The use of DREADDs for dissecting the contribution of cellular and neural circuit mechanisms in models of neurodegenerative disease

Sharma, Puneet and Pienaar, Ilse The use of DREADDs for dissecting the contribution of cellular and neural circuit mechanisms in models of neurodegenerative disease. In: Gerlai, Robert (ed.) Molecular-genetic and statistical techniques for behavioral and neural research. Elsevier, New York. ISBN 9780128040782 (Accepted)

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Abstract

A technology abbreviated as DREADDs (designer receptors exclusively activated by designer drugs) uses synthetically derived receptors and selective, otherwise inert, exogenous ligands to transiently activate or inactivate targeted neuronal types within specific brain regions. A range of transfer strategies (but principally using viral vector infection methods) are used for delivering DREADD receptors into neural tissue, with stereotaxic microinjection of the virus into a particular location that refines spatial specificity of DREADD expression.
Designer Receptors Exclusively Activated by Designer Drugs section of the current chapter will serve readers with a basic overview of the principles underlying the workings of DREADDs (Fig. 24.1), but it does not intend to be exhaustive as to the cellular and molecular mechanisms underlying application of DREADDs. Interested readers seeking greater details pertaining to DREADDs' molecular mechanisms of action are referred to several excellent review articles, e.g., by Armbruster et al.1; Ferguson and Neumaier2; Rogan and Roth3; Sternson and Roth;4 and Roth.5 Designer Receptors Exclusively Activated by Designer Drugs section also reviews recent advances to the DREADD toolbox. Neurodegenerative Disease section seeks to highlight the tremendous potential held by the DREADD approach in many research areas relating to neurodegenerative disease, by highlighting recently developed approaches and applications. In particular, after an overview of the causes and features of two prominent neurodegenerative diseases, namely Alzheimer disease (AD) and Parkinson disease (PD), we review highlights from studies that have applied DREADD technologies to answer questions relating to both diseases, by making use of preclinical models, presented as a series of case studies. The findings from such studies pave the way toward use of DREADDs for relatively noninvasive, selective, reversible responses by neuronal populations and circuits, by means of a dose-responsive orally administered agonist that targets the human brain. Hence, the chapter ends (Translational Potential of Chemogenetics for Treating Neurodegenerative section) by reflecting on the potential that DREADDs offer to aid in the development of novel therapeutic treatments against neurodegenerative disease.

Item Type: Book Section
Schools and Departments: School of Life Sciences > Neuroscience
Depositing User: Ilse Pienaar
Date Deposited: 19 Feb 2018 10:16
Last Modified: 19 Feb 2018 10:16
URI: http://sro.sussex.ac.uk/id/eprint/73654

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