Introduction:

Fetal Alcohol Syndrome (FAS) is a set of specific birth defects

caused by maternal alcohol consumption during pregnancy. Scientists first
identified the syndrome in France in 1968 (Lemoine et al. 1968) and in the
United States in 1973 (Jones et al. 1973). Today, FAS is considered the most
common nonhereditary cause of mental retardation. Prevalence of alcoholrelated conditions is very hard to estimate, though some statistics indicate
that up to 20% of children have been exposed to alcohol prenatally. In some
countries, rate of exposure may be much higher (in Russia, for example).
Because not all children demonstrate the facial features, it is underdiagnosed. Perhaps 60% of individuals in penitentiaries were exposed to
alcohol before birth, according to some studies. Epidemiologic studies in the
US estimate an overall incidence of 1 in 500 live births, occurring in 2-6
births per 1000 Caucasians, 6 per 1000 African-Americans, and up to 20 per
1000 American Indians.
Alcohol crosses the placenta and rapidly reaches the foetus. Extensive
studies have demonstrated equivalent foetal and maternal alcohol
concentrations, suggesting an unimpeded bi-directional movement of alcohol
between the two compartments. The foetus appears to depend on maternal
hepatic detoxification because the activity of alcohol dehydrogenase (ADH)
in the foetal liver is less than 10 percent of that observed in the adult liver.
Furthermore, the amniotic fluid acts as a reservoir for alcohol, prolonging
foetal exposure. The mechanism for the spectrum of adverse effects on
virtually all organ systems of the developing fetus is unknown. Ethanol and
its metabolite acetaldehyde had been reported alter fetal development by
disrupting cellular differentiation and growth, disrupting DNA and protein
synthesis and inhibiting cell migration (Manzo-Avalos and Saavedra-Molina,
2010). Both ethanol and acetaldehyde modify the intermediary metabolism
of carbohydrates, proteins, and fats. Elevated levels of erythropoietin in the
cord blood of newborns exposed to alcohol are reported and suggest a state
of chronic fetal hypoxia (Halmesmaki et al., 1990).
The consequential neurological abnormalities (Goodman et al., 1999;
Mattson et al., 1999) are understood to be one of the major causes of
intellectual disability in Western nations (Mattson et al., 2011). The studies
using developmental animal models have long established that fetal ethanol
exposure is associated with enormous reduction in the number of neurons in
vital brain regions, including the hippocampus (Olney, 2004), in addition to
long-lasting synaptic and memory deficits in adult rodents (Izumi et al.,

2005; Wilson et al., 2011; Sadrian et al., 2012; Subbanna et al., 2013a). Both
animal and human studies have demonstrated that brain structures,
including the hippocampus, frontal lobes, corpus callosum, and basal
ganglia, are important sites of alcohols action on the fetal brain (Clarren et
al. 1978; Coulter et al. 1993; Mattson et al. 1992, 1996b; Pfeiffer et al. 1979;
Riley et al. 1995; Shapiro et al. 1984; Wisniewski et al. 1983). Another
criterion of FAS is the presence of the specific group of facial anomalies (i.e.,
short palpebral fissures, a flattened nasal bridge, an absent or elongated
philtrum, and a thin upper lip). From embryological studies, investigators
know that these morphologic abnormalities occur when the midline of the
face is formed during the first trimester. A significant correlation between
first-trimester alcohol exposure and the rate of these physical anomalies was
found in the MHPCD project (Day et al. 1990).
Neurodegeneration----------------------------Recently, agmatine an endogenous amine has been implicated in
drug addiction (Aricioglu-Kartal and Uzbay, 1997; Li et al., 1999; Aricioglu et
al., 2004; Su et al., 2009). Agmatine is a pleiotropic molecule which is
biosynthesized by decarboxylation of L-arginine by arginine decarboxylase
(ADC) in mammalian brain and other tissues (Reis and Regunathan, 2000)
with central and peripheral functions. Its systemic administration exerts
anxiolytic (Liu et al., 2008; Lavinsky et al., 2003), antidepressant (Zomkowski
et al., 2002; Taksande et al., 2009), antinociceptive (Onal and Soykan, 2001;
Onal et al., 2003), anticonvulsive (Bence et al., 2003; Feng et al., 2005),
antiinflammatory (Satriano et al., 2001), antiproliferative (Isome et al., 2007)
and neuroprotective effects (Lee et al., 2009) and facilitates memory (Liu
and Bergin, 2009).There is noticeable evidences that agmatine have
neuroprotective effect in learning and memory.

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