Ameliorated Neurogenesis Deficits in Dentate Gyrus May Underly the Pronounced Antidepressant Effect of TREK-1 Potassium Channel Blockade in Rats with Depressive-like Behavior.

Abstract

Depression is considered to be the most common mental disorder and is probed by several studies that chronic mild stress contributes to depression, and fortunately, most antidepressants ameliorate depressive-like behavior accompanied with reversed hippocampal neurogenesis defects. In our present study, we confirmed that different antidepressants repaired the stress-induced neuronal and behavioral deficits by modulating adult hippocampal neurogenesis. Antidepressant treatment restored the adult hippocampal neurodegeneration, which was impaired by chronic unpredicted mild stress displaying decreased proliferation and neuronal differentiation but increased apoptosis of newly formed neurons in dentate gyrus. Notably, sucrose preference ratio significantly correlated with both neuronal differentiation proportion and newborn apoptosis proportion, suggesting a mechanistic relationship between neurogenesis and behavior. Indeed, the neotype TREK-1 potassium channel blocker expressed an earlier and pronounced antidepressant manifestation compared to the traditional selective serotonin-reuptake inhibitors fluoxetine. We therefore conclude that the administration of TREK-1 potassium channel antagonism can reverse the depressive deficits caused by chronic stress quickly via regulation of adult hippocampal neurogenesis.