Ameliorated Neurogenesis Deficits in Dentate Gyrus May Underly the Pronounced Antidepressant Effect of TREK-1 Potassium Channel Blockade in Rats with Depressive-like Behavior.
Hua XuYingpeng DingXinyang QiZhi-Jun ZhangJianhua SuPublished in: ACS chemical neuroscience (2022)
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.
Keyphrases
- cerebral ischemia
- stress induced
- major depressive disorder
- subarachnoid hemorrhage
- blood brain barrier
- brain injury
- bipolar disorder
- traumatic brain injury
- oxidative stress
- depressive symptoms
- endoplasmic reticulum stress
- neural stem cells
- cell death
- signaling pathway
- cell cycle arrest
- mental health
- drug induced
- childhood cancer
- heat stress
- replacement therapy
- temporal lobe epilepsy