11.15 A.M.

The role of ILK in spatial learning deficits and neuroprotection in fetal alcohol exposure model

- Martha Escobar* & Dwipayan Bhattacharya^ -

*Oakland University, MI, USA, ^Lake Erie College of Osteopathic Medicine, PA, USA

Alcohol is probably the most commonly used and socially accepted psychoactive drug. An estimated 10% of pregnant women (ages 15-44) consume alcohol during pregnancy, with 3% of them reporting binge drinking while pregnant. Consumption of alcohol during pregnancy can lead to the child developing a Fetal Alcohol Spectrum Disorder (FASD), which is characterized by a wide range of physical and cognitive symptoms. Although FASD is fully preventable by not drinking during pregnancy, many women consume alcohol prior to discovering they are pregnant. Thus, prevention campaigns are of limited effectiveness, and the discovery of palliative agents is of utmost public health relevance. Using a rodent model of FASD, we have shown that early exposure (equivalent to the first two trimesters of a human pregnancy) to moderate levels of alcohol leads to reduced synaptic plasticity and impairments in hippocampal-dependent memory (contextual fear conditioning and spatial memory). These deficits appear to be strongly associated to impaired function of Integrin Linked Kinase (ILK), a synaptic scaffolding protein that has important functions in learning, memory, and glutamatergic synapse development. This view is supported by the observation that inhibition of ILK throughout gestation results in spatial memory deficits equivalent to those observed in alcohol-exposed animals, and activation of ILK through adolescence ameliorates the spatial memory deficits produced by prenatal alcohol exposure. Understanding the neural mechanisms that can lead to FASD-related cognitive deficits is of the utmost importance because it can lead to the discovery of potential treatments that reduce these deficits. Indeed, we have observed that ILK activation and concurrent exposure to nicotine can ameliorate some of the spatial memory deficits that characterize our model of FASD.