Abnormalities of neurogenesis in the R6/2 mouse model of Huntington's disease are attributable to the in vivo microenvironment.
Huntington's disease (HD) is an autosomal dominant neurodegenerative condition characterized by movement disorders, psychiatric disturbance, and cognitive decline. There are no treatments to halt or reverse the disease. Mammalian neurogenesis persists into adulthood in the subventricular zone (SVZ) and dentate gyrus (DG) of the hippocampus. In 2001, our laboratory published the hypothesis that neurogenesis is impaired in neurodegenerative diseases and that this may contribute to disease progression. Since then, it has been shown that neurogenesis is reduced in the DG of transgenic HD mice but increased in the SVZ of HD patients. We sought to characterize neurogenesis further. We found that, in the DG of the transgenic R6/2 mouse model of HD, newborn cell proliferation and morphology, but not differentiation or survival, was compromised. In R6/2 mice, neurogenesis failed to upregulate in the DG in response to seizures. Basal SVZ neurogenesis was similar between R6/2 mice and their wild-type littermates. There was no difference in the in vitro growth of adult neural precursor cells (NPCs) between genotypes. These results suggest that abnormal neurogenesis in the R6/2 mouse is not attributable to an intrinsic impairment of the NPC itself but is attributable to the environment in which the cell is located.
Phillips
Wendy
W
Cambridge Centre for Brain Repair, Cambridge CB2 2PY, United Kingdom. wp212@cam.ac.uk
Morton
A Jennifer
AJ
Barker
Roger A
RA
D000375:Aging / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006816:Huntington Disease / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000473:pathology* / Q000502:physiology; D012640:Seizures / Q000235:genetics / Q000473:pathology; D012720:Severity of Illness Index
D009419:Nerve Tissue Proteins