Stress is the foremost environmental factor involved in the pathophysiology of major depressive disorder (MDD). However, individual differences among people are critical as some people exhibit vulnerability while other are resilient to repeated exposure to stress. Among the others, a recent theory postulates that alterations of energy metabolism might contribute to the development of psychopathologies. Here we show that the bioenergetic status in the ventral hippocampus (vHip), a brain subregion tightly involved in the regulation of MDD, defined the development of vulnerability or resilience following two weeks of chronic mild stress. Among the different metabolomic signatures observed, the glycolysis and tricarboxylic acid cycle may be specifically involved in defining vulnerability, revealing a previously unappreciated mechanism of sensitivity to stress. These findings point to mitochondrial morphology and recycling as critical in the ability to cope with stress. We show that vulnerable rats favor mitochondrial fusion to counteract the overproduction of reactive oxidative species whereas resilient rats activate fission to guarantee metabolic efficiency. Our results indicate that the modulation of the energetic metabolite profile in vHip under chronic stress exposure may represent a mechanism to explain the difference between vulnerable and resilient rats, unraveling novel and promising targets for specific therapeutic interventions.

Metabolomic signature and mitochondrial dynamics outline the difference between vulnerability and resilience to chronic stress / P. Brivio, M. Audano, M.T. Gallo, P. Gruca, M. Lason, E. Litwa, F. Fumagalli, M. Papp, N. Mitro, F. Calabrese. - In: TRANSLATIONAL PSYCHIATRY. - ISSN 2158-3188. - 12:1(2022 Dec), pp. 87.1-87.10. [10.1038/s41398-022-01856-7]

Metabolomic signature and mitochondrial dynamics outline the difference between vulnerability and resilience to chronic stress

P. Brivio
Co-primo
;
M. Audano
Co-primo
;
M.T. Gallo;F. Fumagalli;N. Mitro;F. Calabrese
Ultimo
2022

Abstract

Stress is the foremost environmental factor involved in the pathophysiology of major depressive disorder (MDD). However, individual differences among people are critical as some people exhibit vulnerability while other are resilient to repeated exposure to stress. Among the others, a recent theory postulates that alterations of energy metabolism might contribute to the development of psychopathologies. Here we show that the bioenergetic status in the ventral hippocampus (vHip), a brain subregion tightly involved in the regulation of MDD, defined the development of vulnerability or resilience following two weeks of chronic mild stress. Among the different metabolomic signatures observed, the glycolysis and tricarboxylic acid cycle may be specifically involved in defining vulnerability, revealing a previously unappreciated mechanism of sensitivity to stress. These findings point to mitochondrial morphology and recycling as critical in the ability to cope with stress. We show that vulnerable rats favor mitochondrial fusion to counteract the overproduction of reactive oxidative species whereas resilient rats activate fission to guarantee metabolic efficiency. Our results indicate that the modulation of the energetic metabolite profile in vHip under chronic stress exposure may represent a mechanism to explain the difference between vulnerable and resilient rats, unraveling novel and promising targets for specific therapeutic interventions.
Settore BIO/14 - Farmacologia
   Antidepressant drugs effect on the gender-dependent development of depressive behavior induced by early neuroinflammatory hit: a multitask approach from mice to patients
   MINISTERO DELL'ISTRUZIONE E DEL MERITO
   201779W93T_002

   Dipartimenti di Eccellenza 2018-2022 - Dipartimento di SCIENZE FARMACOLOGICHE E BIOMOLECOLARI
   MINISTERO DELL'ISTRUZIONE E DEL MERITO
dic-2022
28-feb-2022
Article (author)
File in questo prodotto:
File Dimensione Formato  
21-Brivioetal2022.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 2.75 MB
Formato Adobe PDF
2.75 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/913594
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 16
  • ???jsp.display-item.citation.isi??? 16
social impact