El transportador vesicular de glutamato 1 (vglut1) como factor biológico de vulnerabilidad a la depresión mayor

Resumen

VESICULAR GLUTAMATE TRANSPORTER 1 (VGLUT1) AS BIOLOGICAL FACTOR VULNERABILTY TO MAJOR DEPRESSION Alvaro García García Department of Pharmacology, Pharmacy Faculty, University of Navarra 2010 Abnormalities in glutamate and gamma-aminobutyric acid (GABA) signal transmission have been postulated to play a role in depression, but little is known about the underlying molecular mechanisms. At the experimental level, the vesicular glutamate transporter 1 (VGLUT1) has been reported to play a key role in the synaptic release and the efficacy of glutamatergic synaptic transmission. Firstly, we asked whether decreased VGLUT1 levels could negatively interact with well-known environmental risk factors of major depression. We used heterozygous VGLUT1 mice as a model of major depression. Interestingly, these mice showed increased vulnerability to depressive-like behaviour and neurochemical alterations that address clinical features of major depression. In the second study, we suggest for the first time, a key role for VGLUT1 in the glutamatergic regulation of 5-HT activity in the dorsal raphe nucleus from cortical descending pathways. Finally, gene expression studies in the frontal cortex of VGLUT1+/- mice and mice exposed to chronic mild stress revealed changes that could form part of the altered ¿molecular context¿ underlying depressive-like behavior in these models and be new pharmacological targets for the treatment of depression. This study shows the functional implications of decreased VGLUT1 levels for glutamatergic, GABAergic and serotonergic transmission in the context of behavioral paradigms that model major depression. We propose that decreased VGLUT1 levels may be a biological factor of vulnerability to major depression, alone, and in combination with adverse environmental factors.