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

• Published in: Brain Structure and Function Vol. 224; no. 1; pp. 363 - 372
• Main Authors: Leplus, Aurelie, Lauritzen, Inger, Melon, Christophe, Kerkerian-Le Goff, Lydia, Fontaine, Denys, Checler, Frederic
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.01.2019; Springer Nature B.V; Springer Verlag
• Subjects: Alzheimer's disease; Amyloidosis; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cognitive ability; Deep brain stimulation; Fornix; Gliosis; Hippocampus; Inflammation; Life Sciences; Neurology; Neurons and Cognition; Neuroprotection; Neurosciences; Original Article; Rodents; Fornix; Neuroprotection; Neuronal loss; Alzheimer rat model; Alzheimer disease; Deep brain stimulation; Chronic stimulation; Neuromodulation; Beta-amyloid plaques
• ISSN: 1863-2653; 1863-2661; 1863-2661; 0340-2061
• DOI: 10.1007/s00429-018-1779-x

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.