title: Differential rescue of spatial memory deficits in aged rats by L-type voltage-dependent calcium channel and ryanodine receptor antagonism.
abstract: Age-associated memory impairments may result as a consequence of neuroinflammatory induction of intracellular calcium (Ca(+2)) dysregulation. Altered L-type voltage-dependent calcium channel (L-VDCC) and ryanodine receptor (RyR) activity may underlie age-associated learning and memory impairments. Various neuroinflammatory markers are associated with increased activity of both L-VDCCs and RyRs, and increased neuroinflammation is associated with normal aging. In vitro, pharmacological blockade of L-VDCCs and RyRs has been shown to be anti-inflammatory. Here, we examined whether pharmacological blockade of L-VDCCs or RyRs with the drugs nimodipine and dantrolene, respectively, could improve spatial memory and reduce age-associated increases in microglia activation. Dantrolene and nimodipine differentially attenuated age-associated spatial memory deficits but were not anti-inflammatory in vivo. Furthermore, RyR gene expression was inversely correlated with spatial memory, highlighting the central role of Ca(+2) dysregulation in age-associated memory deficits.
authors.affiliation: Department of Neuroscience, Ohio State University, Columbus, OH 43210, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Hopp
authors.affiliation: Department of Psychology, Ohio State University, Columbus, OH 43210, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: D'Angelo
authors.affiliation: Department of Neuroscience, Ohio State University, Columbus, OH 43210, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Royer
authors.affiliation: Department of Psychology, Ohio State University, Columbus, OH 43210, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Kaercher
authors.affiliation: Department of Psychology, Ohio State University, Columbus, OH 43210, USA.
authors.forename: L
authors.initials: L
authors.lastname: Adzovic
authors.affiliation: Department of Neuroscience, Ohio State University, Columbus, OH 43210, USA; Department of Psychology, Ohio State University, Columbus, OH 43210, USA. Electronic address: wenk.6@osu.edu.
authors.forename: G L
authors.initials: GL
authors.lastname: Wenk
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D003620:Dantrolene / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy* / Q000503:physiopathology; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D009553:Nimodipine / Q000494:pharmacology; D018697:Nootropic Agents / Q000494:pharmacology*; D011916:Rats, Inbred F344; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D065852:Spatial Memory / Q000187:drug effects* / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018697:Nootropic Agents; D019837:Ryanodine Receptor Calcium Release Channel; D009553:Nimodipine; D003620:Dantrolene
keywords: L-type voltage-dependent calcium channel; aging; calcium; memory; microglia; ryanodine receptor