Hydrogen Sulfide Prevents Synaptic Plasticity from VD-Induced Damage via Akt/GSK-3β Pathway and Notch Signaling Pathway in Rats

Abstract

Our previous study has demonstrated that hydrogen sulfide (H2S) attenuates neuronal injury induced by vascular dementia (VD) in rats, but the mechanism is still poorly understood. In this study, we aimed to investigate whether the neuroprotection of H2S was associated with synaptic plasticity and try to interpret the potential underlying mechanisms. Adult male Wistar rats were suffered the ligation of bilateral common carotid arteries. At 24 h after surgery, rats were administered intraperitoneally with sodium hydrosulfide (NaHS, 5.6 mg·kg−1·day−1), a H2S donor, for 3 weeks in the VD+NaHS group and treated intraperitoneally with saline in the VD group respectively. Our results demonstrated that NaHS significantly decreased the level of glutamate. It obviously ameliorated cognitive flexibility as well as the spatial learning and memory abilities by Morris water maze. Moreover, NaHS significantly improved the long-term depression (LTD), and was able to elevate the expression of N-methyl-d-aspartate receptor subunit 2A, which plays a pivotal role in synaptic plasticity. Interestingly, NaHS decreased the phosphorylation of Akt, and it could maintain the activity of glycogen synthase kinase-3β (GSK-3β). Surprisingly, NaHS triggered the canonical Notch pathway by increasing expressions of Jagged-1 and Hes-1. These findings suggest that NaHS prevents synaptic plasticity from VD-induced damage partly via Akt/GSK-3β pathway and Notch signaling pathway.Hydrogen sulfide modulated the ratio of NMDAR 2A/2B and improved the synaptic plasticity via Akt/GSK-3β pathway and Notch signaling pathway in VD rats.

Cognitive impairment in a classical rat model of chronic migraine may be due to alterations in hippocampal synaptic plasticity and N-methyl-D-aspartate receptor subunits

“…It has also been shown that selective inhibition of NR2A prevents the induction of LTP without affecting LTD production. 35 In the present study, NR2A levels and the NR2A/NR2B ratio decreased in the IS group, whereas there were no significant difference in NR2B level between the IS and CON groups. These findings are consistent with the results of previous studies.…”

“…However, these subunits have different functions; moreover, NR2A is predominantly confined to the synapses of mature neurons, whereas NR2B is mainly distributed extrasynaptically. 34,35 Liu et al 35 showed that the expression of NR2A, but not NR2B, was markedly decreased in the hippocampus in a rat model of vascular dementia, which indicates that weakened synapses and a reduced capacity for neuronal survival are more related to NR2A than NR2B. It has also been shown that selective inhibition of NR2A prevents the induction of LTP without affecting LTD production.…”

Enriched environment and social isolation affect cognition ability via altering excitatory and inhibitory synaptic density in mice hippocampus

“…After 3 months of treatment, the hippocampus of mouse was separated and stored at -80 °C for the preparation of tissue lysates (n=3). The method of protein extraction was described in our previous studies [30,31]. Each hippocampus was mashed with a grinder and 200 μl lysis buffer (Beyotime Biotechnology, Haimen, China) containing 1% Phenyl methane sulfonyl fluoride (PMSF).…”

Exogenous Hydrogen Sulfide Ameliorates Diabetes-Associated Cognitive Decline by Regulating the Mitochondria-Mediated Apoptotic Pathway and IL-23/IL-17 Expression in db/db Mice

“…It was reported that sodium hydrosulfide attenuated neuroinflammation in beta-amyloid(Aβ)-induced AD models by suppressing the expression of proinflammatory factors in the rat hippocampus [18]. In recent studies, H 2 S improved spatial learning and memory abilities in VD, and the underlying mechanism identified in these studies is the Akt-GSK-3β signalling pathway [19]. Epidemiological studies have shown that the most common form of dementia is AD [20], and that the second most common form dementia is VD [21]; however, the current animal models do not mimic the actual pathophysiological process of DACD.…”