Although learning and memory decline are associated with aging, some older individuals show high cognitive function. The mechanism underlying successful aging is not clear, although augmented N-methyl-D-aspartate receptor-independent long-term depression (LTD) has been found in successfully aged rats. We hypothesized that metabotropic glutamate receptor dependent LTD (mGluR-LTD) is associated with successful aging in mice and explored its molecular mechanisms. We divided aged mice into impaired and unimpaired groups and examined mGluR-LTD in the hippocampus. We examined the role of hydrogen sulfide (H2S) in mGluR-LTD establishment in aged mice and investigated the requirement of protein synthesis and intracellular calcium levels. We assessed learning and memory of mice treated with sodium hydrogen sulfide (NaHS) using behavior tests. We found that unimpaired mice elicited larger mGluR-LTD that correlated with H2S production which was blocked by inhibiting cystathionine synthase. Enhanced H2S production of NaHS treatment augmented mGluR-LTD in impaired group. mGluR-LTD establishment required protein synthesis, as well as intracellular calcium, although NaHS treatment leads to reduced sensitivity to calcium chelator 1,2-bis(o-amino phenoxy)ethane-N,N,N',N'-tetraacetic acid treatment. Finally, we found that NaHS treatment enhanced learning and memory of aged mice as indicated by behavioral assessments. Our results indicate that successful aging mice are associated with the function of H2S.
Keywords: cognition; cystathionine β-synthase; hydrogen sulfide; long-term depression; successful aging.