title: Calcium buffering systems and calcium signaling in aged rat basal forebrain neurons.
abstract: Disturbances of neuronal Ca2+ homeostasis are considered to be important determinants of age-related cognitive impairment. Cholinergic neurons of the basal forebrain (BF) are principal targets of decline associated with aging and dementia. During the last several years, we have attempted to link these concepts in a rat model of 'normal' aging. In this review, we will describe some changes that we have observed in Ca2+ signaling of aged BF neurons and the reversal of one of these changes by dietary caloric restriction. Our evidence supports a scenario in which subtle changes in the properties of voltage-gated Ca2+ channels result in increased Ca2+ influx during aging. This increased Ca2+, in turn, triggers an increase in rapid Ca2+ buffering in the somatic compartment of aged BF neurons. However, this nominal 'compensation', along with other changes in Ca2+ handling machinery (notably mitochondria) alters the Ca2+ signal with age in a way that is dependent on the magnitude of the Ca2+ load. By combining whole-cell patch clamp electrophysiology, ratiometric Ca2+-sensitive microfluorimetry and single-cell reverse transcription-polymerase chain reaction, we have determined that age-related rapid buffering changes are present in identified cholinergic BF neurons and that these changes can be prevented by a caloric restriction dietary regimen. Because caloric restriction extends lifespan and retards the progression of age-related dysfunction, these findings suggest that increased Ca2+ buffering in cholinergic neurons may be relevant to cognitive decline during normal aging. Importantly, calcium homeostatic mechanisms of BF cholinergic neurons are amenable to dietary interventions that could promote cognitive health during aging.
authors.affiliation: Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University System Health Science Center, College Station, TX 77843-1114, USA.
authors.forename: David
authors.initials: D
authors.lastname: Murchison
authors.forename: William H
authors.initials: WH
authors.lastname: Griffith
mesh_terms: D000375:Aging; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D031204:Caloric Restriction; D003071:Cognition; D004594:Electrophysiology; D008959:Models, Neurological; D009474:Neurons / Q000378:metabolism*; D016548:Prosencephalon / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D002118:Calcium