A stereological study of the numbers of neurons and glia in the primary visual cortex across the lifespan of male and female rhesus monkeys

Abstract

Mild age-related declines in visual function occur in humans and monkeys, independent of ocular pathology, suggesting involvement of central visual pathways (Spear, 1993). While many factors might account for this decline, a loss of neurons in primary visual cortex (V1) could be a contributing factor. Previous studies of neuron numbers in V1 reported stability across age, but were limited in the ages and genders studied and sampled only limited parts of V1 or limited cell types, allowing for the possibility of a subtle loss of neurons. We pursued this question in 26 behaviorally tested adult male and female rhesus monkeys ranging from 7.4 to 31.0 years of age using design-based stereology to estimate numbers of NeuN-labeled neurons and thionin-stained glia within three laminar zones, supragranular (layers II–IVB), granular (IVC), and infragranular (V–VI), across the entirety of V1. There were no significant differences between males and females on any measures, except for total brain weight (p=0.0038). There was an average of 416,000,000 neurons in V1, but no effect of age on this total or numbers within any laminar zone. Similarly, there was an average of 184,000,000 glia in V1 (44% the number of neurons), but no effect of age on this total. However, there was a significant age-related increase in numbers of glia in the infragranular zone, perhaps reflecting a glial response to pathology in myelinated projection fibers. This study provides further evidence that in normal aging neurons are not lost and hence cannot account for age-related dysfunction.

Systematic, Cross-Cortex Variation in Neuron Numbers in Rodents and Primates

“…wherein no assumptions about symmetry or shape of counted entities are made are represented in the sources cited here (Suner and Rakic 1996;Giannaris and Rosene 2012). The introduction of the isotropic fractionator and flow-cytometry techniques allow the assessment of cell numbers in large volumes of tissue.…”

“…Cerebral Cortex January 2015, V 25 N 1 149 that study against the mean V1 volume (Giannaris and Rosene 2012). We also report the mean and standard deviation of V1 neuron numbers and volumes (Christensen et al 2007).…”

“…The 2 estimates of total neuron numbers produced by the isotropic fractionator method are notable outliers, reporting ∼50% of the total neuron numbers reported by the other investigators. The neuron/total cell ratio reported by Giannaris and Rosene (2012) (2001) estimate 2950 million neurons in the rhesus monkey isocotex. In contrast, studies using the isotropic fractionator method (Gabi et al 2010;Herculano-Houzel et al 2011) report ∼825 million neurons for the unilateral cerebral cortex of the rhesus monkey.…”

Candidate molecular pathways of white matter vulnerability in the brain of normal aging rhesus monkeys

“…Since BDNF is normally expressed in both neurons and glial cells, especially astrocytes and microglia (Elkabes et al 1996;Wu et al 2004), the exact source of the decreased expression is unknown. However, as the rhesus monkey does not develop Alzheimer's disease (Sloane et al 1997) and does not lose forebrain neurons (Roberts et al 2012;Giannaris and Rosene 2012), this study shows that there is a decrease in the level of BDNF mRNA and proBDNF protein in the absence of the neuron loss that occurs in AD and other neurodegenerative diseases.…”

Investigation of the segregated visual system

“…Although degradation was detected in layer 3 of V1, that did not affect the electrophysiological properties (Luebke et al, 2013), and no relevant deviation was accessed in the total numbers of V1 neurons and glial cells (Giannaris and Rosene, 2012).…”