A website entitled “The fine structure of the aging brain”

Authors

  • Alan Peters,

    Corresponding author
    1. Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts 02118
    • Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA 02118
    Search for more papers by this author
  • Claire Folger

    1. Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts 02118
    Search for more papers by this author

Abstract

original image

Rhesus monkeys offer a strong comparative model for the effects of aging on the human brain, and The Journal of Comparative Neurology is grateful to have the opportunity to feature a unique resource from one of the world's leading authorities on the synaptic and cellular basis of age-related cognitive decline. The 130 high resolution electron micrographs from aging rhesus monkey (Macaca mulatta), provided by Alan Peters and his colleague, Claire Folger, represent 20 years of detailed study, and are a valuable instrument to help gain better insight into the effects of normal aging on the neurons and neuroglial cells in the cerebral hemispheres and associated fiber tracts of the forebrain.

For the past twenty years we have been examining the effects of aging on the fine structure of the components of the cerebral hemispheres of the rhesus monkey. As a result, we have collected a large library of electron microscopic images that have helped us to better understand effects of normal aging on the neurons and neuroglial cells in the cerebral hemispheres and associated fiber tracts of the aging rhesus monkey (Macaca mulatta) forebrain. As we went through our files, it became obvious that we had many interesting images, the majority of which, owing to the constraints on the number of figures that can be used to illustrate journal articles, would never be published. Other images have been languishing in our files because they have not been appropriate to illustrate the theme of an article. It occurred to us that others might be interested in seeing some of these images, because so far as we are aware, a comprehensive collection of images that show the effect of normal aging is presently not available. And obviously the perfect place to share some of these images would be on a website.

In the spirit of sharing knowledge, we decided to provide the means by which these images can be downloaded for educational purposes. The images are grouped into chapters, and users can download the images from each chapter (at a resolution of 6 × 9″ at 240 dpi), but in addition, we have provided a download page so that users can obtain even higher resolution images (most of them 6 × 7″ at 600 dpi) free of labeling and text. All images are available from our website, http://www.bu.edu/agingbrain.

We have not included images of the structural appearance of components of cells and their processes in young monkeys, as such images can be found in the illustrations in the book, “The Fine Structure of the Nervous System: Neurons and Their Supporting Cells” 1991, by Alan Peters, Sanford L. Palay, and Henry deF. Webster, 3rd edition, Oxford University Press.

The reason for choosing to study the effects of normal aging in rhesus monkeys is that these primates provide a good model for understanding and interpreting the effects of normal aging in human brains. Unlike the short-lived rodents, for example, in monkeys the effects of aging extend over many years. Indeed, the life span of rhesus monkeys closely approaches that of humans, because these monkeys live to a maximum of about 35 years. So that if humans are considered to live for about 100 years of age, then 1 monkey year is equivalent to about 3 human years.

Another important consideration for studying the effects of normal aging on the brains of rhesus monkeys is that these monkeys do not develop Alzheimer's disease, so the effects of normal aging are not confounded by pathological changes that might occur during the early stages of Alzheimer's disease. Some senile plaques do occur in the cerebral cortices of rhesus monkeys, but the plaques are few in number and their frequency does not correlate with cognitive decline. Moreover, rhesus monkeys have complex behavior patterns that approach those of humans, so that behavioral tests similar to those used in humans can be employed to accurately assess their cognitive status before their brains are preserved for structural evaluations. This means that determinations can be made about whether the frequency of occurrence of a particular age-related fine structural alteration does or does not correlate with cognitive decline.

The brain tissue used in our studies was fixed by perfusion of aldehyde-containing solutions through the heart. Tissue blocks were then taken, osmicated, and embedded in Araldite for thin sectioning. The thin sections were stained with lead citrate and uranyl acetate, before being photographed in an electron microscope. The 3 × 4″ sheet film negatives were then scanned at high resolution and stored in a computer.

The 130 electron micrographs on this website are presented in 18 chapters, each chapter being devoted to a particular component of the brain, with a brief introduction to explain something about the images presented within it. The images have minimal labeling, and some of the micrographs have colored versions. These colored versions show the distribution and relationships of the various components of the neuropil, and, to help in interpretation of the images, as far as possible a standardized color scheme has been used throughout. Figures 1 and 2 show representative examples from this resource.

Figure 1.

Plate 14.5: A microglial cell in the primary visual cortex of a 35-year-old monkey. Note the phagocytosed material at the two poles of the perikaryon (arrows).

Figure 2.

Plate 15.2: A large hole lying adjacent to a neuronal cell body in the neuropil of layer 3 in the primary visual cortex of a 35-year-old monkey. This hole contains membranous debris and may represent a degenerating dendrite or neuronal cell body.

It should be pointed out that to date very few parts of the non-human primate brain have been examined to determine the effects of normal aging on the central nervous system. Furthermore, only a few studies have been carried out in which the tissue being examined is from primates that have been behaviorally tested to determine their cognitive status. As far as gray matter is concerned, aging studies have been largely confined to area 46 of the prefrontal cortex and to the primary visual cortex, area 17, with a few observations on the dentate gyrus, and on the Betz cells in the motor cortex. More is known about the effects of aging on white matter, because the fine structure of nerve fibers has been examined in a number of well-circumscribed fiber bundles in the cerebral hemispheres. Reviews of the results of these studies can be found in the works by Peters and Kemper (2012) and Morrison and Baxter (2012).

A summary of what is known about the effects of aging on the morphological integrity of the primate brain is as follows:

  • 1A number of structural factors, such as the total volume of the brain, the numbers of neurons, and astrocytes and microglial cells in various parts of the brain, do not appear to alter significantly with increasing age.
  • 2Some structural alterations increase in frequency with age, but the frequency does not correlate with cognitive decline. Among these alterations are age-related losses of nerve fibers that are 20% or lower, and an increased frequency of degenerating myelin sheaths in some fiber tracts. Other alterations in this category are an increase in the frequency of senile plaques; an increase in frequency of oligodendrocytes; and the loss of synapses from the lower layers of the prefrontal cortex.
  • 3Among the structural alterations that increase in frequency with age, the frequency of which correlates with cognitive decline, are the following: an increased frequency of degenerating myelin sheaths, the loss of substantial numbers of nerve fibers from some fiber tracts, and the loss of synapses and dendritic spines from the upper layers of prefrontal area 46.
  • 4What is becoming clear is that the cognitive decline that occurs during normal aging is not attributable to a single factor, and that while degenerative alterations are occurring, some repair is also taking place. The most obvious example of repair is the remyelination that leads to the formation of more numerous and shorter internodal lengths of myelin, and the increased numbers of oligodendrocytes that are generated to effect this repair.

Obviously, this is only a beginning in our understanding of the effects of aging on the primate brain. In the future, additional cortical areas need to be examined to determine whether alterations, such as the synapse losses from the upper layers of area 46 of the cortex, are specific to that area or whether synaptic losses occur throughout the cortex. If synaptic losses are ubiquitous, the origins of the axon terminals that degenerate to account for the losses must be determined.

Ancillary