Treadmill Exercise Reverses Depression Model-Induced Alteration of Dendritic Spines in the Brain Areas of Mood Circuit

Abstract

Depression is one of the most prevalent psychiatric disorders. Exercise has been shown to be effective in the amelioration of depression, but the underlying mechanism remains largely unknown. Alterations in the density and morphology of dendritic spines are associated with psychiatric diseases. Chronic unpredictable mild stress (CUMS) is an established animal model of depression. The aim of this study was to determine whether treadmill exercise reverses CUMS-induced both depression-like behaviors and alterations in spine density and morphology of the principal neurons in the brain areas of the mood circuits including the hippocampus, medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and basolateral amygdala (BLA). Male rats were randomly divided into four groups: control, CUMS, exercise, and CUMS+exercise. CUMS-induced depression-like behaviors were evaluated by the sucrose preference test (SPT). Golgi staining was used to visualize dendritic spines. Our results showed that CUMS-induced depression-like behaviors characterized by a decrease in sucrose consumption were accompanied by a decrease in spine density and a change in spine morphology in the pyramidal neurons of both the hippocampal CA3 area and the mPFC, and an increase in spine density and an alteration in spine shape in both the NAc medium spiny neurons (MSNs) and the BLA neurons; exercise reversed both CUMS-induced depression-like behaviors and alterations in dendritic spines. This study provides important information for understanding the mechanism through which exercise ameliorates CUMS-induced depression-like behaviors.

Pathophysiology linking depression and type 2 diabetes: Psychotherapy, physical exercise, and fecal microbiome transplantation as damage control

“…The effects of physical exercise on depression‐like symptoms and diabetic factors have been monitored independently, but surprisingly, to the best of our knowledge, not concomitantly. For instance, treadmill exercise decreased glycated hemoglobin, hemoglobin A1C (HbA1c), and inflammation levels in T1DM rats (Kazemi, 2019), whereas it reduced depressive behavior and corrected the modification of dendritic spines in the brains of depressed rats (Zhuang et al., 2019). Tables 1 and 2 compile some of the recent studies that test the effect of physical exercise interventions on depression and T2DM in humans and animal models, respectively.…”

Methyl jasmonate rescues structural alterations in cortico-limbic neurons produced by the unpredictable chronic mild stress model of depression

“…Consistently, rodent models of depression trigger structural alterations of neurons [16] and decrease synaptic proteins level [31] in brain regions involved in mood regulation although variations in the severity and localization of these dysfunctions have been reported. For example, coherently with the amygdaloid centered model of stress [32] UCMS administered for periods ranging between 1 to 3 months elicits spine loss and dendritic arbor retraction in hippocampus and medial prefrontal cortex [12,33] but increases spines in amygdala and nucleus accumbens [6,34]. On the functional level, it has been suggested that reduction of mPFC synaptic density decreases cortical activity, prevents fear extinction to develop but, at the same time, is permissive for amygdala hyperactivation due to the diminished control of PFC projections on BLA excitatory neurons.…”

Transthyretin as a Biomarker to Predict and Monitor Major Depressive Disorder Identified by Whole-Genome Transcriptomic Analysis in Mouse Models

“…Accumulating evidence has shown that in the hippocampus, chronic stress may alter cellular functions and plasticity of neurons, and result in dendritic atrophy as well as inhibition of neurogenesis [ 23 ]. In particular, chronic stress can also induce dendritic atrophy and reduce the length of apical dendrites of pyramidal neurons in the CA1 and CA3 regions, which may reduce neuroplasticity [ 24 , 25 , 26 ]. Furthermore, since GABAergic interneurons of the hippocampus are important in the regulation of cellular and neural circuit function, their roles in the pathogenesis of MDD have been well documented [ 27 ].…”