To examine the effect of DBS of the lateral hypothalamic area (LHA) on age-related memory changes, neuronal firing from CA1, oxidative stress, and the expression of Hsp70, BDNF, and synaptophysin. 72 male rats were randomly allocated into 6 equal groups: a) normal young group (8 W), b) sham young group, c) DBS young group, d) normal old group (24 months), e) sham old group and f) DBS old group. Memory tests (passive avoidance and Y maze), oxidative stress markers (MDA, catalase, and GSH) and expression of Nrf2, HO-1, Hsp70, BDNF, and synaptophysin were measured by the end of the experiment. Also, in vivo recording of the neuronal firing of the CA1 region in the hippocampus was done. Old rats show significant decline in memories, antioxidant genes (Nrf2 and HO-1), antioxidants (GSH and catalase), Hsp70, BDNF, and synaptophysin with significant increase in MDA in hippocampus (p <
0.05) and DBS for LHA caused a significant improvement in memories in old rats, with significant rise in fast gamma and theta waves in CA1 region in old rats (p <
0.05). This was associated with a significant increase in antioxidants (GSH and CAT), antioxidant genes (Nrf2, HO-1), Hsp70, BDNF, and synaptophysin with significant reduction in MDA in hippocampus (p <
0.05). DBS for LHA ameliorates the age-induced memory decline. This might be due to increase in fast gamma in CA1, attenuation of oxidative stress, upregulation of Nrf2, HO-1, Hsp70, BDNF, and synaptophysin in the hippocampus.