Dlx5 and Dlx6 expression in GABAergic neurons controls behavior, metabolism, healthy aging and lifespan.: Dlx5/6 control behavior, metabolism and aging.

Camille de Lombares 1 Eglantine Heude 1 Gladys Alfama 1 Anastasia Fontaine 1 Rim Hassouna 2 Cecile Vernochet 3 Fabrice de Chaumont 4 Christophe Olivo-Marin 4 Elodie Ey 5 Sebastien Parnaudeau 6 Francois Tronche 6 Thomas Bourgeron 5 Serge Luquet 2 Giovanni Levi 1 Nicolas Narboux-Nême 1, *
* Corresponding author
1 ERE - Evolution des régulations endocriniennes
2 BFA - Unité de Biologie Fonctionnelle et Adaptative
3 ISBDC - Institut de signalisation, biologie du développement et cancer
4 AIQ - Analyse d'Images quantitatives
5 Génétique humaine et Fonctions cognitives - Human Genetics and Cognitive Functions
6 NPS - Neuroscience Paris Seine
Abstract : Dlx5 and Dlx6 encode two homeobox transcription factors expressed by developing and mature GABAergic interneurons. During development Dlx5/6 are important for the differentiation of Parvalbumin (Pvalb)-expressing neurons. Perinatal lethality of homozygous mice in which Dlx5/6 have been constitutively deleted has, so far, hindered the study of the function of these genes in adult neurons. We first show that Dlx5 and Dlx6 are expressed by all subclasses of adult cortical GABAergic neurons. Then we analyse VgatΔDlx5-6 mice in which Dlx5 and Dlx6 are simultaneously inactivated in all GABAergic interneurons. VgatΔDlx5-6 mice present a behavioral pattern suggesting reduction of anxiety and obsessivecompulsive activities. They rapidly access and spend more time in the central region of an open field, bury few marbles in the marble burying test and show little interest in nest building. Male and female 20-month-old VgatΔDlx5-6 animals have the same size as their normal littermates, but present a 25% body weight reduction associated with a marked decline in white and brown adipose tissue. Remarkably, both VgatΔDlx5-6/+ and VgatΔDlx5-6 mice present a 33% longer median survival than their control littermates. Hallmarks of biological aging such as motility, adipose deposition and coat conditions are improved in mutant animals. Our data imply that GABAergic interneurons can regulate mammalian healthspan and lifespan through Dlx5/6-dependent mechanisms. Understanding these regulations can be an entry point to unravel the processes through which the brain affects body homeostasis and, ultimately, longevity and healthy aging.
Keywords : Dlx5/Dlx6 GABAergic neurons aging behavior longevity
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Journal articles
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https://hal-mnhn.archives-ouvertes.fr/mnhn-02295464
Contributor : Eglantine Heude <>
Submitted on : Tuesday, September 24, 2019 - 11:20:56 AM
Last modification on : Friday, September 27, 2019 - 1:26:51 AM

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Camille de Lombares, Eglantine Heude, Gladys Alfama, Anastasia Fontaine, Rim Hassouna, et al.. Dlx5 and Dlx6 expression in GABAergic neurons controls behavior, metabolism, healthy aging and lifespan.: Dlx5/6 control behavior, metabolism and aging.. Aging, Superintendent of Documents, U.S. Government Printing Office, 2019, 11 (17), pp.6638-6656. ⟨10.18632/aging.102141⟩. ⟨mnhn-02295464⟩

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