Chemical changes in the Brain
In Parkinson’s disease (PD) there is slow and progressive loss and deterioration of nerve cells of the brain especially those involved with regulation and control of movements.
In a healthy person, an adequate amount of dopamine (a chemical messenger present in the body) is present in substantia nigra (an area of cluster of nerve cells in the brain). Normally, dopamine is carried by the nerve cells from this area to another cluster of nerve cells known as the corpus striatum where these nerves terminate. Here, along with dopamine, acetylcholine, another chemical messenger, regulates the bodily movements.
In a patient with Parkinson’s disease there is an imbalance between these two chemical messengers. In most of the cases, there is loss of dopamine in the substantia nigra and degeneration of dopamine nerve terminals in the corpus striatum.
Approximately 60-80% of dopaminergic neurons are lost before the motor signs of Parkinson disease emerge. Rarely, the hyperactivity of acetylcholine nerve cells may be the underlying cause of Parkinson’s disease. Another change observed in some cases is the presence of protein clusters known as “Lewy bodies” in the brain, which are characteristic, but not specific of PD.
At present, it is believed that PD is mainly caused by environmental factors and hereditary factors. A genetic predisposition (i.e. higher risk of disease if any close relative is suffering from PD) has been seen in the patients. There are very rare families where PD is inherited.
Oxidative Stress in Parkinson’s Disease
The possible role of environmental risk factors associated with the development of disease include use of pesticides, consumption of contaminated well water, exposure to herbicides, and proximity to industrial plants or quarries. The most accepted theory establishing the link between these factors and degeneration in the brain is that of “oxidative stress”.
The role of oxidative stress (increased levels of free radicals) in PD has been extensively studied. The utilization of energy in the brain can lead to increase in the concentration of free radicals (unstable highly reactive chemical compounds) e.g. hydrogen peroxide. In healthy individuals a balance is maintained between antioxidants and oxidative ions and thus oxidative stress does not occur. But in patients of PD, increased concentrations of free radicals and decreased levels of antioxidants have been observed which lead to nerve damage by lipid per-oxidation and pore formation in the cell membranes.
Drugs that Affect the Brain Chemistry in PD
The presently available treatments are symptomatic i.e. they treat the disease but do not alter the underlying degenerative process. These are helpful in restoring and maintaining function and quality of life for many years. Most of the drugs help in restoring dopamine levels in the brain. They either :
- increase the synthesis of dopamine (e.g. levodopa and carbidopa combination)
- enhance the action of dopamine (e.g. ropinirole, pramipexole)
- decrease the degradation of dopamine (e.g. selegiline – selective inhibitor of MAO-B / Mono amine Oxidase B, an enzyme degrading dopamine)
- inhibitors (tolcapone and entacapone) of another degrading enzyme, COMT / catechol-O-methyl transferase
The symptoms of PD in patients taking certain drugs especially antipsychotics like chlorpromazine can be treated by giving anticholinergic drugs like benztropine. The drugs which increase the dopamine levels are not helpful in these patients. The preventive role of antioxidants is still under study.