Insulin modulates emotional behavior through a serotonin-dependent mechanism

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 s...

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Vydáno v:	Molecular psychiatry Ročník 29; číslo 6; s. 1610 - 1619
Hlavní autoři:	Martin, Hugo, Bullich, Sébastien, Martinat, Maud, Chataigner, Mathilde, Di Miceli, Mathieu, Simon, Vincent, Clark, Samantha, Butler, Jasmine, Schell, Mareike, Chopra, Simran, Chaouloff, Francis, Kleinridders, Andre, Cota, Daniela, De Deurwaerdere, Philippe, Pénicaud, Luc, Layé, Sophie, Guiard, Bruno P., Fioramonti, Xavier
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 01.06.2024 Nature Publishing Group
Témata:	38/32 631/378 631/477 64/60 82/16 9/74 Administration, Intranasal Animals Anxiety Anxiolytics Behavioral Sciences Biological Psychology Comorbidity Depressive Disorder, Major Diabetes mellitus Diabetes Mellitus, Type 2 Diet, High-Fat Dorsal Raphe Nucleus Emotional behavior Emotional disorders Emotions High fat diet Insulin Insulin Resistance Life Sciences Male Medicine Medicine & Public Health Mental disorders Mice Mice, Inbred C57BL Mood Mood disorders Neuromodulation Neurons Neurons and Cognition Neurosciences Neurotransmission Pharmacotherapy Psychiatry Receptor, Serotonin, 5-HT1A Serotonergic Neurons Serotonin Serotonin S1 receptors Synaptic Transmission
ISSN:	1359-4184, 1476-5578, 1476-5578
On-line přístup:	Získat plný text
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Shrnutí:	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-HT 1A 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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1359-4184 1476-5578 1476-5578
DOI:	10.1038/s41380-022-01812-3