Association of early experience with neurodegeneration in aged primates

Abstract

Environment influences brain development, neurogenesis and, possibly, vulnerability to neurodegenerative disease. We retrospectively examined the brains of aged rhesus monkeys reared during early life in either small cages or larger, "standard-sized" cages; all monkeys were subsequently maintained in standard-sized cages during adulthood. Aged monkeys reared in smaller cages exhibited significantly greater β-amyloid plaque deposition in the neocortex and a significant reduction in synaptophysin immunolabeling in cortical regions compared to aged monkeys reared in standard-sized cages (p<0.001 and p<0.05, respectively). These findings suggest that early environment may influence brain structure and vulnerability to neurodegenerative changes in late life.

Fig. 1

β-Amyloid plaques in the superior temporal gyrus of aged rhesus monkeys housed under either (A) standard or (B) small cage conditions (scale bar A, B, 0.65 mm). (C) Amyloid plaque density per mm², and (D) amyloid load in superior temporal gyrus, were both elevated in primates raised in small cages (two-tailed t-test, *p < 0.001). Data for individual subjects are indicated by closed circles in A. Plaques were not detected in brains of young subjects.

Fig. 2

Synaptophysin immunoreactivity (Syn-IR) in the superior temporal gyrus of (A) a young adult monkey, and (B) an aged monkey from the small cage-rearing group. Scale bar, 1 µm. (C) Quantification of Syn-IR reveals a significant reduction in superior temporal gyrus in aged monkeys raised in small cages (p < 0.05).