TY - JOUR
T1 - Neuronal Mitochondrial Dysfunction and Bioenergetic Failure in Inflammation-Associated Depression
AU - Casaril, Angela Maria
AU - Dantzer, Robert
AU - Bas-Orth, Carlos
N1 - Funding Information:
This work has been supported by the Deutsche Forschungsgemeinschaft (FOR 2289: BA 3679/4-2 to CB-O). RD would like to thank the NARSAD Distinguished Investigator Award, for the MD Anderson Cancer Support Grant (P30 CA016672), and for grants from the National Institutes of Health (R01 CA193522 and R01 NS073939).
Publisher Copyright:
© Copyright © 2021 Casaril, Dantzer and Bas-Orth.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - Depression is a leading cause of disability and affects more than 4% of the population worldwide. Even though its pathophysiology remains elusive, it is now well accepted that peripheral inflammation might increase the risk of depressive episodes in a subgroup of patients. However, there is still insufficient knowledge about the mechanisms by which inflammation induces alterations in brain function. In neurodegenerative and neuroinflammatory diseases, extensive studies have reported that inflammation negatively impacts mitochondrial health, contributing to excitotoxicity, oxidative stress, energy deficits, and eventually neuronal death. In addition, damaged mitochondria can release a wide range of damage-associated molecular patterns that are potent activators of the inflammatory response, creating a feed-forward cycle between oxidative stress, mitochondrial impairment, inflammation, and neuronal dysfunction. Surprisingly, the possible involvement of this vicious cycle in the pathophysiology of inflammation-associated depression remains understudied. In this mini-review we summarize the research supporting the association between neuroinflammation, mitochondrial dysfunction, and bioenergetic failure in inflammation-associated depression to highlight the relevance of further studies addressing this crosstalk.
AB - Depression is a leading cause of disability and affects more than 4% of the population worldwide. Even though its pathophysiology remains elusive, it is now well accepted that peripheral inflammation might increase the risk of depressive episodes in a subgroup of patients. However, there is still insufficient knowledge about the mechanisms by which inflammation induces alterations in brain function. In neurodegenerative and neuroinflammatory diseases, extensive studies have reported that inflammation negatively impacts mitochondrial health, contributing to excitotoxicity, oxidative stress, energy deficits, and eventually neuronal death. In addition, damaged mitochondria can release a wide range of damage-associated molecular patterns that are potent activators of the inflammatory response, creating a feed-forward cycle between oxidative stress, mitochondrial impairment, inflammation, and neuronal dysfunction. Surprisingly, the possible involvement of this vicious cycle in the pathophysiology of inflammation-associated depression remains understudied. In this mini-review we summarize the research supporting the association between neuroinflammation, mitochondrial dysfunction, and bioenergetic failure in inflammation-associated depression to highlight the relevance of further studies addressing this crosstalk.
KW - bioenergetics
KW - depression
KW - inflammation
KW - mitochondria
KW - neurons
UR - http://www.scopus.com/inward/record.url?scp=85119274290&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85119274290&partnerID=8YFLogxK
U2 - 10.3389/fnins.2021.725547
DO - 10.3389/fnins.2021.725547
M3 - Review article
C2 - 34790089
AN - SCOPUS:85119274290
SN - 1662-4548
VL - 15
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
M1 - 725547
ER -