What is it about?
Bioaccumulation of amyloid beta (AB) peptides is implicated in Alzheimer’s disease. Animal models over-expressing AB show memory deficits. Hippocampal sharp-wave ripples have been implicated in memory consolidation. Disruption of these same high frequency oscillations produces memory deficits. Compounds that decrease tonic inhibition mediated by a5 type GABA receptors improve memory function in healthy rodents. It is not known whether these compounds modulate ripples in vivo. We now show for the first time that administration of a putative cognitive enhancer selective for a5 type GABA receptors increases peak ripple amplitudes in wild type adult rats but has no effect on peak ripple amplitudes in adult TgF344-AD rats which show elevated plasma concentrations of AB42 and AB40.
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Why is it important?
This important novel finding has far reaching translational implications for future studies using pharmacologic as well as deep brain stimulation methods to restore the ripple amplitude deficits observed in this preclinical animal model of Alzheimer's disease necessary to move these findings from the bench to the bedside.
Perspectives
My colleagues and I are using in vivo electrophysiology to better understand how chemicals differentially modulate neural network activity in healthy controls and those with age-related amnestic mild cognitive impairment and Alzheimer's disease. We anticipate that coupling this approach with animal models of neurodegenerative disease will improve the translation value of preclinical data while improving our understanding of the relationships between drug targets, neural network activity, and behavior. The ultimate goal of these investigations is to facilitate the development of more effective therapeutics for neurodegenerative disease. We also anticipate that knowledge gained from these investigations will help to detect subclinical adverse effects of novel therapeutics which may evade other less sensitive methods.
Dr. Marcia H. Ratner
Boston University Chobanian & Avedisian School of Medicine
Read the Original
This page is a summary of: Prodromal dysfunction of α5GABA-A receptor modulated hippocampal ripples occurs prior to neurodegeneration in the TgF344-AD rat model of Alzheimer’s disease, Heliyon, September 2021, Elsevier,
DOI: 10.1016/j.heliyon.2021.e07895.
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The State of Alzheimer’s Research, with Dr Marcia Ratner & Dr James Hendrix
Dr. Ratner and Dr. James Hendrix of LuMind IDSC were recently interviewed by Dr. Hackie Reitman of DifferentBrains about their thoughts on the state of the art in Alzheimer’s drug discovery research as it specifically pertains to patients with Down syndrome.
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