Pronounced microgliosis and neurodegeneration in aged rats after tau gene transfer.
Microtubule-associated protein tau gene transfer to the substantia nigra of rats using the adeno-associated virus (AAV) vector previously led to neuropathology and neurodegeneration in young rats. In this study, we compared equal tau gene transfer in either 3 or 20-month-old rats, in order to test the hypothesis that late middle-aged rats are more susceptible to neurodegeneration. Two intervals and two vector doses of the tau vector probed for age-related differences in the initial sensitivity to low-level tau expression. Gene transfer efficiency was similar for both ages, but the tau vector caused more dopaminergic cell loss and a greater behavioral deficit in aged rats at specific doses and time points. Tau gene transfer caused microgliosis relative to the control vector, and to a greater extent in aged rats. The maximal microglial response occurred at 2 weeks preceding the peak dopaminergic cell loss by 8 weeks. The cellular and behavioral outcomes were more severe in the aged rats, validating the model for studies of age-related diseases.
Klein
Ronald L
RL
Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA. Klein@lsuhsc.edu
Dayton
Robert D
RD
Diaczynsky
Cynthia G
CG
Wang
David B
DB
D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D016922:Cellular Senescence / Q000235:genetics; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D018014:Gene Transfer Techniques; D005911:Gliosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000473:pathology / Q000503:physiopathology; D016875:tau Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics*
D016875:tau Proteins