Alzheimer's disease is the commonest cause of dementia in the elderly, but its pathological determinants are still debated. Amyloid-β plaques and neurofibrillary tangles have been implicated either directly as disruptors of neural function, or indirectly by precipitating neuronal death and thus causing a reduction in neuronal number. Alternatively, the initial cognitive decline has been attributed to subtle intracellular events caused by amyloid-β oligomers, resulting in dementia after massive synaptic dysfunction followed by neuronal degeneration and death. To investigate whether Alzheimer's disease is associated with changes in the absolute cell numbers of ageing brains, we used the isotropic fractionator, a novel technique designed to determine the absolute cellular composition of brain regions. We investigated whether plaques and tangles are associated with neuronal loss, or whether it is dementia that relates to changes of absolute cell composition, by comparing cell numbers in brains of patients severely demented with those of asymptomatic individuals-both groups histopathologically diagnosed as Alzheimer's-and normal subjects with no pathological signs of the disease. We found a great reduction of neuronal numbers in the hippocampus and cerebral cortex of demented patients with Alzheimer's disease, but not in asymptomatic subjects with Alzheimer's disease. We concluded that neuronal loss is associated with dementia and not the presence of plaques and tangles, which may explain why subjects with histopathological features of Alzheimer's disease can be asymptomatic; and exclude amyloid-β deposits as causes for the reduction of neuronal numbers in the brain. We found an increase of non-neuronal cell numbers in the cerebral cortex and subcortical white matter of demented patients with Alzheimer's disease when compared with asymptomatic subjects with Alzheimer's disease and control subjects, suggesting a reactive glial cell response in the former that may be related to the symptoms they present.

The central nervous system is a highly complex network composed of various cell types, each one with different subpopulations. Each cell type has distinct roles for the functional operation of circuits, and ultimately, for brain physiology in general. Since the absolute number of each cell type is considered a proxy of its functional complexity, one approach to better understand how the brain works is to unravel its absolute cellularity and the quantitative relations between cell populations; in other words, how one population of cells is quantitatively structured, in relation to another. Oligodendrocytes are one of these cell types – mainly, they provide electric insulation to axons, optimizing action potential conduction. Their function has recently been revisited and their role extended, one example being their capability of providing trophic support to long axons. To determine the absolute cellularity of oligodendroglia, we have developed a protocol of oligodendrocyte quantification using the isotropic fractionator with a pan-marker for this cell type. We report a detailed assessment of specificity and universality of the oligodendrocyte transcription factor 2 (Olig2), through systematic confocal analyses of the C57BL/6 mouse brain. In addition, we have determined the absolute number (17.4 million) and proportion (about 20%) of this cell type in the brain (and in different brain regions), and tested if this population, at the intraspecific level, scales with the number of neurons in an allometric-based approach. Considering these numbers, oligodendrocytes proved to be the most numerous of glial cells in the mouse brain.

The evolution of mating strategies is not well understood. Several hypotheses have been proposed to explain the variation in mating strategies, with varying levels of support. Specifically, female dispersion, adult sex ratio and mate guarding have been proposed as drivers of the evolution of monogamous strategies. In this study, we used an agent-based model (ABM) to examine how different mating behaviors evolve in a population under different conditions related to these putative drivers, looking to understand the interaction between them. We found an interaction among different factors in the evolution of social monogamy, and their impact is in this order: adult sex ratio (ASR), female dispersion and extra-pair copulation. Thus, when the adult sex ratio is male-biased, monogamous strategies are strongly favored. However, this is only the case if mate guarding is fully efficient, i.e., if there is no extra-pair copulation. On the other hand, in scenarios where the population is female-biased, or mate guarding is not efficient, we find that polygamous strategies are favored but proportionally to the dispersion of females. These results confirm previous findings regarding mate guarding and sex ratios, while also showing how female dispersion enters the dynamics.

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Background:The Isotropic Fractionator (IF) is a method used to determine the cellular composition of nervous tissue. It has been mostly applied to assess variation across species, where differences are expected to be large enough not to be masked by methodological error. However, understanding the sources of variation in the method is important if the goal is to detect smaller differences, for example, in same-species comparisons. Comparisons between different mice strains suggest that the IF is consistent enough to detected these differences. Nevertheless, the internal validity of the method has not yet been examined directly. Method:In this study, we evaluate the reliability of the IF method for the determination of cellular and neuronal numbers. We performed repeated cell counts of the same material by different experimenters to quantify different sources of variation.Results: In total cell counts, we observed that for the cerebral cortex most of the variance was at the counter level. For the cerebellum, most of the variance is attributed to the sample itself. As for neurons, random error along with the immunological staining correspond to most of the variation, both in the cerebral cortex and in the cerebellum. Test-retest reliability coefficients were relatively high, especially for cell counts. Conclusions:Although biases between counters and random variation in staining could be problematic when aggregating data from different sources, we offer practical suggestions to improve the reliability of the method. While small, this study is a most needed step towards more precise measurement of the brain's cellular composition.