Transcriptome Analysis and Epigenetics Regulation in the Hippocampus and the Prefrontal Cortex of VPA-Induced Rat Model.
Autism
Grm3
Transcriptome
miRNA
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
17 Aug 2023
17 Aug 2023
Historique:
received:
23
01
2023
accepted:
28
07
2023
medline:
18
8
2023
pubmed:
18
8
2023
entrez:
17
8
2023
Statut:
aheadofprint
Résumé
Autism spectrum disorders (ASD) are a highly heterogeneous group of neurodevelopmental disorders caused by complex interaction between various genes and environmental factors. As the hippocampus and prefrontal cortex are involved in social recognition, they are the regions of the brain implicated in autism. The effects of prenatal exposure to valproic acid (VPA) can induce an ASD phenotype in both humans and rats; this tool is commonly used to model the complexity of ASD symptoms in the laboratory. However, researchers rarely undertake epigenetic regulation of the brain regions using this model. The present study has addressed this gap by examining gene expression abnormalities in the hippocampus and prefrontal cortex in the VPA rat model of ASD. mRNA and miRNA sequencing was performed on samples from the hippocampus and prefrontal cortex of the VPA model of autism. According to the analysis, 3000 mRNAs in the hippocampus and 2187 mRNAs in the prefrontal cortex showed a significant difference in expression between the VPA and saline groups. In addition, there were 115 DE miRNAs in the hippocampus and 14 DE miRNAs in the prefrontal cortex. Further, the predicted and validated target mRNA of DE miRNA enriched pathways involved neurotransmitter uptake, long-term synaptic depression, and AMPA receptor complex (anti-GluA2-b) in the hippocampus; as well as the neuroactive ligand-receptor interaction and regulation of postsynaptic membrane potential in the prefrontal cortex. This revealed the negative regulation network of miRNAs-mRNAs in the hippocampus and prefrontal cortex, while filtering out key genes (miR-10a-5p and Grm3). Finally, the significant variable miR-10a-5p and its negative regulated genes (Grm3) were verified in both brain regions by QPCR. Importantly, the fact that miR-10a-5p downregulated Grm3 in both the hippocampus and the prefrontal cortex may play a potentially significant role in the occurrence and development of autism. This study suggests that the VPA model has the potential to reproduce ASD-related hippocampus and prefrontal cortex abnormalities, at the epigenetic and transcriptional levels. Furthermore, the network of miRNAs-mRNAs was confirmed; this negative regulatory relationship may play a key role in determining the occurrence and development of autism. The study of this topic help better understand the pathogenesis of ASD.
Identifiants
pubmed: 37592184
doi: 10.1007/s12035-023-03560-z
pii: 10.1007/s12035-023-03560-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Natural Science Foundation of China
ID : 81703492
Organisme : Beijing Natural Science Foundation
ID : 7182092
Organisme : the Minzu University Research Fund
ID : 2018CXTD03
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Lai MC, Lombardo MV, Baron-Cohen S (2014) Autism. Lancet 383(9920):896–910
doi: 10.1016/S0140-6736(13)61539-1
pubmed: 24074734
Chen L, Shi XJ, Liu H, Mao X, Gui LN, Wang H, Cheng Y (2021) Oxidative stress marker aberrations in children with autism spectrum disorder: a systematic review and meta-analysis of 87 studies (N = 9109). Transl Psychiatry 11(1):15
doi: 10.1038/s41398-020-01135-3
pubmed: 33414386
pmcid: 7791110
Du Y, Chen L, Yan MC, Wang YL, Zhong XL, Xv CX, Li YB, Cheng Y (2023) Neurometabolite levels in the brains of patients with autism spectrum disorders: a meta-analysis of proton magnetic resonance spectroscopy studies (N = 1501). Mol Psychiatry. https://doi.org/10.1038/s41380-023-02079-y
de la Torre-Ubieta L, Won H, Stein JL, Geschwind DH (2016) Advancing the understanding of autism disease mechanisms through genetics. Nat Med 22(4):345–361
doi: 10.1038/nm.4071
pubmed: 27050589
pmcid: 5072455
Gupta S, Ellis SE, Ashar FN, Moes A, Bader JS, Zhan J, West AB, Arking DE (2014) Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism. Nat Commun 5:5748
doi: 10.1038/ncomms6748
pubmed: 25494366
Zhang R, Zhou J, Ren J et al (2018) Transcriptional and splicing dysregulation in the prefrontal cortex in valproic acid rat model of autism. Reprod Toxicol 77:53–61
doi: 10.1016/j.reprotox.2018.01.008
pubmed: 29427782
Provenzano G, Corradi Z, Monsorno K, Fedrizzi T, Ricceri L, Scattoni ML, Bozzi Y (2016) Comparative gene expression analysis of two mouse models of autism: transcriptome profiling of the BTBR and En2 (-/-) hippocampus. Front Neurosci 10:396
doi: 10.3389/fnins.2016.00396
pubmed: 27610074
pmcid: 4996997
Williams G, King J, Cunningham M, Stephan M, Kerr B, Hersh JH (2001) Fetal valproate syndrome and autism: additional evidence of an association. Dev Med Child Neurol 43(3):202–206
doi: 10.1111/j.1469-8749.2001.tb00188.x
pubmed: 11263692
Williams PG, Hersh JH (1997) A male with fetal valproate syndrome and autism. Dev Med Child Neurol 39(9):632–634
doi: 10.1111/j.1469-8749.1997.tb07500.x
pubmed: 9344057
Narita N, Kato M, Tazoe M, Miyazaki K, Narita M, Okado N (2002) Increased monoamine concentration in the brain and blood of fetal thalidomide- and valproic acid-exposed rat: putative animal models for autism. Pediatr Res 52(4):576–579
pubmed: 12357053
Wang R, Tan J, Guo J, Zheng Y, Han Q, So KF, Yu J, Zhang L (2018) Aberrant development and synaptic transmission of cerebellar cortex in a VPA induced mouse autism model. Front Cell Neurosci 12:500
doi: 10.3389/fncel.2018.00500
pubmed: 30622458
pmcid: 6308145
Schiavi S, Iezzi D, Manduca A et al (2019) Reward-related behavioral, neurochemical and electrophysiological changes in a rat model of autism based on prenatal exposure to valproic acid. Front Cell Neurosci 13:479
doi: 10.3389/fncel.2019.00479
pubmed: 31708750
pmcid: 6824319
Nicolini C, Fahnestock M (2018) The valproic acid-induced rodent model of autism. Exp Neurol 299:217–227
doi: 10.1016/j.expneurol.2017.04.017
pubmed: 28472621
Tartaglione AM, Schiavi S, Calamandrei G, Trezza V (2019) Prenatal valproate in rodents as a tool to understand the neural underpinnings of social dysfunctions in autism spectrum disorder. Neuropharmacology 159:107477
doi: 10.1016/j.neuropharm.2018.12.024
pubmed: 30639388
Du Y, Yu Y, Hu Y et al (2019) Genome-wide, integrative analysis implicates exosome-derived microRNA dysregulation in schizophrenia. Schizophr Bull 45(6):1257–1266
doi: 10.1093/schbul/sby191
pubmed: 30770930
pmcid: 6811837
Yu J, Wang S, Zhao W et al (2018) Mechanistic exploration of cancer stem cell marker voltage-dependent calcium channel alpha2delta1 subunit-mediated chemotherapy resistance in small-cell lung cancer. Clin Cancer Res 24(9):2148–2158
doi: 10.1158/1078-0432.CCR-17-1932
pubmed: 29437792
Robinson MD, McCarthy DJ, Smyth GK (2010) edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26(1):139–140
doi: 10.1093/bioinformatics/btp616
pubmed: 19910308
Wei ZX, Xie GJ, Mao X, Zou XP, Liao YJ, Liu QS, Wang H, Cheng Y (2020) Exosomes from patients with major depression cause depressive-like behaviors in mice with involvement of miR-139–5p-regulated neurogenesis. Neuropsychopharmacology 45(6):1050–1058
doi: 10.1038/s41386-020-0622-2
pubmed: 31986519
pmcid: 7162931
Du Y, Li XS, Chen L, Chen GY, Cheng Y (2020) A network analysis of epigenetic and transcriptional regulation in a neurodevelopmental rat model of schizophrenia with implications for translational research. Schizophr Bull 46(3):612–622
doi: 10.1093/schbul/sbz114
pubmed: 31738422
Zhou J, Zhang X, Ren J, Wang P, Zhang J, Wei Z, Tian Y (2016) Validation of reference genes for quantitative real-time PCR in valproic acid rat models of autism. Mol Biol Rep 43(8):837–847
doi: 10.1007/s11033-016-4015-x
pubmed: 27287459
Thongkorn S, Kanlayaprasit S, Jindatip D, Tencomnao T, Hu VW, Sarachana T (2019) Sex differences in the effects of prenatal bisphenol A exposure on genes associated with autism spectrum disorder in the hippocampus. Sci Rep 9(1):3038
doi: 10.1038/s41598-019-39386-w
pubmed: 30816183
pmcid: 6395584
Kanlayaprasit S, Thongkorn S, Panjabud P, Jindatip D, Hu VW, Kikkawa T, Osumi N, Sarachana T (2021) Autism-related transcription factors underlying the sex-specific effects of prenatal bisphenol A exposure on transcriptome-interactome profiles in the offspring prefrontal cortex. Int J Mol Sci 22(24):13201. https://doi.org/10.3390/ijms222413201
Zhao H, Wang Q, Yan T et al (2019) Maternal valproic acid exposure leads to neurogenesis defects and autism-like behaviors in non-human primates. Transl Psychiatry 9(1):267
doi: 10.1038/s41398-019-0608-1
pubmed: 31636273
pmcid: 6803711
Maynard KR, Collado-Torres L, Weber LM et al (2021) Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex. Nat Neurosci 24(3):425–436
doi: 10.1038/s41593-020-00787-0
pubmed: 33558695
pmcid: 8095368
OldeLoohuis NF, Kole K, Glennon JC et al (2015) Elevated microRNA-181c and microRNA-30d levels in the enlarged amygdala of the valproic acid rat model of autism. Neurobiol Dis 80:42–53
doi: 10.1016/j.nbd.2015.05.006
Casey JP, Magalhaes T, Conroy JM et al (2012) A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder. Hum Genet 131(4):565–579
doi: 10.1007/s00439-011-1094-6
pubmed: 21996756
Liu LJ, Sun XY, Yang CX, Zou XY (2021) MiR-10a-5p restrains the aggressive phenotypes of ovarian cancer cells by inhibiting HOXA1. Kaohsiung J Med Sci 37(4):276–285
doi: 10.1002/kjm2.12335
pubmed: 33332731
Fei X, Jin HY, Gao Y, Kong LM, Tan XD (2020) Hsa-miR-10a-5p promotes pancreatic cancer growth by BDNF/SEMA4C pathway. J Biol Regul Homeost Agents May-Jun 34(3):927–934
Bao M, Pan S, Yang W, Chen S, Shan Y, Shi H (2018) Serum miR-10a-5p and miR-196a-5p as non-invasive biomarkers in non-small cell lung cancer. Int J Clin Exp Pathol 11(2):773–780
pubmed: 31938164
pmcid: 6958018
Worst TS, Previti C, Nitschke K, Diessl N, Gross JC, Hoffmann L, Frey L, Thomas V et al (2019) miR-10a-5p and miR-29b-3p as extracellular vesicle-associated prostate cancer detection markers. Cancers (Basel) 12(1):43. https://doi.org/10.3390/cancers12010043
Saini SM, Mancuso SG, Mostaid MS, Liu C, Pantelis C, Everall IP, Bousman CA (2017) Meta-analysis supports GWAS-implicated link between GRM3 and schizophrenia risk. Transl Psychiatry 7(8):e1196
doi: 10.1038/tp.2017.172
pubmed: 28786982
pmcid: 5611739
Mounce J, Luo L, Caprihan A, Liu J, Perrone-Bizzozero NI, Calhoun VD (2014) Association of GRM3 polymorphism with white matter integrity in schizophrenia. Schizophr Res 155(1–3):8–14
doi: 10.1016/j.schres.2014.03.003
pubmed: 24680030
pmcid: 4022143