ,&nbsp;Liangru Contois ,&nbsp;Yun-Kyung Hahn ,&nbsp;Sara R. Nass ,&nbsp;Pamela E. Knapp ,&nbsp;Kurt F. Hauser","doi":"10.1016/j.neulet.2024.138032","DOIUrl":"10.1016/j.neulet.2024.138032","url":null,"abstract":"<div><div>Intracellular chloride (Cl⁻) homeostasis is a critical regulator of neuronal excitability. Voltage-dependent neuronal Cl⁻ channels remain the least understood in terms of their role as a source of Cl⁻ entry controlling excitability. We have shown recently that striatal medium spiny neurons (MSNs) express a functional Cl⁻ conducting ClC-1-like channel with properties similar but not identical to native ClC-1 channels (Yarotskyy, V., Lark, A.R.S., Nass S.R., Hahn, Y.K., Marone, M.G., McQuiston, A.R., Knapp, P.E., Hauser, K.F. (2022) <em>Am. J. Physiol. Cell. Physiol.</em> 322 (2022) C395-C409). Using a myotonic SWR/J-<em>Clcn1^adr-mto</em>/J mouse model with a premature stop codon for the ClC-1 channel rendering it non-functional, we demonstrate that striatal MSNs isolated from wild type (wt) and homozygous mutant (<em>adr</em>) mouse embryos have identical voltage-dependent outwardly rectifying Cl⁻ currents. In contrast and as expected, homozygous <em>adr</em> skeletal muscle <em>flexor digitorum brevis</em> (FDB) fibers display nominal macroscopic Cl⁻ currents compared to heterozygous wild-type <em>adr</em> FDB fibers. Together, our findings demonstrate that the novel ClC-1-like channels in MSNs are unrelated to skeletal muscle-specific ClC-1 channels, and therefore represent a unique voltage-dependent neuronal Cl⁻ channel of unknown identity.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"844 ","pages":"Article 138032"},"PeriodicalIF":2.5,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of lateral ventricle injection of 5,7-dihydroxytryptamine on neurons in the medial prefrontal cortex of rats: An electrophysiology study","authors":"Lingling Fan ,&nbsp;Bo Deng ,&nbsp;Xueqin Hao ,&nbsp;Xiangjun Qiu ,&nbsp;Yuanyuan Liu","doi":"10.1016/j.neulet.2024.138034","DOIUrl":"10.1016/j.neulet.2024.138034","url":null,"abstract":"<div><div>The medial prefrontal cortex (mPFC) is closely associated with various psychopathologies in humans, and its dysfunction is invariably accompanied by abnormalities in the serotonin (5-hydroxytryptamine, 5-HT) system of the brain. In this study, <em>in-vivo</em> extracellular recording techniques were used to investigate changes in the excitability of pyramidal neurons and interneurons in the rat mPFC following injection of 5,7-dihydroxytryptamine (5,7-DHT) into the bilateral lateral ventricles to damage the serotoninergic neurons. The levels of 5-HT in the mPFC and dorsal raphe nucleus of rats were determined by high-performance liquid chromatography. The results showed that the levels of 5-HT were significantly reduced in the mPFC and dorsal raphe nucleus two weeks after injection of 5,7-DHT into the bilateral lateral ventricles, relative to the normal group. The discharge frequency of pyramidal neurons in the mPFC was markedly increased compared to the normal group, with a significant rise in burst discharge, while the average discharge frequency of interneurons was significantly reduced and tended towards irregular activity. The results of the study indicated that the brain’s 5-HT neurotransmitter system not only directly affects the activity of mPFC pyramidal neurons but also modulates the electrical activity of interneurons, thereby regulating the local microcircuitry within the mPFC and participating in its function.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"844 ","pages":"Article 138034"},"PeriodicalIF":2.5,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabinoid receptor type 1 agonist disrupts methamphetamine-induced conditioned place preference in adolescent male rats","authors":"Effat Ramshini ,&nbsp;Mohammad Shabani","doi":"10.1016/j.neulet.2024.138033","DOIUrl":"10.1016/j.neulet.2024.138033","url":null,"abstract":"<div><div>Addiction can be viewed as a state of compulsive engagement in drug use. It is believed that drug-associated memories maintain compulsive drug-seeking behavior. Therefore, disrupting drug-associated memories may reduce drug-seeking behavior. In the present study, a conditioned place preference (CPP) apparatus was conducted to evaluate the effect of cannabinoid receptor type 1 (CB1R) agonist and antagonist on the acquisition of CPP induced by methamphetamine (METH). Anxiety behaviors and memory retrieval were assessed using elevated plus maze (EPM) and step-through passive avoidance tasks. In this study using a 5-day schedule of CPP, exposure to METH increased the time spent in the drug-paired compartment, and CB1Rs agonist (WIN 55,212–2, WIN) disrupted the METH-induced CPP. In the EPM experiment, METH significantly decreased the ratio of times spent in the open arms to total times spent in any arms (OAT) and the ratio of entries into open arms to total entries (OAE), indicating that METH increases anxiety-like behaviors. However, the CB1Rs antagonist (SR141716A, SR) reversed METH-induced anxiety behaviors. The results obtained in the passive avoidance experiment showed that blockade of brain CB1Rs by SR improves METH-induced amnesia. In summary, CB1Rs appear to modulate METH-associated memories, and antagonists of CB1Rs may serve as a therapeutic target for METH-induced anxiety behaviors.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"844 ","pages":"Article 138033"},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isoform-specific distribution of 14–3-3 proteins in the hippocampus of streptozotocin-induced diabetic rats","authors":"Sachie Sasaki-Hamada ,&nbsp;Arisa Hara ,&nbsp;Yume Tainaka ,&nbsp;Sho Satoh ,&nbsp;Jun-Ichiro Oka ,&nbsp;Hitoshi Ishibashi","doi":"10.1016/j.neulet.2024.138027","DOIUrl":"10.1016/j.neulet.2024.138027","url":null,"abstract":"<div><div>Diabetes mellitus is associated with cognitive deficits in humans and animal models. These deficits are paralleled by neurophysiological and structural changes in the central nervous system, particularly in the hippocampus, which plays an important role in memory formation. We previously reported that the magnitude of long-term potentiation at hippocampal Schaffer collateral-CA1 synapses was significantly impaired in streptozotocin (STZ)-induced type 1 diabetic rats (STZ rats). The present study investigated the mechanisms underlying morphological changes in the hippocampus of STZ rats. We performed a proteomic analysis of the hippocampus of STZ rats using two-dimensional gel electrophoresis followed by mass spectrometry. The distribution of 14–3-3 proteins identified by the proteomic analysis was then examined using immunohistochemistry. The results obtained revealed that 14–3-3 η immunoreactivity in the dorsal hippocampus was weaker in STZ rats than in age-matched control rats. Moreover, the density of glial fibrillary acidic protein-immunoreactive astrocytes in the dorsal hippocampus of STZ rats was increased, whereas 14–3-3 η immunoreactivity in astrocytes and neurons in the dentate gyrus was significantly decreased. These results suggest that changes in 14–3-3 η expression are involved in hippocampal astrogliosis or/and neurogenesis in STZ rats.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"843 ","pages":"Article 138027"},"PeriodicalIF":2.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurosteroids foster sedation by engaging tonic GABAA-Rs within the mesopontine tegmental anesthesia area (MPTA)","authors":"Mark Baron ,&nbsp;Marshall Devor","doi":"10.1016/j.neulet.2024.138030","DOIUrl":"10.1016/j.neulet.2024.138030","url":null,"abstract":"<div><div>Neurosteroids are endogenous molecules with anxiolytic, anticonvulsant, sleep-promoting and sedative effects. They are biosynthesized <em>de novo</em> within the brain, among other tissues, and are thought to act primarily as positive allosteric modulators of high-affinity extrasynaptic GABA_Aδ-receptors. The location of action of neurosteroids in the brain, however, remains unknown. We have demonstrated that GABAergic anesthetics act within the brainstem mesopontine tegmental anesthesia area (MPTA) to induce and maintain anesthetic loss-of-consciousness. Here we asked whether endogenous and synthetic neurosteroids might also act in the MPTA to induce their suppressive effects. Direct exposure of the MPTA to the endogenous neurosteroids pregnenolone and progesterone, their metabolites testosterone, allopregnanolone and 3α5α-THDOC, and the synthetic neurosteroids ganaxolone and alphaxalone, was found to be pro-anesthetic. Although we cannot rule out additional sites of action, results of this study suggest that the suppressive effects of neurosteroids are due, at least in part, to actions within the MPTA, presumably by recruitment of dedicated neuronal circuitry. This undermines the usual presumption that neurosteroids, like other sedatives, endogenous somnogens and anesthetics, act by nonspecific global distribution.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"843 ","pages":"Article 138030"},"PeriodicalIF":2.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurometabolic substrate transport across brain barriers in diabetes mellitus: Implications for cognitive function and neurovascular health","authors":"Ritwick Mondal ,&nbsp;Shramana Deb ,&nbsp;Dipanjan Chowdhury ,&nbsp;Shramana Sarkar ,&nbsp;Aakash Guha Roy ,&nbsp;Gourav Shome ,&nbsp;Vramanti Sarkar ,&nbsp;Durjoy Lahiri ,&nbsp;Julián Benito-León","doi":"10.1016/j.neulet.2024.138028","DOIUrl":"10.1016/j.neulet.2024.138028","url":null,"abstract":"<div><div>Neurometabolic homeostasis in the brain depends on the coordinated transport of glucose and other essential substrates across brain barriers, primarily the blood-brain barrier and the blood-cerebrospinal fluid barrier. In type 2 diabetes mellitus (T2DM), persistent hyperglycemia disrupts these processes, leading to neurovascular dysfunction and cognitive impairment. This review examines how T2DM alters glucose and neurometabolite transport, emphasizing the role of glucose transporters and the astrocyte-neuron lactate shuttle in maintaining cerebral energy balance. Reduced expression of glucose transporters and impaired neurovascular coupling are key contributors to cognitive decline in T2DM. Additionally, the review highlights insulin’s pivotal role in the hippocampus, where it enhances neuro-glial coupling and modulates astrocyte glucose uptake to support neuronal energy demands. Synthesizing current findings, we underscore the importance of therapeutic strategies aimed at correcting glucose transport dysregulation to alleviate diabetes-associated cognitive decline.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"843 ","pages":"Article 138028"},"PeriodicalIF":2.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}