Biology 202
2000 First Web Report
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Pieces of a Whole

Susan Lee

Oftentimes we do not fully appreciate the paradox that is created by our attempts to better understand the living body. At first glance one would be more than willing to accept that the human body is a highly complex piece of machinery. However, to look deeper than that, looking at the pieces that together form this machinery, one finds that the complexity is in fact formed of simple building blocks. Take for example the central nervous system; it produces a great diversity of functions. Not only does the central nervous system control what the body relays to the outside world, but it also controls internal functions. All of this is accomplished by an intricate system of neurons, more importantly this complex system is composed of individual neurons. By understanding this hierarchy of structure we can better attempt and possibly succeed at healing the whole body by looking at the individual pieces. One such case involves the treatment of a neurodegenerative disorder such as Parkinsonís Disease.

Parkinsonís disease is the result of neuronal cell death in a localized region; the substantia nigra pars compacta (SNpc) (1). . This structure is located in the ventral part of the tegmentum of the midbrain and is identified by its dark pigmentation(1).. The pigmentation is due to the production of neuromelanin during the synthesis of dopamine, a neurotransmitter (1).. Neurons of the SNpc are associated with the release of dopamines; thus, loss of these neurons results in decreased levels of dopamine (1).(2).. Physically the loss of SNpc neurons results in the loss of voluntary motor control (1).. Symptoms include bradykinesia, ridgity, tremor, and impairment of postural reflexes (1). By the time the symptoms manifest themselves 80% of the SNpc neurons have already been lost (1).. It is not fully understood what causes the degeneration of these cells; however treatment research is well underway.

In terms of treatment there exists two possible avenues: 1) slowing the degeneration of cells and 2) replacing damaged cells through neuronal transplants (1).(2).. One possibility in the slowing of the progression of cell death in SNpc relies upon the inhibitor of the enzyme Mono-Amine-Oxidase B (MAO-B) (2).. This treatment was derived from observations of symptoms of Parkinsonís in people who had used the drug MPTP (2).. Conclusions were drawn that the debilitating symptoms of Parkinsonís were due to the production of toxins from MPTP in the brain (2).. MAO-B inhibitors work by preventing this toxin production (2).. Initial clinical trials suggest that this treatment is effective; yet, upon extensive trials these effects were attributed to other factors (2).. Although treatments to hinder the progression of Parkinsonís is highly beneficial in alleviating symptoms of the disease it does not halt nor reverse the effects.

The next logical step in treatment would appear to be in the regeneration or replacement of those neurons that were already lost to the disease. Two sources of transplant tissue under consideration are tissues from the adrenal medulla and fetal tissue(1).(2).(3)..It was believed that adrenal medulla grafts could produce the dopamine that was deficient (2).. Adrenal medulla grafts consist of the removal of one of the patientís own adrenal glands which is then dissected for the medulla (1).. The medulla is then placed in a cavity created in the right caudate nucleus located in the head (1)..Although this procedure seems quite possible in theory, there still exists no evidence that this graft produces sufficient amounts of dopamine to compensate for the lost SNpc cells (2)..Also these grafts do not produce synapses; therefore, there does not exist communication between nerve cells (2)..In order for the treatment to be effective the nervous system must form contacts (synapses) with the grafted tissue. How then can such synapses be creatcontacts ed?

In laboratory animal experiments it has been found that implanted fetal neurons are capable of forming synapses and producing neurotransmitters(1).(2).(3)..These neurons are obtained as neuroblasts from the embryonic substantia nigra region (3). .Once implanted they were found to reinnervate and restore dopamine release to near normal levels (3). . They were also found to function for extended periods of time (3)..Before the transition can be made from laboratory animals to humans several considerations must be made. The survival and growth of dopamine neurons must be greatly improved, under current conditions the size of implant is not feasible for larger brain sizes such as that of humans (3)..Also the transplanted cells may also be under the detrimental effects of the disease as are their host cells (1). . Another implication of fetal tissue implantation lies in the acquirement of the tissue(1).(2).(3).(4).(5)..

Problems that arise from the use of fetal tissue are not only ethical, but also involve the maintenance and availability (3)..Therefore, alternative sources must be considered. One such alternative is the use of manufactured human neurons (4).(5). . The source of these neurons originated from a 22 year old male patient at Memorial Sloan-Kettering Cancer Institute (4).(5). . He suffered from a rare cancer of the reproductive organs, called teratocarcinoma (4).(5). . Cells from this tumor were similar to those of an embryo in that they were still immature and could form cells of specific functions such as nerve cells (4).. When retinoic acid was added to these cells mature neurons were formed (4).(5).. These manufactured neurons were termed LBS-neurons after the lab in which they were produced (4).(5). . Experimentation using the LBS-neurons has so far only been performed on stroke victims. As of yet it is still too early to determine the full effects of the transplant(4).(5). .

The more that one learns of dysfunctions of the body such as neuro-degenerative disease the more that one learns about how the body should function. By looking closer and closer at the sources of the problem one comes to better understand how the body should normally function and how the smaller pieces must be fixed in order to maintain the well-being of the overall structure.

WWW Sources

1)Transplantation: A New Era in the Treatment of Parkinsonís Disease

2)The Harvard Mahoney Neuroscience Istitute Letter On the Brain,

3)Cell Transplantation Strategies In parkinsonís Disease,

4)PG News: One step closer to brain repair,

5)UPMC: News Bureau,

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