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dc.contributor.author
Fanibunda, S. E.
dc.contributor.author
Deb, Sukrita
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Maniyadath, Babukrishna
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Tiwari, Praachi
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Ghai, Utkarsha
dc.contributor.author
Gupta, Samir
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Figueiredo, Dwight
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Weisstaub, Noelia V.
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Gingrich, Jay A.
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Vaidya, Ashok D.B.
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Kolthur Seetharam, Ullas
dc.contributor.author
Vaidya, Vidita A.
dc.date.available
2021-07-13T12:44:35Z
dc.date.issued
2019-05
dc.identifier.citation
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.issn
0027-8424
dc.identifier.uri
http://hdl.handle.net/11336/135930
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.format
application/pdf
dc.language.iso
eng
dc.publisher
National Academy of Sciences
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
5-HT
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5-HT2A RECEPTOR
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MITOCHONDRIA
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NEURONAL SURVIVAL
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SIRTUIN 1
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Neurociencias
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
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
dc.date.updated
2020-11-20T17:39:36Z
dc.journal.volume
166
dc.journal.number
22
dc.journal.pagination
11028-11037
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Fanibunda, S. E.. International Centre Of Theoretical Science. Tata Institute Of Fundamental Research; España. Kasturba Health Society; India
dc.description.fil
Fil: Deb, Sukrita. International Centre Of Theoretical Science. Tata Institute Of Fundamental Research; España
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Fil: Maniyadath, Babukrishna. International Centre Of Theoretical Science. Tata Institute Of Fundamental Research; España
dc.description.fil
Fil: Tiwari, Praachi. International Centre Of Theoretical Science. Tata Institute Of Fundamental Research; España
dc.description.fil
Fil: Ghai, Utkarsha. International Centre Of Theoretical Science. Tata Institute Of Fundamental Research; España
dc.description.fil
Fil: Gupta, Samir. International Centre Of Theoretical Science. Tata Institute Of Fundamental Research; España
dc.description.fil
Fil: Figueiredo, Dwight. International Centre Of Theoretical Science. Tata Institute Of Fundamental Research; España
dc.description.fil
Fil: Weisstaub, Noelia V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentina
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Fil: Gingrich, Jay A.. Columbia University; Estados Unidos
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Fil: Vaidya, Ashok D.B.. Kasturba Health Society; India
dc.description.fil
Fil: Kolthur Seetharam, Ullas. International Centre Of Theoretical Science. Tata Institute Of Fundamental Research; España
dc.description.fil
Fil: Vaidya, Vidita A.. International Centre Of Theoretical Science. Tata Institute Of Fundamental Research; España
dc.journal.title
Proceedings of the National Academy of Sciences of The United States of America
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1073/pnas.1821332116
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.pnas.org/content/116/22/11028
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