D-Cycloserine ameliorates innate fear deficits in young adult male APP/PS1 mice: Involvement of GluN2B-containing NMDA receptor.

Authors

Bin Zhang, Zheye Wang, Xinjie Zhao, Jiaqi Zhu, Yutong Zhang, Yifei Wang, Jialu Yang, Jiaqi Cheng, Xinyi Yang, Feng Zhu, Weida Shen, Wen Lu

Published in

Pharmacology, biochemistry, and behavior. Pages 174272. Sep 19, 2026. Epub Sep 19, 2026.

Abstract

Neuropsychiatric symptoms can emerge early in Alzheimer's disease (AD), but whether innate fear is altered prior to amyloid plaque deposition remains unclear. This study aimed to examine innate fear responses in young adult male APP/PS1 mice and to evaluate whether D-cycloserine (DCS) rescues such deficits via GluN2B-containing NMDA receptors. Male APP/PS1 mice (2-3 months old) exhibited impaired innate fear responses in the looming disk test, while their motor function and contextual fear memory remained intact. Hippocampal Grin2b expression was reduced in the APP/PS1 mice. DCS restored normal fear responses, an effect blocked by GluN2B antagonists but unaffected by GluN2A inhibition. Our results demonstrate that innate fear deficits emerge early in male APP/PS1 mice and are rescued by DCS through activation of hippocampal GluN2B-containing NMDA receptor, highlighting a potential target for early AD-related neuropsychiatric symptoms.

PMID:
42763022
Bibliographic data and abstract were imported from PubMed on 20 Sep 2026.

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