dc.creator | Fanibunda, S. E. | |
dc.creator | Deb, Sukrita | |
dc.creator | Maniyadath, Babukrishna | |
dc.creator | Tiwari, Praachi | |
dc.creator | Ghai, Utkarsha | |
dc.creator | Gupta, Samir | |
dc.creator | Figueiredo, Dwight | |
dc.creator | Weisstaub, Noelia V. | |
dc.creator | Gingrich, Jay A. | |
dc.creator | Vaidya, Ashok D.B. | |
dc.creator | Kolthur Seetharam, Ullas | |
dc.creator | Vaidya, Vidita A. | |
dc.date.accessioned | 2021-07-13T12:44:35Z | |
dc.date.accessioned | 2022-10-15T08:29:33Z | |
dc.date.available | 2021-07-13T12:44:35Z | |
dc.date.available | 2022-10-15T08:29:33Z | |
dc.date.created | 2021-07-13T12:44:35Z | |
dc.date.issued | 2019-05 | |
dc.identifier | Fanibunda, S. E.; Deb, Sukrita; Maniyadath, Babukrishna; Tiwari, Praachi; Ghai, Utkarsha; et al.; Serotonin regulates mitochondrial biogenesis and function in rodent cortical neurons via the 5-HT2A receptor and SIRT1–PGC-1α axis; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 166; 22; 5-2019; 11028-11037 | |
dc.identifier | 0027-8424 | |
dc.identifier | http://hdl.handle.net/11336/135930 | |
dc.identifier | CONICET Digital | |
dc.identifier | CONICET | |
dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/4365158 | |
dc.description.abstract | Mitochondria in neurons, in addition to their primary role in bioenergetics, also contribute to specialized functions, including regulation of synaptic transmission, Ca2+ homeostasis, neuronal excitability, and stress adaptation. However, the factors that influence mitochondrial biogenesis and function in neurons remain poorly elucidated. Here, we identify an important role for serotonin (5-HT) as a regulator of mitochondrial biogenesis and function in rodent cortical neurons, via a 5-HT2A receptor-mediated recruitment of the SIRT1–PGC-1α axis, which is relevant to the neuroprotective action of 5-HT. We found that 5-HT increased mitochondrial biogenesis, reflected through enhanced mtDNA levels, mitotracker staining, and expression of mitochondrial components. This resulted in higher mitochondrial respiratory capacity, oxidative phosphorylation (OXPHOS) efficiency, and a consequential increase in cellular ATP levels. Mechanistically, the effects of 5-HT were mediated via the 5-HT2A receptor and master modulators of mitochondrial biogenesis, SIRT1 and PGC-1α. SIRT1 was required to mediate the effects of 5-HT on mitochondrial biogenesis and function in cortical neurons. In vivo studies revealed that 5-HT2A receptor stimulation increased cortical mtDNA and ATP levels in a SIRT1-dependent manner. Direct infusion of 5-HT into the neocortex and chemogenetic activation of 5-HT neurons also resulted in enhanced mitochondrial biogenesis and function in vivo. In cortical neurons, 5-HT enhanced expression of antioxidant enzymes, decreased cellular reactive oxygen species, and exhibited neuroprotection against excitotoxic and oxidative stress, an effect that required SIRT1. These findings identify 5-HT as an upstream regulator of mitochondrial biogenesis and function in cortical neurons and implicate the mitochondrial effects of 5-HT in its neuroprotective action. | |
dc.language | eng | |
dc.publisher | National Academy of Sciences | |
dc.relation | info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1073/pnas.1821332116 | |
dc.relation | info:eu-repo/semantics/altIdentifier/url/https://www.pnas.org/content/116/22/11028 | |
dc.rights | https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | 5-HT | |
dc.subject | 5-HT2A RECEPTOR | |
dc.subject | MITOCHONDRIA | |
dc.subject | NEURONAL SURVIVAL | |
dc.subject | SIRTUIN 1 | |
dc.title | Serotonin regulates mitochondrial biogenesis and function in rodent cortical neurons via the 5-HT2A receptor and SIRT1–PGC-1α axis | |
dc.type | info:eu-repo/semantics/article | |
dc.type | info:ar-repo/semantics/artículo | |
dc.type | info:eu-repo/semantics/publishedVersion | |