February 13, 2013

Homocysteine Toxicity:

Glutamate - A Chemical Messenger:

In this Blog Update we will look at some of the direct effects of homocysteine in the nervous system - in particular its effects on a chemical in the brain called 'Glutamate.'

Glutamate is a major chemical messenger or 'neurotransmitter' in the brain. It is involved to some degree in all brain functions from perception to cognition.

Glutamate, Learning and Memory:

Glutamate activates several types of receptors or 'channels' in brain cells. These include two important receptors called AMPA and NMDA. They receive chemical messages from other brain cells.  At rest only the AMPA receptors are open. But an electrical signal makes the NMDA channels sensitive to glutamate.  Glutamate causes calcium to flow into the cell. This triggers a cascade of events that alters the AMPA channels sensitivity. It is this unique feature of glutamate receptors working together that makes them suitable mediators for learning and memory.

Homocysteine and Glutamate Receptors:

Homocysteine can interfere with this delicate chemical balance between glutamate receptors.  If its level increases it can overstimulate glutamate receptors and interfere with their function.  The brain is usually protected from high homocysteine by a 'blood brain barrier.' But this can become 'leaky' in conditions like Alzheimer's Disease and vascular dementia, exposing the nerve cells to high levels of homocysteine.

Oxidative Stress:

There is also another way in which homocysteine can damage nerve cells. Oxidative stress can cause homocysteine to change into other forms including homocysteic acid.  These other forms are 250-fold more efficient in disrupting nerve cell activity than homocysteine itself.  This overstimulation of glutamate receptors can lead to excess calcium in the cell, free radical generation, damage to the mitochondrial 'power house' in the cell, and eventually nerve cell death.

This is yet another important way in which a high homocysteine is bad for your brain.



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