Abstract:
In vascular dementia (VD), memory impairment caused by the damage of
synaptic plasticity is the most prominent feature that afflicts patients
and their families. Treadmill exercise has proven beneficial for memory
by enhancing synaptic plasticity in animal models including stroke,
dementia, and mental disorders.
The aim of this study was to
examine the effects of treadmill exercise on recognition memory, and
structural synaptic plasticity in VD rat model. Here, our study
demonstrated that VD rat exhibited significantly recognition impairment,
while treadmill exercise improved recognition memory in VD rat. To
further investigate potential mechanisms for the treadmill
exercise-induced improvement of recognition memory, we examined
hippocampal structural synaptic plasticity by means of transmission
electron microscopy and golgi staining in VD rat that had undergone 4
weeks of treadmill exercise. The results demonstrated that VD rat causes
the damage of structural synaptic plasticity. However, treadmill
exercise led to increases in synapse numbers and the number of dendritic
spines in VD rat. Together, the improvement of VD-associated recognition
memory by treadmill exercises is associated with enhanced structural
synaptic plasticity in VD rat model.
Keywords: Treadmill exercise; VD; Recognition memory;
Structural synaptic plasticity.
Introduction
Vascular dementia (VD) is considered to be the second most common form
of dementia after alzheimer’s disease (AD) and accounts for at least
20% of dementia cases[1-2]. VD may be caused by
cerebrovascular disease, including ischemic or hemorrhagic stroke, and
hypoperfusion ischemic brain injury due to cardiovascular and
circulatory disorders[3]. The persistent and
irreversible memory impairment in VD patients leads to a serious
deterioration in quality of life and places a heavy economic burden on
the families of patients[4-5]. Together with the
increasing age of the population and improved survival rates from
cardiovascular diseases, VD may affect more individuals in the
future[6]. Therefore, prevention and treatment of
VD is increasingly important at home and abroad, especially in countries
with aging populations. It was mentioned as early as 1980’s that VD at
present may be more amenable to prevention and treatment than
AD[7]. Until now, many more drugs exerts memory
protective effects in VD patients, including donepezil and tanzhi
granules, targeted the amelioration of cognitive impairment by
inhibiting neuroinflammation and
acetylcholinesterase[8]. But the drug’s side
effects can include drug dependence and depression.
As a non-pharmacological treatment, physical exercise has proven
beneficial for support brain health and function, including but not
limited to dampen brain inflammation[9], reducing
neuroinflammation[10], and the redistribution of
blood flow and neural activity[11]. Among new
therapeutic strategies being pursued to minimize cognitive damage,
clinical studies have confirmed that physical exercise is associated
with lower incidence of vascular dementia[12].
Moreover, various animal models
have demonstrated that regular volunteer running or treadmill exercise
all can improve memory function in VD rats, in association with
protected the function of astrocytes[13-14].
However, the molecular mechanism for exercise-improved memory in VD
model remains poorly understood and still need
for further study.
The brain changes throughout life at synaptic levels, including
morphological and physiological changes. Structural synaptic plasticity
is relative with synaptic morphology, which is thought to underlie
higher cognitive processes such as memory storage and
recall[15]. The role of structural synaptic
plasticity between physical exercise and memory function has been
recognized on both animal models and humans. Strong clinical and
experimental evidence support that during exercise, modifications in the
morphology of synaptic generate structural synaptic plasticity changes
that is assumed to underlie enhanced cognitive processes such as memory
function[16-17]. Furthermore, in vivo evidence has
been provided to illustrate the molecular mechanisms of exercise on
memory function possibly via regulating dendritic spine
formation[18] and the ultrastructural morphology
of synapses[19], in addition to memory recovery in
VD[20] and other mental
disease[21]. These findings suggest an important
role for structural synaptic plasticity in the pathogenesis of VD and it
has become an interesting target for therapeutic intervention. However,
whether exercise improve memory function is related with structural
synaptic plasticity still needs to be further explored. Here, the aim of
our present study is to determine the regulatory paradigm of physical
exercise on memory function and structural synaptic plasticity in the
hippocampus under VD model.
Methods
Experimental animals and grouping
Male Sprague-Dawley rats (8 weeks of age) were purchased from Shanghai
SLAC Laboratory Animal Co., Ltd and housed three per cage under normal
light-dark cycle with food and water (Temperature: 22 ± 3°C; Humidity:
40 to 70%). All rats were randomly assigned into four groups (n = 6
each): Control group (C group), vascular dementia group (VD group),
treadmill exercise and vascular dementia group (Exe-VD group), treadmill
exercise and black group (Exe group). Body weight was measured every
three days, and other treatments were performed at designated times
according to the experimental
timeline
(Fig.
1).