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P2‐336: Cognitive impairment induced by beta‐amyloid peptide in mice depends on the NMDA receptor activation and nNOS up‐regulation
Author(s) -
Bicca Maíra Assunçao,
Figueiredo Cláudia Pinto,
Passos Giselle Fazzioni,
Joaquim Yuri Assunção,
Meotti Flávia Carla,
Prediger Rui Daniel,
Medeiros Rodrigo,
Calixto João Batista
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.1387
Subject(s) - synaptophysin , nmda receptor , morris water navigation task , hippocampus , neurotoxicity , open field , glutamate receptor , dizocilpine , antagonist , glutamatergic , amyloid beta , oxidative stress , pharmacology , receptor , medicine , neuroscience , endocrinology , psychology , immunohistochemistry , toxicity , disease
In addition, the sensitized ER calcium source has a lower threshold for being triggered by calcium entry through other calcium-permeable channels in the synapse, such as glutamatergic NMDA receptors. This leads to a supra-additive calcium response upon concurrent activation of calcium channels on the plasma membrane with intracellular calcium stores in the AD mice. This localized feed-forward calcium dynamic in synaptic regions may underlie the deficits in plasticity that are also observed in the AD mice, particularly in long term depression and calcineurin activity. Conclusions: Based on the calcium imaging, electrophysiological, and molecular data, we conclude that the early and profound dysregulations in calcium dynamics are a significant factor in synaptic breakdown and are likely linked to AD cognitive deficits. The most profound calcium increases occur in dendritic spines heads and distal processes, which are sites of dense excitatory synaptic contacts in the cortex and hippocampus, and therefore alter synaptic transmission, plasticity mechanisms and synaptic structural integrity. Novel therapeutic opportunities targeting mechanisms of memory impairment can arise from normalizing this calcium dysregulation.