Increased cell proliferation and neurogenesis in the adult human Huntington's disease brain.
Neurogenesis has recently been observed in the adult human brain, suggesting the possibility of endogenous neural repair. However, the augmentation of neurogenesis in the adult human brain in response to neuronal cell loss has not been demonstrated. This study was undertaken to investigate whether neurogenesis occurs in the subependymal layer (SEL) adjacent to the caudate nucleus in the human brain in response to neurodegeneration of the caudate nucleus in Huntington's disease (HD). Postmortem control and HD human brain tissue were examined by using the cell cycle marker proliferating cell nuclear antigen (PCNA), the neuronal marker beta III-tubulin, and the glial cell marker glial fibrillary acidic protein (GFAP). We observed a significant increase in cell proliferation in the SEL in HD compared with control brains. Within the HD group, the degree of cell proliferation increased with pathological severity and increasing CAG repeats in the HD gene. Most importantly, PCNA+ cells were shown to coexpress beta III-tubulin or GFAP, demonstrating the generation of neurons and glial cells in the SEL of the diseased human brain. Our results provide evidence of increased progenitor cell proliferation and neurogenesis in the diseased adult human brain and further indicate the regenerative potential of the human brain.
Curtis
Maurice A
MA
Department of Anatomy with Radiology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Penney
Ellen B
EB
Pearson
Andree G
AG
van Roon-Mom
Willeke M C
WM
Butterworth
Niqi J
NJ
Dragunow
Michael
M
Connor
Bronwen
B
Faull
Richard L M
RL
D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D002455:Cell Division; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D008875:Middle Aged; D018598:Minisatellite Repeats; D009416:Nerve Regeneration; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D018911:Trinucleotide Repeats; D014404:Tubulin / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D018809:Proliferating Cell Nuclear Antigen; D014404:Tubulin