14 Jul 2003

A report in this week's PNAS suggests that neurogenesis can occur in response to neurodegeneration in human brains. Principal author Richard Faull and colleagues at the University of Auckland, New Zealand, report that significantly more neuronal proliferation occurs in the subependymal layer (SEL) of Huntington's disease (HD) brains than in normal SEL. These results add to the growing weight of evidence suggesting that mammalian brains can regenerate damaged circuitry (see ARF related news story).

First author Maurice Curtis and colleagues measured neuronal proliferation by identifying cells that contained both bIII tubulin, a neuronal marker, and proliferating cell nuclear antigen (PCNA), a protein that is only expressed in dividing cells. When Curtis tallied the number of PCNA-positive cells in postmortem brain samples he found many more in the SEL taken from HD donors. Significantly, the numbers of dividing cells directly correlated with the severity of the disease and with the number of polyglutamine repeats present in mutated huntingtin, the cause of HD. The authors found that about 5 percent of these newly dividing cells are neurons, testing positive for bIII tubulin, while about 50 percent appeared to be glia, expressing glial fibrillary acidic protein (GFAP). Significantly, the neurons were found in the deepest layers of the SEL adjacent to the caudate nucleus, the area of the brain that is primarily and most severely affected by Huntington's.

These data provide the first evidence in humans for neural regeneration in response to disease and, together with evidence from neuronal proliferation in mouse models of Parkinson's disease (see related news above), suggests that neurogenesis in mammalian brains may be more widespread, and tissue graft treatment more feasible, than previously thought.-Tom Fagan.

Reference:
Curtis MA, Penney EB, Pearson AG, van Roon-Mom WMC, Butterworth NJ, Dragunow M, Connor B, Faull RLM. Increased cell proliferation and neurogenesis in the adult human Huntington's disease brain. Proc Natl Acad Sci U S A. 2003 Jul 22 ; 100(15):9023-7. Abstract