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Adult brain continues to regenerate neurons

Elvira Manzano
01 Dec 2013

Neurogenesis, the birth of neurons or nerve cells in the hippocampus, continues during adulthood, new research suggests.

A retrospective study of hippocampal cells from deceased patients has shown that a significant proportion (35 percent) of these neural cells are subject to exchange, resulting in the addition of 700 new cells to the brain per day per individual. This corresponds to an average turnover rate of 1.75 percent of the renewing cells per year during adulthood, with no difference in rates between genders (p=0.41). [Cell 2013;153:1219-1227]

“Human studies like this are sparse but encouraging,” said Dr. Robert Hoerr, head of geriatrics/CNS, Department of Clinical Research, Dr. Willmar Schwabe GmbH & Co. KG, in Karlsruhe, Germany, who was not involved in the study. He said this adds weight to the issue of adult neurogenesis in humans and gives indirect indication of the extent of neurogenesis which may have an impact on brain function. Hoerr cited data from this study, and other studies, during his plenary lecture on hippocampal neurogenesis.

It has long been debated whether adult neurogenesis decreases or increases throughout life. A seminal study in 1998 provided the only direct evidence so far of adult neurogenesis in humans, although it did not show the extent of neurogenesis, or if there is any functional significance to it. [Nat Med 1998;4:1313-1317]

In the current study, researchers measured the amount of radioactive carbon 14 isotope (14C) in genomic DNA from the hippocampal cells of deceased patients (19-92 years of age), to determine cell age. A mathematical model was then developed to determine the rate of cell turnover in both neural and non-neural cells of the patients.

A higher rate of cell turnover existed in the non-neural cells than in the neural cells (51 percent vs 35 percent), with an annual turnover rate of 3.5 percent. This however declined with age. By comparison, the neural cells appeared to be less affected by aging.

Studies in mice and in humans linking neurogenesis to Alzheimer’s disease (AD) yielded conflicting results [J Neurosci 2007;27:6771-6780; PNAS 2004;101:343-347]. In one study in humans, neurogenic abnormalities with AD differed between phases and areas of neurogenesis, as well as stages of AD. [Neurobiol Dis 2012;47:155-162]

“With progressing AD, choline-acetyltransferase activity and hippocampal stem cells decrease, proliferation of progenitor cells increase, but migratory and post-miotic cells largely remain unchanged,” Hoerr said.

Several factors may influence hippocampal neurogenesis, he added. These include signaling molecules, transcription factors, growth factors, neurotransmitters and hormones. Animal studies have shown that all currently available anti-dementia drugs (donepezil, galantamine, memantine), as well as antidepressants (eg, fluoxetine), physical and mental activities promote neurogenesis.

Ginkgo biloba extract (EGb 761) has also been shown to stimulate neurogenesis in mice. It reduced amyloid beta oligomers and restored cAMP response element-binding protein (CREB) phosphorylation in the hippocampus, suggesting that EGb 761 not only has benefit in the treatment of patients with AD, but may also have an effect in prevention or disease modification. [FASEB J 2007;21:2400-2408]

Overall, the studies provide new information on hippocampal neurogenesis and encourage additional research. Further studies to determine if reduced neurogenesis is associated with depression in humans would be of interest, Hoerr concluded.

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