Effect of age on neocortical brain cells in 90+ year old human females—a cell counting study

Fabricius, Katrine; Jacobsen, Jette Stub; Pakkenberg, Bente

doi:10.1016/j.neurobiolaging.2012.06.009

Cited by 79 publications

(68 citation statements)

References 25 publications

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“…Several studies have estimated neuron, astrocyte, oligodendrocyte and microglia numbers in the primate cerebral cortex in Nissl stained sections using unbiased stereological methods (O’Kusky and Colonnier, 1982; Pelvig et al, 2008; Fabricius et al, 2013; Salvesen et al, 2015). Others have estimated neuron and glial cell number without distinction of glial types (Ongur et al, 1998; Rajkowska et al, 1999; Selemon et al, 1999; Cotter et al, 2001; Dombrowski et al, 2001; Lidow and Song, 2001; Christensen et al, 2007).…”

Section: Anticipated Results and Discussionmentioning

confidence: 99%

Distinction of Neurons, Glia and Endothelial Cells in the Cerebral Cortex: An Algorithm Based on Cytological Features

et al. 2016

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The estimation of the number or density of neurons and types of glial cells and their relative proportions in different brain areas are at the core of rigorous quantitative neuroanatomical studies. Unfortunately, the lack of detailed, updated, systematic and well-illustrated descriptions of the cytology of neurons and glial cell types, especially in the primate brain, makes such studies especially demanding, often limiting their scope and broad use. Here, following an extensive analysis of histological materials and the review of current and classical literature, we compile a list of precise morphological criteria that can facilitate and standardize identification of cells in stained sections examined under the microscope. We describe systematically and in detail the cytological features of neurons and glial cell types in the cerebral cortex of the macaque monkey and the human using semithin and thick sections stained for Nissl. We used this classical staining technique because it labels all cells in the brain in distinct ways. In addition, we corroborate key distinguishing characteristics of different cell types in sections immunolabeled for specific markers counterstained for Nissl and in ultrathin sections processed for electron microscopy. Finally, we summarize the core features that distinguish each cell type in easy-to-use tables and sketches, and structure these key features in an algorithm that can be used to systematically distinguish cellular types in the cerebral cortex. Moreover, we report high inter-observer algorithm reliability, which is a crucial test for obtaining consistent and reproducible cell counts in unbiased stereological studies. This protocol establishes a consistent framework that can be used to reliably identify and quantify cells in the cerebral cortex of primates as well as other mammalian species in health and disease.

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Section: Anticipated Results and Discussionmentioning

confidence: 99%

Distinction of Neurons, Glia and Endothelial Cells in the Cerebral Cortex: An Algorithm Based on Cytological Features

et al. 2016

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“…These methods have provided us with new information about, for example, differences in cell number between men and women, the effect of age on selected brain cell populations, and disease-related changes associated with a loss of function (Pakkenberg and Gundersen, 1997; Andersen et al, 2003; Fabricius et al, 2007; Karlsen and Pakkenberg, 2011; Fabricius et al, 2013). Normal neocortical neuron numbers were found in chronic alcoholics (Jensen and Pakkenberg, 1993; Fabricius et al, 2007, 2013). This finding can have a major impact on the treatment of chronic alcoholism in that brain cells are not lost even after years of excessive alcohol consumption.…”

Section: Discussionmentioning

confidence: 99%

“…This age-dependent neuronal decrease is equivalent for both sexes. Finally, Fabricius et al (2013) found that the total neocortical neuron number in individuals between 94 and 105 years of age (seven females, one male) is the same in very old females compared with younger women, group 1: 65–75 years ( n = 8), and group 2: 76–85 years ( n = 8). Although the total neuron number was the same in the 3 groups, the variance of the estimates increased substantially with age, indicating that apart from their high age, the variance in cell numbers suggests a relatively inhomogeneous sample.…”

Section: Estimates Of the Total Number Of Neocortical Neurons In Thementioning

confidence: 97%

Stereological estimation of total cell numbers in the human cerebral and cerebellar cortex

Walløe

Pakkenberg

Fabricius

2014

Front. Hum. Neurosci.

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Our knowledge of the relationship between brain structure and cognitive function is still limited. Human brains and individual cortical areas vary considerably in size and shape. Studies of brain cell numbers have historically been based on biased methods, which did not always result in correct estimates and were often very time-consuming. Within the last 20–30 years, it has become possible to rely on more advanced and unbiased methods. These methods have provided us with information about fetal brain development, differences in cell numbers between men and women, the effect of age on selected brain cell populations, and disease-related changes associated with a loss of function. In that this article concerns normal brain rather than brain disorders, it focuses on normal brain development in humans and age related changes in terms of cell numbers. For comparative purposes a few examples of neocortical neuron number in other mammals are also presented.

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“…An early study used two‐year‐old mice (equivalent to the human age group of 65) with two subgroups (5 mice in each group) representing the worst and best performers in the Morris water maze and found that there is no loss of principal hippocampal and subicular neurons (Rasmussen, Schliemann, Sørensen, Zimmer, & West, 1996). A more recent study in human also showed that very old individuals have comparable number of neocortical neurons to younger individuals, while there is significant difference in the total number of neocortical oligodendrocytes (Fabricius, Jacobsen, & Pakkenberg, 2013). Overall, cell counting methods show that significant neuron loss does not occur during normal aging and changes are subtle and region‐specific (Burke & Barnes, 2006).…”

Section: Cellular Changes In Aging and Admentioning

confidence: 99%

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

et al. 2018

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Alzheimer's disease is the most prevalent cause of dementia, which is defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of linear causality proposed by the original amyloid hypothesis. Aging is the main risk factor for Alzheimer's disease that cannot be explained by amyloid hypothesis. To evaluate how aging and Alzheimer's disease are intrinsically interwoven with each other, we review and summarize evidence from molecular, cellular, and system level. In particular, we focus on study designs, treatments, or interventions in Alzheimer's disease that could also be insightful in aging and vice versa.

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Effect of age on neocortical brain cells in 90+ year old human females—a cell counting study

Cited by 79 publications

References 25 publications

Distinction of Neurons, Glia and Endothelial Cells in the Cerebral Cortex: An Algorithm Based on Cytological Features

Distinction of Neurons, Glia and Endothelial Cells in the Cerebral Cortex: An Algorithm Based on Cytological Features

Stereological estimation of total cell numbers in the human cerebral and cerebellar cortex

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

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