Activation of NLRP3-Caspase-1 pathway contributes to age-related impairments in cognitive function and synaptic plasticity.

Abstract

Aging is characterized by a progressive deterioration in physiological functions that is associated with cognitive decline as well as other physical functional impairments. Microglia activation leading to neuroinflammation has been generally recognized as playing a critical role in the development of age-related cognitive decline. NLRP3 inflammasome in microglia is fundamental for IL-1β maturation and subsequent inflammatory events. However, it remains unknown whether NLRP3 activation contributes to aging-induced cognitive decline in vivo. Here, our study demonstrated that aging rats showed declined cognitive function and impaired synaptic plasticity as well as decreased density of dendritic spines. Importantly, our data demonstrated strongly enhanced expression of NLRP3, ASC and Caspase-1 in the hippocampus of aged rats as well as decreased AMPA receptor and phosphorylated levels of CaMKII and CREB in the hippocampus of natural aging rats. Furthermore, NLRP3 inflammasome inhibitor elevated the surface expression of AMPA receptor and the phosphorylated levels of CaMKII, CREB in hippocampus, and finally contributed to the attenuation of hippocampal long-term potentiation (LTP) deficits and the improvement of cognitive decline of natural aging rats. These results revealed an important role for the NLRP3-Caspase-1 pathway in aging-induced cognitive decline and suggested that inhibition of NLRP3 inflammasome represented a novel therapeutic intervention for aging-related cognitive impairment.

• Authors: Ting Wang, Bo Ruan, Jinxin Wang, Zhiyong Zhou, Xulan Zhang, Changcheng Zhang, Haixia Zhao, Yuanjian Yang, Ding Yuan
• Journal: Neurochemistry international (Neurochem Int) Vol. 152 Pg. 105220 (01 2022) ISSN: 1872-9754 [Electronic] England
• PMID: 34743016 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021. Published by Elsevier Ltd.

Chemical References

• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, rat
• Caspase 1

Topics

• Aging (physiology)
• Animals
• Caspase 1 (metabolism)
• Cognition (physiology)
• Cognitive Dysfunction (metabolism)
• Inflammasomes (metabolism)
• Long-Term Potentiation (physiology)
• Microglia (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Neuronal Plasticity (physiology)