A novel rhesus macaque model of Huntington’s disease recapitulates key neuropathological changes along with motor and cognitive decline
Year: 2022
Type: article
Abstract: ABSTRACT We created a new nonhuman primate model of the genetic neurodegenerative disorder, Huntington’s disease (HD), by injecting a mixture of recombinant adeno-associated viral vectors, serotypes AAV2 and AAV2.retro, each expressing a fragment of human mutant HTT ( mHTT) into the caudate and putamen of adult rhesus macaques. This novel modeling strategy results in robust expression of mutant huntingtin protein (mHTT) in the injected brain regions, as well as dozens of other cortical and subcortical brain regions that are also affected in human HD patients. We queried the disruption of cortico-basal ganglia circuitry for 20-months post-surgery using a variety of behavioral and imaging readouts. Compared to controls, mHTT-treated macaques developed progressive working memory decline and motor impairment. Multimodal imaging revealed circuit-wide white and gray matter degenerative processes in several key brain regions affected in HD. This novel model will aid in the development of disease biomarkers and therapeutic strategies for this devastating disorder.
Source: eLife
DOI: 10.7554/elife.77568
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: G1294778923, Limbic-basal ganglia connectivity in a non-human primate model of Huntington's disease, Laser Scanning Confocal Microscope, G1893357618, Cortico-basal ganglia connectivity in a non-human primate model of Huntington's disease, G6492514785, G9000117758, G9000292184, Project 7/8: INIA Stress and Chronic Alcohol Interactions: Cross-species studies of metabolic allostasis and altered striatal circuitry, Support for National Primate Research Center, G991120161
OpenAlex ID: W4303423792