Accéder au contenu
Merck

Neuronal activation of Gαq EGL-30/GNAQ late in life rejuvenates cognition across species.

Cell reports (2023-09-15)
Morgan E Stevenson, Gregor Bieri, Rachel Kaletsky, Jonathan St Ange, L Remesal, Karishma J B Pratt, Shiyi Zhou, Yifei Weng, Coleen T Murphy, Saul A Villeda
RÉSUMÉ

Loss of cognitive function with age is devastating. EGL-30/GNAQ and Gαq signaling pathways are highly conserved between C. elegans and mammals, and murine Gnaq is enriched in hippocampal neurons and declines with age. We found that activation of EGL-30 in aged worms triples memory span, and GNAQ gain of function significantly improved memory in aged mice: GNAQ(gf) in hippocampal neurons of 24-month-old mice (equivalent to 70- to 80-year-old humans) rescued age-related impairments in well-being and memory. Single-nucleus RNA sequencing revealed increased expression of genes regulating synaptic function, axon guidance, and memory in GNAQ-treated mice, and worm orthologs of these genes were required for long-term memory extension in worms. These experiments demonstrate that C. elegans is a powerful model to identify mammalian regulators of memory, leading to the identification of a pathway that improves memory in extremely old mice. To our knowledge, this is the oldest age at which an intervention has improved age-related cognitive decline.

MATÉRIAUX
Référence du produit
Marque
Description du produit

Sigma-Aldrich
5-Fluoro-2′-désoxyuridine, thymidylate synthase inhibitor
Sigma-Aldrich
Anti-MAP2 (2a+2b) antibody, Mouse monoclonal, clone AP-20, ascites fluid
Sigma-Aldrich
Monoclonal Anti-PSD95 antibody produced in mouse, clone 7E3-1B8, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Anti-Mouse IgG (H+L), highly cross-adsorbed, CF 647 antibody produced in donkey, ~2 mg/mL, affinity isolated antibody
Sigma-Aldrich
Anti-Rabbit IgG (H+L), highly cross-adsorbed, CF 555 antibody produced in donkey, ~2 mg/mL, affinity isolated antibody