THE AGING RHESUS MONKEY: PATTERNS OF NEUROBIOLOGICAL CHANGE IN
SUCCESSFUL AND UNSUCCESSFUL AGING
D.L. Rosene, Ph.D.
Department of Anatomy & Neurobiology, Boston University School of
Medicine, Boston, MA 02118
It is now clear that normal aging is characterized by an increase in
the incidence and severity of cognitive impairments and that among aged
subjects the majority are 'successful' agers with mild impairments
while a minority are severely impaired 'unsuccessful' agers and are.
With the ultimate goal of using the rhesus monkey model of normal aging
to develop interventions or therapies to prevent or reverse this
cognitive decline, the immediate challenge for neurobiological studies
of the monkey brain is to determine first, the changes in the brain
that are associated with or cause specific behavioral impairments and
second to identify potential causal mechanisms that produce these brain
changes. In aged rhesus monkeys (i.e. over 20 years of age) examination
of neuron numbers in the medial temporal lobe (hippocampus, entorhinal
cortex, amygdala), visual cortex (area 17), primary motor cortex (area
4) and prefrontal cortex (area 46) reveals no significant age-related
loss of neurons. Examination of the number of axosomatic synapses in
primary motor cortex and axospinous synapses in the dentate gyrus
molecular layer reveals that synapse numbers are also stable with age.
In contrast, ligand binding studies of a multiple neurotransmitter
receptors demonstrates that there is a significant loss in a number of
receptors (especially the NMDA and kainate subtypes of the amino acid
receptors in the hippocampus and the alpha-1 adrenergic receptor in the
prefrontal cortex) while the benzodiazepine modulatory site on the
GABAA receptor is increased. In addition MRI studies reveal a loss of
forebrain white matter with age while ultrastructural studies reveal an
age-related increase in abnormal myelin and electrophysiological
studies reveal a reduction in conduction velocity. Studies of glial
markers demonstrate an age-related increase in reactive microglia and
astrocytes in white matter. Overall these white matter changes show the
strongest relationship with cognitive impairments, differentiate
successful from unsuccessful agers and suggest that white matter may
be a critical target of age-related pathology and that inflammation may
be part of that process. (Supported by NIH grant P01-AG00001).
keywords: Aging, Monkey, Receptors, Myelin, MRI
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