Fetal Alcohol Spectrum Disorder-Is This a Ciliopathy?

Background: The term "fetal alcohol spectrum disorder" (FASD) describes a broad spectrum of neurodevelopmental presentations resulting from alcohol exposure in utero. The prevalence has been estimated at 1 in 100 people, and estimated to be more than 330 000 affected individuals in Canada. The Canadian Diagnostic Guidelines describe the physical and neurodevelopmental effects resulting from prenatal alcohol exposure. These include distinct facial features, microcephaly and neurodevelopmental deficits.

Ethanol toxicity is researched in association to the concentration, duration, and timing of ethanol exposure and the possible pathways leading to phenotypic translation to teratogenesis. Studies of FASD in animal models are beginning to implicate a number of susceptibility genes that are involved in various molecular pathways on gene-ethanol interactions. Some of which are reportedly involved in ethanol teratogenesis as a part of their roles in DNA damage control, Central Nervous System axis formation, cellular survival as well as proliferation and growth.

A mutation in one particular gene, neuronal nitric oxide synthase (nNOS)) is known to worsen alcohol induced neuronal death both in vivo and in vitro, and expression of the nNOS gene protects neurons against alcohol toxicity Nitric Oxide (NO) is synthesized by the enzyme nitric oxide synthase (NOS through) L-arginine There are three NOS isoforms: neuronal NOS (nNOS, NOS-1), inducible NOS (iNOS, NOS-2), and endothelial NOS (eNOS, NOS-3) .NO is associated with modulation of neurotransmission and memory formation along with other vital activities. In the presence of O2, radicals form that can lead to toxicity. They may be disruptive to cell signaling processes and result in pathological conditions.

Data suggest that ethanol alters NOS expression and activity in the brain There are known effects of ethanol on production of NO, NOS activities, and interactions of NO with alcohol metabolism enzymes.

Dose and length of ethanol exposure are the main factors determining ethanol effects on NO production, NOS activity or NOS expression.