Donaldson Lab Post-Doc @ CU Boulder 🦬 interested in subcortical contributions to social deficits in Alzheimer's disease | Locus coeruleus enthusiast 🔵
Michael Kelberman
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Use of inhibitory, ultrafast, step-function opsins, as well as analyzing dynamic connectivity measures across a variety of disease models could uncover viable therapeutic strategies for treating neurological disorders
We start by describing our own setup followed by the potential of these studies for understanding pathological disease processes, using our own data in the TgF344-AD rat model as proof-of-concept. We stress the importance of validating optogenetic stimulation and employing the proper controls.
Published studies using opto-fMRI have largely deployed excitatory opsins and focus on changes in static functional connectivity.
Shout out to all the amazing co-authors on this study!
Our study suggests that LC lesions exacerbate pre-existing behavioral deficits and AD pathology, rather than accelerating their onset. Such nuance in understanding the contributions of LC dysfunction to dementia progression is necessary for developing effective therapeutics targeting this system.
Specifically, TgF344-AD rats displayed anxiety-like phenotypes and social recognition deficits whereas DSP-4 treatment induced apathy-like behaviors and changed arousal. There was relatively little pathology present in young TgF344-AD rats and DSP-4 didn't accelerate the appearance of tau or amyloid
We induced LC lesions using multiple doses of DSP-4 prior to significant accumulation of pathology in TgF344-AD rats. Contrary to our initial hypothesis, we found that TgF344-AD genotype and DSP-4 independently induced behavioral dysfunction and rarely interacted to exacerbate AD-related phenotypes
