Interplay of MeCP2/REST/Synaptophysin-BDNF and intranasal oxytocin influence on Aβ-induced memory and cognitive impairments.

Background: Alzheimer's disease (AD) is linked to the accumulation of Aβ, increased tau hyperphosphorylation, persistent neuroinflammation, and a decline in neurotrophic factors, neurogenesis, and synaptic plasticity. Oxytocin (OT) has a significant impact on memory and learning. We examined the influence of intranasal (IN) OT on synaptic plasticity, neurogenesis, histone acetylation, and spatial and cognitive memories in rats.

Methods: Aβ (5 µg/2.5 µl) was administered bilaterally in the CA1 of male Wistar rats for four consecutive days. After seven days of recovery, OT (2 µg/µl, 10 µl in each nostril) was administered IN for seven consecutive days. Working, spatial, and cognitive memories, and gene expression of neurogenesis- and synaptic plasticity-involved factors were measured in the hippocampus. Histone acetylation (H3K9 and H4K8) was also measured using western blotting.

Results: IN administration of OT significantly improved working and spatial memory impairment induced by Aβ and increased the factors involved in synaptic plasticity (MeCP2, REST, synaptophysin, and BDNF) and neurogenesis (Ki67 and DCX). We also found an enhancement in the levels of H3K9ac and H4K8ac following OT administration.

Conclusion: These findings indicated that IN OT could improve hippocampus-related behaviors by increasing synaptic plasticity, stimulating neurogenesis, and chromatin plasticity.