In vivo growth trajectories of regional brain volumes in the Wistar rat

Abstract

Normative, longitudinal data are necessary for effective modeling of factors underlying disease processes on the brain. Large scale national and international consortium data have characterized human regional brain volume trajectories as complex and prolonged gray and white matter maturation through the third decade of life followed by progressive senescence of cortical and then subcortical gray matter. By middle age (>40 years), white matter volume is also in decline. Although rodents are the mainstay of experimental gerontology, the few studies on brain volume trajectories are based on small samples. Here, 16 longitudinal neuroimaging experiments in Wistar rats were merged to describe regional brain volume growth from peripuberty (32 days, human equivalent ∼12 years) to late middle age (18.8 months, human equivalent ∼60 years). As female relative to male rodents are significantly smaller in weight, brain growth was expected to scale to smaller female size. In a total sample of 1009 male and female wildtype Wistar rats and male, alcohol-preferring P rats derived from the Wistar strain, regional brain volumes peaked at different ages: the cortex, for example, reached a vertex at 6.4 months, and the ventral hippocampus at 13.6 months, but thalamus had yet to plateau at 18.8 months. Age at which regional volumes peaked was differentially modulated by strain and sex. These data provide empirical evidence to recommend that preclinical experiments consider distinct patterns of regional brain volume growth and that studies on senescence, at least in Wistar rats, focus on animals older than 18 months.