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Mortera P.,Federal University of Rio de Janeiro | Herculano-Houzel S.,Instituto Nacional Of Neurociencia Translacional
Frontiers in Neuroanatomy | Year: 2012

Aging-related changes in the brain have been mostly studied through the comparison of young adult and very old animals. However, aging must be considered a lifelong process of cumulative changes that ultimately become evident at old age. To determine when this process of decline begins, we studied how the cellular composition of the rat brain changes from infancy to adolescence, early adulthood, and old age. Using the isotropic fractionator to determine total numbers of neuronal and non-neuronal cells in different brain areas, we find that a major increase in number of neurons occurs during adolescence, between 1 and 2-3 months of age, followed by a significant trend of widespread and progressive neuronal loss that begins as early as 3 months of age, when neuronal numbers are maximal in all structures, until decreases in numbers of neurons become evident at 12 or 22 months of age. Our findings indicate that age-related decline in the brain begins as soon as the end of adolescence, a novel finding has important clinical and social implications for public health and welfare. © 2012 Morterá and Herculano-houzel. Source

Herculano-Houzel S.,Federal University of Rio de Janeiro | Herculano-Houzel S.,Instituto Nacional Of Neurociencia Translacional
PLoS ONE | Year: 2011

It is usually considered that larger brains have larger neurons, which consume more energy individually, and are therefore accompanied by a larger number of glial cells per neuron. These notions, however, have never been tested. Based on glucose and oxygen metabolic rates in awake animals and their recently determined numbers of neurons, here I show that, contrary to the expected, the estimated glucose use per neuron is remarkably constant, varying only by 40% across the six species of rodents and primates (including humans). The estimated average glucose use per neuron does not correlate with neuronal density in any structure. This suggests that the energy budget of the whole brain per neuron is fixed across species and brain sizes, such that total glucose use by the brain as a whole, by the cerebral cortex and also by the cerebellum alone are linear functions of the number of neurons in the structures across the species (although the average glucose consumption per neuron is at least 10× higher in the cerebral cortex than in the cerebellum). These results indicate that the apparently remarkable use in humans of 20% of the whole body energy budget by a brain that represents only 2% of body mass is explained simply by its large number of neurons. Because synaptic activity is considered the major determinant of metabolic cost, a conserved energy budget per neuron has several profound implications for synaptic homeostasis and the regulation of firing rates, synaptic plasticity, brain imaging, pathologies, and for brain scaling in evolution. © 2011 Suzana Herculano-Houzel. Source

Herculano-Houzel S.,Federal University of Rio de Janeiro | Herculano-Houzel S.,Instituto Nacional Of Neurociencia Translacional
Annals of the New York Academy of Sciences | Year: 2011

It is usually considered a paradox that the human brain, although smaller than elephant and cetacean brains, is the most cognitively able. The concept that humans are more encephalized than all other mammals appeared in the 1970s as a solution to that paradox: humans have a brain that is much larger than expected from their body mass. Such an "excess brain mass" would provide increased cognitive abilities across species, thus explaining our cognitive superiority. However, behind the paradox lies the assumption that large mammalian brains are scaled-up versions of smaller brains, always containing more neurons than smaller ones-an assumption that we have recently shown to be invalid. Here, it is proposed that the absolute number of neurons, irrespective of brain or body size, is a better predictor of cognitive ability-in which case, the cognitive superiority of humans would come as no paradox, surprise, or exception to evolutionary rules. © 2011 New York Academy of Sciences. Source

Herculano-Houzel S.,Federal University of Rio de Janeiro | Herculano-Houzel S.,Instituto Nacional Of Neurociencia Translacional
GLIA | Year: 2014

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. © 2014 Wiley Periodicals, Inc. Source

Herculano-Houzel S.,Federal University of Rio de Janeiro | Herculano-Houzel S.,Instituto Nacional Of Neurociencia Translacional | von Bartheld C.S.,University of Nevada, Reno | Miller D.J.,Vanderbilt University | Kaas J.H.,Vanderbilt University
Cell and Tissue Research | Year: 2015

The number of cells comprising biological structures represents fundamental information in basic anatomy, development, aging, drug tests, pathology and genetic manipulations. Obtaining unbiased estimates of cell numbers, however, was until recently possible only through stereological techniques, which require specific training, equipment, histological processing and appropriate sampling strategies applied to structures with a homogeneous distribution of cell bodies. An alternative, the isotropic fractionator (IF), became available in 2005 as a fast and inexpensive method that requires little training, no specific software and only a few materials before it can be used to quantify total numbers of neuronal and non-neuronal cells in a whole organ such as the brain or any dissectible regions thereof. This method entails transforming a highly anisotropic tissue into a homogeneous suspension of free-floating nuclei that can then be counted under the microscope or by flow cytometry and identified morphologically and immunocytochemically as neuronal or non-neuronal. We compare the advantages and disadvantages of each method and provide researchers with guidelines for choosing the best method for their particular needs. IF is as accurate as unbiased stereology and faster than stereological techniques, as it requires no elaborate histological processing or sampling paradigms, providing reliable estimates in a few days rather than many weeks. Tissue shrinkage is also not an issue, since the estimates provided are independent of tissue volume. The main disadvantage of IF, however, is that it necessarily destroys the tissue analyzed and thus provides no spatial information on the cellular composition of biological regions of interest. © 2015, Springer-Verlag Berlin Heidelberg. Source

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