Extrapolating brain development from experimental species to humans

Abstract

To better understand the neurotoxic effects of diverse hazards on the developing human nervous system, researchers and clinicians rely on data collected from a number of model species that develop and mature at varying rates. We review the methods commonly used to extrapolate the timing of brain development from experimental mammalian species to humans, including morphological comparisons, "rules of thumb" and "event-based" analyses. Most are unavoidably limited in range or detail, many are necessarily restricted to rat/human comparisons, and few can identify brain regions that develop at different rates. We suggest this issue is best addressed using "neuroinformatics", an analysis that combines neuroscience, evolutionary science, statistical modeling and computer science. A current use of this approach relates numeric values assigned to 10 mammalian species and hundreds of empirically derived developing neural events, including specific evolutionary advances in primates. The result is an accessible, online resource (http://www.translatingtime.net/) that can be used to equate dates in the neurodevelopmental literature across laboratory species to humans, predict neurodevelopmental events for which data are lacking in humans, and help to develop clinically relevant experimental models.

FIGURE 1

Despite the challenges, it is essential to find a way to relate neural development across experimental species to humans.

FIGURE 2

The chart depicts the proportion of recent studies performed in nine of the most commonly used species (2005– 2006 to date; Medline title search).

FIGURE 3

The graph depicts the wide gestation range for mammalian species commonly used as experimental models and studied to satisfy a variety of scientific contingencies.

FIGURE 4

A neuroinformatics approach can be used to relate neurodevelopment across species. The model predicts that the peak of subplate neurogenesis occurs in rat development at 12.3 days post conception (PC), which translates into PC 54.6 in human cortical development, PC 40.5 in human limbic system development, and PC 43.5 for non- cortical, non-limbic neural events.