Thursday, December 2, 2010

Early Life Experience and Neurodegeneration

Although some studies have found that early life environmental factors can affect our vulnerability to neurodegenerative diseases such as Alzheimer’s disease in later life, the underlying neuronal mechanisms of such vulnerability are not well understood. By looking at post mortem rhesus monkey brains, Merrill et al. (2011) finds an association between early life experience and subsequent risk of exhibiting neurodegeneration in later life.

In the study, β-amyloid plaque density and synaptophysin immunoreactivity in the brains of the rhesus monkeys that had lived in standard sized cages VS small cages (29% smaller than standard cages) for the first 15 years were compared. Young monkeys were also used as a basis for comparison.

β-amyloid plaque density

β-amyloid deposition has been established as the central cause of Alzheimer’s disease (Hardy & Allsop, 1991). The researchers found that monkeys that were housed in small cages had higher β-amyloid plaque density and amyloid load in the superior temporal gyrus compared to monkeys that were housed in standard sized cages. Young monkeys had no detectable amyloid deposition and were not graphed.
click to enlarge

However, I think the β-amyloid density results should be taken with a pinch of salt. Although the authors did mention that there is considerable individual variation - which parallels data in human studies, the effects seemed to be heavily driven by the monkey which had almost 140 plaques per mm square. Also, there were only 5 monkeys in the small cage condition and 3 of them appear to have comparable β-amyloid density levels. The authors also did not include individual data for the superior temporal gyrus amyloid load graph but the large error bar again suggests significant individual variations.

Synaptophysin Immunoreactivity

Monkeys reared in small cages also showed a reduction in synaptophysin immunoreactivity - a presynaptic marker, in the superior temporal gyrus. This indicates a decrease in synaptic density and activity which has been linked with cognitive impairment in Alzheimer's disease.
All said, the value of the study lies in their finding “early life experience is associated with degenerative change in the non-diseased aged brain” (emphasis theirs). Therefore, even in normal aging, our early life experiences can affect the rate of neural degeneration. Remind me to get a bigger crib for my child in the future.
Merrill DA, Masliah E, Roberts JA, McKay H, Kordower JH, Mufson EJ, & Tuszynski MH (2011). Association of early experience with neurodegeneration in aged primates. Neurobiology of aging, 32 (1), 151-6 PMID: 19321231

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