Slow Release of Hydrogen Sulfide in CA1 Hippocampal Neurons Rescues Long-Term Synaptic Plasticity and Associativity in an Amyloid-β Induced Model of Alzheimer’s Disease

Abstract

Background: Impairment of synaptic plasticity along with the formation of amyloid-β (Aβ) plaques and tau-protein neurofibrillary tangles have been associated with Alzheimer’s disease (AD). Earlier studies with rat and mouse hippocampal slices have revealed the association of AD with the absence of synthesis of memory related proteins leading to impairment in cognitive functions. The role of hydrogen sulfide (H2S), a gaseous neurotransmitter, has been gaining attention as a neuroprotective agent. However, its role in AD-like conditions has not been studied so far. Objective: To study the neuroprotective role of H2S in AD conditions using rat hippocampal slices and the organic molecule GYY4137, a slow releasing H2S donor. Methods: Electrophysiological recordings were carried out in rat hippocampal slices to look into the impairment of LTP, a cellular correlate of memory. The Aβ42 peptide was bath-applied to mimic AD-like conditions and checked for both late-LTP and synaptic tagging and capture (STC) mechanisms of the synapses. GYY4137 was applied to look into its neuroprotective role at different stages during the recording of fEPSP. Results: There has been a steady decline in the plasticity properties of the synapses, in the form of late-LTP and STC, after the application of Aβ42 peptide in the hippocampal slices. However, application of GYY4137 rescued these conditions in vitro. Conclusions: GYY4137, with its slow release of H2S, could possibly act as a therapeutic agent in cognitive dysfunctions of the brain, mainly AD.