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Currently, therapeutics for RTT is aimed at restoring the loss\u2010of\u2010function by MeCP2 gene therapy, but that approach has multiple challenges. We have already reported impaired mitochondrial bioenergetics in MeCP2 deficient astrocytes. Docosahexaenoic acid (DHA), a polyunsaturated fatty acid, has been shown with health benefits, but its impact on mitochondrial functions in MeCP2 deficient astrocytes has never been paid much attention. The present study aimed to investigate the effects of DHA on mitochondrial respiratory chain regulation in MeCP2 knockdown astrocytes. We determined NADH dehydrogenase (ubiquinone) flavoprotein 2 (Ndufv2\u2010complex\u2010I), Ubiquinol cytochrome c reductase core protein (Uqcrc1\u2010complex\u2010III) genes expression, Ndufv2 protein expression, respiratory electron transport chain complex I, II, III, and IV enzyme activities, intracellular Ca<jats:sup>+2<\/jats:sup>, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) in DHA pre\u2010incubated MeCP2 knock\u2010down rat primary cortical astrocytes. Our study demonstrates that 100\u2009\u00b5M DHA increases MeCP2 gene and protein expression. Increases brain\u2010derived neurotrophic factor (BDNF) and Uqcrc1 gene expression, Ndufv2 protein expression, but has no effect on glial fibrillary acidic protein (GFAP) gene expression. DHA treatment also increases mitochondrial respiratory Complexes II and III activities and reduces intracellular calcium levels. Taken together, the effects of DHA seem independent of MeCP2 deficiency in astrocytes. Hence, further studies are warranted to understand the complicated mechanisms of DHA and for its therapeutic significance in MeCP2\u2010mediated mitochondrial dysfunction and in RTT disease.<\/jats:p>","DOI":"10.1002\/jbt.23002","type":"journal-article","created":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T12:27:15Z","timestamp":1645100835000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Docosahexaenoic acid increased MeCP2 mediated mitochondrial respiratory complexes II and III enzyme activities in cortical astrocytes"],"prefix":"10.1002","volume":"36","author":[{"given":"Arpita","family":"Dave","sequence":"first","affiliation":[{"name":"Department of Zoology,\u00a0Division of Neurobiology The Maharaja Sayajirao University of Baroda  Gujarat India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6391-880X","authenticated-orcid":false,"given":"Prakash 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