РефератыИностранный языкExExcitotoxicity Essay Research Paper ExcitotoxicityThis theory is

Excitotoxicity Essay Research Paper ExcitotoxicityThis theory is

Excitotoxicity Essay, Research Paper


Excitotoxicity


This theory is based on the fact that glutamate, an amino acid present in proteins, can cause neuronal cell death when


present in high concentration. The specific evidence for the excitotoxic theory comes from the demonstration of


decreased levels of glutamate in ALS spinal cord, with the assumption that glutamate must have been released and must


have been present in high concentrations that would have been toxic. In addition, there is a decreased ability of


glutamate to be taken up in fractions of spinal cord tissue of ALS patients taken at autopsy. Such data would suggest


once again that glutamate might have been elevated as a result of a failure of uptake. However, the changes in glutamate


could also be secondary to damage or loss of motor neurons. Thus, it is not clear what triggers the release of glutamate


and the failure of glutamate uptake. Nevertheless, the fact that glutamate can be toxic for motor neurons does suggest


that glutamate may play a role, if not in causing ALS, then possibly as a participant in motor neuron injury.


Trophic factors


Recent research has documented that the growth and maintenance of motor neurons are dependent on protein nutritive


hormones called neurotrophic factors. Insulin like growth factor-1 (IGF-1), ciliary neurotrophic factor (CNTF), and


brain-derived neurotrophic factor (BDNF) are all examples of such neurotrophic factors which have been documented


to influence motor neuron development and maintenance. In addition, such factors appear to influence the regenerative


and repair capacity of motor neurons. IGF-1 is now considered to be the major factor which produces sprouting of


nerves in man. These neurotrophic factors have considerable potential in motor neuron repair and could possibly


function as neuroprotective agents and play a meaningful role in therapy.


iopsy of affected tissue early in disease is often a necessary step in finding or v

erifying a cause for that disease. Therefore, it is


important that we attempt to study more easily accessible neurons that are affected after the diagnosis of ALS is made, but still


early in the course of the disease. But where might such neurons be found? For the past decade, Dr. Ono (a researcher from


Japan) has reported abnormalities in the skin of patients with ALS. These changes, that alter the normal structure of the


connective tissue between cells, may explain why patients with ALS who are confined to the bed or wheelchair seldom get


bedsores. While these changes occur relatively late in the disease, Dr. Provenciali and others from Italy published findings


suggesting that neurons to skin sweat glands and arterioles may be affected much earlier in the course of ALS. Following the


publication of recent work of Dr. Siklos in our laboratory, we were excited to discover that some of the same structural


changes found at the ends (or synapses) of motoneurons in early ALS are similar to changes reported for skin neuron terminals.


Since then, we have performed functional tests on forearm skin neurons in persons with ALS, and have found that those


neurons that control the increase of blood flow through small skin blood vessels are not working properly early in disease, with


obvious dysfunction observed in patients with more severe disease.


So, if skin neurons are affected early in ALS, can we gain a better understanding of why motoneurons die in ALS by studying


skin? We won’t know unless we try. For those patients seen at the MDA sponsored Baylor Neurology ALS Clinic (many of


whom have already had functional skin tests performed on their forearms), we will soon be asking for a small piece of skin. We


will be studying the skin of patients in the early as well as those in the later stages of ALS. We need to see if later skin changes


may be caused by the same processes that affects skin neurons early in the disease.


http://www.bcm.tmc.edu/neurol/struct/als/als6.h

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