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Citrulline supplementation modifies cognitive decline by changes in arginine and nitric oxide levels in a murine model for AD
Author(s) -
Martinez Katia L,
Garcia de la Torre Paola,
Serrano Leonor,
Gutiérrez Eduardo
Publication year - 2020
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 - 10.1002/alz.047305
Subject(s) - arginine , nitric oxide , citrulline , hippocampus , neurodegeneration , medicine , cognitive decline , endocrinology , morris water navigation task , synaptic plasticity , neuroscience , nitric oxide synthase , dementia , psychology , chemistry , biochemistry , disease , amino acid , receptor
Background Alzheimer’s disease (AD) is a neurological disorder defined by progressive and irreversible neurodegeneration of the central nervous system and is the most common cause of dementia in older adults. This disease leads to a gradual decline of cognitive function manifested by memory impairment. The synaptic deregulation starts in the hippocampus and eventually leads to neuronal loss and cognitive impairment, this is mainly due to structural changes involving the accumulation of neuritic β‐amyloid plaques and neurofibrillary tangles (NFT) of the hyperphosphorylated tau protein. In addition to the neuronal injury, new evidence suggests the involvement of the arginine metabolism in AD pathogenesis with a decreased level found in AD patients’ brains. L‐arginine is a semi‐essential amino acid that can be metabolized to form a number of bioactive molecules such as nitric oxide, a gaseous signaling molecule that plays an important role in synaptic plasticity, learning, and memory, and can be a key factor for the stabilization and regulation of the vascular microenvironment Method Hence citrulline supplementation, an arginine precursor, allowed us to study of changes in arginine (by UPLC) and NO (ny the Griess method) levels, as well as changes in cognitive decline (measured by Morris Water Maze task) in a 3xTgAD mouse model. Result Citrulline supplementation at 5 months of age for 3 months, improved long‐term spatial memory in male mice. We found an elevation of arginine levels in CSF from both male and female mice. Finally, we found elevated arginine and nitric oxide levels in brain tissue (hippocampus), Conclusion Citrulline supplementation is a viable early treatment to ameliorate cognitive decline in males from this murine model of AD.