Neurotoxicant exposure causing neurodegenerative diseases

The study of the chemicals that pose bad effects on the nervous system is known as neurotoxicology and such chemicals are named neurotoxicants. These chemicals may be synthetic or natural. There are hundreds of those chemicals known to scientists that are affecting the normal functioning of the nervous system either directly or indirectly.

NEURODEGENERATION:

Neurodegeneration involves a wide range of critical disorders of neurons and the nervous system. These disorders are known from the early history of humans and shown the brain malfunctioning for hundreds of years. During the last 100 years, the relationship between Neurodegeneration and neurologic diseases has been explained in great detail.

NEUROTOXICANTS EXPOSURE:

Several toxicants have been exposed to humans from early times including both natural and manmade. Minimum 10,000 toxins have been exposed in the last 10 years including drugs, cosmetics products, food preservatives and additives, pest control chemicals, and fumigants, these all have been registered for commercial use in several countries in the United States. 2/3rd of all xenobiotics uses in agriculture include herbicides. About 1/8th includes insecticides and that of fumigants, fungicides, and other pesticides cover 20% of agricultural xenobiotics.

A link between human health and exposure to xenobiotics is indicated by several recent reports, which highly involves the defects in Central Nervous System.

In addition, various reports have suggested and described the effect of a pesticide poisoning event on long-term neurologic and behavioral disorders.

For example:

Many studies on animals had shown evidence that 8 weeks of continual exposure to lead results in a remarkable increase in lead accumulation in the brains as wells as the blood of animals that had exposure to it, these animals become more suspected of the disorders and toxic effects of this toxin. Thus, animals exposed to only lead have less level of lead in their brains than those who were exposed to lead and ethanol (they have twice higher levels).

NEUROTOXIC AGENTS:

1.Beta-amyloid

Beta-amyloid if present in high concentration, is likely to cause cell death and toxicity of neurons in the brain. When protein chains are made of wrong lengths by mutations these wrong length chains are unable to be used by the body and thus consequently result in the formation of beta-amyloid. Thus, these chains remain inside the brain until they are broken down if they accumulate in the brain at high levels, resulting in plaque formation that is toxic for brain cells.

2.Glutamate

Glutamate is a poisonous chemical that is found inside the brain, it poses threat to neurons if it is present in a high amount in the brain. The concentration of glutamate in the brain is highly sensitive it is commonly found in millimolar concentration in the brain outside the cells.

Glutamates transporters are special pumps to drain out the glutamate from the brain, if any mutation occurs in these transporters then glutamate accumulates in the brain and causes disorders due to excessive amounts of glutamate. If these transporters work normally then the level of glutamate becomes higher in blood than in the brain. And then the body must act to maintain the balance.

3.Oxygen radicals:

The oxygen radicals are formed in the brain via the pathway known as the nitric oxide synthase pathway or NOS. it occurs in response to the increase of concentration of calcium ions in the brain cells.

The interaction among these ions and NOS leads to the formation of cofactor BH4 known as tetrahydrobiopterin. It further moves into the cytoplasm from plasma membranes and finally, dephosphorylation occurs of NOS and yields nitric oxide (NO). this oxide accumulates in the brain and leads to an increase in the oxidative

MAJOR NEURODEGENERATIVE DISEASES:

Several diseases related to humans can be listed among neurodegenerative diseases, a few of those diseases among them are found less and they are found to be occurred because of some genetic factors. Very few diseases are responsible for most of the case’s prevalency.

Moreover, exposure to environmental toxicants also related to several diseases of neurons. It is essential to know that one environmental factor can be responsible for several cases.

1.Alzheimer’s Disease (AD):

About 5.4 million Americans have been affected by the most common neurodegenerative disease which is known as Alzheimer’s disease, AD. It is a harmful disease and its most commonly occurring symptom in a wide range of patients includes dementia. Dementia is a disease related to memory loss. The average life expectancy of such patients is 7 years and it can be 14 years for less than 3% of people. This disease cannot be diagnosed at the age of 65 years or less.

Some of the vital features of AD include exposure to Aluminum in rodents. Meanwhile, the results of exposure mainly affect the reproduction process in that rodent’s population. Aluminum is found to cause aggression in vitro media but not in the in vivo media.

 The process is still left to be found out by which aluminum play role in the pathogenesis of AD. The concentration of aluminum that occurred in the brain of human patients who passed on due to AD indicated that the carbohydrate metabolism was inhibited in the brain.

 2.Parkinson’s Disease (PD):

It is the common neurodegenerative disease at second number. It has been affected about an estimated size of 5 million people throughout the world.

It is found to be responsible for disorders of many brain stem nuclei and other areas of the human brain. It also involves the commonly occurring systemic pathology.

The estimated size of about 10% of cases is due to genetic factors of the disease. And are inherited but, most of those cases are known to be evolved due to unknown causes. In contrast to AD, PD includes massive links with environmental exposures.

The behavioral phenotype of PD which is called Parkinsonism is induced due to various chemical agents. This phenotype like some of the features of behavioral origin of PD, but it is distinguished from its mechanisms and pathological features. Examples is known for the compounds including insecticides containing organophosphate type compounds, gases from industries, and various pharmaceuticals.

3.Multiple cases of sclerosis: (M.S.):

M.S. (Multiple Scleroses) is the disorder of the nervous system in which myelin sheath, a fatty layer, around axons of the brain and the spinal cord degenerates. Thus, it leads to demyelination and damaging of axons.

This disease is highly variable in forms such as genetic basis, geographic basis, and ethnic variables. In the United States, estimated size of about 200,000 people is known to be affected. Their symptoms of the disease are widespread damage to all types of functional neurons involving sensory, motor, and autonomic functions.

4.Amyotrophic Lateral Scleroses (ALS):

Amyotrophic lateral sclerosis (ALS) is a disease in the motoneurons which is mainly characterized by the damage of brain stem neurons. Also, in the efferent and dorsal horns of spinal cords within motor neurons. It mainly includes the brain.  The risk of ALS is less in the young’s approximately about 1-2 in 100,000 individuals in a lifetime but later it approaches about 1/400 and then to 1/700. The most common symptoms of ALS include weakness, muscular atrophy, and spasticity of the brain.

ALS is a disease that can be fatal with progressive severances. It normally has 3-5 years survival rates in patients due to respiratory malfunctions.it also causes bulbar dysfunction. Only about 2% of cases are found to be caused due to mutations in the superoxide dismutase 1 and 10% of cases of ALS are found to be familial.

5. Guam-ALS-Parkinsonism-Dementia

It is a disease characterized by the combined effect of disorders caused by ALS, Parkinsonism, and dementia. It forms a complex known as ALS-PDC (ALS- Parkinson dementia complex). A wide literature range has focused on this combination of three different neurologic disorders in a single person.

NERVOUS SYSTEM SENSITIVITY TO EXPOSURE TO NEUROTOXICANTS.

There are highly variable symptoms of neurotoxicant exposure. The variety of these symptoms arises due to the specific disease factors. Such as the area of the nervous system being affected. Cognitive effects may be included in the manifestation of neurodegenerative diseases.

The mental defects and movement abnormalities, sensory and motor dysfunctions, and sensory defects.  The nervous system in mammals is among the special ones of all creatures due to the diverse functions and requirements of their body systems. These features cause it to be sensitive and highly suspected to these neurodegenerative diseases.

ANATOMICAL LIMITATIONS:

The central nervous system is limited anatomically of its major parts i.e. brain and of the spinal cord. In the other systems of the body such as respiratory, digestive and circulatory system, the change in organ sizes could be tolerable to some limit but in case of the central and peripheral nervous system, these minor change can be detrimental and leads to the ultimate or sudden death of an individual.

Reviewed by:
Dr. Muhammad Adnan Asghar (Ph.D.)

Chinese Academy of Sciences Fuzhou, Fujian