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.