Pure Pedantry

There has been a big debate over the last couple years about whether the adult human brain is capable of generating new neurons.

A new study in Neuroscience by Larsen et al. provides some relevant new evidence to that debate. It used rigorous stereological measurement — a technique called the optical fractionator — to show that in newborn humans there are the same number of neurons as in the adult brain. This result would lend credibility to the notion that large numbers of new neurons are not being produced in the postnatal human brain.

This is the first time the total number of cortical neurons in the brains of human newborn has been estimated. The largest population of neurons in the human brain is the cerebellar granule cells reading approximately 100 billion (Andersen et al., 2003). The second largest population of neurons in the human brain is the neocortex, with a range from 15 billion to 32 billion (Pakkenberg and Gundersen, 1997). The total number of neurons (19.8×109) in the MZ/CP is about the same number as the one in neocortex in the adult brain ranging from an average of 19 billion in the female brain to an average of 23 billion in the male brain with a high biological variance. The total cell population in the CP was estimated to approximately 32.6 x 10^9, which is in accordance with previous estimates on the total cell number in the human brain during development (Samuelsen et al., 2003).

The total cell population in the adult neocortex reach approximately 50 x 10^9 (Pelvig et al., 2003) probably due to an increase of neocortical glial cells with an intensive production taking place postnatally. It has generally been accepted that the number of neurons in the human brain is determined at birth and that the total neuron number postnatally can only decrease. However, in the last decades, research has found the brain to be capable of some potential for self-repair and regeneration. Neurogenesis in the adult human brain has raised hopes that self-renewal leading to structural repair by new neurons may be possible even in the mature CNS (Hallbergson et al., 2003). Nevertheless under normal conditions, neurogenesis in the adult human brain appears to be primarily concentrated in the discrete germinal centers: the SVZ and the hippocampal dentate gyrus (Eriksson et al., 1998). The neurogenesis in the subgranular zone of the dentate gyrus gives rise to the granule cells, and the VZ/SVZs in the anterior part of the lateral ventricles generate new interneurons of the olfactory bulb (Bjorklund and Lindvall, 2000). Progenitor cells in other parts of the CNS contribute to ongoing formation of new non-neuronal cells and the neurogenesis that has been described in parts of intact neocortex of adult monkeys is still controversial (Gould et al 1999 and Koketsu et al 2003). More studies are needed to establish the origin, extent, survival and function of new neurons in other regions. We found the total number of neocortical neurons to be the same in the newborn brain as in the adult neocortex, supporting the theory that the neocortical neuron population is determined prenatally. (Emphasis mine.)

This study does not preclude the possibility that new neurons are being produced. There is still the possibility of a certain level of turnover — cells being produced at the rate that old cells are dying. However, it does preclude the possibility of massive production of new neurons over the course of postnatal life. It would appear that the vast majority of new cells in the postnatal human brain are of glial origin.

Studies like this may seem somewhat pedantic, but they are very difficult and time consuming to do, and they need to be done in order to help clearly resolve contreversies like adult neurogenesis.

Hat-tip: Faculty of 1000.

Comments

  1. #1 Peter Znamenskiy
    July 11, 2006

    Hmm… The relevance of this to study of adult neurogenesis is limited by the fact that the authors only estimate the number of neurons in the neocortex. As far as I know, evidence for adult cortical neurogenesis is blurry at best. The place to look is the hippocampus. The literature on hippocampal neurogenesis in rodents is massive. In humans, for obvious reasons, it is much more limited. It has been illustrated when the thymidine analogue bromodeoxyuridine (BrdU) was administered to brain cancer patients for therapeutic reasons. BrdU, a marker of DNA synthesis, could later be detected in cells of the hippocampal dentate gyrus that possessed neuronal characteristics.

    Nevertheless, your comment about turnover is valid indeed. Antidepressants are well established to increase the number of newborn hippocampal neurones in rodents. However, the number of apoptotic neurones increases simultaneously. So, if antidepressants do act by stimulating neurogenesis, they do so by increasing the number of new neurones for the hippocampus to choose from, rather than their total growth rate.

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