The influence of age and sex on the absolute cell numbers of the human brain cerebral cortex

Abstract

The human cerebral cortex is one of the most evolved regions of the brain, responsible for most higher-order neural functions. Since nerve cells (together with synapses) are the processing units underlying cortical physiology and morphology, we studied how the human neocortex is composed regarding the number of cells as a function of sex and age. We used the isotropic fractionator for cell quantification of immunocytochemically labeled nuclei from the cerebral cortex donated by 43 cognitively healthy subjects aged 25–87 years old. In addition to previously reported sexual dimorphism in the medial temporal lobe, we found more neurons in the occipital lobe of men, higher neuronal density in women’s frontal lobe, but no sex differences in the number and density of cells in the other lobes and the whole neocortex. On average, the neocortex has ~10.2 billion neurons, 34% in the frontal lobe and the remaining 66% uniformly distributed among the other 3 lobes. Along typical aging, there is a loss of non-neuronal cells in the frontal lobe and the preservation of the number of neurons in the cortex. Our study made possible to determine the different degrees of modulation that sex and age evoke on cortical cellularity.

The uniqueness of the human brain: a review

“…Three studies conducted by different authors with a variable number of adult and aged individuals of both genders, using the (optical dissector) stereological and isotropic fractionator methods, showed that the cerebral cortex contains between 10-25, 14.7-32, and 7.2-14.4 billion neurons, respectively, the average number being 16.5, 21, and 10.2 billion, respectively. There was ample individual variation (100% or more) in all three studies, with no differences between males and females 6,13,14 , and no reduction in neuron numbers with age 6,14 . A neuronal loss of about 10% was reported by Pakkenberg and Gundersen 13 (Table 2), yet no histopathological study was made by these authors to exclude the presence of neurodegenerative diseases that could explain neuronal loss.…”

“…Expansion of the cortical area of the brain, especially the neocortex, occurred in all mammals, although it was particularly more intense and faster in primates. This expansion was both in absolute terms and relative to the rest of the brain, causing the human brain to acquire more folds and grooves, with the gyri becoming more tortuous 14 , 49 , 50 .…”

“…The frontal lobe contains 34% of the cerebral cortex neurons, of which 85% are in the prefrontal cortex and 15% in the primary motor cortex (on the precentral gyrus) 14 . These data indicate that, as the frontal lobe is the largest region of the brain, the prefrontal cortex is the brain area with the largest number of cerebral cortex neurons.…”