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  1. Pubblicazioni

Long-Term Dynamic Changes of NMDA Receptors Following an Excitotoxic Challenge

Articolo
Data di Pubblicazione:
2022
Abstract:
Excitotoxicity is a form of neuronal death characterized by the sustained activation of N-methyl-D-aspartate receptors (NMDARs) triggered by the excitatory neurotransmitter glutamate. NADPH-diaphorase neurons (also known as nNOS (+) neurons) are a subpopulation of aspiny interneurons, largely spared following excitotoxic challenges. Unlike nNOS (−) cells, nNOS (+) neurons fail to generate reactive oxygen species in response to NMDAR activation, a critical divergent step in the excitotoxic cascade. However, additional mechanisms underlying the reduced vulnerability of nNOS (+) neurons to NMDAR-driven neuronal death have not been explored. Using functional, genetic, and molecular analysis in striatal cultures, we indicate that nNOS (+) neurons possess distinct NMDAR properties. These specific features are primarily driven by the peculiar redox milieu of this subpopulation. In addition, we found that nNOS (+) neurons exposed to a pharmacological maneuver set to mimic chronic excitotoxicity alter their responses to NMDAR-mediated challenges. These findings suggest the presence of mechanisms providing long-term dynamic regulation of NMDARs that can have critical implications in neurotoxic settings.
Tipologia CRIS:
1.1 Articolo in rivista
Keywords:
Calcium; Excitotoxicity; NADPH diaphorase; Neurodegeneration; Nitric oxide synthase; Reactive oxygen species; Cell Death; Corpus Striatum; Glutamic Acid; Neurons; Receptors, N-Methyl-D-Aspartate
Elenco autori:
Granzotto, A.; D'Aurora, M.; Bomba, M.; Gatta, V.; Onofrj, M.; Sensi, S. L.
Autori di Ateneo:
BOMBA Manuela
GATTA Valentina
GRANZOTTO ALBERTO
SENSI Stefano
Link alla scheda completa:
https://ricerca.unich.it/handle/11564/777890
Link al Full Text:
https://ricerca.unich.it//retrieve/handle/11564/777890/312262/cells-11-00911.pdf
Pubblicato in:
CELLS
Journal
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URL

https://www.mdpi.com/2073-4409/11/5/911
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