Orexin axon density and bouton quantification in the aging rhesus macaque thalamus: a novel methodology

Abstract

Sleep fragmentation and disturbances of normal circadian rhythms are inherent in the aging human population. The rhesus macaque (Mucaca mulatta) exhibits similar disruption in sleep patterns and is a useful model to study these disturbances. Orexin is an excitatory neuropeptide that has been implicated in the regulation of wakefulness and alertness. Specifically, it has projections from its neuronal bodies in the lateral and perifornical hypothalamus to various forebrain and brainstem regions that control arousal state. One of the regions of high innervation by these orexigenic neurons is the thalamus. This study used a semi-quantitative means to determine if there are age dependent changes in Orexin innervation in the thalamus. There was a general trend of decreasing axon density when analyzed with a novel semi-quantitative method (r = -0.515, p = 0.024, df = 17) and approached significance when assessed with a previously published method (r = -0.454, p = 0.0509, df = 17), indicating a decrease with age. Additionally, there was no significant decrease in unilateral bouton counts iii when examined with age using either method. Although the findings in this study point to an age-related decrease in axon terminals, further research should examine the total orexigenic positive content in the thalamus to explain why bouton counts do not seem to change.