Neurobiological Bases of Age-Related Cognitive Decline in the Rhesus Monkey

Peters, Alan; Rosene, Douglas L.; Moss, Mark B.; Kemper, Thomas L.; Abraham, Carmela R.; Tigges, Johannes; Albert, Mareike

doi:10.1097/00005072-199608000-00001

Cited by 314 publications

(174 citation statements)

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“…During normal aging, the volume of the hippocampus (total or any of its subfields) remains stable in rhesus monkeys (Peters et al 1996;Calhoun et al 2004;Shamy et al 2006Shamy et al , 2010Makris et al 2010). This is in contrast to a substantial number of MRI studies reporting a reliable age-related decline in hippocampal volume in healthy humans (Kaye et al 1997;Mueller et al 1998;Tisserand et al 2000;Raz et al 2004;Walhovd et al 2009).…”

Section: Gross Anatomy Of Hippocampal and Related Cortical Regionsmentioning

confidence: 85%

“…When unbiased stereological methods are applied, there are no age-dependent differences in neuronal number or density in the subiculum, CA1, CA2, CA3, DG, and EC in rhesus monkeys Amaral 1993;Rapp 1995;Peters et al 1996;Gazzaley et al 1997;Merrill et al 2000;Keuker et al 2003). Although based on a small number of monkeys, there is no evidence for a relationship between DNMS scores and neuronal numbers in these regions Rapp 1995).…”

Section: Neurons Of the Hippocampus And Related Cortical Regionsmentioning

confidence: 98%

“…Age-related cognitive decline begins as early as the late teens in rhesus monkeys, although as in humans, some aged monkeys are resistant to the decline and exhibit cognitive abilities similar to those of young adults (Presty et al 1987;Bachevalier et al 1991;Rapp and Amaral 1991;Peters et al 1996). Additionally, not all functional abilities are affected equally within an individual aged monkey (Voytko 1999).…”

Section: Nonhuman Primate As a Model Of Agingmentioning

confidence: 99%

“…Even in very mild stages of Alzheimer's disease, neurons are lost from the EC (35% overall, 50% in layer II) and CA1 (46%), while no significant decrease in neuronal number is observed in healthy nondemented aged individuals . There is no convincing evidence for a significant loss of neurons from the human hippocampus during the normal, nonpathological, aging process (Peters et al 1996).…”

Section: Neurons Of the Hippocampus And Related Cortical Regionsmentioning

confidence: 99%

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Neuronal and morphological bases of cognitive decline in aged rhesus monkeys

Hara

Rapp

Morrison

2011

AGE

114

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Rhesus monkeys provide a valuable model for studying the basis of cognitive aging because they are vulnerable to age-related decline in executive function and memory in a manner similar to humans. Some of the behavioral tasks sensitive to the effects of aging are the delayed response working memory test, recognition memory tests including the delayed nonmatching-to-sample and the delayed recognition span task, and tests of executive function including reversal learning and conceptual set-shifting task. Much effort has been directed toward discovering the neurobiological parameters that are coupled to individual differences in age-related cognitive decline. Area 46 of the dorsolateral prefrontal cortex (dlPFC) has been extensively studied for its critical role in executive function while the hippocampus and related cortical regions have been a major target of research for memory function. Some of the key age-related changes in area 46 include decreases in volume, microcolumn strength, synapse density, and α1-and α2-adrenergic receptor binding densities. All of these measures significantly correlate with cognitive scores. Interestingly, the critical synaptic subtypes associated with cognitive function appear to be different between the dlPFC and the hippocampus. For example, the dendritic spine subtype most critical to task acquisition and vulnerable to aging in area 46 is the thin spine, whereas in the dentate gyrus, the density of AGE (2012) large mushroom spines with perforated synapses correlates with memory performance. This review summarizes age-related changes in anatomical, neuronal, and synaptic parameters within brain areas implicated in cognition and whether these changes are associated with cognitive decline.

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Section: Gross Anatomy Of Hippocampal and Related Cortical Regionsmentioning

confidence: 85%

Section: Neurons Of the Hippocampus And Related Cortical Regionsmentioning

confidence: 98%

Section: Nonhuman Primate As a Model Of Agingmentioning

confidence: 99%

Section: Neurons Of the Hippocampus And Related Cortical Regionsmentioning

confidence: 99%

See 2 more Smart Citations

Neuronal and morphological bases of cognitive decline in aged rhesus monkeys

Hara

Rapp

Morrison

2011

AGE

114

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“…Indeed, recent reports using modern stereological cell-counting methods did not show any significant agerelated loss of hippocampal neurons in rats [44], mice [13], monkeys [30,41], or humans [51]. Peters and Sethares reported that even with significant thinning with age of cortical layer 1, accompanied by a loss of some dendrites and spines and a decrease in the frequency of synapses, in the occipital and prefrontal cortex in Rhesus monkeys, there was no significant age-related changes in the number of neurons, astrocytes, or microglia and oligodendrocytes in the layer [42].…”

Section: Discussionmentioning

confidence: 97%

Regional protein levels of cytosolic phospholipase A2 and cyclooxygenase-2 in Rhesus monkey brain as a function of age

Weerasinghe

Coon

Bhattacharjee

et al. 2006

Brain Research Bulletin

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Limited evidence suggests that brain cytosolic phospholipase A 2 (cPLA 2 ), which selectively releases arachidonic acid (AA) from membrane phospholipids, and cyclooxygenase-2 (COX-2), the ratelimiting enzyme for AA metabolism to prostanoids, change as a function of normal aging. In this study, we examined the protein levels of cPLA 2 and COX-2 enzymes in hippocampus, frontal pole and cerebellum from young (2-5 year-old), middle-aged (8-11 year-old) and old (23 year-old) male and female Rhesus monkeys. In the cerebellum, cPLA 2 protein level was higher in the young brain as compared to levels seen at both middle-aged and old. Similarly, in the frontal pole, the young brain showed a higher level of COX-2 protein as compared to the levels seen at both older ages. For both, once an animal reached 8-11 years of age the levels appeared to remain relatively constant over the next decade. Immunohistochemistry of COX-2 protein within the brain demonstrated no significant change in the localization to neurons within the frontal pole. In the young brain, the distribution of a low level of COX-2 protein within numerous neurons was different than the decreased number of neurons stained at a greater intensity in the adult brain. Based on the previous reports of localization of cPLA 2 and COX-2 at post-synaptic sites in neurons results from the current study suggest that the elevated protein levels of the two enzymes seen in the younger brain is related to the greater potential for synaptic plasticity across multiple neurons as a function of age and that cPLA 2 and COX-2 may be considered as post-synaptic markers.

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