Affiliations:
Capital University of Physical Education and Sports, 100191 Beijing, China
China Athletics College, Beijing Sport University, Beijing 100084, China
# These two authors contributed equally to this work.
*Correspondence:
Cheng Guo, Ph.D.
Capital University of Physical Education and Sports
Phone: 86-18131126063 (mobile)
E-mail: guocheng2018@cupes.edu.cn
Abstract
Stress-related memory deficit is correlated with neurotransmitter system impairment. Exercise improves memory function and neurotransmitter. However, no studies have been performed to directly observe exercise-related effects on neurotransmitter in stress model, in association with memory function and hippocampal neuron. This study aimed to investigate the effect of exercise on hippocampal neuron and dopamine in stress model, followed by working memory in a passive avoid test. Our study found that stress rat had significantly neuron impairment and dopamine loss in hippocampus plus working memory deficit, which can be rescued by exercise. In summary, this study demonstrated that the neuroprotective effect of stress-associated working memory by treadmill exercise via ameliorated neuron impairment and dopamine loss.
Keywords: Treadmill exercise; Stress; Working memory; Neuron; Dopamine.
Introduction
As an important psychiatric disease, stress is one of the most common triggers of clinical depression, causing lasting anxiety, depressed mood and memory deficit[1]. Extensive studies at different molecular levels aimed at understanding the mechanisms underlying stress-induced memory deficit. Synaptic pathway[2], inflammation[3]and neurotransmitter[4] all can be regard as an important partner to induced memory deficit. Importantly, long-term memory, working memory, and self-reported memory all can be affected by stress[5]. As the basic structure of cognitive formation, stress disrupts the structural and functional integrity of neuronal networks in the brain of rats[6]. Neuron injury may further contribute to stress induced memory deficit[7]. Therefore, how to improve memory by rescue neuron injury have been a hot topic in the field of stress research.
Accumulating evidence demonstrates that exercise plays a key role in stress model and it has become an interesting target for therapeutic intervention[8-9]. Various clinical studies have revealed that exercise improve cognition and mental health[10-11]. Loprinzi PD et al. demonstrated that exercise at 70%–85% of estimated maximum heart rate are effective in enhancing long-term memory function[12]. And abundant animal model further elucidated beneficial effects of exercise on memory function possibly via facilitating local neurogenesis, neurons activity, the excitability of neurons, and so on[13-15]. These molecular studies have elucidated neuron that may be important in the neuroprotective effect of exercise. In addition, as an important material for transmitting information between neurons, neurotransmitter is necessary for the beneficial effect of running on motor skill learning[16]. exercise improve memory by increase dopamine level, in addition to functional recovery in AD and other diseases of the central nervous system[17-18]. No direct study, however, has been elucidated the molecular mechanism connecting exercise and hippocampal neuron on working memory in stress model. The molecular mechanism connecting exercise and dopamine in hippocampus is also lacking.
To determine the regulatory of exercise-related effects on neurotransmitter in stress model, in association with working memory function and hippocampal neuron. We used passive avoid test to evaluate working memory after exercise in stress rat model. Immunofluorescence, ELISA to label NeuN cells and dopamine in the hippocampus, respectively.
Materials and methods
Experimental animals and grouping
Adult male Sprague–Dawley rats (Experimental Animal Center of Peking University, Peaking, China), weighing 200-250 g at the onset of the experiment, were housed in groups of 3 per cage. All experimental protocols have been pre-approved by the Laboratory Animal Ethics Committee in accordance with National Guidance for Animal Experiment. The animal room was maintained on a 12 hour reversed light-dark cycle a with a temperature of 23 ± 2°C, and 30 to 70% humidity.
Rats were allowed one week to habituate to the animal facility. Following 1 week of habituation, rats (n = 24) were enrolled in this study and randomly divided into following 4 groups: control group (Con group, n = 6), stress group (n = 6), exercise and stress group (Exe-stress group, n = 6), exercise group(Exe group, n = 6). The rats in Exe-stress and Exe groups were received 4 weeks treadmill exercise interventions, respectively. Then, the rats in stress group and Exe-stress group were received repeated restraint stress to establish stress model. Next, all rats received behavior test, including open file test and passive avoidance test. Last, hippocampal dopamine level were detected by ELISA. Immunofluorescence was performed to observe the number of the neural cells in hippocampus. Timeline in our study is shown in Fig. 1.