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

Biochemical and Biophysical Research Communications

Volume 528, Issue 1, 12 July 2020, Pages 174-178

Author links open overlay panelJunpeiTakahashia1DaisukeYamadaa1YudaiUetaaTakashiIwaibEriKogaaMitsuoTanabebJun-IchiroOkaaAkiyoshiSaitoha

aLaboratory of Pharmacology, Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan

bLaboratory of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8641, Japan

Received 25 March 2020, Accepted 12 April 2020, Available online 29 May 2020.

https://doi.org/10.1016/j.bbrc.2020.04.046Get rights and content

Highlights

•Aβ25–35 decreased hippocampal LTP.

•Oxytocin reversed the Aβ25–35–induced impairment of hippocampal LTP.

•ERK phosphorylation is involved in the effect of oxytocin on LTP.

•Ca2+-permeable AMPA receptors are involved in the effect of oxytocin on LTP.

Abstract

Aim

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.

Methods

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 (Aβ2535) in the absence and presence of oxytocin.

Results

We found that oxytocin reversed the impairment of LTP induced by Aβ2535 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.

Conclusion

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.

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About S. R. Zelenz 119 Articles
S.R. Zelenz has worked in education for 20 years. Working with students from all walks of life, cultures, races, and social diversity, Zelenz’s research in Educational Leadership led to finding a better way to approach learning for students with trauma histories. Many were juvenile offenders, gang members, diagnosed with varying behavioral disorders, or had family histories of violence, murder, or narcissistic parenting. This research could not be effectively accomplished without further understanding: how epigenetic trauma inheritance may be impacting these students; how brain development from trauma may be impacting their behavioral and emotional development; as well as deep understanding of psychology and its varying classifications for behavioral and personality disorders. The goal is to find solutions for changing the conversation and making a real difference for these students. She has also worked with nonprofits of varying focus areas for the last 25 years. Her undergraduate degree in Arts Administration and Music prepared her for managing nonprofits of any size as well as procuring funding so that they can achieve their goals. Pairing her nonprofit background with her education background, she has been able to make a difference for over 200 nonprofits worldwide, written curriculum for schools across the globe, and assisted many arts organizations through performance and management.