title: Riluzole rescues alterations in rapid glutamate transients in the hippocampus of rTg4510 mice.
abstract: Those at risk for Alzheimer's disease (AD) often exhibit hippocampal hyperexcitability in the years preceding diagnosis. Our previous work with the rTg(TauP301L)4510 tau mouse model of AD suggests that this increase in hyperexcitability is likely mediated by an increase in depolarization-evoked glutamate release and a decrease in glutamate uptake, alterations of which correlate with learning and memory deficits. Treatment with riluzole restored glutamate regulation and rescued memory deficits in the TauP301L model. Here, we used enzyme-based ceramic microelectrode array technology to measure real-time phasic glutamate release and uptake events in the hippocampal subregions of TauP301L mice. For the first time, we demonstrate that perturbations in glutamate transients (rapid, spontaneous bursts of glutamate) exist in a tau mouse model of AD mouse model and that riluzole mitigates these alterations. These results help to inform our understanding of how glutamate signaling is altered in the disease process and also suggest that riluzole may serve as a clinically applicable therapeutic approach in AD.
authors.affiliation: Behavioral Neuroscience, Department of Psychology, West Virginia University, Morgantown, 26506, WV, USA.|Drug Discovery & Development Department, School of Pharmacy, Auburn University, 4306 Walker Building, Auburn, AL, 36849, USA.
authors.forename: Holly C
authors.initials: HC
authors.lastname: Hunsberger
authors.affiliation: Behavioral Neuroscience, Department of Psychology, West Virginia University, Morgantown, 26506, WV, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Hickman
authors.affiliation: Drug Discovery & Development Department, School of Pharmacy, Auburn University, 4306 Walker Building, Auburn, AL, 36849, USA. reedmir@auburn.edu.
authors.forename: Miranda N
authors.initials: MN
authors.lastname: Reed
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019782:Riluzole / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018696:Neuroprotective Agents; D018698:Glutamic Acid; D019782:Riluzole
keywords: Alzheimer’s disease; Glutamate uptake; Hippocampus; Riluzole; Tau; Tg4510