Alcohol is actually ethanol that is being ingested- C2H5OH. This is a teratogen itself. Its metabolism additionally releases products which are toxic.
Acetaldehyde is a toxic compound released from the metabolism of ethanol in the liber, which can accumulate in the brain. It causes death in certain groups of brain cells, and causes depletion in others, and reduced function in others.
Cell death can occur by necrosis -affecting surrounding cells also; and by apoptosis (a form of 'cell suicide')
In the example of apoptosis, this tends to happen when mitochondria are under oxidative stress (caused by alcohol + Calcium levels) - the process of apoptosis requires 'caspase' enzymes.
In the metabolism of alcohol, free radicals are formed which cause mitochondrial damage. Mitochondria store Ca++. The Calcium regulation is critical. The free radicals released affect mitochondrial permeability by damage so the mitochondria can break down, releasing Calcium and Cytochrome C. This leads to Caspase activation = cell apoptosis (and some necrosis)
During cell division, in a developing fetal brain, alcohol interferes with IGF-1 and IGF-11 (insulin like growth factor) by binding the receptors, and blocking the signalling function of the IGF-1 receptor. This means cell division does not proceed - it blocks central nervous system cell production ,and induces cell death by inhibiting IGF-1 receptor.
For example - in the brain you have Glial cells, which are non neuronal. These migrate (radial glia - known as 'scaffolding proteins') up through the brain and change into astrocytes. With the interference of alcohol, these radial glia become astrocytes prematurely. This leads to an abnorma positioning of cells within the brain itself.
Looking now at neurotransmitter systems - NTs help to organise the fetal CNS. Serotinin and Glutamate are crucial here. Glutamate acts with NMDA receptors. Alcohol reduces the number of NMDA receptors.
Serotonin is key for cortical development , promoting growth.
Excess NT activity leads to cellular excitotoxicity. This tends to be induced by Glutamate, and leads to neuronal death in the brain.
Glutamate + NMDA = Ca++ influx to the neuron. Excessive activation = Increased Ca++ accumulation in the neuron = necrosis and apoptosis in the brain.
Glucose uptake/transport is key in all cells, for NT/DNA/RNA production of developing fetal brains.
GLUT-1 - GLUT-7 are key - especially GLUT1 + GLUT3 in the brain. Alcohol exposure = decreased GLUT1 and GLUT3 receptors in the brain, and decreased gene expression.
And, crucially, the 'cell adhesion' molecules. CAMs. Ethanol itself interferes with L1 mediated cell adhesion. (L1-CAMs). This + altered gene expression = decrease retinoic acid
etc etc etc