Oxytocin reverses Aβ-induced impairment of hippocampal synaptic plasticity in mice

Oxytocin, a peptide hormone synthesized in the hypothalamic paraventricular nucleus, has been reported to participate in the regulation of learning and memory performance. However, no report has demonstrated the effect of oxytocin on the amyloid-beta (Aβ)-induced impairment of synaptic plasticity. In this study, we examined the effects of oxytocin on the Aβ-induced impairment of synaptic plasticity in mice.

To investigate the effect of oxytocin on synaptic plasticity, we prepared acute hippocampal slices for extracellular recording and assessed long-term potentiation (LTP) with perfusion of the Aβ active fragment (Aβ_25-35) in the absence and presence of oxytocin.

We found that oxytocin reversed the impairment of LTP induced by Aβ_25-35 perfusion in the mouse hippocampus. These effects were blocked by pretreatment with the selective oxytocin receptor antagonist L-368,899. Furthermore, the treatment with the ERK inhibitor U0126 and selective Ca²⁺-permeable AMPA receptor antagonist NASPM completely antagonized the effects of oxytocin.

This is the first report to demonstrate that oxytocin could reverse the effects of Aβ on hippocampal LTP in mice. We propose that ERK phosphorylation and Ca²⁺-permeable AMPA receptors are involved in this effect of oxytocin.