The effects of pre-natal alcohol on adolescent learning and memory

Foetal alcohol spectrum disorders (FASD) are a result of prenatal exposure to ethanol and are characterised by impaired learning and memory, growth retardation, structural brain abnormalities and facial anomalies: they affect close to 1% of births in Europe.

Diagnosis of FASD is often extremely difficult as the learning deficits may present at 10 years of age or older when details of prenatal alcohol exposure are long forgotten and unobtainable. This leaves many children without a clear diagnosis and thus without correctly targeted interventions. Currently maternal hair analysis or the presence of elevated fatty acid ethyl esters in meconium at the time of birth are the only biochemical markers for intra-uterine alcohol exposure. These markers are of no value shortly after the birth and do not allow for retrospective diagnosis when a child presents later in life.

Animal studies led researchers to believe that prenatal exposure to ethanol may cause long-lasting alteration to a group of aminopeptidase enzymes, and that this change in enzyme activity may be associated with impaired learning and memory. Researchers went onto explore the potential of these plasma enzymes as enduring markers of prenatal alcohol exposure / FASD in a human population.

Diagnostic criteria for Foetal alcohol spectrum disorders are controversial, and under-diagnosis is believed to be common. It is likely that there are many more children with FASD in schools than records suggest. In early life, differential diagnosis of FASD, autistic spectrum disorder and attention deficit hyperactivity disorder is problematic, although distinct intervention strategies with differential degrees of success have been identified.

This research determined whether plasma aminopeptidase activity is measureable in neonates and assessed the potential of plasma aminopeptidase activity to identify prenatal alcohol exposure and possible FASD in neonates. Only follow-up later in life would allow differentiation of prenatal alcohol exposure and FASD.

The research also determined whether any observed changes in neonates endure into adolescents, and whether there was a clear association of enzyme activity with FASD, rather than prenatal alcohol exposure. The biochemical parameter may also correlate with severity of learning disability. The predictive validity of any correlation would allow assessment of the usefulness of this biochemical assay as a selective diagnostic tool for FASD, to allow appropriate intervention.

Outputs

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Fidalgo, S., Onaji, V., Gard, P.R., Effect of acute administration of angiotensin IV in a mouse model of Foetal Alcohol syndrome. For presentation to 9th FENS forum of neuroscience, July 5-9th 2014 Milan, Italy,

Gard, P.R., Fidalgo, S. Lotter, I., Richardson, C., Farina, C., Tabet, N., Rusted, J.(2015). Changes of IRAP-related aminopeptidases in early stage Alzheimer’s disease and a model of foetal alcohol syndrome. Presented to the 2nd IRAP Symposium, Uppsala, Sweden, September 2015

Fidalgo, S.,Tucker, R., Tsiligkaridis, T., Takyi, A., Murphy, D., Silva, N.M., Sadiq, W., Gard, P.R. (2015) Effect of acute administration of angiotensin IV in a mouse model of Foetal Alcohol syndrome. Presented to the 2nd IRAP Symposium, Uppsala, Sweden, September 2015

Fidalgo, S., Tucker, R., Payne, R., Linsdall, S., McIver, A., Sadiq, W., Patel, M., Gard, P.R. (Submitted for publication) Sex differences in the effects of angiotensin IV and oxytocin on insulin-regulated aminopeptidase function and mouse cognition in different paradigms of novel object recognition. International Journal of Neuropsychopharmacology