Background
Agrin
is a proteoglycan that aggregates nicotinic acetylcholine receptors
(AChRs) on neuromuscular junctions and takes part in synaptogenesis in
the development of the central nervous system. However, its effects on
neural repair and synaptogenesis after stroke are still unclear.
Objective
This
study aimed to investigate the effects of agrin on neural repair and
synaptogenesis after stroke and the effects of exercise on this process
in vivo and in vitro.
Methods
Exercise
with gradually increased intensity was initiated at 1 day after middle
cerebral artery occlusion (MCAO) for a maximum of 14 days. Neurological
deficit scores and foot fault tests were used to assess the behavioral
recovery. Western blotting, immunofluorescence, and electron microscopic
images were used to detect the expression of agrin,
synaptogenesis-related proteins, and synaptic density in vivo. In vitro,
the ischemic neuron model was established via oxygen-glucose
deprivation (OGD). The lentivirus overexpressed agrin and CREB inhibitor
were used to investigate the mechanism by which agrin promoted
synaptogenesis.
Results
Exercise
promoted behavioral recovery and this beneficial role was linked to the
upregulated expression of agrin and increased synaptic density.
Overexpressed agrin promoted synaptogenesis in OGD neuron, CREB
inhibitor downregulated the expression of agrin and hampered
synaptogenesis in cultured neurons.
Conclusions
These
results indicated that exercise post stroke improved the recovery of
behavioral function after stroke. Synaptogenesis was an important and
beneficial factor, and agrin played a critical role in this process and
could be a potential therapeutic target for the treatment of stroke and
other nervous system diseases.
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