Astroglial Calcium Signaling in Aging and Alzheimer's Disease

Astrocytes are the homeostatic and protective cells of the central nervous system (CNS).In neurological diseases, astrocytes undergo complex changes, which are subclassified into (1) reactive astrogliosis, an evolutionary conserved defensive rearrangement of cellular phenotype aimed at neuroprotection; (2) pathological remodeling, when astrocytes acquire new features driving pathology; and (3) astrodegeneration, which is manifested by astroglial atrophy and loss of homeostatic functions.In aging brains as well as in the brains affected by Alzheimer's disease (AD), astrocytes acquire both atrophic and reactive phenotypes in a region-and disease-stage-dependent manner.Prevalence of atrophy overreactivity, observed in certain brain regions and in terminal stages of the disease, arguably facilitates the development of neurological deficits.Astrocytes exhibit ionic excitability mediated by changes in intracellular concentration of ions, most importantly of Ca 2+ and Na + , with intracellular ion dynamics triggered by the activity of neural networks.AD astrocytes associated with senile plaques demonstrate Ca 2+ hyperactivity in the form of aberrant Ca 2+ oscillations and pathological long-range Ca 2+ waves.Astroglial Ca 2+ signaling originating from Ca 2+ release from the endoplasmic reticulum is a key factor in initiating astrogliotic response; deficient Ca 2+ signaling toolkits observed in entorhinal and prefrontal cortices of AD model animals may account for vulnerability of these regions to the pathology. THE BRAIN AGINGT he cellular mechanisms of aging in general, and of brain aging in particular, remain controversial; many hypotheses have been proposed, while no unifying theory has been agreed upon.Brain senescence(definition) is associated with a progressive loss of function with deficits in learning and memory, and yet, surprisingly, the healthy brain withstands the process of aging remark-ably better than other organs and systems.Indeed, the physical fitness of youth cannot be matched even at middle age, when the cognitive capabilities are reaching their zenith.Indeed, brain cognitive capacity lasts well into advanced age.This bright scenario of extended cognitive capacity, however, is not universal because aging is the chief risk factor for the development of neurodegenerative pathologies that invariably end in senile dementia characterized by severe