The present study aimed to investigate whether apigenin elicits antidepressant effects in depressant-like mice via the regulation of autophagy. The depressant-like behaviors were established in a chronic restraint stress model. Male BalB/c mice were subjected to restraint stress for 6 h/day for a period of 21 days, and deficits in sucrose preference, tail suspension and forced swim tests were confirmed to be improved following oral apigenin. To investigate the underlining mechanisms, the hippocampal levels of p62 and microtubule-associated protein light chain 3-ii/i (lc3-ii/i) were measured using western blot analysis. The expression levels of lc3-ii/i and p62 indicated that the significantly inhibited autophagy level induced by chronic restraint stress can be increased following apigenin treatment. Similar to the level of autophagy, the expression levels of adenosine monophosphate-activated protein kinase (aMPK) and unc-51 like autophagy activating kinase-1 were downregulated after chronic restraint stress stimulation and, subsequently upregulated following treatment with apigenin. conversely, the levels of mammalian target of rapamycin (mTor) were increased in chronic restraint stress mice and inhibited by apigenin. Collectively, the present findings indicated that apigenin potentially promotes autophagy via the aMPK/mTor pathway and induces antidepressive effects in chronic restraint stress mice.
AMP-activated kinase (AMPK) is a heterotrimeric complex composed of three subunits and is the core energy sensor of the cell. The AMPK activity is important for survival during periods of stress and starvation and also has implications in type II diabetes, obesity, metabolic syndrome, longevity and cancer, etc. The activation of AMPK is triggered through binding of Adenosine Monophosphate Activated Proteins (AMP) to the Bateman domains of the gamma subunit, leading to increased phosphorylation of the threonine 172 on the alpha subunit by inducing allosteric activation and inhibiting dephosphorylation. AMPK and its subunits have been the focuses of many researchers dealing with genetic and metabolic issues. The study makes a comprehensive review on the structure, function, distribution, enzyme activity, the genetic mutation and other aspects of AMPK and its subunit genes, with the aim to outline main aspects of present researches on AMPK and its subunits in animal genetics.
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