Abstract
In addition to its role as a neuronal energy substrate and signaling molecule involved in synaptic plasticity and memory consolidation, recent evidence shows that lactate produces antidepressant effects in animal models. However, the mechanisms underpinning lactate’s antidepressant actions remain largely unknown. In this study, we report that lactate reverses the effects of corticosterone on depressive-like behavior, as well as on the inhibition of both the survival and proliferation of new neurons in the adult hippocampus. Furthermore, the inhibition of adult hippocampal neurogenesis prevents the antidepressant-like effects of lactate. Pyruvate, the oxidized form of lactate, did not mimic the effects of lactate on adult hippocampal neurogenesis and depression-like behavior. Finally, our data suggest that conversion of lactate to pyruvate with the concomitant production of NADH is necessary for the neurogenic and antidepressant effects of lactate.
Highlights
Post-mortem studies have shown that major depression is associated with a reduction in the number and density of astrocytes in various frontolimbic areas of depressed patients, suggesting that astrocyte dysfunction may contribute to the pathogenesis of depression [1,2,3]
As a first step toward assessing the role of adult hippocampal neurogenesis in the antidepressant effects of lactate, we investigated whether chronic peripheral administration of lactate reverses the effects of corticosterone on cell proliferation in the subgranular zone (SGZ) of the dentate gyrus
Chronic treatment with lactate reversed the effects of corticosterone both on the immobility in the forced swim test (FST) (Fig. S2b) and on the decreased SGZ cell proliferation (Fig. 1b, c)
Summary
Post-mortem studies have shown that major depression is associated with a reduction in the number and density of astrocytes in various frontolimbic areas of depressed patients, suggesting that astrocyte dysfunction may contribute to the pathogenesis of depression [1,2,3]. Astrocytes are involved in essential CNS functions including energy metabolism, synaptic transmission, synaptic plasticity, and adult neurogenesis [4,5,6,7]. With regard to adult hippocampal neurogenesis, blockade of vesicular release from astrocytes impairs the synaptic maturation and survival of new. These authors jointly supervised this work: Pierre J.
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