The birth of neurons, called neurogenesis, is known to continue throughout life in some areas of the brain. Research continues to show that the process is one of the brain’s methods of self-repair that could be harnessed for therapeutic purposes; abnormal neurogenesis may contribute to some disorders and may provide new avenues for therapy. So too do the immature and versatile cells known as stem cells continue to show promise as treatments. Researchers made progress in 2006 in unraveling the pathways through which stem cells develop into neurons. But can stem cells take on specific jobs in the brain?

Neurogenesis in the Cortex

Neurogenesis has been known since 1998 to occur in the hippocampus of the adult human brain. Less clear is whether new neurons are produced in other areas, and whether the brain’s remarkable adaptability, or plasticity, results from the remodeling of existing cells or the production of new ones.

An innovative method for dating brain cells is the use of radiocarbon (14C), which was released in massive amounts during aboveground nuclear testing in the 1950s and has declined measurably ever since, taken up by the earth’s atmosphere and into the DNA of plants, animals, and humans. In 2005 a team led by Jonas Frisen of the Karolinska Institute in Stockholm used 14C dating to establish that in the cortex of adult humans, 14C levels matched those in the atmosphere at the time of the individual’s birth—suggesting that few, if any, cortical neurons had been produced later in life.

Frisen and colleagues teamed up with several other laboratories for a more extensive study, reported in Proceedings of the National Academy of Sciences.¹ Working with autopsied brain tissue from seven individuals born between 1933 and 1973, the investigators measured neurons from all lobes of the cortex. They again found 14C levels corresponding to those at the time of each subject’s birth, providing strong evidence that neurogenesis in the cortex is limited to the developing brain.

They surmise that although neurogenesis in the hippocampus may play a role in some types of memory, cognitive functions such as learning and analysis are handled by cortical cells that have been in place since birth, and that in the cortex stability is favored over plasticity.

The cortex is the seat of “higher” functions such as reason and analysis and is considered the part of the brain that distinguishes humans from other species. A study reported in Nature Neuroscience shows that cortical neurons may be some of the first cells produced as the human embryo takes form. 

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2. Bystron I, Rakic P, Molnar Z, and Blakemore C. The first neurons of the human cerebral cortex. Nature Neuroscience 2006 9(7):880–886.

3. Shen Q, Wang Y, Dimos JT, Fasano CA, Phoenix TN, Lemischka IR, Ivanova NB, Stifani S, Morrisey EE, and Temple S. The timing of cortical neurogenesis is encoded within lineages of individual progenitor cells. Nature Neuroscience 2006 9(6):743–751.

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6. Yang H, Lu P, McKay HM, Bernot T, Keirstead H, Steward O, Gage FH, Edgerton VR, and Tuszynski MH. Endogenous neurogenesis replaces oligodendrocytes and astrocytes after primate spinal cord injury. Journal of Neuroscience 2006 26(8):2157–2166.

7. Parent JM, von dem Bussche N, and Lowenstein DH. Prolonged seizures recruit caudal subventricular zone glial progenitors into the injured hippocampus. Hippocampus 2006 16(3):321–328.

8. Parent JM, Elliott RC, Pleasure SJ, Barbaro NM, and Lowenstein DH. Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy. Annals of Neurology 2006 59(1):81–91.

9. Encinas JM, Vaahtokari A, Enikolopov G. Fluoxetine targets early progenitor cells in the adult brain. Proceedings of the National Academy of Sciences USA 2006 103(21):8233–8238.

10. Steele AD, Emsley JG, Ozdinler PH, Lindquist S, and Macklis JD. Prion protein (PrPc) positively regulates neural precursor proliferation during developmental and adult mammalian neurogenesis. Proceedings of the National Academy of Sciences USA 2006 103(9):3416–3421.

11. Kwak YD, Brannen CL, Qu T, Kim HM, Dong X, Soba P, Majumdar A, Kaplan A, Beyreuther K, and Sugaya K. Amyloid precursor protein regulates differentiation of human neural stem cells. Stem Cells Development 2006 15(3):381–389.

12. Jackson EL, Garcia-Verdugo JM, Gil-Perotin S, Roy M, Quinones-Hinojosa A, VandenBerg S, and Alvarez-Buylla A. PDGFR alpha-positive B cells are neural stem cells in the adult SVZ that form glioma-like growths in response to increased PDGF signaling. Neuron 2006 51(2):187–199.

13. Gil-Perotin S, Marin-Husstege M, Li J, Soriano-Navarro M, Zindy F, Roussel MF, Garcia-Verdugo JM, and Casaccia-Bonnefil P. Loss of p53 induces changes in the behavior of subventricular zone cells: Implication for the genesis of glial tumors. Journal of Neuroscience 2006 26(4):1107–1116.

14. Androutsellis-Theotokis A, Leker RR, Soldner F, Hoeppner DJ, Ravin R, Poser SW, Rueger MA, Bae SK, Kittappa R, and McKay RD. Notch signalling regulates stem cell numbers in vitro and in vivo. Nature 2006 442(7104):823–826.