Neurochemical Research最新文献

{"title":"Spontaneous Calcium Transients Recorded from Striatal Astrocytes in a Preclinical Model of Autism","authors":"Hugo Saavedra-Bonilla,&nbsp;Durairaj Ragu Varman,&nbsp;Daniel Reyes-Haro","doi":"10.1007/s11064-024-04218-5","DOIUrl":"10.1007/s11064-024-04218-5","url":null,"abstract":"<div><p>Autism spectrum disorder (ASD) is known as a group of neurodevelopmental conditions including stereotyped and repetitive behaviors, besides social and sensorimotor deficits. Anatomical and functional evidence indicates atypical maturation of the striatum. Astrocytes regulate the maturation and plasticity of synaptic circuits, and impaired calcium signaling is associated with repetitive behaviors and atypical social interaction. Spontaneous calcium transients (SCT) recorded in the striatal astrocytes of the rat were investigated in the preclinical model of ASD by prenatal exposure to valproic acid (VPA). Our results showed sensorimotor delay, augmented glial fibrillary acidic protein -a typical intermediate filament protein expressed by astrocytes- and diminished expression of GABA_A-ρ3 through development, and increased frequency of SCT with a reduced latency that resulted in a diminished amplitude in the VPA model. The convulsant picrotoxin, a GABA_A (γ-aminobutyric acid type A) receptor antagonist, reduced the frequency of SCT in both experimental groups but rescued this parameter to control levels in the preclinical ASD model. The amplitude and latency of SCT were decreased by picrotoxin in both experimental groups. Nipecotic acid, a GABA uptake inhibitor, reduced the mean amplitude only for the control group. Nevertheless, nipecotic acid increased the frequency but diminished the latency in both experimental groups. Thus, we conclude that striatal astrocytes exhibit SCT modulated by GABA_A-mediated signaling, and prenatal exposure to VPA disturbs this tuning.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"49 11","pages":"3069 - 3077"},"PeriodicalIF":3.7,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905503","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":"Circ_0001361/miR-490-5p/IGF2 Axis Regulates the Viability and Apoptosis of Neuroblastoma Cells","authors":"Jian Bian,&nbsp;Hao Ding,&nbsp;Anla Hu,&nbsp;Jian Wang","doi":"10.1007/s11064-024-04225-6","DOIUrl":"10.1007/s11064-024-04225-6","url":null,"abstract":"<div><p>Background: Circular RNAs (circRNAs) are involved in the neuroblastoma (NB) development. Objectie: The study aimed to determine the biological behaviors of circ_0001361 and explore its underlying mechanism in NB. Methods: The circ_0001361, miR-490-5p, and IGF2 levels were measured using quantitative real-time polymerase chain reaction. Cellular processes were analyzed using MTT assay or fluorescence-activated cell sorting (FACS). Phosphorylated (p)-PI3K, p-AKT, Bax, and caspase-3 were tested by western blot. Dual-luciferase reporter analysis together with RNA pull-down analysis were utilized to evaluate the correlation of miR-490-5p and circ_0001361 or IGF2. Results: The results in this study illustrated that an elevation of circ_0001361 levels was observed in NB. Depletion of circ_0001361 suppressed the viability but facilitated apoptosis of NB cells. Circ_0001361 sponged miR-490-5p, which targeted to regulate IGF2. Inhibition of miR-490-5p rescued the effect induced by circ_0001361 knockdown, while deletion of IGF2 rescued the effect induced by the miR-490-5p inhibitor. Conclusions: In summary, a loss of circ_0001361 inhibited NB progression via targeting the miR-490-5p/IGF2 axis, suggesting that circ_0001361 may be a novel therapeutical target of NB.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"49 11","pages":"3060 - 3068"},"PeriodicalIF":3.7,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896439","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":"Changes in Noradrenergic Synthesis and Dopamine Beta-Hydroxylase Activity in Response to Oxidative Stress after Iron-induced Brain Injury","authors":"Antonio Verduzco-Mendoza,&nbsp;Daniel Mota-Rojas,&nbsp;Adriana Olmos-Hernández,&nbsp;Alberto Avila-Luna,&nbsp;Karla García-García,&nbsp;Arturo Gálvez-Rosas,&nbsp;Alberto Hidalgo-Bravo,&nbsp;Camilo Ríos,&nbsp;Carmen Parra-Cid,&nbsp;Sergio Montes,&nbsp;Julieta García-López,&nbsp;Laura E. Ramos-Languren,&nbsp;Francisca Pérez-Severiano,&nbsp;Rigoberto González-Piña,&nbsp;Antonio Bueno-Nava","doi":"10.1007/s11064-024-04222-9","DOIUrl":"10.1007/s11064-024-04222-9","url":null,"abstract":"<div><p>Noradrenaline (NA) levels are altered during the first hours and several days after cortical injury. NA modulates motor functional recovery. The present study investigated whether iron-induced cortical injury modulated noradrenergic synthesis and dopamine beta-hydroxylase (DBH) activity in response to oxidative stress in the brain cortex, pons and cerebellum of the rat. Seventy-eight rats were divided into two groups: (a) the sham group, which received an intracortical injection of a vehicle solution; and (b) the injured group, which received an intracortical injection of ferrous chloride. Motor deficits were evaluated for 20 days post-injury. On the 3rd and 20th days, the rats were euthanized to measure oxidative stress indicators (reactive oxygen species (ROS), reduced glutathione (GSH) and oxidized glutathione (GSSG)) and catecholamines (NA, dopamine (DA)), plus DBH mRNA and protein levels. Our results showed that iron-induced brain cortex injury increased noradrenergic synthesis and DBH activity in the brain cortex, pons and cerebellum at 3 days post-injury, predominantly on the ipsilateral side to the injury, in response to oxidative stress. A compensatory increase in contralateral noradrenergic activity was observed, but without changes in the DBH mRNA and protein levels in the cerebellum and pons. In conclusion, iron-induced cortical injury increased the noradrenergic response in the brain cortex, pons and cerebellum, particularly on the ipsilateral side, accompanied by a compensatory response on the contralateral side. The oxidative stress was countered by antioxidant activity, which favored functional recovery following motor deficits.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"49 11","pages":"3043 - 3059"},"PeriodicalIF":3.7,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892604","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":"Intranasal AdipoRon Mitigated Anxiety and Depression-Like Behaviors in 6-OHDA-Induced Parkinson ’s Disease Rat Model: Going Beyond Motor Symptoms","authors":"Negin Azizifar,&nbsp;Gisou Mohaddes,&nbsp;Rana Keyhanmanesh,&nbsp;Seyed Zanyar Athari,&nbsp;Soraya Alimohammadi,&nbsp;Fereshteh Farajdokht","doi":"10.1007/s11064-024-04223-8","DOIUrl":"10.1007/s11064-024-04223-8","url":null,"abstract":"<div><p>Depression and anxiety are prevalent neuropsychiatric conditions among patients with Parkinson’s disease (PD), which may manifest prior to motor symptoms. As levodopa, a prominent treatment for PD motor symptoms, provides few benefits for mood-related abnormalities, tackling non-motor symptoms is particularly important. AdipoRon (Ad), an adiponectin agonist, has demonstrated neuroprotective effects by suppressing neuroinflammatory responses and activating the AMPK/Sirt-1 signaling pathway. This study looked at the potential advantages and underlying mechanisms of intranasal Ad in a rat model of PD induced by 6-hydroxydopamine (6-OHDA). We found that Ad at doses of 1 and 10 µg for 21 days exhibited anxiolytic- and antidepressant effects in the open field (OF) test, elevated plus maze (EPM), sucrose splash test, and forced swimming test in a PD model caused by a unilateral 6-OHDA injection into the medial forebrain bundle (MFB). The Ad also lowered the levels of corticosterone in the blood, decreased inflammasome components (NLRP3, caspase 1, and IL-1β), and increased Sirt-1 protein levels in the prefrontal cortex (PFC) of PD rats. We conclude that Ad ameliorates anxious and depressive-like behaviors in the PD rat model through stimulating the AMPK/Sirt-1 signaling and blocking the NLRP3 inflammasome pathways in the PFC.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"49 11","pages":"3030 - 3042"},"PeriodicalIF":3.7,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141884145","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":"Characterization of a Fatty Acid Amide Hydrolase (FAAH) in Hirudo Verbana","authors":"Emily Kabeiseman,&nbsp;Riley T. Paulsen,&nbsp;Brian D. Burrell","doi":"10.1007/s11064-024-04216-7","DOIUrl":"10.1007/s11064-024-04216-7","url":null,"abstract":"<div><p>The endocannabinoid system plays a critical role in modulating both peripheral and central nervous system function. Despite being present throughout the animal kingdom, there has been relatively little investigation of the endocannabinoid system beyond traditional animal models. In this study, we report on the identification and characterization of a putative fatty acid amide hydrolase (FAAH) in the medicinal leech, <i>Hirudo verbana</i>. FAAH is the primary enzyme responsible for metabolizing the endocannabinoid signaling molecule arachidonoyl ethanolamide (anandamide or AEA) and therefore plays a critical role in regulating AEA levels in the nervous system. mRNA encoding <i>Hirudo</i> FAAH (HirFAAH) is expressed in the leech central nervous system (CNS) and sequence analysis suggests that this is an orthologue of FAAH-2 observed in vertebrates. Functionally, HirFAAH has serine hydrolase activity based on activity-based protein profiling (ABPP) studies using the fluorophosphonate probe TAMRA-FP. HirFAAH also hydrolyzes arachidonyl 7-amino, 4-methyl coumarin amide (AAMCA), a substrate specific to FAAH. Hydrolase activity during both the ABPP and AAMCA assays was eliminated by a mutation at a conserved catalytic serine. Activity was also blocked by the known FAAH inhibitor, URB597. Treatment of <i>Hirudo</i> ganglia with URB597 potentiated synapses made by the pressure-sensitive mechanosensory neuron (P cell), mimicking the effects of exogenously applied AEA. The <i>Hirudo</i> CNS has been a useful system in which to study properties of endocannabinoid modulation of nociception relevant to vertebrates. Therefore, this characterization of HirFAAH is an important contribution to comparative studies of the endocannabinoid system.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"49 11","pages":"3015 - 3029"},"PeriodicalIF":3.7,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873893","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":"The Identification of Potential Anti-Depression/Anxiety Drug Targets by Stress-Induced Rat Brain Regional Proteome and Network Analyses","authors":"Nan Liu,&nbsp;Jiaxin Tu,&nbsp;Faping Yi,&nbsp;Xiong Zhang,&nbsp;Xianhui Zhong,&nbsp;Lili Wang,&nbsp;Liang Xie,&nbsp;Jian Zhou","doi":"10.1007/s11064-024-04220-x","DOIUrl":"10.1007/s11064-024-04220-x","url":null,"abstract":"<div><p>Depression and anxiety disorders are prevalent stress-related neuropsychiatric disorders and involve multiple molecular changes and dysfunctions across various brain regions. However, the specific and shared pathophysiological mechanisms occurring in these regions remain unclear. Previous research used a rat model of chronic mild stress (CMS) to segregate and identify depression-susceptible, anxiety-susceptible, and insusceptible groups; then the proteomes of six distinct brain regions (the hippocampus, prefrontal cortex, hypothalamus, pituitary, olfactory bulb, and striatum) were separately and quantitatively analyzed. To gain a comprehensive and systematic understanding of the molecular abnormalities, this study aimed to investigate and compare differential proteomics data from the six regions. Differentially expressed proteins (DEPs) were identified in between specific regions and across all regions and subjected to a series of bioinformatics analyses. Regional comparisons showed that stress-induced proteomic changes and corresponding gene ontology and pathway enrichments were largely distinct, attributable to differences in cell populations, protein compositions, and brain functions of these areas. Additionally, a notable degree of overlap in the significantly enriched terms was identified, potentially suggesting strong connections in the enrichment across different regions. Furthermore, intra-regional and inter-regional protein–protein interaction networks and drug-target-DEP networks were constructed. Integrated analysis of the three association networks in the six regions, along with the DisGeNET database, identified ten DEPs as potential targets for anti-depression/anxiety drugs. Collectively, these findings revealed commonalities and differences across different brain regions at the protein level induced by CMS, and identified several novel protein targets for the development of new therapeutics for depression and anxiety.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"49 10","pages":"2957 - 2971"},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858722","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":"Neuroprotective Effects Exerted by a Combination of Selected Lactic Acid Bacteria in a Mouse Parkinsonism Model under Levodopa-Benserazide Treatment","authors":"Daiana Pérez Visñuk,&nbsp;Jean Guy LeBlanc,&nbsp;Alejandra de Moreno de LeBlanc","doi":"10.1007/s11064-024-04217-6","DOIUrl":"10.1007/s11064-024-04217-6","url":null,"abstract":"<div><p>Alterations of the microbiota-gut-brain axis has been associated with intestinal and neuronal inflammation in Parkinson’s disease (PD). The aim of this work was to study some mechanisms associated with the neuroprotective effect of a combination (MIX) of lactic acid bacteria (LAB) composed by <i>Lactiplantibacillus plantarum</i> CRL2130 (riboflavin overproducing strain), <i>Streptococcus thermophilus</i> CRL808 (folate producer strain), and CRL807 (immunomodulatory strain) in cell cultures and in a chronic model of parkinsonism induced with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in aged mice, and under levodopa-benserazide treatment. In vitro, N2a differentiated neurons were exposed to the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) and treated with intracellular bacterial extracts or with conditioned media from BV-2 cells exposed to the bacterial extracts. In vivo, motor skills, tyrosine hydrolase (TH) in brain and cytokine concentrations in serum and in brain were evaluated. The study of the faecal microbiota and the histology of the small intestine was also performed. The results showed that the neuroprotective effect associated with LAB MIX administration did not interfere with levodopa-benserazide treatment. This effect could be associated with the antioxidant and immunomodulatory potential of the LAB selected in the MIX, and was associated with the significant improvement in the motor tests and a higher number of TH + cells in the brain. In addition, LAB MIX administration was associated with modulation of the immune response. LAB administration decreased intestinal damage with an increase in the villus length /crypt depth ratio. Finally, the administration of the LAB MIX in combination with levodopa-benserazide treatment was able to partially revert the intestinal dysbiosis observed in the model, showing greater similarity to the profiles of healthy controls, and highlighting the increase in the Lactobacillaceae family. Different mechanisms of action would be related to the protective effect of the selected LAB combination which has the potential to be evaluated as an adjuvant for conventional PD therapies.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"49 10","pages":"2940 - 2956"},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858721","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":"Correction: Arne Schousboe: in Memoriam (1944–2024)","authors":"Henry Sershen","doi":"10.1007/s11064-024-04215-8","DOIUrl":"10.1007/s11064-024-04215-8","url":null,"abstract":"","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"49 9","pages":"2652 - 2652"},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142409183","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":"Dexmedetomidine Promotes NREM Sleep by Depressing Oxytocin Neurons in the Paraventricular Nucleus in Mice","authors":"Ying Zhang,&nbsp;Jiaxin Li,&nbsp;Yan Li,&nbsp;Wei Wang,&nbsp;Daming Wang,&nbsp;Junli Ding,&nbsp;Licheng Wang,&nbsp;Juan Cheng","doi":"10.1007/s11064-024-04221-w","DOIUrl":"10.1007/s11064-024-04221-w","url":null,"abstract":"<div><p>Dexmedetomidine (DEX) is a highly selective α₂-adrenoceptor agonist with sedative effects on sleep homeostasis. Oxytocin-expressing (OXT) neurons in the paraventricular nucleus (PVN) of the hypothalamus (PVN^OXT) regulate sexual reproduction, drinking, sleep-wakefulness, and other instinctive behaviors. To investigate the effect of DEX on the activity and signal transmission of PVN^OXT in regulating the sleep-wakefulness cycle. Here, we employed OXT-cre mice to selectively target and express the designer receptors exclusively activated by designer drugs (DREADD)-based chemogenetic tool hM3D(Gq) in PVN^OXT neurons. Combining chemogenetic methods with electroencephalogram (EEG) /electromyogram (EMG) recordings, we found that cannula injection of DEX in PVN significantly increased the duration of non-rapid eye movement (NREM) sleep in mice. Furthermore, the chemogenetic activation of PVN^OXT neurons using i.p. injection of clozapine N-oxide (CNO) after cannula injection of DEX to PVN led to a substantial increase in wakefulness. Electrophysiological results showed that DEX decreased the frequency of action potential (AP) and the spontaneous excitatory postsynaptic current (sEPSC) of PVN^OXT neurons through α₂-adrenoceptors. Therefore, these results identify that DEX promotes sleep and maintains sleep homeostasis by inhibiting PVN^OXT neurons through the α₂-adrenoceptor.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"49 10","pages":"2926 - 2939"},"PeriodicalIF":3.7,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791625","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":"Epigenetic Mechanisms of Aluminum-Induced Neurotoxicity and Alzheimer’s Disease: A Focus on Non-Coding RNAs","authors":"Michael Aschner,&nbsp;Anatoly V. Skalny,&nbsp;Abel Santamaria,&nbsp;Joao B. T. Rocha,&nbsp;Borhan Mansouri,&nbsp;Yousef Tizabi,&nbsp;Roberto Madeddu,&nbsp;Rongzu Lu,&nbsp;Eunsook Lee,&nbsp;Alexey A. Tinkov","doi":"10.1007/s11064-024-04214-9","DOIUrl":"10.1007/s11064-024-04214-9","url":null,"abstract":"<div><p>Aluminum (Al) is known to induce neurotoxic effects, potentially contributing to Alzheimer’s disease (AD) pathogenesis. Recent studies suggest that epigenetic modification may contribute to Al neurotoxicity, although the mechanisms are still debatable. Therefore, the objective of the present study was to summarize existing data on the involvement of epigenetic mechanisms in Al-induced neurotoxicity, especially AD-type pathology. Existing data demonstrate that Al exposure induces disruption in DNA methylation, histone modifications, and non-coding RNA expression in brains. Alterations in DNA methylation following Al exposure were shown to be mediated by changes in expression and activity of DNA methyltransferases (DNMTs) and ten-eleven translocation proteins (TETs). Al exposure was shown to reduce histone acetylation by up-regulating expression of histone deacetylases (HDACs) and impair histone methylation, ultimately contributing to down-regulation of brain-derived neurotrophic factor (BDNF) expression and activation of nuclear factor κB (NF-κB) signaling. Neurotoxic effects of Al exposure were also associated with aberrant expression of non-coding RNAs, especially microRNAs (miR). Al-induced patterns of miR expression were involved in development of AD-type pathology by increasing amyloid β (Aβ) production through up-regulation of Aβ precursor protein (APP) and β secretase (BACE1) expression (down-regulation of miR-29a/b, miR-101, miR-124, and Let-7c expression), increasing in neuroinflammation through NF-κB signaling (up-regulation of miR-9, miR-125b, miR-128, and 146a), as well as modulating other signaling pathways. Furthermore, reduced global DNA methylation, altered histone modification, and aberrant miRNA expression were associated with cognitive decline in Al-exposed subjects. However, further studies are required to evaluate the contribution of epigenetic mechanisms to Al-induced neurotoxicity and/or AD development.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"49 11","pages":"2988 - 3005"},"PeriodicalIF":3.7,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764722","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}