A systems-based computational model of alcohol's toxic effects on brain development.

Important stages during neurodevelopment include the generation of new nerve cells (i.e., neurogenesis), differentiation and migration of these cells to their final location in the brain, formation of connections with neighboring cells (i.e., synaptogenesis), and cell death of neurons that fail to form the appropriate connections. Research found that alcohol exposure during fetal development can interfere with all of these processes. A systems biology approach using computational models of brain development in different species has been used to determine the relative contributions of alcohol-induced impairment of neurogenesis and synaptogenesis to alcohol-related neurodevelopmental deficits in mice, rats, rhesus monkeys, and humans. The results obtained with these models suggest that alcohol's impact on cell division during neurogenesis results in greater deficits in neuron numbers in the adult than the alcohol-induced increase in cell death during synaptogenesis. In primates, the accelerated development of susceptible brain regions may convey increased sensitivity to alcohol-induced neurodevelopmental deficits. Systems-based approaches, such as the computational models described here, can help to translate research findings obtained at a molecular or cellular level in different species into assessment of risk associated with alcohol exposure during human development.