Interfering Spastin Expression In Hippocampus Mediates Cognitive Dysfunction Of Mice By Weakening Synaptic Transmission

AIM:To explore the effect of hereditary spastic paraplegia protein(Spastin)on the cognitive function in mice.METHODS:Stereotactic injection of the recombinant adeno-associated virus vector(r AAV)that interfering the expression of Spastin into the hippocampus CA1 area of C57BL/6 mice.Open field test,elevated plus maze experiment,novel objects recognition experiment and Morris water maze experiment were performed to analyze the behavior of mice that interfere with the expression of Spastin in hippocampal CA1 area.Golgi staining was performed to analyze the morphology hippocampal pyramidal neurons.Brain slice electrophysiology recording was performed to analyze synaptic transmission in hippocampal CA1 neurons.RESULTS:The results of the open open field test showed that the bouts of the experimental group and the control group entered the central area did not differ,and the percentage of time spent in the central area did not differ;The results of the elevated maze test showed the bouts of the experimental group and the control group entered the open arm no difference,no difference in the percentage of time spent in the open arm;the results of the novel object cognition experiment showed that the experimental group of mice had no difference in the exploration time of novel and familiar objects,and the number of explorations did not differ,while and the mice in the control group’s exploration time for novel objects was significantly reduced(P<0.05),and the number of explorations was significantly reduced(P<0.05);In the Morris water maze experiment,the escape latency of mice in the experimental group during the training phase was significantly increased(P<0.05).During the test phase,the duration of mice in the target quadrant was significantly reduced(P<0.05),and the number of crossing the target quadrant was significantly reduced(P<0.05).Similarly during the reverse training phase the escape latency of experimental group was significantly increased(P<0.05),and the mice in the reverse test phase the duration in the target quadrant was significantly reduced(P<0.05),and the number of crossing the target quadrant was significantly reduced(P<0.05);Golgi staining showed that the density both of basal dendritic spines and apical dendritic spines were decreased significantly in mice that interfere with the expression of Spastin in hippocampal CA1 area,mainly due to the reduction of mature dendritic spines(P<0.05).Moreover,the amplitude and frequency of miniature excitatory postsynaptic currents(m EPSC)in CA1 pyramidal cell of mice that interfere with the expression of Spastin in hippocampal CA1 area were reduced(P<0.05).Similarly,the maximum amplitude of evoked-EPSC in CA1 pyramidal cell also reduced and long-term potentiation(LTP)was impaired(P<0.05).CONCLUSION: Knocking down of Spastin in hippocampal CA1 region mediates cognitive dysfunction of mice by inhibiting synaptic transmission.