suggesting that sex bias could be independent of hormonal control in certain aspects. observing sex-biased genes has the potential for clinical significance in observing brain physiology and the potential for related (whether directly or indirectly) neurological disorders. examples of diseases with sex biases in development include huntington's disease, cerebral ischemia, and alzheimer's disease. epigenetics of the brain many brain functions can be influenced at the cellular and molecular level by variations and changes in gene expression, without altering the sequence of dna in an organism. this is otherwise known as epigenetic regulation. examples of epigenetic mechanisms include histone modifications and dna methylation. such changes have been found to be strongly influential in the incidence of brain disease, mental illness, and addiction. epigenetic control has been shown to be involved in high levels of plasticity in early development, thereby defining its importance in the critical period of an organism. examples of how epigenetic changes can affect the human brain are as follows: higher methylation levels in rrna genes in the hippocampus of the brain results in a lower production of proteins and thus limited hippocampal function can result in learning and memory impairment and resultant suicidal tendencies. in a study comparing genetic differences between healthy people and psychiatric patients 60 different epigenetic markers associated with brain cell signaling were found. environmental factors such as child abuse appears to cause the expression of an epigenetic tag on glucocorticoid receptors (associated with stress responses) that was not found in suicide victims. this is an example of experience-dependent plasticity. environmental enrichment in individuals is associated with increased hippocampal gene histone acetylation and thus improved memory consolidation (notably spatial memory). molecular mechanisms of neurodegenerative diseases excitotoxicity and glutamate receptors excitotoxicity is phenomenon in which glutamate receptors are inappropriately activated. it can be caused by prolonged excitatory synaptic transmission in which high levels of glutamate neurotransmitter cause excessive activation in a postsynaptic neuron that can result in the death of the postsynaptic neuron. following brain injury (such as from ischemia), it has been found that excitotoxicity is a significant cause of neuronal damage. this can be understandable in the case where sudden perfusion of blood after reduced blood flow to the brain can result in excessive synaptic activity caused by the presence of increased glutamate and aspartate during the period of ischemia. alzheimer's disease alzheimer's disease is the most common neurodegenerative disease and is the most common form of dementia in the elderly. the disorder is characterized by progressive loss of memory and various cognitive functions. it is hypothesized that the deposition of amyloid-β peptide (40-42 amino acid residues) in the brain is integral in the incidence of alzheimer's disease. accumulation is purported to block hippocampal long-term potentiation. it is also possible that a receptor for amyloid-β oligomers could be a prion protein. parkinson's disease parkinson's disease is the second most common neurodegenerative disease after alzheimer's disease. it is a hypokinetic movement basal ganglia disease caused by the loss of dopaminergic neurons in the substantia nigra of the human brain. the inhibitory outflow of the basal ganglia is thus not decreased, and so upper motor neurons, mediated by the thalamus, are not activated in a timely manner. specific symptoms include rigidity, postural problems, slow movements, and tremors. blocking gaba receptor input from medium spiny neurons to reticulata cells, causes inhibition of upper motor neurons similar to the inhibition that occurs in parkinson's disease. huntington's disease huntington's disease is a hyperkinetic movement basal ganglia disease caused by lack of normal inhibitory inputs from medium spiny neurons of the basal ganglia. this poses the opposite effects of those associated with parkinson's disease, including inappropriate activation of upper motor neurons. as with the gabaergic mechanisms observed in relation to parkinson's disease, a gaba agonist injected into the substantia nigra pars reticulata decreases inhibition of upper motor neurons, resulting in ballistic involuntary motor movements, similar to symptoms of huntington's disease.