3′-Daidzein sulfonate sodium protects against memory impairment and hippocampal damage caused by chronic cerebral hypoperfusion

3'-Daidzein sulfonate sodium (DSS) is a new synthetic water-soluble compound derived from daidzein, a soya isoflavone that plays regulatory roles in neurobiology. In this study, we hypothesized that the regulatory role of DSS in neurobiology exhibits therapeutic effects on hippocampal damage and memory impairment. To validate this hypothesis, we established rat models of chronic cerebral hypoperfusion (CCH) by the permanent occlusion of the common carotid arteries using the two-vessel occlusion method. Three weeks after modeling, rat models were intragastrically administered 0.1, 0.2, and 0.4 mg/kg DSS, once a day, for 5 successive weeks. The Morris water maze test was performed to investigate CCH-induced learning and memory deficits. TUNEL assay was used to analyze apoptosis in the hippocampal CAI, CA3 regions and dentate gyrus. Hematoxylin-eosin staining was performed to observe the morphology of neurons in the hippocampal CAI, CA3 regions and dentate gyms. Western blot analysis was performed to investigate the phosphorylation of PICA, ERK1/2 and CREB in the hippocampal PICA/ERK1/2/CFtEB signaling pathway. Results showed that DSS treatment greatly improved the learning and memory deficits of rats with CCH, reduced apoptosis of neurons in the hippocampal CAI, CA3 regions and dentate gyrus, and increased the phosphorylation of PKA, ERK1/2, and CREB in the hippocampus. These findings suggest that DSS protects against CCH-induced memory impairment and hippocampal damage possibly through activating the PKA/ERK1/2/CREB signaling pathway.