Frontiers in Molecular Neuroscience最新文献

{"title":"A sex-specific effect of M₄ muscarinic cholinergic autoreceptor deletion on locomotor stimulation by cocaine and scopolamine.","authors":"Anna Berezovskaia, Morgan Thomsen, Anders Fink-Jensen, Gitta Wörtwein","doi":"10.3389/fnmol.2024.1451010","DOIUrl":"10.3389/fnmol.2024.1451010","url":null,"abstract":"<p><strong>Objective: </strong>Acetylcholine modulates the activity of the direct and indirect pathways within the striatum through interaction with muscarinic M₄ and M₁ receptors. M₄ receptors are uniquely positioned to regulate plasticity within the direct pathway and play a substantial role in reward and addiction-related behaviors. However, the role of M₄ receptors on cholinergic neurons has been less explored. This study aims to fill this gap by addressing the role of M₄ receptors on cholinergic neurons in these behaviors.</p><p><strong>Methods: </strong>To investigate the significance of M₄-dependent inhibitory signaling in cholinergic neurons we created mutant mice that lack M₄ receptors on cholinergic neurons. Cholinergic neuron-specific depletion was confirmed using <i>in situ</i> hybridization. We aimed to untangle the possible contribution of M₄ autoreceptors to the effects of the global M₄ knockout by examining aspects of basal locomotion and dose-dependent reactivity to the psychostimulant and rewarding properties of cocaine, haloperidol-induced catalepsy, and examined both the anti-cataleptic and locomotion-inducing effects of the non-selective anticholinergic drug scopolamine.</p><p><strong>Results: </strong>Basal phenotype assessment revealed no developmental deficits in knockout mice. Cocaine stimulated locomotion in both genotypes, with no differences observed at lower doses. However, at the highest cocaine dose tested, male knockout mice displayed significantly less activity compared to wild type littermates (<i>p</i> = 0.0084). Behavioral sensitization to cocaine was similar between knockout and wild type mice. Conditioned place preference tests indicated no differences in the rewarding effects of cocaine between genotypes. In food-reinforced operant tasks knockout and wild type mice successfully acquired the tasks with comparable performance results. M₄ receptor depletion did not affect haloperidol-induced catalepsy and scopolamine reversal of catalepsy but attenuated scopolamine-induced locomotion in females (<i>p</i> = 0.04). Our results show that M₄ receptor depletion attenuated the locomotor response to high doses of cocaine in males and scopolamine in females, suggesting sex-specific regulation of cholinergic activity.</p><p><strong>Conclusion: </strong>Depletion of M₄ receptors on cholinergic neurons does not significantly impact basal behavior or cocaine-induced hyperactivity but may modulate the response to high doses of cocaine in male mice and the response to scopolamine in female mice. Overall, our findings suggest that M₄-dependent autoregulation plays a minor but delicate role in modulating specific behavioral responses to pharmacological challenges, possibly in a sex-dependent manner.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1451010"},"PeriodicalIF":3.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907060","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":"VNS paired with training enhances recognition memory: mechanistic insights from proteomic analysis of the hippocampal synapse.","authors":"Seung H Jung, Laura K Olsen, Krysten A Jones, Raquel J Moore, Sean W Harshman, Candice N Hatcher-Solis","doi":"10.3389/fnmol.2024.1452327","DOIUrl":"10.3389/fnmol.2024.1452327","url":null,"abstract":"<p><strong>Introduction: </strong>Recognition memory, an essential component of cognitive health, can suffer from biological limitations of stress, aging, or neurodegenerative disease. Vagus nerve stimulation (VNS) is a neuromodulation therapy with the potential to improve cognitive function. This study investigated the effectiveness of multiple sessions of VNS to enhance recognition memory in healthy rodents and the underlying cognitive benefits of VNS by proteomic analysis of the synaptosome.</p><p><strong>Methods: </strong>Rats demonstrated VNS-induced recognition memory improvements using a novel object recognition (NOR) task. Using the LC-MS/MS method, roughly 3,000 proteins in the synaptosome of the hippocampus were analyzed.</p><p><strong>Results: </strong>Protein-protein interaction (PPI) enrichment analysis found differentially expressed proteins related to synaptic signaling and neurotransmitter pathways. PPI network analysis identified six unique protein clusters, including a cluster of synaptic signaling related pathways. Using ingenuity pathway analysis (IPA), rapamycin-insensitive companion of mTOR was identified as an upstream regulator of synaptosome changes due to VNS-paired training.</p><p><strong>Discussion: </strong>Based on these results, it is proposed that VNS may mediate cognitive enhancement via increases in glutamatergic signaling and early LTP during the consolidation period, followed by sustained synaptic plasticity via modified post-synaptic receptor expression and dendritic outgrowth. Further investigation is required to determine if VNS is a good candidate to ameliorate cognitive impairment.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1452327"},"PeriodicalIF":3.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913939","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":"Excitatory neuron-prone prion propagation and excitatory neuronal loss in prion-infected mice.","authors":"Temuulen Erdenebat, Yusuke Komatsu, Nozomi Uwamori, Misaki Tanaka, Takashi Hoshika, Takeshi Yamasaki, Ayano Shimakura, Akio Suzuki, Toyotaka Sato, Motohiro Horiuchi","doi":"10.3389/fnmol.2024.1498142","DOIUrl":"10.3389/fnmol.2024.1498142","url":null,"abstract":"<p><p>The accumulation of a disease-specific isoform of prion protein (PrP^Sc) and histopathological lesions, such as neuronal loss, are unevenly distributed in the brains of humans and animals affected with prion diseases. This distribution varies depending on the diseases and/or the combinations of prion strain and experimental animal. The brain region-dependent distribution of PrP^Sc and neuropathological lesions suggests a neuronal cell-type-dependent prion propagation and vulnerability to prion infection. However, the underlying mechanism is largely unknown. In this study, we provided evidence that the prion 22L strain propagates more efficiently in excitatory neurons than inhibitory neurons and that excitatory neurons in the thalamus are vulnerable to prion infection. PrP^Sc accumulation was less intense in the striatum, where GABAergic inhibitory neurons predominate, compared to the cerebral cortex and thalamus, where glutamatergic excitatory neurons are predominant, in mice intracerebrally or intraperitoneally inoculated with the 22L strain. PrP^Sc stains were observed along the needle track after stereotaxic injection into the striatum, whereas they were also observed away from the needle track in the thalamus. Consistent with inefficient prion propagation in the striatum, the 22L prion propagated more efficiently in glutamatergic neurons than GABAergic neurons in primary neuronal cultures. RNAscope <i>in situ</i> hybridization revealed a decrease in <i>Vglut1</i>- and <i>Vglut2</i>-expressing neurons in the ventral posterolateral nuclei of the thalamus in 22L strain-infected mice, whereas no decrease in <i>Vgat</i>-expressing neurons was observed in the adjacent reticular nucleus, mainly composed of <i>Vgat</i>-expressing interneurons. The excitatory neuron-prone prion propagation and excitatory neuronal loss in 22L strain-infected mice shed light on the neuropathological mechanism of prion diseases.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1498142"},"PeriodicalIF":3.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893938","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":"Chaperones vs. oxidative stress in the pathobiology of ischemic stroke.","authors":"Vladislav Soldatov, Artem Venediktov, Andrei Belykh, Gennadii Piavchenko, Mukhammad David Naimzada, Nastasya Ogneva, Natalia Kartashkina, Olga Bushueva","doi":"10.3389/fnmol.2024.1513084","DOIUrl":"10.3389/fnmol.2024.1513084","url":null,"abstract":"<p><p>As many proteins prioritize functionality over constancy of structure, a proteome is the shortest stave in the Liebig's barrel of cell sustainability. In this regard, both prokaryotes and eukaryotes possess abundant machinery supporting the quality of the proteome in healthy and stressful conditions. This machinery, namely chaperones, assists in folding, refolding, and the utilization of client proteins. The functions of chaperones are especially important for brain cells, which are highly sophisticated in terms of structural and functional organization. Molecular chaperones are known to exert beneficial effects in many brain diseases including one of the most threatening and widespread brain pathologies, ischemic stroke. However, whether and how they exert the antioxidant defense in stroke remains unclear. Herein, we discuss the chaperones shown to fight oxidative stress and the mechanisms of their antioxidant action. In ischemic stroke, during intense production of free radicals, molecular chaperones preserve the proteome by interacting with oxidized proteins, regulating imbalanced mitochondrial function, and directly fighting oxidative stress. For instance, cells recruit Hsp60 and Hsp70 to provide proper folding of newly synthesized proteins-these factors are required for early ischemic response and to refold damaged polypeptides. Additionally, Hsp70 upregulates some dedicated antioxidant pathways such as FOXO3 signaling. Small HSPs decrease oxidative stress via attenuation of mitochondrial function through their involvement in the regulation of Nrf- (Hsp22), Akt and Hippo (Hsp27) signaling pathways as well as mitophagy (Hsp27, Hsp22). A similar function has also been proposed for the Sigma-1 receptor, contributing to the regulation of mitochondrial function. Some chaperones can prevent excessive formation of reactive oxygen species whereas Hsp90 is suggested to be responsible for pro-oxidant effects in ischemic stroke. Finally, heat-resistant obscure proteins (Hero) are able to shield client proteins, thus preventing their possible over oxidation.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1513084"},"PeriodicalIF":3.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893937","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":"Development of KCC2 therapeutics to treat neurological disorders.","authors":"Shilpa D Kadam, Shane V Hegarty","doi":"10.3389/fnmol.2024.1503070","DOIUrl":"10.3389/fnmol.2024.1503070","url":null,"abstract":"<p><p>KCC2 is CNS neuron-specific chloride extruder, essential for the establishment and maintenance of the transmembrane chloride gradient, thereby enabling synaptic inhibition within the CNS. Herein, we highlight KCC2 hypofunction as a fundamental and conserved pathology contributing to neuronal circuit excitation/inhibition (E/I) imbalances that underly epilepsies, chronic pain, neuro-developmental/-traumatic/-degenerative/-psychiatric disorders. Indeed, downstream of both acquired and genetic factors, multiple pathologies (e.g., hyperexcitability and inflammation) converge to impair KCC2-dependent inhibition in CNS. When KCC2 hypofunction occurs, affected neurons are disinhibited due to impaired inhibitory responses to GABA/glycine. This causes neuronal hyperexcitability, disinhibition within neuron circuits, and disrupted neurological functions. More recently, KCC2 was identified as a genetically-validated target for epilepsy, intellectual disability, and autism spectrum disorder, and pathogenic mutations in human SLC12A5 gene were linked to psychiatric/mood disorders. The broad therapeutic utility of KCC2-upmodulating drugs relates to its critical role in determining inhibitory activity of GABAergic neurotransmission, a mechanism widely targeted by several drugs. However, in cases of KCC2 hypofunction GABAergic neurotransmission can be depolarizing/excitatory, thereby impairing endogenous neuronal inhibition while also limiting the effectiveness of existing therapeutics targeting/requiring GABAergic pathway inhibition. Several preclinical reports have shown that KCC2 upmodulating treatments rescue and increase the efficacy of anti-seizure and analgesic medications. Thus, a first-in-class KCC2-potentiating therapy would provide a novel mechanism for restoring physiological CNS inhibition and addressing drug resistance in patients with E/I imbalance pathologies. Herein, we discuss progress toward and further work needed to develop the first-in-class KCC2 therapeutics to treat neurological disorder patients.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1503070"},"PeriodicalIF":3.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885709","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-sensor proteins but not bicarbonate ion activate retinal photoreceptor membrane guanylyl cyclase in photoreceptors.","authors":"Igor V Peshenko, Elena V Olshevskaya, Alexander M Dizhoor","doi":"10.3389/fnmol.2024.1509366","DOIUrl":"10.3389/fnmol.2024.1509366","url":null,"abstract":"<p><p>Retinal membrane guanylyl cyclase (RetGC), regulated by guanylyl cyclase activating proteins (GCAPs) via negative calcium-feedback, is one of the most critically important enzymes in vertebrate rod and cone physiology, enabling their sensitivity to light. It was also reported that, similarly to olfactory receptor guanylyl cyclase, bicarbonate anion directly stimulates RetGC activity in photoreceptors as a novel phototransduction-linked regulating factor. We directly tested whether or not RetGC is a bicarbonate-activated enzyme using recombinant human RetGC expressed in HEK293 cells and the native RetGC in mouse retinas. Whereas RetGC in all cases was activated by GCAPs, we found no evidence indicating that bicarbonate can produce direct stimulating effect on RetGC catalytic activity, either basal or GCAP-activated, even at concentrations as high as 100 mM. Instead, near-physiological concentrations of bicarbonate only slightly reduced RetGC activity, whereas concentrations substantially exceeding physiological levels caused a more pronounced reduction of RetGC activity measured in mouse retinas. Our results argue that photoreceptor guanylyl cyclase is not a bicarbonate-stimulated enzyme and rule out the possibility that effects of bicarbonate on photoreceptor physiology are mediated by a direct stimulation of retinal guanylyl cyclase by HCO₃ ^-.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1509366"},"PeriodicalIF":3.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881546","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":"Transcorneal electrical stimulation restores DNA methylation changes in retinal degeneration.","authors":"Ben Yi Tew, Gerald C Gooden, Pei-An Lo, Dimitrios Pollalis, Brandon Ebright, Alex J Kalfa, Alejandra Gonzalez-Calle, Biju Thomas, David N Buckley, Thomas Simon, Zeyi Yang, Ege Iseri, Cody L Dunton, Vadim Backman, Stan Louie, Gianluca Lazzi, Mark S Humayun, Bodour Salhia","doi":"10.3389/fnmol.2024.1484964","DOIUrl":"10.3389/fnmol.2024.1484964","url":null,"abstract":"<p><strong>Background: </strong>Retinal degeneration is a major cause of irreversible blindness. Stimulation with controlled low-level electrical fields, such as transcorneal electrical stimulation (TES), has recently been postulated as a therapeutic strategy. With promising results, there is a need for detailed molecular characterization of the therapeutic effects of TES.</p><p><strong>Methods: </strong>Controlled, non-invasive TES was delivered using a custom contact lens electrode to the retinas of Royal College of Surgeons (RCS) rats, a model of retinal degeneration. DNA methylation in the retina, brain and cell-free DNA in plasma was assessed by reduced representation bisulfite sequencing (RRBS) and gene expression by RNA sequencing.</p><p><strong>Results: </strong>TES induced DNA methylation and gene expression changes implicated in neuroprotection in the retina of RCS rats. We devised an epigenomic-based retinal health score, derived from DNA methylation changes observed with disease progression in RCS rats, and showed that TES improved the epigenomic health of the retina. TES also induced DNA methylation changes in the superior colliculus: the brain which is involved in integrating visual signaling. Lastly, we demonstrated that TES-induced retinal DNA methylation changes were detectable in cell-free DNA derived from plasma.</p><p><strong>Conclusion: </strong>TES induced DNA methylation changes with therapeutic effects, which can be measured in circulation. Based on these changes, we were able to devise a liquid biopsy biomarker for retinal health. These findings shed light on the therapeutic potential and molecular underpinnings of TES, and provide a foundation for the further development of TES to improve the retinal health of patients with degenerative eye diseases.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1484964"},"PeriodicalIF":3.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863215","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":"Mitochondrial pathways of copper neurotoxicity: focus on mitochondrial dynamics and mitophagy.","authors":"Michael Aschner, Anatoly V Skalny, Rongzhu Lu, Airton C Martins, Yousef Tizabi, Sergey V Nekhoroshev, Abel Santamaria, Anton I Sinitskiy, Alexey A Tinkov","doi":"10.3389/fnmol.2024.1504802","DOIUrl":"10.3389/fnmol.2024.1504802","url":null,"abstract":"<p><p>Copper (Cu) is essential for brain development and function, yet its overload induces neuronal damage and contributes to neurodegeneration and other neurological disorders. Multiple studies demonstrated that Cu neurotoxicity is associated with mitochondrial dysfunction, routinely assessed by reduction of mitochondrial membrane potential. Nonetheless, the role of alterations of mitochondrial dynamics in brain mitochondrial dysfunction induced by Cu exposure is still debatable. Therefore, the objective of the present narrative review was to discuss the role of mitochondrial dysfunction in Cu-induced neurotoxicity with special emphasis on its influence on brain mitochondrial fusion and fission, as well as mitochondrial clearance by mitophagy. Existing data demonstrate that, in addition to mitochondrial electron transport chain inhibition, membrane damage, and mitochondrial reactive oxygen species (ROS) overproduction, Cu overexposure inhibits mitochondrial fusion by down-regulation of Opa1, Mfn1, and Mfn2 expression, while promoting mitochondrial fission through up-regulation of Drp1. It has been also demonstrated that Cu exposure induces PINK1/Parkin-dependent mitophagy in brain cells, that is considered a compensatory response to Cu-induced mitochondrial dysfunction. However, long-term high-dose Cu exposure impairs mitophagy, resulting in accumulation of dysfunctional mitochondria. Cu-induced inhibition of mitochondrial biogenesis due to down-regulation of PGC-1α further aggravates mitochondrial dysfunction in brain. Studies from non-brain cells corroborate these findings, also offering additional evidence that dysregulation of mitochondrial dynamics and mitophagy may be involved in Cu-induced damage in brain. Finally, Cu exposure induces cuproptosis in brain cells due mitochondrial proteotoxic stress, that may also contribute to neuronal damage and pathogenesis of certain brain diseases. Based on these findings, it is assumed that development of mitoprotective agents, specifically targeting mechanisms of mitochondrial quality control, would be useful for prevention of neurotoxic effects of Cu overload.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1504802"},"PeriodicalIF":3.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863214","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":"Differential timing of mitochondrial activation in rat dorsal striatum induced by procedural learning and swimming.","authors":"Rogelio Pegueros-Maldonado, Antonio Fuentes-Ibañez, Mónica M Monroy, Oscar A Gutiérrez, Norma Serafín, Santiago M Pech-Pool, Mauricio Díaz-Muñoz, Gina L Quirarte","doi":"10.3389/fnmol.2024.1495027","DOIUrl":"10.3389/fnmol.2024.1495027","url":null,"abstract":"<p><p>Stressful experiences form stronger memories due to enhanced neural plasticity mechanisms linked to glucocorticoid hormones (cortisol in humans, corticosterone in rats). Among other neural structures, the dorsal striatum plays a role in the corticosterone-induced consolidation of stressful memories, particularly in the cued water maze task. Neural plasticity is related to mitochondrial activity due to the relevance of energy production and signaling mechanisms for functional and morphological neuronal adaptations. Corticosterone has been shown to enhance brain mitochondrial activity by activating glucocorticoid receptors. In this context, striatum functions are susceptible to change in relation to mitochondrial responses. Based on this evidence, we hypothesized that training in the cued water maze would induce an increase in corticosterone levels and mitochondrial activity (mitochondrial membrane potential and calcium content) in the dorsal striatum, and that these adaptations might be related to memory consolidation of the task. We used an ELISA assay to evaluate plasma and striatal corticosterone levels; mitochondrial activity was determined with the florescent probes MitoTracker Red (mitochondrial membrane potential) and Rhod-2 (calcium content) in brain slices containing the dorsal striatum of rats trained in the cued water maze and euthanized at different times after training (0.5, 1.5, or 6.0 h). We also analyzed the effect of post-training inhibition of striatal mitochondrial activity by OXPHOS complex 1 inhibitor rotenone, on the consolidation of the cued water maze task. We found that cued water maze training induced an increase in corticosterone levels and a time-dependent elevation of mitochondrial membrane potential and mitochondrial calcium content in the dorsal striatum. Unexpectedly, rotenone administration facilitated the retention test. Altogether, our results suggest that enhanced mitochondrial activity in the dorsal striatum is relevant for cued water maze consolidation. The increase in mitochondrial activity was contextually associated with an elevation of corticosterone in plasma and the dorsal striatum. Additionally, our swimming groups also showed an increase in mitochondrial activity in the dorsal striatum, but with a different pattern, which could suggest a differential functional adaptation in this structure.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1495027"},"PeriodicalIF":3.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853913","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":"Corrigendum: Mechanisms of mitophagy and oxidative stress in cerebral ischemia-reperfusion, vascular dementia, and Alzheimer's disease.","authors":"Yujie Lyu, Zhipeng Meng, Yunyun Hu, Bing Jiang, Jiao Yang, Yiqin Chen, Jun Zhou, Mingcheng Li, Huping Wang","doi":"10.3389/fnmol.2024.1507345","DOIUrl":"10.3389/fnmol.2024.1507345","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fnmol.2024.1394932.].</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1507345"},"PeriodicalIF":3.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853911","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}