Linked Life Data

11739583

Source:http://linkedlifedata.com/resource/pubmed/id/11739583

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2001-12-12
pubmed:abstractText
Considerable evidence supports a Ca(2+) dysregulation hypothesis of brain aging and Alzheimer's disease. However, it is still not known whether (1) intracellular [Ca(2+)](i) is altered in aged brain neurons during synaptically activated neuronal activity; (2) altered [Ca(2+)](i) is directly correlated with impaired neuronal plasticity; or (3) the previously observed age-related increase in L-type voltage-sensitive Ca(2+) channel (L-VSCC) density in hippocampal neurons is sufficient to impair synaptic plasticity. Here, we used confocal microscopy to image [Ca(2+)](i) in single CA1 neurons in hippocampal slices of young-adult and aged rats during repetitive synaptic activation. Simultaneously, we recorded intracellular EPSP frequency facilitation (FF), a form of short-term synaptic plasticity that is impaired with aging and inversely correlated with cognitive function. Resting [Ca(2+)](i) did not differ clearly with age. Greater elevation of somatic [Ca(2+)](i) and greater depression of FF developed in aged neurons during 20 sec trains of 7 Hz synaptic activation, but only if the activation triggered repetitive action potentials for several seconds. Elevated [Ca(2+)](i) and FF also were negatively correlated in individual aged neurons. In addition, the selective L-VSCC agonist Bay K8644 increased the afterhyperpolarization and mimicked the depressive effects of aging on FF in young-adult neurons. Thus, during physiologically relevant firing patterns in aging neurons, postsynaptic Ca(2+) elevation is closely associated with altered neuronal plasticity. Moreover, selectively increasing postsynaptic L-VSCC activity, as occurs in aging, negatively regulated a form of short-term plasticity that enhances synaptic throughput. Together, the results elucidate novel processes that may contribute to impaired cognitive function in aging.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9744-56
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11739583-3-Pyridinecarboxylic acid..., pubmed-meshheading:11739583-Action Potentials, pubmed-meshheading:11739583-Aging, pubmed-meshheading:11739583-Animals, pubmed-meshheading:11739583-Calcium, pubmed-meshheading:11739583-Calcium Channel Agonists, pubmed-meshheading:11739583-Calcium Channels, L-Type, pubmed-meshheading:11739583-Dendrites, pubmed-meshheading:11739583-Electric Stimulation, pubmed-meshheading:11739583-Excitatory Postsynaptic Potentials, pubmed-meshheading:11739583-Fluorescent Dyes, pubmed-meshheading:11739583-Hippocampus, pubmed-meshheading:11739583-Intracellular Fluid, pubmed-meshheading:11739583-Male, pubmed-meshheading:11739583-Microscopy, Confocal, pubmed-meshheading:11739583-Neuronal Plasticity, pubmed-meshheading:11739583-Neurons, pubmed-meshheading:11739583-Patch-Clamp Techniques, pubmed-meshheading:11739583-Rats, pubmed-meshheading:11739583-Rats, Inbred F344, pubmed-meshheading:11739583-Synapses
pubmed:year
2001
pubmed:articleTitle
Elevated postsynaptic [Ca2+]i and L-type calcium channel activity in aged hippocampal neurons: relationship to impaired synaptic plasticity.
pubmed:affiliation
Department of Molecular and Biomedical Pharmacology, MS-307 University of Kentucky College of Medicine, Lexington, Kentucky 40536-0298, USA. othibau@uky.edu
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S.