Neurogenesis in the adult human brain

One of the central dogmas of neuroscience was that the brains of adult mammals cannot generate new nerve cells. But about 10 years ago, this changed, when it was discovered that in the hippocampi of adult rodents there are stem cells which are capable of generating new neurons. It has also been known for some years that, in rodents at least, neurogenesis also produces new cells that migrate to the olfactory bulb. Although a study published in 1998 provided some evidence that neurogenesis takes place in the adult human hippocampus, the idea that neurogenesis takes place in adult humans remained contentious.

Now, an advance online publication on the website of the journal Science provides evidence that neurogenesis may also occur in the olfactory bulb of the human brain:

The rostral migratory stream (RMS) is the main pathway by which newly born subventricular zone (SVZ) cells reach the olfactory bulb in rodents. However, the RMS in the adult human brain has been elusive. Here we demonstrate the presence of a human RMS, which is unexpectedly organized around a lateral ventricular extension reaching the olfactory bulb (OB), and illustrate the neuroblasts in it. The RMS ensheathing the lateral olfactory ventricular extension, as seen by MRI, cell specific markers and electron microscopy, contains progenitor cells with migratory characteristics and cells which incorporate BrdU and become mature neurons in the OB.

In rats and mice, a structure called the rostral extension connects the lateral ventricles and the olfactory bulb. This tube-like structure, which is filled with cerebrospinal fluid, provides a pathway for neurons generated in the subventricular zone (a proliferative tissue lining the cerebral ventricles) to migrate to the olfactory bulb, which contains neurons that bind to odorant receptors and produce nervous impulses related to smell. The rostral migratory stream is the equivalent of the rostral extension in rodents, and was not known to exist in humans before this study.

Maurice Curtis and his colleagues examined the brains of deceased cancer patients who had previously been injected with bromo- deoxyuridine (BrdU), a chemical which is incorporated into newly-synthesized DNA, and which is therefore used by oncologists to visualize and monitor the growth of tumours. To their surprise, they found BrdU-positive cells in the olfactory bulbs of the patients’ brains, suggesting that it contained newly-generated neurons. Curtis’s team then used antibody staining to show that the neuroblasts begin to differentiate into olfactory neurons while migrating through the rostral migratory stream. Upon arriving at the bulb, the cells continued to differentiate, forming mature olfactory neurons. Using electron microscopy, they also showed that this ‘tube’ is 3.5 mm long and 1.5 mm in diameter.

Because the cancer patients whose brains were examined were aged between 38-70 years of age, the findings suggest that neuro- genesis may occur throughout the duration of the human lifespan. The function of these newly-generated cells is unclear, but they may be involved in recognizing and remembering new smells in the later years of life.

The researchers also have preliminary unpublished data that the stem cells not only migrate to the olfactory bulb, but also leave the RMS and migrate into the basal ganglia and cerebral cortex. This is significant, because parts of the basal ganglia degenerate in movement disorders such as Parkinson’s Disease, and specific regions of the cortex degenerate in Alzheimer’s. The possibility that stem cells enter these regions from the RMS could therefore provide a means for developing new treatments for neurodegenerative diseases.

Update: Evidence of neurogenesis in the adult human olfactory bulb was obtained by Bedard and Parent in 2004.

Update 2: The figure on the right (from Gray’s Anatomy) shows the simple cellular structure of the distal tip of the human olfactory bulb. The olfactory cell is a primary sensory neuron that contains olfactory receptors, which are activated by the binding of odorant molecules. In the glomerulus, olfactory cells synapse with the secondary cells, which form the olfactory nerve (cranial nerve I).

The olfactory epithelium is a neuroepthelium – a single layer of cells, in which the cell bodies of the olfactory cells nestle in between specialized epithelial cells. This single cell layer forms the roof of the nasal cavity, so one side of layer is exposed to the open air. It is therefore easily damaged by, for example, inhalation of toxic fumes; olfactory epithelial cells retain their capacity for neurogenesis into adulthood, so that damaged cells can be replaced after minor injuries. The other cells in the olfactory bulb are similarly exposed to air, but to a lesser extent. This is the likely reason that the tissue has retained its regenerative capacity.

References:

Curtis, M. A. et al. (2007). Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science (Advance online publication) DOI: 10.1126/science.1136281

Gritti, A., et al. (2002). Multipotent neural stem cells reside in the rostral extension and olfactory bulb of adult rodents. J. Neurosci. 22: 437-445.

Bedard, A. & Parent, A. (2004). Evidence of newly generated neurons in the human olfactory bulb. Brain Res. Dev. Brain Res. 151: 159-168.

Costanzo, R. M. (2005). Regeneration and rewiring of the olfactory bulb. Chem. Senses Suppl 1: i133-i134.