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A migratory stream in the human brain

Nature Reviews Neuroscience 8, 4 (April 2007) | doi:10.1038/nrn2115

Throughout the postnatal life of rodents, neural progenitor cells migrate from the subventricular zone (SVZ) of the forebrain through the rostral migratory system (RMS) to the olfactory bulb. Although humans also have an SVZ, until now the existence of an RMS had not been demonstrated. In a paper published in Science, Curtis et al. describe evidence of a well-defined RMS in the human brain.

The authors stained sections of adult human brains with an antibody for proliferating cell nuclear antigen (PCNA), which is expressed in dividing cells. They identified a Nissl-positive structure containing a stream of PCNA-positive cells that, starting in the SVZ, followed a caudal and ventral path (which they named the descending limb of the stream), wrapping itself around the rostral side of the caudate nucleus. From the bottom of the caudate the stream turned rostrally and ventrally (and was named the rostral limb of the RMS) towards the anterior olfactory cortex, where it entered the olfactory tract and eventually the olfactory bulb. 90% of the PCNA-positive cells were found in the descending limb of the human RMS, whereas the rostral limb only contained 10%, indicating that more proliferation took place early in the RMS and that, as in the rodent RMS, cells may start differentiating as they approach the olfactory tract.

To assess whether the cells forming the RMS were indeed migratory, the authors stained sections for polysialylated neural cell adhesion molecule (PSA–NCAM), which is expressed by migrating neurons. PSA–NCAM-positive cells were found throughout the RMS. Furthermore, betaIII-tubulin, a marker of immature neurons, colocalized with PSA–NCAM in cells in the SVZ, olfactory tract and olfactory bulb. Electron microscopy confirmed that the SVZ cells resembled the migratory cells found in the rodent SVZ. Together, these data indicate that the human brain contains an RMS consisting of migrating neuroblasts.

The researchers also used a BrdU antibody to stain olfactory bulb sections taken from the brains of people who had been given BrdU infusions. Using laser scanning confocal microscopy, they found that BrdU colocalized with NeuN, a marker of mature neurons, demonstrating that the olfactory bulb contains adult-born neurons, which may have migrated there through the RMS.

Examination of the human olfactory bulb by microscopy and MRI revealed the presence of a fluid-containing ventricle connected to a tube-like structure that was surrounded by the descending and rostral limbs of the RMS. This indicates the possibility, previously proposed for neuronal migration in the rodent RMS, that cerebrospinal fluid in these structures might support the migration of neuroblasts from the SVZ to the olfactory bulb.

The shape of the human RMS differs substantially from that in rodents. Curtis et al. suggest that the large prefrontal cortex and the position of the SVZ in humans have forced the RMS to turn caudally before moving rostrally in order to reach the olfactory tract and bulb. They speculate that this shape made it hard to identify the human RMS in coronal brain sections used in previous studies. The identification of a human RMS will no doubt inspire research into the function of SVZ stem cells as well as newborn neurons in the human olfactory system.

Leonie Welberg - Copyright © 2007 Nature Publishing Group, a division of MacMillan Publishers Limited; used with permission

ORIGINAL RESEARCH PAPER

  1. Curtis, M. A. et al. Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science 315, 1243–1249 (2007). | Article | PubMed | ChemPort |