The Effects Of ROCK-ERK1/2Passway On Synaptic Structure And Function In Hippocampus Of A Streptozotocin-treated Rat Model

ObjectivesThis study discusses the relationship between synapse and AD as well as the molecular mechanisms about Streptozotocin’s beneficial effect to AD through observing the spatial learning/memory, the ultramicrostructure of CA1area, the changed expression of extracellular signal-regulated kinase1/2(ERK1/2) in hippocampus of intracerebral Streptozotocin injected rat and fasudil hydrochloride’s effect to these factors. These provide theoretical for elucidating the pathogenesy of AD and finding effective medicine to treating AD.Methods1. Grouping and building model:Thirty-six Sprague-Dawley rats were randomly divided into the control, STZ (streptozotocin-treated) and FH(fasudil treatment) groups. Rats in the STZ and FH groups received two divided doses of STZ (1.5mg/kg) intracerebroventricularly (ICV) on days1and3, whereas control group rats were given citric acid/sodium citrate buffer. Rats in the FH group were then treated intraperitoneally with FH (10mg/kg) for4weeks, and rats in the STZ and control groups were treated with saline.2. Experimental observation of animal behavior:Morris water maze test was used to measure learning and memory fuction after4weeks 3. After Morris maze test at the6th day, six Animals in each group were decapitated rapidly. Took the brain stem from rat and stored them in negative80degrees refrigerator. Another six were Perfusion fixed.4. The synaptic ultrastructure in the CA1region of the hippocampus was observed using electronic microscopy. The activation of ERK1/2was detected using western blot analysis.Results1. Behavioral performance:Comparing with control and FH groups, the STZ group showed typical signs of learning/memory deterioration in that escape latency was prolonged (days2-5), the number of crossings of the target area decreased and the time spent in the target quadrant was shorter(P<0.05).The statistics has no difference between control and FH groups(P>0.05).2. Electron microscopy:In the hippocampal CA1region of the rats in STZ group, the number of synapse reduced apparently along with the thickness of PSD, In addition, the width of synaptic cleft remarkably increased and the length of synaptic appositions shortened(P<0.05). But FH can reverse these pathological change of the synaptic interface(P<0.05). The statistics has no difference between control and FH groups(P>0.05).3. The activity of ERK1/2in the hippocampus of the rats in STZ group was much higher than it in the control group and FH group(P<0.05). the administration of FH decreased the activation of ERK1/2(P<0.05).The statistics has no difference between control and FH groups(P>0.05).Conclusions1. ICV STZ injection existed cognitive disorder may through the impairment of synapse in the hippocampus partly induced by abnormally activating of ERK1/2.2. Treatment with FH could protect the synaptic structure and attenuate the cognitive impairment.These may related to its ability of alleviating ERK1/2excessive activation.