Fig. 6. Exercise rescued spine density caused by VD. A). Representative
hippocampus microphotographs of the spines on secondary dendrites of
neurons in each group. B). Number of spine per 10μm in each group.#P<0.05 vs. C group;*P<0.05 vs. VD group.
Discussion
Our study aimed at understanding the link between exercise and AD have
focused on structural synaptic plasticity. In this study, we used
recognition memory test coupled with transmission electron microscope
and golgi staining methods to track dynamics of structural synaptic in
the hippocampus after treadmill exercise on VD rat. We found that the
restore of synaptic ultrastructure and spine density in the hippocampus
with exercise, in additional to improved recognition memory in VD model.
Our findings suggest that strengthening structural synaptic plasticity
may represent a potential mechanism by which treadmill exercise prevents
impairment of recognition memory in VD model.
In our study, we first found that the discrimination index in VD rats
was significantly lesser than control rats when exposed to the novel
object 5 minutes and 24 hours after they were familiarized with an
identical set of objects. As the disease progresses, patients experience
progressive memory loss and emotional disorder in
daily life, including communication disorder and
anxiety[28-29]. In vivo study also confirms
impaired discrimination index in recognition memory
test[30], which is one of the most common
paradigms to assess hippocampal-dependent memory, including short-term
recognition memory and long-term recognition
memory[31]. In general, short-term memory only
refers to the short-term storage of information, whereas long-term
memories are required for remembering
information[32]. In addition, we also provided
vivo evidence that VD rats have a mild anxiety in open field test. It
was consisted with clinical investigations. Thus, we demonstrated that
the impairment of recognition memory and anxiety-like behavior in VD
progression. Furthermore, our study also revealed that treadmill
exercise rescued recognition memory impairment and
anxiety-like
behavior in VD model in the recognition memory test. This result was
consisted with previous studies[33-34]. Taken
together, VD rats exhibited impairment recognition memory, and the
robust decrease of recognition memory errors under the recognition
memory test indicate that treadmill exercise pretreatments prevent
decline in recognition memory in the VD rat model.
Next, we examined the potential mechanisms that might underline the
treadmill exercise-induced improvement of recognition memory function in
VD rats. It has been suggested that hippocampal structural synaptic
plasticity constitutes the cellular basis of learning and memory, which
requires the connections of synapses[35]. Our
results showed decreased synapse numbers in the hippocamps of VD rats.
In normal state, presynaptic terminal secretes memory-related substances
via a canonical release machinery, while postsynaptic specialization
senses substances via diverse receptors[36].
Therefore, the changes of synapse of synapse number are bound to affect
synaptic structural plasticity. The study performed by Huang Y et al. on
a murine model of vascular dementia by HE staining further indicate that
significantly neuronal damage in the hippocampal of VD
rat[37]. In this study, we also found that
treadmill exercise led to an increase in the hippocampal synapse numbers
of VD rats. Meanwhile, treadmill exercise increased the synapse numbers
in the hippocampus in control group. The form and rearrange synapses
under exercise is associated with enhancement of structural synaptic
plasticity. Animal studies showed that exercise-induced enhancement of
structural synaptic plasticity by regulating synaptic formation and
rearrangement in normal states[38-39]. Thus, our
study shed some light on the increase of synapse number by exercise that
could be effective in exerting beneficial effects in VD rats.
Axons, dendrites, and dendritic spines constitute the structural basis
of synaptic plasticity. The axon is functionally specialized to transmit
signals, whereas the dendrites are specialized to receive
signals[40]. In vivo imaging by FJB staining
revealed that impaired of axonal and dendritic in the hippocampus after
vascular dementia[41]. Dendritic spines are
specialized postsynaptic structures that transduce presynaptic signals,
are regulated by neural activity and correlated with learning and
memory[42]. Our findings supported that the spine
numbers of hippocampus were significantly decreased in the VD group
compared to the control group. A review by Frankfurt M et al. reported
that strong relationship between dendritic spine in the hippocampus and
memory has been demonstrated in different spatial memory
tasks[43]. Our study further revealed that
treadmill exercise increased the spine numbers of hippocampus in VD
rats.
It is likely that treadmill exercise pretreatment potentiates synaptic
connections via an increase in dendritic spines under normal and
dementia conditions[35, 44]. Such mechanisms might
explain why treadmill exercise ameliorates the impairment of recognition
memory in VD rat model.
In summary, treadmill exercise improved recognition memory, which can be
contributed to the enhancement of hippocampal synapses number and
dendritic spine density in VD rats. Our results collectively establish
the central role of structural synaptic plasticity for neural network
adaptations to exercises and provide more evidence for clinical
intervention of memory deficits using exercise interventions.
Conclusions
Strengthening structural synaptic plasticity may represent a potential
mechanism by which treadmill exercise prevents decline in recognition
memory and synapse loss in 2-VO induced VD rat model.