Effects Of Sodium Ferulate On Cognitive Function And AD-like Pathology Of Hippocampus In Chronic Cerebral Hypoperfusion Rats

Objective Chronic cerebral hypoperfusion plays an important role in the pathogenesis of Alzheimer’s disease(AD)and vascular dementia(VD).The mechanism of cognitive impairment induced by chronic cerebral hypoperfusion is related not only to the energy metabolism disorder,abnormal neuronal activity,oxidative stress,free radical damage,inflammatory response,but also to amyloid cascade,tau protein pathology and brain-derived neurotrophic factor.Sodium ferulate(SF)is the sodium salt of ferulic acid(FA),which is the main component of Angelica sinensis and other traditional chinese medicine.Its role includes regulating hematopoietic and immune function,inhibiting inflammatory reaction,inhibiting tumor cell proliferation,prevention and treatment of cardiovascular and cerebrovascular diseases.Therefore,in the present study,We observed the effect of sodium ferulate on cognitive function and AD-like pathology of hippocampus in chronic cerebral hypoperfusion rats,for exploring the protective effect of sodium ferulate on cognitive impairment induced by chronic cerebral hypoperfusion and the possible molecular mechanism..Method The rats were randomly divided into three groups:sham operation group(SHAM-NS group),model group(2VO-NS group)and sodium ferulate treatment group(2VO-SF).One week after surgery started drug intervention.The treatment group given 50mg/kg SF intraperitoneal injection,the other two groups were given equal volume of saline.Treatment time is once a day for four weeks.After the end of the intervention,object recognition test and Morris water maze were used to evaluate the recognition memory ability and spatial learning and memory ability of the rats.The morphological changes in hippocampus were observed by HE staining.Aβ40 and Aβ42 in the hippocampus were detected by ELISA.Western blot was used to detect the expression of BACE1,phosphorylated tau protein and tau protein related phosphorylated kinase in hippocampus.Western blot was used to detect the expression of p-ERK1/2,p-CREB,BDNF in three group.Results After 5 weeks of 2VO operation,the recognition memory ability and spacial learning memory ability were impirements,while sodium ferulate can improve the recognition memory and enhance the ability of spatial learning and memory,reduce the damage of hippocampal neurons,decrease the production of Aβ40 and Aβ42,inhibit the hyperphosphorylation of tau protein in hippocampus,accompanied by the expression of BACE1 decreased,tau protein phosphorylation-related protein kinase signaling pathway recovery and brain-derived neurotrophic factor(BDNF)and its upstream signaling molecules expression increased.Conclusion Sodium ferulate can improve learning and memory ability of chronic cerebral hypoperfusion rats,which may be related to the reduction of β-amyloid protein production,the alleviation of tau protein phosphorylation and the increase of BDNF expression.The molecular mechanism is associated with downregulation of BACE1 enzyme expression,recovery of Akt/GSK-3β signaling pathway and upregulation of ERK/CREB/BDNF signaling pathway.Sodium ferulate has a protective effect on the vascular cognitive impairment induced by chronic cerebral hypoperfusion,and its mechanism may be related to the AD-like pathology.