Neuropsychiatric disease and treatment · 2021
Inhibition of NOD1 Attenuates Neonatal Hypoxia-Ischemia Induced Long-Term Cognitive Impairments in Mice Through Modulation of Autophagy-Related Proteins.
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Liu Fang, Shao Mingyu, Xu Feng, Rong Fang
Аннотация
BACKGROUND: Autophagy is implicated in neonatal hypoxia-ischemia (HI) induced cognitive impairment. The nucleotide-oligomerizing domain-1 (NOD1), a protein involved in inflammatory responses, has been shown to activate autophagy to promote progression of other diseases. We aimed to investigate whether and how NOD1 is involved in HI-induced brain injury using an HI mouse model.
METHODS: We induced HI in neonatal mice and examined levels of NOD1 and genes associated with autophagy. We then inhibited NOD1 by intracerebroventricular injection of si-NOD1 following HI induction and tested the effects on autophagy, inflammatory responses and long-term behavioral outcomes through Morris water maze and open field tests.
RESULTS: We found that HI induction significantly elevated mRNA levels of NOD1 (3.54 folds change) and autophagy-related genes including Atg5 (3.89 folds change) and Beclin-1 (3.34 folds change). NOD1 inhibition following HI induction suppressed autophagy signaling as well as HI induced proinflammatory cytokine production. Importantly, NOD1 inhibition after HI improved long-term cognitive function, without impacting exploratory and locomotor activities.
CONCLUSION: We show here that NOD1 is involved in the pathogenesis of HI-induced brain injury through modulation of autophagy-related proteins and inflammatory responses. Our findings suggest that NOD1 may be a potent target for developing therapeutic strategies for treating HI-induced brain injury.
METHODS: We induced HI in neonatal mice and examined levels of NOD1 and genes associated with autophagy. We then inhibited NOD1 by intracerebroventricular injection of si-NOD1 following HI induction and tested the effects on autophagy, inflammatory responses and long-term behavioral outcomes through Morris water maze and open field tests.
RESULTS: We found that HI induction significantly elevated mRNA levels of NOD1 (3.54 folds change) and autophagy-related genes including Atg5 (3.89 folds change) and Beclin-1 (3.34 folds change). NOD1 inhibition following HI induction suppressed autophagy signaling as well as HI induced proinflammatory cytokine production. Importantly, NOD1 inhibition after HI improved long-term cognitive function, without impacting exploratory and locomotor activities.
CONCLUSION: We show here that NOD1 is involved in the pathogenesis of HI-induced brain injury through modulation of autophagy-related proteins and inflammatory responses. Our findings suggest that NOD1 may be a potent target for developing therapeutic strategies for treating HI-induced brain injury.