Brain Cell Regeneration Shows Hope for Repairs
Anna Nidecker, Senior Writer

Clinical Psychiatry News 26(12):23, 1998.
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Brain cells continue to divide and regenerate in adulthood, suggesting that damage caused by injury and disease is reparable.

Postmortem examination of the brains of five cancer patients in their 50s, 60s, and 70s revealed evidence of neurogenesis, reported Dr. Peter S. Eriksson of the Institute of Neurology at Sahlgrenska University Hospital, Göteborg, Sweden, and his colleagues in Sweden and at the Salk Institute for Biological Studies in La Jolla, Calif. New neurons were found in the hippocampus, the brain's primary information processing area, and in the subventricular zone, which sends neurons out to the olfactory bulb.

Neurogenesis was documented by labeling cells with the nucleic acid analogue bromodeoxyuridine (BrdU). The five patients received injections of BrdU, which is used on an investigational basis to monitor the rapidity of cancer cell replication. BrdU only incorporates into the newly synthesized DNA of dividing cells, so its presence in cellular DNA indicates that these cells were created soon after the label was injected (Nat. Med. 4[11]:1313-17, 1998).

The label was found in undifferentiated progenitor cells as well as in differentiated neurons and glial cells. In all five patients, the progenitor cells were found just below the granular layer of the hippocampus and the ventricles, fluid-filled spaces in the brain. Differentiated neurons and glia were found in the granular layer of the hippocampus, just above the stem cells.

"We think that at some point, some signal tells progenitor cells to stop growing and dividing, [to] migrate up into the granular cell layer, and [to] differentiate into neurons," said Dr. Fred Gage, one of the investigators who conducted the study at the Salk Institute of Biological Studies, La Jolla, Calif.

These types of continually dividing stem cells also are found in other areas of the brain and spinal cord, where they give rise to glial cells or become quiescent and die. The therapeutic trick will be to figure out the trigger within the subgranular and subventricular zones that causes certain stem cells to stop dividing, migrating, and differentiating into neurons, Dr. Gage said in a telephone interview.

If these new neurons are functional, stem cells in areas of the brain damaged by neurodegenerative disorders or ischemic injury can be recruited to form new neurons.

Roughly 500-1,000 new neurons were born per day in these patients, a rate that probably varies according to age, genetics, and environment. That number represents an incredibly small proportion of total neurons. The hippocampus alone, for example, contains around 70 million neurons.

The number of labeled cells detected in each patient declined with the length of time between the BrdU injection and the patient's death. This suggests that newly generated neurons progressively died in a natural course, and were subsequently replaced by unlabeled neurons that had migrated from the subgranular pool of stem cells.

Results of previous studies on rodents and primates have indicated that only in these areas are cells able to differentiate into neurons. These studies also have shown that proliferation of neurons can be suppressed or enhanced.

The findings force a consideration that new neurons, not just new or stronger connections between neurons, underlie processes such as learning and memory. Autologous repair and regeneration may be able to slow down or reverse diseases like Parkinson's, Huntington's, and Alzheimer's, an accompanying editorial pointed out (Nat. Med. 4[11]:1207, 1998). Furthermore, brain cell loss underlying these diseases involves not only cell death, but cell failure to regenerate.

Dr. Gage cautioned that there probably isn't a direct link between a defect in progenitor cells and these disorders. But improved understanding of regeneration may result in probes to uncover processes that are out of kilter in these disorders.