Use of adeno-associated virus-mediated delivery of mutant huntingtin to study the spreading capacity of the protein in mice and non-human primates.

Use of adeno-associated virus-mediated delivery of mutant huntingtin to study the spreading capacity of the protein in mice and non-human primates.

Publication date: May 18, 2020

In order to model various aspects of Huntington’s disease (HD) pathology, in particular protein spread, we administered adeno-associated virus (AAV) expressing green fluorescent protein (GFP) or GFP coupled to HTT-Exon1 (19Q or 103Q) to the central nervous system of adult wild-type (WT) mice and non-human primates. All animals underwent behavioral testing and post-mortem analyses to determine the long-term consequences of AAV injection. Both mice and non-human primates demonstrated behavioral changes at 2-3?weeks post-surgery. In mice, these changes were absent after 3?months while in non-human primates, they persisted in the majority of tested animals. Post-mortem analysis revealed that spreading of the aggregates was limited, although the virus did spread between synaptically-connected brain regions. Despite the small degree of spreading, the presence of mHTT generated changes in endogenous huntingtin (HTT) levels in both models. Together, these results suggest that viral expression of mHTTExon1 can induce spreading and seeding of HTT in both mice and non-human primates.

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Concepts Keywords
Brain Primate
Central Nervous System AAV
Endogenous Viral vector
Fluorescent Huntingtin
GFP Gene delivery
Huntingtin HTT
Huntington Branches of biology
Mice Surgery
Mutant Photon intravital imaging
Pathology
Post Mortem
Primates
Viral
Virus
Wild Type

Semantics

Type Source Name
disease MESH pathology
drug DRUGBANK Diethylstilbestrol
disease MESH neurodegenerative diseases
drug DRUGBANK L-Glutamine
disease MESH death
drug DRUGBANK Tetracycline
disease MESH atrophy
disease MESH anxiety
disease MESH neuroblastoma
drug DRUGBANK Streptomycin
drug DRUGBANK Amphotericin B
drug DRUGBANK Pepsin
disease MESH dissociation
drug DRUGBANK Gelatin
drug DRUGBANK L-Lysine
drug DRUGBANK Phosphate ion
drug DRUGBANK Trypsin
drug DRUGBANK Glycerin
drug DRUGBANK Sodium lauryl sulfate
drug DRUGBANK Edetic Acid
disease MESH separated
drug DRUGBANK Flunarizine
drug DRUGBANK Sodium bisulfite
drug DRUGBANK Bicine
drug DRUGBANK Tromethamine
drug DRUGBANK Human Serum Albumin
drug DRUGBANK Calcium
drug DRUGBANK Magnesium
drug DRUGBANK Water
disease MESH Communities
drug DRUGBANK Isoflurane
drug DRUGBANK Ethanol
drug DRUGBANK Ketamine
drug DRUGBANK Oxygen
disease MESH bleeding
drug DRUGBANK Aminosalicylic Acid
drug DRUGBANK Tricyclazole
drug DRUGBANK Xylazine
drug DRUGBANK Sucrose
drug DRUGBANK Sodium phosphate monobasic
drug DRUGBANK Sodium phosphate dibasic
drug DRUGBANK Pentobarbital
drug DRUGBANK Heparin
drug DRUGBANK Chondroitin sulfate
drug DRUGBANK Deoxycholic Acid
drug DRUGBANK Esomeprazole
drug DRUGBANK Aspartame
drug DRUGBANK Amino acids

Original Article

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