Role of adult hippocampal neurogenesis in the antidepressant effects of lactate

Abstract

Astrocytes are key players in energy metabolism and glutamate transport. In particular, astrocytes respond to glutamate by increasing the rate of glucose utilization and the release of lactate (Magistretti and Allaman, 2018, Nat Rev Neurosci.). Growing evidence indicates that astrocytes are also involved in the pathophysiology and treatment of depression. For instance, SSRIs stimulate lactate release from cortical astrocytes. Recently, we showed that acute lactate administration increased lactate concentration in the hippocampus and reduced immobility in the forced swim test (Carrard et al., 2018, Mol Psychiatry). We further investigated the antidepressant-like effects of lactate in two animal models of depression that respond to chronic antidepressant treatment; the corticosterone model of depression and the open-space forced swim model of depression. We found that chronic administration of lactate reversed the corticosterone-induced anhedonia-like behavior and partially restored mobility in the open-space forced swim model of depression, in a manner similar to desipramine. The antidepressant effects of lactate are associated with changes in the expression of specific target genes of which Hes5 is involved in adult hippocampal neurogenesis. These findings led us to investigate the role of adult hippocampal neurogenesis in the antidepressant effects of lactate