Sodium Hydrosulfide Attenuates Learning And Memory Impairment Induced By β-amyloid 1-42 And Its Underlying Mechanisms In Rats

Objective: This study was designed to investigate the protective effect of sodium hydrosulfide(Na HS) on spatial learning and memory impairment in rats induced by β-amyloid 1-42 petide(Aβ), and further explore the possible underlying mechanisms.Methods: 60 male Sprague-Dawley(SD) rats were randomly divided to 4 groups: sham, sham+Na HS, Aβ, Aβ+Na HS groups. To establish the model with learning and memory impairment, rats in the Aβ-treated groups were injected with Aβ 5 μL(1 μg/μL)into the bilateral hippocampal CA1 regions. Na HS-treated groups were administered with Na HS at the dose of 5 mg/kg, while sham and model were done with volume-matched vehicle, instead. Morris water maze was used to examine the learning and memory ability. HE staining and Nissl staining were performed to observe neuronal morphology in hippocampus. The protein expression of CBS, 3MST, TNF-α, IL-1β, COX-2, IκB-α and the levels of p-NF-κB-p65, p-p38, p-ERK1/2 and p-JNK were detected by Western blot, and the m RNA levels of cystathionine-β-synthase(CBS), 3-mercaptopyruvate sulfurtransferase(3MST), TNF-α, IL-1β and COX-2 m RNA were assayed by real time RT-PCR, respectively.Results: Compared with the sham-control rats, the mean escape latency was dramatically increased in Aβ-treated rats. Morever, the mean number of pyramidal cells and neurons in the Aβ-injected hippocampus was significantly decreased, with concomitant production of TNF-α, IL-1β and COX-2 m RNA and protein. These effects occurred via reduction of H2 S levels and main H2S-producing enzyme CBS and 3MST and activation of phospho-MAPK and phospho-NF-κB p65 in rat’s hippocampus. However, treatment with Na HS clearly decreased the escape latency and significantly enhanced the mean number of pyramidal cells and neurons in the hippocampal regions compared with Aβ treatment rats, withconcomitant inhibitions of expressions of TNF-α, IL-1β and COX-2 m RNA and protein. These effects occurred via repressing H2 S levels and main H2S-producing enzyme CBS and 3MST and activation of p-p38, p-ERK1/2 and p-NF-κB p65 but not p-JNK that occurred in the Aβ-injected hippocampus.Conclusion: Under the experimental conditions, Na HS significantly ameliorates spatial memory impairment induced by Aβ1-42 in rats. The protential mechanisms of the protection may be related with the reduction of proinflammatory cytokines production, with the inhibition of p-p38, p-ERK1/2 and p-NF-κB-p65 activity, as well as the activation of IκB-α, suggesting that Na HS can provide an effective treatment for AD.