The glia/neuron ratio: How it varies uniformly across brain structures and species and what that means for brain physiology and evolution

Abstract

It is a widespread notion that the proportion of glial to neuronal cells in the brain increases with brain size, to the point that glial cells represent "about 90% of all cells in the human brain." This notion, however, is wrong on both counts: neither does the glia/neuron ratio increase uniformly with brain size, nor do glial cells represent the majority of cells in the human brain. This review examines the origin of interest in the glia/neuron ratio; the original evidence that led to the notion that it increases with brain size; the extent to which this concept can be applied to white matter and whole brains and the recent supporting evidence that the glia/neuron ratio does not increase with brain size, but rather, and in surprisingly uniform fashion, with decreasing neuronal density due to increasing average neuronal cell size, across brain structures and species. Variations in the glia/neuron ratio are proposed to be related not to the supposed larger metabolic cost of larger neurons (given that this cost is not found to vary with neuronal density), but simply to the large variation in neuronal sizes across brain structures and species in the face of less overall variation in glial cell sizes, with interesting implications for brain physiology. The emerging evidence that the glia/neuron ratio varies uniformly across the different brain structures of mammalian species that diverged as early as 90 million years ago in evolution highlights how fundamental for brain function must be the interaction between glial cells and neurons.

You Do Not Mess with the Glia

“…Because lower neuronal densities indicate larger neurons, that means that larger neurons are accompanied by more non-neuronal cells than smaller neurons [73,96]. Importantly, the same relationship applies across all brain structures in all mammalian species analyzed so far, as illustrated in Figure 11.…”

“…The existence of such a continuum, with no evidence of grade shifts across structures, species, or clades, argues strongly for a highly conserved mechanism governing how glial cells are added to tissue in development and evolution [63,73,96]. We have found recently that different neuronal densities in the cerebral cortex are not accompanied by significantly different energetic costs per neuron [101], which makes it unlikely that the larger glia/neuron ratios that accompany larger neurons are due to a higher metabolism in larger neurons, at least not across species.…”

Insulin resistance in brain alters dopamine turnover and causes behavioral disorders

“…It is unclear why MAO dysregulation was detected in the striatum and NAC of NIRKO mice, and not in the prefrontal cortex. This may suggest that discrete compartments in the brain differ in their response to insulin (53), or that different cellular compositions in discrete brain areas result in different effects of insulin resistance (54). MAO A and B also degrade serotonin, thus affecting serotonin signaling.…”

Fluorescence Guided Resection of Brain Tumors: Evaluation of a Hand-held Spectroscopic Probe

“…Oligodendrocytes build up the myelin sheaths around axons in the white matter forming interneuronal connections and tracts between different cortical areas and nuclei in the brain and spinal cord. In the white matter glia cells outnumber the neuronal tissue at a ratio of 10:1 (von Bartheld et al, 2016, Herculano-Houzel, 2014. The optical properties of the axonal sheaths giving the white color tone are related to the relatively high partition of lipids in the myelin cells (O'Brien and Sampson, 1965).…”

“…to cobalamin, but in humans almost solely to synthesis of heme, a process that takes place in every cell of the body. Externally administered, depending on the dosage, it can interfere in the heme cycle of the tumor cells by overload of the enzyme ferrochelatase with its photosensitizing metabolite protoporphyrin IX (PpIX) (Heyerdahl et al, 1997). It has peak fluorescence at 635 nm when excited at wavelengths around 400 nm.…”