RESUMEN
Major depressive disorder (MDD) is a devastating psychiatric disease, and current therapies could not well meet the demand for MDD treatment. Exercise benefits mental illness, and notably, exercise has been recommended as an alternative option for MDD treatment in some countries. However, the paradigm and intensity of exercise for MDD treatment has yet to be determined. High-intensity interval training (HIIT) is a potent and time-efficient type of exercise training and has gained popularity in recent years. In this study, we exposed the mice to chronic unpredictable mild stress (CUMS) and found HIIT exerted substantial antidepressant effect. Moreover, HIIT further enhanced the antidepressant effect of fluoxetine, a classic antidepressant in the clinic, confirming the antidepressant role of HIIT. HIIT significantly reversed the CUMS-induced upregulations in HDAC2 mRNA and protein level in the ventral hippocampus. We also found HIIT rescued the CUMS-induced downregulation in the expression of brain-derived neurotrophic factor (BDNF) and HDAC2 overexpression counteracted the HIIT-induced increase in BDNF level. More importantly, both virus-mediated HDAC2 overexpression and microinfusion of TrkB-Fc, a BDNF scavenger, in the ventral hippocampus abolished the antidepressant effect of HIIT. Together, our results strongly demonstrate that HIIT attenuates depressive behaviors, probably via HDAC2-BDNF signaling pathway and reveal that HIIT may serve as an alternative option for MDD treatment.
Asunto(s)
Trastorno Depresivo Mayor , Entrenamiento de Intervalos de Alta Intensidad , Animales , Ratones , Antidepresivos/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Depresión/terapia , Depresión/metabolismo , Trastorno Depresivo Mayor/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Transducción de Señal , Estrés Psicológico/terapia , Estrés Psicológico/metabolismo , Histona Desacetilasa 2/metabolismoRESUMEN
Some of the statins have been shown to have antidepressant effects, but whether atorvastatin (AV) has antidepressant effects is unknown. This study was to investigate the effect of AV treatment on depressive behaviors. Herein, we show that AV treatment had antidepressant-like effect in physiological conditions and antidepressant effect in depressive state which depended on α7 nicotinic acetylcholine receptor (α7nAChR) expression in the ventral hippocampus (vHPC), but not α4ß2 nicotinic acetylcholine receptor (α4ß2nAchR) expression in vHPC, nor the α7nAChR and α4ß2nAchR expression in dorsal hippocampus (dHPC). By using MLA, a selective α7nAChR antagonist, we investigated the role of α7nAChR in AV treatment. Behavior tests demonstrated that MLA abolished the antidepressant effect of AV. Besides, our data showed that AV treatment increased Akt phosphorylation, brain-derived neurotrophic factor (BDNF), synaptic related protein synapsin and spinophilin expression. The phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002 reversed AV-induced increase of BDNF expression, newborn neurons and antidepressant behavior effects. Our study suggests that AV plays an antidepressant role by regulating synaptic plasticity of vHPC through PI3K/Akt-BDNF signaling pathway, which may be a good choice for depression treatment.