The Role of Astrocytes in Lou Gehring’s Disease


A study from Columbia University and Harvard University has uncovered a complex interplay between neurons and support cells known as astrocytes that contributes to the pathology of ALS. Such an intricate interplay complicates regenerative therapies for this disease.

In the spinal cord, a group of neurons called motor neurons extend their axons to skeletal muscles and provide the neural signals for the muscles to contract, which allows movement. Motor neurons also have associated support cells known as glial cells, and a specific group of glial cells known as astrocytes associate with motor neurons in the spinal cord.

Astrocytes are star-shaped cells that surround neurons in the brain and spinal cord, and they outnumber neurons 50:1. Astrocytes are very active in the central nervous system, and serve to maintain, support, and repair the nervous tissue that they serve, and are responsible, in large part, for the plasticity of the nervous system.

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Motor neurons die off during the course of ALS, which leads to paralysis and death within two to fives years of diagnosis. ALS also affects neurons in the brain and it completely robs the individual of the ability to initiate movement or even breathe. There is, at present, no cure and no life-prolonging treatment for ALS.

Data from the ALS Association group suggests that astrocytes in ALS patients go from supporting neurons to strangling them. According to Lucie Bruijn, the chief scientist at the ALS Association in Washington D.C.,, these results seem to “strengthen the case that astrocytes are central to the ALS disease process.” She continued: “Furthermore, the results are based on an exciting new disease model system, one that will allow us to test important hypotheses and search for new therapeutic targets.”

In a cell culture system of ALS, in which neurons derived from embryonic cells were co-cultured with normal and ALS astrocytes, Bruijn’s team found that gene expression patterns in those neurons associated with ALS astrocytes were abnormal. In this experiment, neurons derived from embryonic stem cells with co-cultured with normal and ALS affected astrocytes. In a time course experiment in which gene expression profiles were analyzed from the neurons after specific amounts of time, the gene expression patterns from the normal astrocytes co-cultured with neurons were compared with those of the ALS-affected astrocytes co-cultured with neurons. From these experiments, it became clear that the ALS-affected astrocytes did not communicate properly with the nearby neurons.

Even though neurons communicated with each other by means of the release of neurotransmitters, astrocytes and other glial cells also communicate with each other by means of the release of various molecules. This astrocyte-neuron communication maintains healthy neuron function. However, in the case of ALS, the neuron-astrocyte communication is “profoundly disrupted” and is disruption is not neuron dependent, since in this experiment, the neurons were normal. Without proper communication with their astrocytes, motor neurons the spinal cords of ALS patients are not able to function properly.

According to Bruijn, “This study points out several potential points for treatment intervention.” The protection of motor neurons is the goal, since the astrocytes seem to be doing little to protect and support the neurons and also might be hurting them.

An added bonus to this study is that when spinal cords from mice with a disease that shows some similarities to ALS have their gene expression profiles compared to these gene expression profiles observed in the cultured neurons, the results are remarkably similar. This shows that culture system does recapitulate what goes on in the spinal cord.

The next step is to show that the molecular abnormalities discovered in this system mimics those that occur in human disease. This publication utilized mouse cells, and the human disease, while similar, is not exactly the same.

Local Anesthesia Inhibits Mesenchymal Stem Cells


Anyone who has had dental work or particular out-patient procedures has had local anesthesia. Local anesthesia inhibits local sensory nerve function and induces numbness. Several studies have shown that when used at high concentrations, local anesthesia can cause particular cells to die. Therefore, some physicians worry that local anesthesia might affect stem cells, but the effects of local anesthesia on mesenchymal stem cells is largely unknown.

To this end, Michael Zaugg from the University of Alberta and his talented co-workers examined the effects of local anesthesia on mesenchymal stem cells from bone marrow. Their results were from experiments on cultured mesenchymal stem cells.

When mouse bone marrow mesenchymal stem cells were isolated and grown in culture and exposed to 100 micromolar concentrations of three different local anesthetics, lidcocaine, ropivacaine, and bupivacaine, they discovered that the mesenchymal stem cells grew much more slowly. In fact, the stem cells seemed to divide and then give up the ghost. Therefore, local anesthetics seemed to inhibit mesenchymal stem cell proliferation.

Upon further investigation, the stem cells stopped dividing at the point when they were supposed to start making new DNA. This phase of the life of the cell is called the S phase for synthesis phase, and the molecule made by the cell at this time is DNA. However, the mesenchymal stem cells exposed to local anesthetics failed to initiate DNA synthesis.

The next question Zaugg and his team asked was whether or not the stem cells had trouble making energy, which is a common feature of cell exposed to too much local anesthetic. Indeed, the mesenchymal stem cells exposed to local anesthetics showed reduced energy production.

A more sophisticated analysis called “microarray analysis,” which examines the gene expression patterns in a cell by a gene-by-gene basis, showed that those genes necessary for cell membrane synthesis were greatly decreased when the cells were exposed to local anesthetics. Furthermore, the mesenchymal stem cells exposed to local anesthetics differentiated quite poorly, and the microarray analysis confirmed this observation, since those genes necessary for differentiation in mesenchymal stem cells were down regulated in the presence of local anesthetics.

Before conclusions can be drawn about what local anesthetics do to a living creature during wound healing, more work must be done, First of all, these results from cultured cells may not hold true in a living organism. Also, the concentration of anesthetic used in this study is well above what are acknowledged to be toxic levels for these drugs. Therefore, while these results are informative and interesting, the must be interpreted with some caution.