Oxytocin Attenuates Hypothalamic Injury-induced Cognitive Dysfunction by Inhibiting Hippocampal ERK Signaling and Aβ Deposition

Overview

Journal Transl Psychiatry

Specialties Psychiatry
Public Health

Date 2024 May 25

PMID 38796566

Authors

Guangsen Wu

YiChao Ou

ZhanPeng Feng

Zhiwei Xiong

Kai Li

Mengjie Che

Songtao Qi

Mingfeng Zhou

Affiliations

Soon will be listed here.

Abstract

In clinical settings, tumor compression, trauma, surgical injury, and other types of injury can cause hypothalamic damage, resulting in various types of hypothalamic dysfunction. Impaired release of oxytocin can lead to cognitive impairment and affect prognosis and long-term quality of life after hypothalamic injury. Hypothalamic injury-induced cognitive dysfunction was detected in male animals. Behavioral parameters were measured to assess the characteristics of cognitive dysfunction induced by hypothalamic-pituitary stalk lesions. Brains were collected for high-throughput RNA sequencing and immunostaining to identify pathophysiological changes in hippocampal regions highly associated with cognitive function after injury to corresponding hypothalamic areas. Through transcriptomic analysis, we confirmed the loss of oxytocin neurons after hypothalamic injury and the reversal of hypothalamic-induced cognitive dysfunction after oxytocin supplementation. Furthermore, overactivation of the ERK signaling pathway and β-amyloid deposition in the hippocampal region after hypothalamic injury were observed, and cognitive function was restored after inhibition of ERK signaling pathway overactivation. Our findings suggest that cognitive dysfunction after hypothalamic injury may be caused by ERK hyperphosphorylation in the hippocampal region resulting from a decrease in the number of oxytocin neurons, which in turn causes β-amyloid deposition.

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