title: Chelation of hippocampal zinc enhances long-term potentiation and synaptic tagging/capture in CA1 pyramidal neurons of aged rats: implications to aging and memory.
abstract: Aging is associated with decline in cognitive functions, prominently in the memory consolidation and association capabilities. Hippocampus plays a crucial role in the formation and maintenance of long-term associative memories, and a significant body of evidence shows that impairments in hippocampal function correlate with aging-related memory loss. A number of studies have implicated alterations in hippocampal synaptic plasticity, such as long-term potentiation (LTP), in age-related cognitive decline although exact mechanisms underlying are not completely clear. Zinc deficiency and the resultant adverse effects on cognition have been well studied. However, the role of excess of zinc in synaptic plasticity, especially in aging, is not addressed well. Here, we have investigated the hippocampal zinc levels and the impairments in synaptic plasticity, such as LTP and synaptic tagging and capture (STC), in the CA1 region of acute hippocampal slices from 82- to 84-week-old male Wistar rats. We report increased zinc levels in the hippocampus of aged rats and also deficits in the tetani-induced and dopaminergic agonist-induced late-LTP and STC. The observed deficits in synaptic plasticity were restored upon chelation of zinc using a cell-permeable chelator. These data suggest that functional plasticity and associativity can be successfully established in aged neural networks by chelating zinc with cell-permeable chelating agents.
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Block MD9, 2 Medical Drive, Singapore, 117 597, Singapore.|Neurobiology/Aging Program, Life Sciences Institute (LSI), National University of Singapore, #04-44, 28 Medical Drive, Singapore, 117 456, Singapore.
authors.forename: Mahesh Shivarama
authors.initials: MS
authors.lastname: Shetty
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Block MD9, 2 Medical Drive, Singapore, 117 597, Singapore.|Neurobiology/Aging Program, Life Sciences Institute (LSI), National University of Singapore, #04-44, 28 Medical Drive, Singapore, 117 456, Singapore.
authors.forename: Mahima
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Block MD9, 2 Medical Drive, Singapore, 117 597, Singapore.|Neurobiology/Aging Program, Life Sciences Institute (LSI), National University of Singapore, #04-44, 28 Medical Drive, Singapore, 117 456, Singapore.
authors.forename: Sreedharan
authors.initials: S
authors.lastname: Sajikumar
mesh_terms: D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology*; D002614:Chelating Agents / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004558:Electric Stimulation; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects*; D014176:Protein Biosynthesis / Q000187:drug effects; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D015032:Zinc / Q000302:isolation & purification*
chemical_list: D002614:Chelating Agents; D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D016194:Receptors, N-Methyl-D-Aspartate; D015032:Zinc
keywords: D1/D5 receptor; aging; dopamine; long-term potentiation; synaptic tagging and capture; zinc