Insulin modulates emotional behavior through a serotonin-dependent mechanism.

1. Mol Psychiatry. 2024 Jun;29(6):1610-1619. doi: 10.1038/s41380-022-01812-3.
Epub 2022 Oct 7.

Insulin modulates emotional behavior through a serotonin-dependent mechanism.

Martin H(#)(1), Bullich S(#)(2), Martinat M(1), Chataigner M(1), Di Miceli
M(1)(3), Simon V(4), Clark S(4), Butler J(5), Schell M(6), Chopra S(6),
Chaouloff F(4), Kleinridders A(6), Cota D(4), De Deurwaerdere P(5), Pénicaud
L(7), Layé S(1), Guiard BP(#)(2), Fioramonti X(#)(8).

Author information:
(1)Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux,
France.
(2)Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie
Intégrative (CBI), CNRS UMR5169, Toulouse, France.
(3)Worcester Biomedical Research Group, University of Worcester, WR2 6AJ,
Worcester, UK.
(4)University of Bordeaux, Neurocentre Magendie, INSERM U1215, Bordeaux, France.
(5)INCIA, UMR CNRS, Bordeaux University, Neurocampus, Bordeaux, France.
(6)University of Potsdam, Institute of Nutritional Science, Molecular and
Experimental Nutritional Medicine, Nuthetal, Germany.
(7)RESTORE, UMR INSERM 1301/CNRS 5070/Université Paul Sabatier/EFS/ENVT,
Toulouse, France.
(8)Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux,
France. .
(#)Contributed equally

Type-2 Diabetes (T2D) is characterized by insulin resistance and accompanied by
psychiatric comorbidities including major depressive disorders (MDD). Patients
with T2D are twice more likely to suffer from MDD and clinical studies have
shown that insulin resistance is positively correlated with the severity of
depressive symptoms. However, the potential contribution of central insulin
signaling in MDD in patients with T2D remains elusive. Here we hypothesized that
insulin modulates the serotonergic (5-HT) system to control emotional behavior
and that insulin resistance in 5-HT neurons contributes to the development of
mood disorders in T2D. Our results show that insulin directly modulates the
activity of dorsal raphe (DR) 5-HT neurons to dampen 5-HT neurotransmission
through a 5-HT1A receptor-mediated inhibitory feedback. In addition,
insulin-induced 5-HT neuromodulation is necessary to promote anxiolytic-like
effect in response to intranasal insulin delivery. Interestingly, such an
anxiolytic effect of intranasal insulin as well as the response of DR 5-HT
neurons to insulin are both blunted in high-fat diet-fed T2D animals.
Altogether, these findings point to a novel mechanism by which insulin directly
modulates the activity of DR 5-HT neurons to dampen 5-HT neurotransmission and
control emotional behaviors, and emphasize the idea that impaired
insulin-sensitivity in these neurons is critical for the development of
T2D-associated mood disorders.

© 2022. The Author(s), under exclusive licence to Springer Nature Limited.

DOI: 10.1038/s41380-022-01812-3
PMID: 36207585 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus