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19.10.2018 | Original Article

Chronic fornix deep brain stimulation in a transgenic Alzheimer’s rat model reduces amyloid burden, inflammation, and neuronal loss

verfasst von: Aurelie Leplus, Inger Lauritzen, Christophe Melon, Lydia Kerkerian-Le Goff, Denys Fontaine, Frederic Checler

Erschienen in: Brain Structure and Function | Ausgabe 1/2019

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Abstract

Recent studies have suggested deep brain stimulation (DBS) as a promising therapy in patients with Alzheimer’s disease (AD). Particularly, the stimulation of the forniceal area was found to slow down the cognitive decline of some AD patients, but the biochemical and anatomical modifications underlying these effects remain poorly understood. We evaluated the effects of chronic forniceal stimulation on amyloid burden, inflammation, and neuronal loss in a transgenic Alzheimer rat model TgF344-AD, as well as in age-matched control rats. 18-month-old rats were surgically implanted with electrodes in stereotactic conditions and connected to a portable microstimulator for chronic DBS in freely moving rats. The stimulation was continuous during 5 weeks and animals were immediately sacrificed for immunohistochemical analysis of pathological markers. Implanted, but non-stimulated rats were used as controls. We found that chronic forniceal DBS in the Tg-AD rat significantly reduces amyloid deposition in the hippocampus and cortex, decreases astrogliosis and microglial activation and lowers neuronal loss, as determined by NeuN staining. In control animals, the stimulation neither affects neuroinflammation nor neuronal count. In the Tg-F344-AD rat model, 5 weeks of forniceal DBS decreased amyloidosis, inflammatory responses, and neuronal loss in both cortex and hippocampus. These findings strongly suggest a neuroprotective effect of DBS and support the beneficial effects of targeting the fornix in Alzheimer’s disease patients.

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Titel: Chronic fornix deep brain stimulation in a transgenic Alzheimer’s rat model reduces amyloid burden, inflammation, and neuronal loss
verfasst von: Aurelie Leplus
Inger Lauritzen
Christophe Melon
Lydia Kerkerian-Le Goff
Denys Fontaine
Frederic Checler
Publikationsdatum: 19.10.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Brain Structure and Function / Ausgabe 1/2019
Print ISSN: 1863-2653
Elektronische ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-018-1779-x

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