ALS – A Total Neural Loss

21. February 2011
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Massive changes in immature neurons, which normally persist in the nervous system, are possibly a key mechanism in incurable amyotrophic lateral sclerosis (ALS).

The CNS of mammals contains a population of glial stem cells that can potentially develop into oligodendrocytes. These cells, called NG2+, grow and expand during early development, so that later in life they slowly but steadily transform into oligodendrocytes, which are involved in the formation and preservation of the cell-protective substance myelin. The isolation of nerve cells by myelin allows the acceleration of the transmission of electrical impulses to occur and in diseases like multiple sclerosis is broken.

Oligomeric precursors out of control

That NG2+ cells behave completely differently in the nervous system of mice with induced ALS to those NG2+ cells in healthy mice is revealed in an investigation by neuroscientists working with Dwight Bergles at Johns Hopkins University School of Medicine in Baltimore, USA.

They followed the development of these progenitor cells in healthy mice and animals with a mutation of the gene SOD2, which causes ALS. A colour marker permitted their localisation and tracking at different points of their development.
While the growth scheme of the NG2+ cells in healthy tissue of the spinal cord quietly elapsed, mature cells steadily developed or precursor cells were replaced, the cells in the degeneratively-altered tissue appeared to be out of control. The researchers compare the behaviour of these cells with a high-speed treadmill. They multiplied excessively and transformed much more easily into oligrodendrocytes, that looked neither normal nor were viable for a long time. Cell death after differentiation was rapid. Natural mechanisms, which interrupt this process and keep the cells in check, seemed to have been overriden.

Protection or destruction?

Thus, NG2+ cells are the cell population with the highest rate of proliferation in the spinal cord of mice with ALS. Improperly-functioning oligodendrocytes are continually produced, according to the researchers. They suspect that already before the degeneration of nerve tissue, it gets to the point where massive destruction of oligodendrocytes occurs, which could play a role in the progression of the disease.

But the importance of, on the one hand, massive cell activity with the production of oligodendrocytes in the grey matter of the CNS and, on the other, the destruction of motor neurons, remains in the final analysis unclear. It is known that oligodendrocytes are attacked particularly easy by oxidative stress. It is also known, however, that after acute trauma of the CNS an increase in NG2+ activity can be observed, which possibly represents an attempt to limit the damage.

Trauma and ALS

That there may indeed be a relationship between CNS trauma and ALS was revealed in a recent investigation by the Center for the Study of Traumatic Encepalopathy (CSTE) at the Boston University School of Medicine. Studies of the brain and spinal cord of professional football players and one boxer showed that they more often develop a disease which is strikingly similar to ALS. Three in twelve former professional athletes presented an abnormal protein that is also found in the sporadically occurring form of ALS. Four of the twelve men had during their lifetime been diagnosed with ALS.

NG2+ not multipotent, but perhaps influenceable

The research group led by Bergles was able to obtain further insights: NG2+ cells had long been considered multipotent. Consequently, it was assumed that they were in fact stem cells, which have the ability to develop into different cell types in the nervous system. This is obviously not true. In the present investigation no proof has been found that the cells develop into anything other than oligodendrocytes, in both the sick and the healthy.

There are perhaps factors that inhibit the development of other cells of the nervous system, say the scientists. To track and to influence them might be possible in the future and thus influence the course of ALS and a new approach to ALS.

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