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Biology 202
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How Does Lead Effect the Nervous System?

Anjali Patel

In 1890, the first case of lead poisoning was discovered in Australia. However the source of the lead was not traced to the paint on the verandahs and railings until 1904. In the United States the first recorded case of lead poisoning occurred in 1914 when a little baby ate the paint chips from his crib; this characteristic of children to taste everything the touch is referred to as pica. Lead is an extremely common metal that can be found almost anywhere. Some common sources of lead include: water, paint, electric storage batteries, insecticides, auto body shops, gasoline, etc. Even though there have been steps taken against lead with the Lead-Based Paint Poisoning Prevention Act, lead is still a public health risk today. (1) What does lead do exactly that is so harmful to the human body? More specifically how does lead effect the nervous system?

Most of the dysfunctions produced by the absorption of lead are due to lead's ability to mimic and inhibit the actions of calcium. (2) In humans the lead is directly absorbed, distributed, and excreted. Once in the bloodstream lead is distributed to three main compartments: blood, soft tissue (kidney, bone marrow, liver, and brain), and mineralized tissue (bones and teeth). (3) Lead effects children and adults in different ways. Low lead levels in children can cause the following side effects:

In adults high levels of lead in their systems can cause the following: Once lead enters the body it interferes with normal cell function and physiological processes. Some of the physiological effects of lead include harm done to the peripheral and central nervous system (PNS, CNS), blood cells, metabolism of vitamin D and calcium, and reproductive toxicity. The nervous system seems to be the most sensitive to lead poisoning. (3)

Neurons are the functional unit of the nervous system and are specialized for the transmission of signals from one location to the next. The dendrites of the neuron receive the input signal and relay it to the rest of the neuron. The axon of the neuron relays this input signal in the direction of its tips. The tips of the axon have specialized endings known as synaptic terminals that relay the signal to other cells by using a chemical messengers, neurotransmitters. The neuron will release the neurotransmitter molecules, located in synaptic vesicles, into the synapse only when an action potential arrives and depolarizes the surface of the synaptic terminal that before the cleft. Calcium ions play an important role in the nervous system; they help convert the electrical pulse into a chemical signal. The depolarization of the presynaptic membrane causes the calcium ions to travel through voltage gated channels into the neuron. The sudden increase in the concentration of calcium triggers the synaptic vesicles to fuse with the presynaptic membrane, spilling the neurotransmitters into the synaptic cleft by means of exocytosis. The neurotransmitters then go on to diffuse through to the postsynaptic cleft, which is the plasma cell body (or dendrite) on the other side of the synapse. (5)

Cells absorb lead through the same channels they absorb calcium from. The drugs that regulate the intake of calcium also increase the amount of lead uptake. High levels of lead decrease transport of calcium and vice versa, therefore these two metals function as competitive inhibitors. Lead can enter through the same ion channels as calcium and regulate the activity of those channels to uptake more lead into the cell. (2)

Lead, even at low concentrations, has the ability to increase the basal release of the neurotransmitters from the presynaptic nerve endings. This can occur both in the PNS and CNS. Micromolar concentrations of lead can cause the spontaneous release of dopamine, acetylcholine (ACh), and gama-aminobutyric acid (GABA). (2) Control movement and emotional response are some of the brain processes that are affected by dopamine. (6) An acetylcholine receptor has the responsibility for transducting nerve impulses to muscular contraction. (7) GABA is an amino acid classified as a neurotransmitter. GABA is thought to play a role in the secretion of growth hormones according to some studies. (8) Lead can also block the release of neurotransmitters when the action potential is taking place. This double effect of lead can have serious consequences on a developing nervous system. It can result in a decrease of pruning, what shapes the early brain, of an infant. The early brain, which has more synapses than an adult brain, is patterned according to the stimuli received during development. If there is an increase in neural activity, brought about by lead, the development process can be inhibited and have permanent effects on synaptic anatomy and function of the brain. It is believed that this is one of the causes of learning and behavioral problems that occur in children. (2)

The lead found in the cells has the capabilities of affecting the calmodulin protein kinase II (CPK II) system. This system is thought to play a role in the release of neurotransmitters mentioned earlier. The CPK II is believed to phosphorylate a specific protein (synapsin I) on the surface of the synaptic vesicles. This protein is what allows the vesicle to fuse its membrane and release the neurotransmitter chemicals. This might be how lead increases the rate of release of the neurotransmitters. Another protein, kinase C, is also affected by lead. It is believed that protein kinase C regulates long term potentiation, a functional equivalent of memory storage. Lead and calcium both have an affinity for this protein; However, lead has a higher affinity for it and can therefore activate the enzyme at lower concentrations and for a longer duration of time. The interference of lead on protein kinase C may also be another cause of learning disabilities and behavior deficits observed in children with lead poisoning. (2)

In the CNS lead increases the permeability of the blood-brain barrier (BBB) which produces brain edema (an accumulation of fluid in the body tissues or cavities that causes swelling or distention). Usually the BBB seals the neural tissue from the circulating blood; this is done by linking a series of epithelial cells together. This arrangement would only let solutes pass through via specialized transport proteins. Lead exposure causes a disruption in the BBB allowing large molecules, such as albumin, to enter a developing brain. Osmotic pressure causes ions and water to follow resulting in edema of the brain and intracranial pressure. With the pressure increasing towards the systemic blood pressure, a cerebral perfusion decrease causes ischemia. It is believed that lead changes the functional state of BBB's endothelium, which might be losing their ability to distinguish between outside tissue and the brain. Lead poisons the astrocyte, an important component of the BBB. With the BBB despecialized the neurological development of a maturing child is altered. (2)

Lead, a metal that can be found every where, can cause irreversible damage to the body's nervous system. The damage caused by lead ranges from learning disabilities to high blood pressure and to death. Lead poisoning can also have hematologic and endocrine effects in the human body. (3) In most cases the symptoms of lead are misdiagnosed and people are unaware of the damage that can be caused by lead. It recent years more attention and research has been directed towards lead poisoning and its effect on the human body.

WWW Sources and Other Sources

1) Lead Toxicity in Children by Melissa Sizemore , Gives background information on lead toxicity and studies done with children that have lead poisoning.

2) Lead Toxicity: Its Effects on Fetal and Infant Development by Mark J. Schuld , Goes into detail about the neurological effects of lead on the nervous system.

3) Case Studies in Environmental Medicine: Lead Toxicity , Gives information on effects of lead on other systems in the body.

4) Where Communities and Organizations Meet: Applying Anthropology to Lead Education in Philadelphia by Johnelle Lamarque , A report about lead poisoning in Philadelphia

5) Biology, fifth Edition; Campbell, Reece, Mitchell , Chapter 48: Sensory and Motor Mechanisms

6) Dopamine - A Sample Neurotransmitter , A web site on Dopamine.

7) Laboratory for Electron Microscopy and Image Analysis , States a small paragraph on what an acetylcholine receptor is.

8) An advertisement for GABA supplements.

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