Study on the Motor-dependent Plasticity of Dendritic Spines of Striatal Medium Spiny Neurons in PD Model Rats
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Graphical Abstract
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Abstract
Objective:To reveal the target cells of striatum MSNs plasticity depending on exercise in PD model rats.MethodsHeanth adult SD rats were randomly divided into three groups:sham operation group (Con),PD group (PD) and PD with exercise group(PD+Ex).6-Hydroxydopamine (6-OHDA) was injected into the medial forebrain bundle (MFB) of the right brain to induce PD model of unilateral injury in rats.The sham-operation group was received the same dose of saline as the control group.The reliability of the model was evaluated by apomorphine (APO)-induced rotational behavior test combined with immunohistochemica staining of the substantial nigra and tyrosine 3-monooxygenase striatum.In the exercise group,treadmill training (11 m/min,30 min day,5days/week,4weeks) was performed at 1 week after operation.Free locomotor activity was evaluated by open field test,D1-MNs and D2-MSNs of striatum were labeled by retrograde neural tracing and fluorescein labeling the expression of streptolysin(Syn) and streptolysin (PSD-95) in striatum were detected by Western Blotting.Results:The results of APO-induced rotation behavior test and TH immunohistochemical test showed that PD model rats were reliable and the molding rate was 75%.In the pole test,the delay time of climbing from pole top to bottom was longer in PD group compared with control group (P<0.01);compared with PD group,the delay time of climbing from pole top to bottom was decreased significantly in PD+Ex group (P<0.05).The results of retrograde nerve tracing combined with fluorescein labeling showed that the density of dendritic spines in D1-MSNs was not changed obviously in PD and PD+Ex group than that of control group,but the density of dendritic spines in D2-MSNs of PD group was decreased compared with control group (P<0.01);in addition,the density of dendritic spines in D2-MSNs of PD+Ex group was increased compared with PD group (P<0.05).Western Blotting results showed that the expression level of PSD-95 and Syn protein in striatum of PD group were decreased compared with control group (P<0.01).The expression level of PSD-95 and Syn protein of PD+Ex group were increased compared with PD group (P<0.05).Conclusion:The loss of D2-MSNs dendritic spine in striatum of PD model rats were selectively alleviated by treadmill exercise intervention.Exercise promotes the morphological and structural remodeling of MSNs in the striatum of PD model rats by up-regulating the expression of synaptophysin.The movementdependent plasticity of striatal MSNs dendritic spines provides a necessary anatomical basis for the improvement of motor dysfunction in PD model rats.
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