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Prefrontal cortex miR‐874‐3p prevents lipopolysaccharide‐induced depression‐like behavior through inhibition of indoleamine 2,3‐dioxygenase 1 expression in mice
Author(s) -
Suento Willy Jaya,
Kunisawa Kazuo,
Wulaer Bolati,
Kosuge Aika,
Iida Tsubasa,
Fujigaki Suwako,
Fujigaki Hidetsugu,
Yamamoto Yasuko,
Tanra Andi Jayalangkara,
Saito Kuniaki,
Mouri Akihiro,
Nabeshima Toshitaka
Publication year - 2021
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.15222
Subject(s) - indoleamine 2,3 dioxygenase , kynurenine pathway , prefrontal cortex , lipopolysaccharide , sickness behavior , kynurenine , behavioural despair test , microrna , microglia , major depressive disorder , medicine , pathophysiology , endocrinology , neuroscience , inflammation , psychology , chemistry , tryptophan , gene , biochemistry , hippocampus , amygdala , cognition , amino acid , antidepressant
Indoleamine 2,3‐dioxygenase 1 (IDO1) is the first rate‐limiting enzyme that metabolizes tryptophan to the kynurenine pathway. Its activity is highly inducible by pro‐inflammatory cytokines and correlates with the severity of major depressive disorder (MDD). MicroRNAs (miRNAs) are involved in gene regulation and the development of neuropsychiatric disorders including MDD. However, the role of miRNAs in targeting IDO1 in the pathophysiology of MDD is still unknown. In this study, we investigated the role of novel miRNAs in the regulation of IDO1 activity and its effect on lipopolysaccharide (LPS)‐induced depression‐like behavior in mice. LPS up‐regulated miR‐874‐3p concomitantly with increase in IDO1 expression in the prefrontal cortex (PFC), increase in immobility in the forced swimming test as depression‐like behavior and decrease in locomotor activity as sickness behavior without motor dysfunction. The miR‐874‐3p increased in both neuron and microglia after LPS. Its mimic significantly suppressed LPS‐induced IDO1 expression in the PFC. Infusion of IDO1 inhibitor (1‐methyl‐ l ‐tryptophan) and miR‐874‐3p into PFC prevented an increase in immobility in the forced swimming test, but did not decrease in locomotor activity induced by LPS. These results suggest that miR‐874‐3p may play an important role in preventing the LPS‐induced depression‐like behavior through inhibition of IDO1 expression. This may also serve as a novel potential target molecule for the treatment of MDD.