HDAC1-Mediated MicroRNA-124-5p Regulates NPY to Affect Learning and Memory Abilities in Rats with Depression

Researches pivoting on histone deacetylases (HDACs) in depression have been excessively conducted, but not much on HDAC1. Therein, the present study is launched to disclose the mechanism of HDAC1/microRNA (miR)-124-5p/neuropeptide Y (NPY) axis in depression. Sprague Dawley rats were stimulated by chronic unpredictable mild stress to establish depression models. Depressed rats were injected with inhibited HDAC1 or suppressed miR-124-5p to explore their roles in body weight, learning and memory abilities, oxidative stress and inflammation in serum and neurotransmitter expression in hippocampal tissues. MiR-124-5p, HDAC1 and NPY expression in the hippocampus were tested. The interactions of miR-124-5p, HDAC1 and NPY expression were also confirmed. Higher miR-124-5p and HDAC1 and lower NPY expression levels were found in the hippocampus of depressed rats. Inhibited miR-124-5p or suppressed HDAC1 attenuated learning and memory abilities and increased body weight of depressed rats. Knockdown of miR-124-5p or inhibition of HDAC1 suppressed oxidative stress and inflammation and promoted neurotransmitter expression of depressed rats. HDAC1 mediated miR-124-5p to regulate NPY. Knockdown of NPY abolished the protective effects of inhibited miR-124-5p on depressed rats. Our study illustrates that suppression of either miR-124-5p or HDAC1 up-regulates NPY to improve memory and learning abilities in depressed mice, which may update the existed knowledge of depression and provide a novel reference for treatment of depression.