Atoh1 Mediated Disturbance of Neuronal Maturation by Perinatal Hypoxia Induces Cognitive Deficits

Overview

Journal Commun Biol

Specialty Biology

Date 2024 Sep 11

PMID 39261625

Authors

Xin-Yu Cai

Si-Yu Ma

Ming-Hui Tang

Liang Hu

Ke-de Wu

Zhen Zhang

Ya-Qi Zhang

Ye Lin

Nishant Patel

Zhao-Cong Yang

Xu-Ming Mo

Affiliations

Soon will be listed here.

Abstract

Neurodevelopmental disorders are currently one of the major complications faced by patients with congenital heart disease (CHD). Chronic hypoxia in the prenatal and postnatal preoperative brain may be associated with neurological damage and impaired long-term cognitive function, but the exact mechanisms are unknown. In this study, we find that delayed neuronal migration and impaired synaptic development are attributed to altered Atoh1 under chronic hypoxia. This is due to the fact that excessive Atoh1 facilitates expression of Kif21b, which causes excess in free-state α-tubulin, leading to disrupted microtubule dynamic stability. Furthermore, the delay in neonatal brain maturation induces cognitive disabilities in adult mice. Then, by down-regulating Atoh1 we alleviate the impairment of cell migration and synaptic development, improving the cognitive behavior of mice to some extent. Taken together, our work unveil that Atoh1 may be one of the targets to ameliorate hypoxia-induced neurodevelopmental disabilities and cognitive impairment in CHD.

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