Prenatal exposure to methanesulfonyl fluoride (MSF): Correlating gene expression with development and behavior
This work attempted to investigate the complex relationship between the cholinergic system in the CNS and the effects of its interference on specific behaviors, as they relate to gene expression in the brain. Prenatal treatment with methanesulfonyl fluoride (MSF), an irreversible acetylcholinesterase (AChE) inhibitor, had significant and sexually dimorphic effects on adult behavior and on global gene expression in the developing rat brain. In a one-trial learning task, prenatally treated animals, paradoxically, showed significantly reduced swim-escape latencies compared to control animals. Open field exploration of familiarized and novel objects was also significantly reduced in MSF-exposed animals, with females more highly affected than males, and had a tendency to increase as the animals aged. Analysis of global patterns in hippocampal gene expression showed a robust sexual dimorphism, with males being more highly affected than females by MSF treatment. Furthermore, MSF-induced changes in specific genes tended to correlate with preliminary histological data showing reduced cortical width in postnatal MSF-treated males, and increased cortical width in females. Shown here for the first time is a specific group of genes that appear to be directly involved in the dimorphic ontogeny of the brain. The developmental effect of MSF on gene expression was also significantly greater in males than in females. Furthermore, the treatment effect on a specific group of genes associated with neurogenesis and affective disorders show correlations with behavior and cortical development, in the context of those pathologies. In summary, the interruption of a single neural pathway during embryogenesis, directly or indirectly, results in a greatly amplified down-stream effect on gene expression, with resultant sex-specific physiological consequences. ^
Biology, Neuroscience|Health Sciences, Human Development
Byers, Donna M, "Prenatal exposure to methanesulfonyl fluoride (MSF): Correlating gene expression with development and behavior" (2004). ETD Collection for University of Texas, El Paso. AAI3125566.