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N-Methyl-D-Aspartate receptor signaling and modulation of NA+,K+-ATPase in klotho hypomorphic mice: effects in hippocampus and cerebellum.

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Marina Minto Cararo
Total Authors: 1
Document type: Master's Dissertation
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas
Defense date:
Examining board members:
Elisa Mitiko Kawamoto Iwashe; Regina Pekelmann Markus; Tatiana Rosado Rosenstock
Advisor: Elisa Mitiko Kawamoto Iwashe

Alterations in N-Methyl-D-Aspartate receptor (NMDAR) are typical features of aging. Nitric oxide synthase (NOS) activation and cyclic GMP (cGMP) production, promoting Na+,K+-ATPase modulation are key events in NMDAR signaling. αKlotho protein has anti-aging function, and mice carrying hypomorph allele for klotho gene (kl-/-) are characterized by systemic and central nervous system (CNS) damage. The aim of this work is to verify whether alterations in NMDAR-NOS-cGMP pathway and in Na+,K+-ATPase occur in the CNS of kl-/- mice. Present data point for an increase in NMDAR phosphorylation, NOS activity and reduction in cGMP levels. In cerebellum, a decrease in NMDAR phosphorylation and NOS activity occur, with no changes in cGMP levels. Both situations are followed by changes in GluN2 subunity expression. Furthermore, we saw a reduction in α2/α3-Na+,K+-ATPase activity in cerebellum, and alterations in α2 and α3 in hippocampus and in cerebellar α2. Data presented support these pathways participation in age related conditions, using kl-/- mice as a model to study CNS damage. (AU)

FAPESP's process: 14/14199-6 - Modulation of Na, K-ATPase through cyclic GMP and nitric oxide pathway in central nervous system of Klotho knockout mice
Grantee:Marina Minto Cararo
Support type: Scholarships in Brazil - Master