Peripheral administration of lactate produces antidepressant-like effects.

Autor: Carrard A; Center for Psychiatric Neurosciences, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland., Elsayed M; Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., Margineanu M; King Abdullah University of Science and Technology (KAUST), BESE Division, Thuwal, Saudi Arabia., Boury-Jamot B; Center for Psychiatric Neurosciences, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.; Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., Fragnière L; Center for Psychiatric Neurosciences, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland., Meylan EM; Center for Psychiatric Neurosciences, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland., Petit JM; Center for Psychiatric Neurosciences, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.; Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., Fiumelli H; King Abdullah University of Science and Technology (KAUST), BESE Division, Thuwal, Saudi Arabia., Magistretti PJ; Center for Psychiatric Neurosciences, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.; Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.; King Abdullah University of Science and Technology (KAUST), BESE Division, Thuwal, Saudi Arabia., Martin JL; Center for Psychiatric Neurosciences, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2018 Feb; Vol. 23 (2), pp. 392-399. Date of Electronic Publication: 2016 Oct 18.
DOI: 10.1038/mp.2016.179
Abstrakt: In addition to its role as metabolic substrate that can sustain neuronal function and viability, emerging evidence supports a role for l-lactate as an intercellular signaling molecule involved in synaptic plasticity. Clinical and basic research studies have shown that major depression and chronic stress are associated with alterations in structural and functional plasticity. These findings led us to investigate the role of l-lactate as a potential novel antidepressant. Here we show that peripheral administration of l-lactate produces antidepressant-like effects in different animal models of depression that respond to acute and chronic antidepressant treatment. The antidepressant-like effects of l-lactate are associated with increases in hippocampal lactate levels and with changes in the expression of target genes involved in serotonin receptor trafficking, astrocyte functions, neurogenesis, nitric oxide synthesis and cAMP signaling. Further elucidation of the mechanisms underlying the antidepressant effects of l-lactate may help to identify novel therapeutic targets for the treatment of depression.
Databáze: MEDLINE
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