Brain deficits associated with fetal alcohol exposure may be protected, in part, by peptides derived from activity-dependent neurotrophic factor and activity-dependent neuroprotective protein

The Effect of Binge Fetal Alcohol Exposure on the Number of Vasoactive Intestinal Peptide-Producing Neurons in Fetal Sheep Brain

“…The neuroprotective and neurotrophic effects of VIP are modulated in part by the VIP-induced expression and secretion of astroglia-derived factors [Brenneman and Gozes, 1996]. These VIP-regulated factors including activity-dependent neurotrophic factor and activity-dependent neuroprotective protein (peptides of femtomolar neuroprotective potency) as well as peptides derived from them have been shown to protect against some of the effects associated with fetal alcohol exposure [Brenneman et al, 2000;Spong et al, 2001;Gozes et al, 2003;Endres et al, 2005;Sari and Gozes, 2006]. Therefore, an alcohol-modulated decrease in brain VIP expression could account for the impaired hypoxic cerebral vasodilation seen in our earlier work as well as a decrease in VIP-derived neuromodulation, resulting in decreased brain growth during later development.…”

“…The current study suggests that a reduced number of VIP neurons may be responsible in part for this impaired hypoxic cerebral vasodilation. In addition, a reduction in the number of brain-VIP-producing neurons may decrease the developing brain's innate neuroprotective and neurotrophic potential, rendering it more sensitive to injurious events [Dejda et al, 2005;Sari and Gozes, 2006].…”

Fetal Alcohol Exposure Alters Cerebrovascular Reactivity to Vasoactive Intestinal Peptide in Adult Sheep

“…It is known that alcohol exposure in utero leads to abnormal development of specific neurotransmitter pathways, such as glutamatergic neurons, which have been associated with the mental retardation and cognitive impairment recognized in children born with fetal alcohol syndrome [37] . Activation of specific neural circuitry evokes hemodynamic responses that are vital for normal brain function [10] .…”

“…If such changes in VIPcontaining neurons and VIP expression persist into adulthood, the resultant decrease in perivascular VIP levels could potentially cause a compensatory augmentation in vascular VIP receptor density or sensitivity. Moreover, VIP is known to regulate neuronal differentiation and embryonic growth [37] . Thus, reduced VIP expression in the fetal sheep may itself provide a mechanism for a loss in neural pathways, including VIP-containing neurons, in the adult brain.…”

Neuroprotective Protein and Carboxypeptidase E

“…Furthermore, the heterozygous ADNP +/− mice showed neuronal/glial pathology and reduced cognitive functions (Vulih-Shultzman et al 2007). In turn, the neuroprotective peptide motif of ADNP, NAP (Bassan et al 1999;Gozes et al 2005a, b), was shown to enhance neural tube closure which is compromised in conditions of fetal alcohol intoxication (Chen et al 2005;Sari and Gozes 2006) and to enhance cognitive function in various animal models (Gozes et al 2005a, b), including the heterozygous ADNP +/− mice (Vulih-Shultzman et al 2007). …”