Molecular and Cellular Neuroscience最新文献

{"title":"Knockdown of BMP7 induced oligodendrocyte apoptosis, demyelination and motor function loss","authors":"Xiaojin Wei ,&nbsp;Shuxin Liu ,&nbsp;Kai Chen ,&nbsp;Meng Wang ,&nbsp;Yaping Wang ,&nbsp;Dingquan Zou ,&nbsp;Yanying Xiao","doi":"10.1016/j.mcn.2024.103973","DOIUrl":"10.1016/j.mcn.2024.103973","url":null,"abstract":"<div><h3>Background</h3><div>Demyelinating diseases, including multiple sclerosis (MS) and spinal cord injury (SCI), lead to significant neurological deficits primarily due to the loss of oligodendrocytes (OLs). Bone Morphogenetic Protein 7 (BMP7) is expressed abundantly in the central nervous system and previous studies showed its protective effect in reducing OL loss. In this study, we aim to explore BMP7's potential as a biomarker and therapeutic target for demyelinating diseases by investigating its expression and effects on OLs and myelin sheath integrity.</div></div><div><h3>Method</h3><div>We analyzed multiple Gene Expression Omnibus datasets for BMP7 expression profiles in demyelinating conditions such as MS and SCI. Experimentally, we employed a BMP7 knockdown model in rat spinal cords using adeno-associated virus8 vectors to specifically reduce BMP7 expression. Western blotting, immunofluorescence, and Nissl staining were used to assess the effect on OL and other types of cells. The structure of myelin sheath and locomotor function were evaluated using transmission electron microscopy and BBB scores, and statistical analysis included ROC curves and ANOVA to evaluate BMP7's diagnostic and therapeutic potential.</div></div><div><h3>Results</h3><div>BMP7 expression consistently decreased across various demyelinating models, and BMP7 knockdown led to increased OL apoptosis through the Smad1/5/9 pathway, with no apparent effect on other cell types. This reduction in OLs was associated with myelin degeneration, axonal damage, and impaired motor function.</div></div><div><h3>Conclusion</h3><div>The study confirms BMP7's significant involvement in the pathophysiology of demyelinating diseases and supports its potential as a therapeutic target or biomarker. Future research should focus on therapeutic strategies to enhance BMP7 function and further investigate the mechanisms by which BMP7 supports myelin integrity.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"131 ","pages":"Article 103973"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350268","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":"Cannabinoid receptor 2 agonist AM1241 alleviates epileptic seizures and epilepsy-associated depression via inhibiting neuroinflammation in a pilocarpine-induced chronic epilepsy mouse model","authors":"Yiying Cai ,&nbsp;Fangchao Tong ,&nbsp;Kexian Li ,&nbsp;Qiang Wang ,&nbsp;Jing Ding ,&nbsp;Xin Wang","doi":"10.1016/j.mcn.2024.103958","DOIUrl":"10.1016/j.mcn.2024.103958","url":null,"abstract":"<div><p>Increasing evidence suggests that cannabinoid receptor 2 (CB₂R) serves as a promising anti-inflammatory target. While inflammation is known to play crucial roles in the pathogenesis of epilepsy, the involvement of CB₂R in epilepsy remains unclear. This study aimed to investigate the effects of a CB₂R agonist, AM1241, on epileptic seizures and depressive-like behaviors in a mouse model of chronic epilepsy induced by pilocarpine. A chronic epilepsy mouse model was established by intraperitoneal administration of pilocarpine. The endogenous cannabinoid system (eCBs) in the hippocampus was examined after status epilepticus (SE). Animals were then treated with AM1241 and compared with a vehicle-treated control group. Additionally, the role of the AMPK/NLRP3 signaling pathway was explored using the selective AMPK inhibitor dorsomorphin. Following SE, CB₂R expression increased significantly in hippocampal microglia. Administration of AM1241 significantly reduced seizure frequency, immobility time in the tail suspension test, and neuronal loss in the hippocampus. In addition, AM1241 treatment attenuated microglial activation, inhibited pro-inflammatory polarization of microglia, and suppressed NLRP3 inflammasome activation in the hippocampus after SE. Further, the therapeutic effects of AM1241 were abolished by the AMPK inhibitor dorsomorphin. Our findings suggest that CB₂R agonist AM1241 may alleviate epileptic seizures and its associated depression by inhibiting neuroinflammation through the AMPK/NLRP3 signaling pathway. These results provide insight into a novel therapeutic approach for epilepsy.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"130 ","pages":"Article 103958"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996200","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":"Reduced platelet activation and thrombus formation in male transgenic model mice of Alzheimer's disease suggests early sex-specific differences in platelet pathophysiology","authors":"Lili Donner ,&nbsp;Irena Krüger ,&nbsp;Susanne Pfeiler ,&nbsp;Norbert Gerdes ,&nbsp;Martin Schaller ,&nbsp;Malte Kelm ,&nbsp;Margitta Elvers","doi":"10.1016/j.mcn.2024.103952","DOIUrl":"10.1016/j.mcn.2024.103952","url":null,"abstract":"<div><p>Alzheimer's disease (AD) is the most common form of dementia and characterized by extracellular amyloid-β (Aβ) plaques, intracellular neurofibrillary tau tangles and neurodegeneration. Over 80 % of AD patients also exhibit cerebral amyloid angiopathy (CAA). CAA is a cerebrovascular disease caused by deposition of Aβ in the walls of cerebral blood vessels leading to vessel damage and impairment of normal blood flow. To date, different studies suggest that platelet function, including activation, adhesion and aggregation, is altered in AD due to vascular Aβ deposition. For example, the transgenic AD model mice APP23 mice that exhibit CAA and parenchymal Aβ plaques, show pre-activated platelets in the blood circulation and increased platelet integrin activation leading to a pro-thrombotic phenotype in these mice late stages of AD. However, it is still an open question whether or not platelets exhibit changes in their activation profile before they are exposed to vascular Aβ deposits. Therefore, the present study examined platelets from middle-aged transgenic APP23 mice at the age of 8–10 months. At this age, APP23 mice show amyloid plaques in the brain parenchyma but not in the vasculature. Our analyses show that these APP23 mice have unaltered platelet numbers and size, and unaltered surface expression of glycoproteins. However, the number of dense granules in transgenic platelets was increased while the release was unaltered. Male, but not female APP23 mice, exhibited reduced platelet activation after stimulation of the thrombin receptor PAR4 and decreased thrombus stability on collagen under flow conditions <em>ex vivo</em> compared to control mice. In an arterial thrombosis model <em>in vivo</em>, male APP23 mice showed attenuated occlusion of the injured artery compared to controls. These findings provide clear evidence for early changes in platelet activation and thrombus formation in male mice before development of overt CAA. Furthermore, reduced platelet activation and thrombus formation suggest sex-specific differences in platelet physiology in AD that has to be considered in future studies of platelets and their role in AD.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"130 ","pages":"Article 103952"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603893","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":"Corrigendum to “Progress of reprogramming astrocytes into neuron” [Molecular and Cellular Neuroscience, Volume 130, September 2024, 103947, DOI: 10.1016/j.mcn.2024.103947]","authors":"Sitong Liu ,&nbsp;Ximing Xu ,&nbsp;Emmanuel Omari-Siaw ,&nbsp;Jiangnan Yu ,&nbsp;Wenwen Deng","doi":"10.1016/j.mcn.2024.103955","DOIUrl":"10.1016/j.mcn.2024.103955","url":null,"abstract":"","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"130 ","pages":"Article 103955"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S104474312400040X/pdfft?md5=67762289201cfc8c332c953906f075db&pid=1-s2.0-S104474312400040X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759792","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":"Study on the involvement of microglial S100A8 in neuroinflammation and microglia activation during migraine attacks","authors":"Ning An ,&nbsp;Yingying Zhang ,&nbsp;Jinding Xie ,&nbsp;Jingchao Li ,&nbsp;Jing Lin ,&nbsp;Qiuyan Li ,&nbsp;Yating Wang ,&nbsp;Yang Liu ,&nbsp;Yindong Yang","doi":"10.1016/j.mcn.2024.103957","DOIUrl":"10.1016/j.mcn.2024.103957","url":null,"abstract":"<div><h3>Background</h3><p>Microglia is the primary source of inflammatory factors during migraine attacks. This study aims to investigate the role of microglia related genes (MRGs) in migraine attacks.</p></div><div><h3>Methods</h3><p>The RNA sequencing results of migraineurs and the panglaodb database were used to obtain differentially expressed genes (DEGs) in migraine related to microglia. A migraine rat model was established for validating and localizing of the MRGs, and subsequent screening for target genes was conducted. A shRNA was designed to interference the expression of target genes and administered into the trigeminal ganglion (TG) of rats. Pain sensitivity in rats was evaluated via the hot water tail-flick (HWTF) and formalin-induced pain (FIP) experiments. ELISA was used to quantify the levels of inflammatory cytokines and CGRP. WB and immunofluorescence assays were applied to detect the activation of microglia.</p></div><div><h3>Results</h3><p>A total of five DEGs in migraine related to microglia were obtained from RNA sequencing and panglaodb database. Animal experiments showed that these genes expression were heightened in the TG and medulla oblongata (MO) of migraine rats. The gene S100A8 co-localized with microglia in both TG and MO. The HWTF and FIP experiments demonstrated that interference with S100A8 alleviated the sense of pain in migraine rats. Moreover, the levels of TNFα, IL-1β, IL-6, and CGRP in the TG and MO of rats in the model rats were increased, and the expression of microglia markers IBA-1, M1 polarization markers CD86 and iNOS was upregulated. Significantly, interference with S100A8 reversed these indicators.</p></div><div><h3>Conclusion</h3><p>Interference with S100A8 in microglia increased the pain threshold during migraine attacks, and inhibited neuroinflammation and microglia activation.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"130 ","pages":"Article 103957"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902369","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":"β2-adrenoceptor agonist formoterol attenuates NLRP3 inflammasome activation and GSDMD-mediated pyroptosis in microglia through enhancing IκBα/NF-κB inhibition, SQSTM1/p62-dependent selective autophagy and ESCRT-III-mediated plasma membrane repair","authors":"Mehmet Erdem ,&nbsp;Şeniz Erdem ,&nbsp;Ahmet Alver ,&nbsp;Tuğba Raika Kıran ,&nbsp;Süleyman Caner Karahan","doi":"10.1016/j.mcn.2024.103956","DOIUrl":"10.1016/j.mcn.2024.103956","url":null,"abstract":"<div><p>Microglia are immune cells that play important roles in the formation of the innate immune response within the central nervous system (CNS). The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a multiple protein complex that is crucial for innate immunity, and excessive activation of the inflammasome for various reasons contributes to the pathogenesis of neurodegenerative diseases (NDs). β₂-adrenoceptor agonists have become the focus of attention in studies on NDs due to the high synthesis of β₂-adrenoceptors in the central nervous system (CNS). Promising results have been obtained from these studies targeting anti-inflammatory and neuroprotective effects. Formoterol is an effective, safe for long-term use, and FDA-approved β₂-adrenoceptor agonist with demonstrated anti-inflammatory features in the CNS. In this study, we researched the effects of formoterol on LPS/ATP-stimulated NLRP3 inflammasome activation, pyroptosis, NF-κB, autophagy, and ESCRT-III-mediated plasma membrane repair pathways in the N9 microglia cells. The results showed that formoterol, through the IκBα/NF-κB axis, significantly inhibited NLRP3 inflammasome activation, reduced the level of active caspase-1, secretion of IL-1β and IL-18 proinflammatory cytokine levels, and the levels of pyroptosis. Additionally, we showed that formoterol activates autophagy, autophagosome formation, and ESCRT-III-mediated plasma membrane repair, which are significant pathways in the inhibition of NLRP3 inflammasome activation and pyroptosis. Our study suggests that formoterol efficaciously prevents the NLRP3 inflammasome activation and pyroptosis in microglial cells regulation through IκBα/NF-κB, autophagy, autophagosome formation, and ESCRT-III-mediated plasma membrane repair.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"130 ","pages":"Article 103956"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889698","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":"Progress of reprogramming astrocytes into neuron","authors":"Sitong Liu ,&nbsp;Ximing Xu ,&nbsp;Emmanuel Omari-Siaw ,&nbsp;Jiangnan Yu ,&nbsp;Wenwen Deng","doi":"10.1016/j.mcn.2024.103947","DOIUrl":"10.1016/j.mcn.2024.103947","url":null,"abstract":"<div><p>As the main players in the central nervous system (CNS), neurons dominate most life activities. However, after accidental trauma or neurodegenerative diseases, neurons are unable to regenerate themselves. The loss of this important role can seriously affect the quality of life of patients, ranging from movement disorders to disability and even death. There is no suitable treatment to prevent or reverse this process. Therefore, the regeneration of neurons after loss has been a major clinical problem and the key to treatment. Replacing the lost neurons by transdifferentiation of other cells is the only viable approach. Although much progress has been made in stem cell therapy, ethical issues, immune rejection, and limited cell sources still hinder its clinical application. In recent years, somatic cell reprogramming technology has brought a new dawn. Among them, astrocytes, as endogenously abundant cells homologous to neurons, have good potential and application value for reprogramming into neurons, having been reprogrammed into neurons <em>in vitro</em> and <em>in vivo</em> in a variety of ways.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"130 ","pages":"Article 103947"},"PeriodicalIF":3.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306302","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":"Ionic mechanisms involved in arginine vasopressin-mediated excitation of auditory cortical and thalamic neurons","authors":"Phani K. Kola,&nbsp;Chidiebele S. Oraegbuna,&nbsp;Saobo Lei","doi":"10.1016/j.mcn.2024.103951","DOIUrl":"10.1016/j.mcn.2024.103951","url":null,"abstract":"<div><p>The axons containing arginine vasopressin (AVP) from the hypothalamus innervate a variety of structures including the cerebral cortex, thalamus, hippocampus and amygdala. A plethora amount of evidence indicates that activation of the V_1a subtype of the vasopressin receptors facilitates anxiety-like and fear responses. As an essential structure involved in fear and anxiety responses, the amygdala, especially the lateral nucleus of amygdala (LA), receives glutamatergic innervations from the auditory cortex and auditory thalamus where high density of V_1a receptors have been detected. However, the roles and mechanisms of AVP in these two important areas have not been determined, which prevents the understanding of the mechanisms whereby V_1a activation augments anxiety and fear responses. Here, we used coronal brain slices and studied the effects of AVP on neuronal activities of the auditory cortical and thalamic neurons. Our results indicate that activation of V_1a receptors excited both auditory cortical and thalamic neurons. In the auditory cortical neurons, AVP increased neuronal excitability by depressing multiple subtypes of inwardly rectifying K⁺ (Kir) channels including the Kir2 subfamily, the ATP-sensitive K⁺ channels and the G protein-gated inwardly rectifying K⁺ (GIRK) channels, whereas activation of V_1a receptors excited the auditory thalamic neurons by depressing the Kir2 subfamily of the Kir channels as well as activating the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and a persistent Na⁺ channel. Our results may help explain the roles of V_1a receptors in facilitating fear and anxiety responses.</p><p>Categories: Cell Physiology.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"130 ","pages":"Article 103951"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469545","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":"Activation of angiotensin converting enzyme 2 promotes hippocampal neurogenesis via activation of Wnt/β-catenin signaling in hypertension","authors":"Priya Tiwari ,&nbsp;Sumbul Mueed ,&nbsp;Adam Olaitan Abdulkareem ,&nbsp;Kashif Hanif","doi":"10.1016/j.mcn.2024.103953","DOIUrl":"10.1016/j.mcn.2024.103953","url":null,"abstract":"<div><p>Hypertension-induced brain renin-angiotensin system (RAS) activation and neuroinflammation are hallmark neuropathological features of neurodegenerative diseases. Previous studies from our lab have shown that inhibition of ACE/Ang II/AT1R axis (by AT1R blockers or ACE inhibitors) reduced neuroinflammation and accompanied neurodegeneration via up-regulating adult hippocampal neurogenesis. Apart from this conventional axis, another axis of RAS also exists i.e., ACE2/Ang (1–7)/MasR axis, reported as an anti-hypertensive and anti-inflammatory. However, the role of this axis has not been explored in hypertension-induced glial activation and hippocampal neurogenesis in rat models of hypertension. Hence, in the present study, we examined the effect of ACE2 activator, Diminazene aceturate (DIZE) at 2 different doses of 10 mg/kg (non-antihypertensive) and 15 mg/kg (antihypertensive dose) in renovascular hypertensive rats to explore whether their effect on glial activation, neuroinflammation, and neurogenesis is either influenced by blood-pressure. The results of our study revealed that hypertension induced significant glial activation (astrocyte and microglial), neuroinflammation, and impaired hippocampal neurogenesis. However, ACE2 activation by DIZE, even at the low dose prevented these hypertension-induced changes in the brain. Mechanistically, ACE2 activation inhibited Ang II levels, TRAF6-NFκB mediated inflammatory signaling, NOX4-mediated ROS generation, and mitochondrial dysfunction by upregulating ACE2/Ang (1–7)/MasR signaling. Moreover, DIZE-induced activation of the ACE2/Ang (1–7)/MasR axis upregulated Wnt/β-catenin signaling, promoting hippocampal neurogenesis during the hypertensive state. Therefore, our study demonstrates that ACE2 activation can effectively prevent glial activation and enhance hippocampal neurogenesis in hypertensive conditions, regardless of its blood pressure-lowering effects.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"130 ","pages":"Article 103953"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627182","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":"Interneurons in the CA1 stratum oriens expressing αTTP may play a role in the delayed-ageing Pol μ mouse model","authors":"J. Selva-Clemente ,&nbsp;P. Marcos ,&nbsp;J. González-Fuentes ,&nbsp;N. Villaseca-González ,&nbsp;M.J. Lagartos-Donate ,&nbsp;R. Insausti ,&nbsp;M.M. Arroyo-Jiménez","doi":"10.1016/j.mcn.2024.103960","DOIUrl":"10.1016/j.mcn.2024.103960","url":null,"abstract":"<div><p>Neurodegeneration associated with ageing is closely linked to oxidative stress (OS) and disrupted calcium homeostasis. Some areas of the brain, like the hippocampus – particularly the CA1 region – have shown a high susceptibility to age-related changes, displaying early signs of pathology and neuronal loss. Antioxidants such as α-tocopherol (αT) have been effective in mitigating the impact of OS during ageing. αT homeostasis is primarily regulated by the α-tocopherol transfer protein (αTTP), which is widely distributed throughout the brain – where it plays a crucial role in maintaining αT levels within neuronal cells.</p><p>This study investigates the distribution of αTTP in the hippocampus of 4- and 24-month-old Pol μ knockout mice (Pol μ^−/−), a delayed-ageing model, and the wild type (Pol μ^+/+). We also examine the colocalisation in the <em>stratum oriens</em> (<em>st.or</em>) of CA1 region with the primary interneuron populations expressing calcium-binding proteins (CBPs) (calbindin (CB), parvalbumin (PV), and calretinin (CR)). Our findings reveal that αTTP immunoreactivity (-IR) in the <em>st.or</em> of Pol μ mice is significantly reduced. The density of PV-expressing interneurons (INs) increased in aged mice in both Pol μ genotypes (Pol μ^−/− and Pol μ^+/+), although the density of PV-positive INs was lower in the aged Pol μ^−/− mice compared to wild-type mice. By contrast, CR- and CB-positive INs in Pol μ mice remained unchanged during ageing.</p><p>Furthermore, double immunohistochemistry reveals the colocalisation of αTTP with CBPs in INs of the CA1 <em>st.or</em>. Our study also shows that the PV/αTTP-positive IN population remains unchanged in all groups. A significant decrease of CB/αTTP-positive INs in young Pol μ^−/− mice has been detected, as well as a significant increase in CR/αTTP-IR in older Pol μ^−/− animals. These results suggest that the differential expression of αTTP and CBPs could have a crucial effect in aiding the survival and maintenance of the different IN populations in the CA1 <em>st.or</em>, and their coexpression could contribute to the enhancement of their resistance to OS-related damage and neurodegeneration associated with ageing.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"130 ","pages":"Article 103960"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046896","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}