Related Experiment Video
Updated: Apr 5, 2026
The Use of Trace Eyeblink Classical Conditioning to Assess Hippocampal Dysfunction in a Rat Model of Fetal Alcohol Spectrum Disorders
Published on: August 5, 2017
Impaired ILK Function Is Associated with Deficits in Hippocampal Based Memory and Synaptic Plasticity in a FASD Rat
D Bhattacharya1, E P Dunaway2, S Bhattacharya1
1Department of Drug, Discovery and Development, Auburn University, Auburn, Alabama, United States of America.
Insights
Prenatal alcohol exposure impairs memory and synaptic plasticity in rats by disrupting the Integrin Linked Kinase (ILK) signaling pathway, affecting Glycogen Synthase Kinase 3β (GSK3β) and GluR2 AMPA receptors.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Fetal Alcohol Spectrum Disorder (FASD) causes cognitive deficits due to prenatal alcohol exposure.
- Current treatments for FASD are ineffective due to incomplete understanding of its cellular and molecular mechanisms.
- Alcohol impacts integrins and growth factor signaling, with Integrin Linked Kinase (ILK) being a key effector.
Purpose of the Study:
- To investigate the role of the ILK signaling pathway in cognitive deficits associated with FASD.
- To determine if ILK pathway impairments contribute to memory and synaptic plasticity deficits in alcohol-exposed offspring.
- To examine the relationship between ILK, GSK3β, and glutamate receptor expression in FASD.
Main Methods:
- Pregnant Sprague Dawley rats were exposed to alcohol or a sucrose control throughout gestation.
- Cognitive function was assessed using contextual fear conditioning in 32-33-day-old pups.
- Synaptic plasticity (LTP) and hippocampal ILK signaling, including GSK3β phosphorylation and GluR2/PSD95 interactions, were evaluated.
Main Results:
- Alcohol-exposed pups exhibited impaired contextual fear conditioning and reduced long-term potentiation (LTP).
- Hippocampal ILK activity and GSK3β phosphorylation were significantly decreased in alcohol-exposed pups.
- Increased synaptic GluR2 AMPA receptor expression was observed, with a decreased interaction between ILK and GluR2.
Conclusions:
- The ILK signaling pathway is implicated in memory and synaptic plasticity impairments observed in FASD.
- These impairments are linked to reduced GSK3β regulation and altered synaptic stabilization of GluR2 AMPA receptors.
- Targeting the ILK pathway may offer potential therapeutic strategies for FASD-related cognitive deficits.
Abstract:
Fetal Alcohol Spectrum Disorder (FASD) is an umbrella term that encompasses a wide range of anatomical and behavioral problems in children who are exposed to alcohol during the prenatal period. There is no effective treatment for FASD, because of lack of complete characterization of the cellular and molecular mechanisms underlying this condition. Alcohol has been previously characterized to affect integrins and growth factor signaling receptors. Integrin Linked Kinase (ILK) is an effector of integrin and growth-factor signaling which regulates various signaling processes. In FASD, a downstream effector of ILK, Glycogen Synthase Kinase 3β (GSK3β) remains highly active (reduced Ser9 phosphorylation). GSK3β has been known to modulate glutamate receptor trafficking and channel properties. Therefore, we hypothesize that the cognitive deficits accompanying FASD are associated with impairments in the ILK signaling pathway. Pregnant Sprague Dawley rats consumed a "moderate" amount of alcohol throughout gestation, or a calorie-equivalent sucrose solution. Contextual fear conditioning was used to evaluate memory performance in 32-33-day-old pups. Synaptic plasticity was assessed in the Schaffer Collateral pathway, and hippocampal protein lysates were used to evaluate ILK signaling. Alcohol exposed pups showed impaired contextual fear conditioning, as compared to control pups. This reduced memory performance was consistent with decrease in LTP as compared to controls. Hippocampal ILK activity and GSK3β Ser21/9 phosphorylation were significantly lower in alcohol-exposed pups than controls. Increased synaptic expression of GluR2 AMPA receptors was observed with immunoprecipitation of post-synaptic density protein 95 (PSD95). Furthermore, immunoprecipitation of ILK revealed a decreased interaction with GluR2. The ILK pathway appears to play a significant role in memory and synaptic plasticity impairments in FASD rats. These impairments appear to be mediated by reduced GSK3β regulation and increased synaptic stabilization of the calcium-impermeable GluR2 AMPA receptors.
