Reduced hippocampal neurogenesis in R6/2 transgenic Huntington's disease mice.
We investigated whether cell proliferation and neurogenesis are altered in R6/2 transgenic Huntington's disease mice. Using bromodeoxyuridine (BrdU), we found a progressive decrease in the number of proliferating cells in the dentate gyrus of R6/2 mice. This reduction was detected in pre-symptomatic mice, and by 11.5 weeks, R6/2 mice had 66% fewer newly born cells in the hippocampus. The results were confirmed by immunohistochemistry for the cell cycle markers Ki-67 and proliferating cell nuclear antigen (PCNA). We did not observe changes in cell proliferation in the R6/2 subventricular zone, indicating that the decrease in cell proliferation is specific for the hippocampus. This decrease corresponded to a reduction in actual hippocampal neurogenesis as assessed by double immunostaining for BrdU and the neuronal marker neuronal nuclei (NeuN) and by immunohistochemistry for the neuroblast marker doublecortin. Reduced hippocampal neurogenesis may be a novel neuropathological feature in R6/2 mice that could be assessed when evaluating potential therapies.
Gil
Joana M A C
JM
Neuronal Survival Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Sciences, Lund University, BMC A10, SE-221 84 Lund, Sweden.
Mohapel
Paul
P
Araújo
Inês M
IM
Popovic
Natalija
N
Li
Jia-Yi
JY
Brundin
Patrik
P
Petersén
Asa
A
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D001973:Bromodeoxyuridine; D002455:Cell Division / Q000235:genetics; D049109:Cell Proliferation; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009473:Neuronal Plasticity / Q000235:genetics; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009479:Neuropeptides / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism
D015415:Biomarkers; D004268:DNA-Binding Proteins; D000089622:Doublecortin Domain Proteins; C086055:HTT protein, human; D000071058:Huntingtin Protein; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009479:Neuropeptides; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D001973:Bromodeoxyuridine