title: Reactive oxygen species and related haem pathway components as possible epigenetic modifiers in neurobehavioural pathology.
abstract: The neuroendocrine response to stress utilizes several bio-communicative pathways which also play a role in neurodevelopmental plasticity. The mechanism of action of steroidal compounds includes DNA alteration by reactive oxygen species (ROS) arising through redox cycling of reactive hormone derivatives. ROS and reactive nitrogen species play a significant role in signaling networks affecting gene transcriptional regulation during normal as well as stress-induced responses. ROS-associated synaptic and regulatory region plasticity may have been important for normal brain evolution, but probably simultaneously lowered the threshold for inducing neuropathology. A shift from 'plasticity' to 'instability' is likely to be associated with the emergence of complex effects depending on the timing, duration and intensity of the ROS insult, and is suggested to include heritable epigenetic chromatin/regulatory region remodeling differentially influencing expression levels of significant neuropsychiatric genes and their variant alleles. Neurobehavioural disorder clinical manifestations have been linked with ROS effects. The concepts discussed here relate to ROS-associated instability of DNA regulatory region sequences and a proposal that it may play an important modifying role in brain and neuro-behaviourally related gene expression. Genes encoding key steps in mitochondrial, haem, iron and bilirubin ROS metabolic pathways have been used as examples to illustrate how ROS-modified regulatory networks could possibly alter the context within which (even ostensibly unrelated) neuropsychiatric gene candidates may sometimes be recruited. Furthermore, reactions of certain radicals release sufficient energy to generate UV-photons. DNA conformational changes accompanied by changes in photon emission suggest that functional neuroimaging findings probably reflect interaction on the level of ROS/biophoton/genome regulatory region domains rather than the signatures of individual neurobehavioural disorder candidate genes.
authors.affiliation: Genetics Division, Ampath National Pathology Laboratories, P.O. Box 2040, Brooklyn Square, 0075 Pretoria, Gauteng, South Africa. gerickegs@webmail.co.za
authors.forename: G S
authors.initials: GS
authors.lastname: Gericke
mesh_terms: D001663:Bilirubin / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D003244:Consciousness Disorders / Q000209:etiology* / Q000378:metabolism*; D005072:Evoked Potentials, Auditory / Q000502:physiology; D005786:Gene Expression Regulation; D006418:Heme / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009473:Neuronal Plasticity / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D017382:Reactive Oxygen Species; D006418:Heme; D001663:Bilirubin