Cerebral amyloid angiopathy and plaques, and visceral amyloidosis in aged macaques

Uno, Hideo; Alsum, Pamela; Dong, Sophie; Richardson, R.L.; Zimbric, Michele L.; Thieme, Carol; Houser, Wallace D.

doi:10.1016/0197-4580(95)02063-2

Cited by 64 publications

(34 citation statements)

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“…As apoE has an integral role in the catabolism of amyloid within the brain, apoE might be increased in the elderly rhesus monkey brain for clearance of the age-related increase in Aβ (Cork et al 1990;Uno et al 1996;Sani et al 2003). Similar to previous studies, we demonstrate that apoE clusters are colocalized with Aβ deposits in aged rhesus macaques (Mufson et al 1994;Hartig et al 1997;Sani et al 2003).…”

Section: Discussionmentioning

confidence: 99%

“…One report indicated that no difference in MAP-2 and SYN was observed between young adult (5-year) and old (18-year) nonhuman primates; however, there were only two old animals in the study and the analysis was performed in the pallidonigral region (Fukuda et al 2005). However, since rhesus macaques in captivity can live longer than 30 years (Uno et al 1996), the current study includes much older animals and examined cortical regions linked to cognitive function. Additionally, studying older animals could provide more translational insight into the elderly human brain and bridge the translational efforts of rodent and human research (Chauhan and Siegel 1997;Calhoun et al 1998;Benice et al 2006;Kadish et al 2009).…”

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confidence: 99%

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Age-related decreases in SYN levels associated with increases in MAP-2, apoE, and GFAP levels in the rhesus macaque prefrontal cortex and hippocampus

Haley

Kohama

Urbanski

et al. 2010

AGE

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Loss of synaptic integrity in the hippocampus and prefrontal cortex (PFC) may play an integral role in age-related cognitive decline. Previously, we showed age-related increases in the dendritic marker microtubule associated protein 2 (MAP-2) and the synaptic marker synaptophysin (SYN) in mice. Similarly, apolipoprotein E (apoE), involved in lipid transport and metabolism, and glial fibrillary acidic protein (GFAP), a glia specific marker, increase with age in rodents. In this study, we assessed whether these four proteins show similar age-related changes in a nonhuman primate, the rhesus macaque. Freefloating sections from the PFC and hippocampus from adult, middle-aged, and aged rhesus macaques were immunohistochemically labeled for MAP-2, SYN, apoE, and GFAP. Protein levels were measured as area occupied by fluorescence using confocal microscopy as well as by Western blot. In the PFC and hippocampus of adult and middle-aged animals, the levels of SYN, apoE, and GFAP immunoreactivity were comparable but there was a trend towards higher MAP-2 levels in middle-aged than adult animals. There was significantly less SYN and more MAP-2, apoE, and GFAP immunoreactivity in the PFC and hippocampus of aged animals compared to adult or middle-aged animals. Thus, the age-related changes in MAP-2, apoE, and GFAP levels were similar to those previously observed in rodents. On the other hand, the age-related changes in SYN levels were not, but were similar to those previously observed in the aging human brain. Taken together, these data emphasize the value of the rhesus macaque as a pragmatic translational model for human brain aging.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Age-related decreases in SYN levels associated with increases in MAP-2, apoE, and GFAP levels in the rhesus macaque prefrontal cortex and hippocampus

Haley

Kohama

Urbanski

et al. 2010

AGE

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“…A␤ plaques are associated with angiopathy (32). Although A␤ accumulates in older rhesus brains, neurofibrillary tangles, another hallmark of AD pathology, have not been observed (33). Driven by the success in mice, there is growing interest in producing transgenic monkeys in which AD and other neurodegenerative diseases can be accurately modeled (34).…”

Section: Aging Parallelsmentioning

confidence: 99%

Aging in Rhesus Monkeys: Relevance to Human Health Interventions

Roth

Mattison

Ottinger

et al. 2004

Science

321

237

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Progress in gerontological research has been promoted through the use of numerous animal models, which have helped identify possible mechanisms of aging and age-related chronic diseases and evaluate possible interventions with potential relevance to human aging and disease. Further development of nonhuman primate models, particularly rhesus monkeys, could accelerate this progress, because their closer genetic relationship to humans produces a highly similar aging phenotype. Because the relatively long lives of primates increase the administrative and economic demands on research involving them, new emphasis has emerged on increasing the efficient use of these valuable resources through cooperative, interdisciplinary research.As gerontological research continues to gain both visibility and interest within the broader scientific community, the relevance of various model systems for eventual application of findings to humans has become a critical issue. Although rodents remain the most widely used animal model for gerontology, an increasing use of invertebrates has provided many new insights into aging processes, especially regarding possible longevity genes (1). Given the complexity of human physiology, however, models more phylogenetically similar to humans are needed. Advantages and Disadvantages of Nonhuman Primate ModelsResearch using nonhuman primates can provide a valuable approach for elucidating the nature and causes of aging processes observed in humans as well as evaluating potential interventions. An ongoing longitudinal study of aging and nutrition in rhesus monkeys (Macaca mulatta) conducted since 1987 by the National Institute on Aging (NIA), as well as studies conducted at other sites, has revealed much about aging and age-related disease in these monkeys and has shed light on the advantages and disadvantages of their use in gerontological research. Because of their genetic homology to humans (92.5 to 95%), many biological similarities are observed in the profile of aging. Another advantage is that rhesus monkeys are well adapted for laboratory research, including established husbandry, nutrition, breeding practices, and veterinary medicine. Disadvantages of rhesus monkeys include their current limited availability, costs of procurement and maintenance, and genetic heterogeneity. In addition, cross-species risks of disease transmission exist, and issues of animal welfare require constant vigilance. Research in monkeys is only as good as their physical and emotional health.The major scientific disadvantage is that rhesus monkeys are long-lived. Sexual maturity occurs at 3 to 5 years of age, median life-span is 25 years, and maximum life-span is 40 years (2, 3). With an estimated maximum life-span of 122 years in humans (4), the rate of aging in rhesus monkeys is roughly three times as fast. Thus, rhesus monkeys offer a distinct advantage over long-term human aging research, but longitudinal studies in these primates require a major investment of time, resources, and effort. Scope of Rhesus Monkey Res...

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“…The BBB plays a significant role in maintaining the homcostasis of the CNS microenvironment Jensen et al, 1998). Further, the cerebrovasculature is a site of injury in a number of neurological diseases and is involved in toxicant-induced injury to the nervous system (.lacobs, 1982;Aschncr and Gannon, 1994;Uno et al, 1996). A study by Nitsch and Klatzo (198.1) suggested that cerebrovascular alterations can also occur following seizures.…”

Section: Seizures Ami Bbb Disniplionmentioning

confidence: 99%

Long-term effects of subchronic exposure to sarin, alone and with stress or other chemicals

Abou‐Donia¹

2002

PsycEXTRA Dataset

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Sewices, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and to the Office of Management and Budget, Papenaiork Reduction Project (0704-0188), Washington, DC 20503 Final (25 March 1998 -24 September 2002 AGENCY USE ONLY (Leave blank) REPORT DATE October 2002 REPORT TYPE AND DATES COVERED TITLE AND SUBTITLE Long-Term Effects of Subchronic Exposure to Sarin, Alone and With Stress or Other Chemicals AUTHOR(S)Mohamed B. Abou-Donia, Ph.D. FUNDING NUMBERS DAMD17-98-C-8027 PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)Duke University Medical Center Durham, North Carolina 27710donia@acpub.duke.edu PERFORMING ORGANIZATION REPORT NUMBER SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) U.S. Army Medical Research and Materiel CommandFort Detrick, Maryland 21702-5012 SPONSORING / MONITORING AGENCY REPORT NUMBER SUPPLEMENTARY NOTESReport contains color. 12a. DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited 12b. DISTRIBUTION CODE ABSTRACT (Maximum 200 Words)The major objective of this proposal is to investigate the consequences of long-term, lowlevel exposure to sarin, alone, and in combination with pyridostigmine bromide (PB) and stress on the development of chronic and neurologic deficits. An important finding from our studies is that brain AChE and plasma BChE inhibition might be used as a biomarker for exposure, not for sarin-induced neurologic deficits. Rats treated with toxic doses of sarin showed inhibition of brain and plasma cholinesterases, that subsequently recovered.On the other hand, these animals exhibited sensorimotor deficit that persisted throughout the six-month observation period. Another significant result from our studies is that a brief insult from a single lethal or sub-lethal dose of sarin, can generate a series of events to result in a diffuse neuronal cell death. Neuronal degeneration was exhibited in the cerebral cortex, the hippocampus, and Purkinje cell neurons in the cerebellum. Stress, caused by immobilization or heat also exacerbated sarin-induced neurotoxicity.The results show that prophylactic treatment with PB offered some protection of peripheral AChE against sarin inhibition.On the other hand, PB exacerbated the toxicity of high doses of sarin.Furthermore, the results showed that treatment with either sarin or PB alone resulted in sensorimotor impairments that persisted throughout the six-month observation period. Neuronal cell death of the motor cortex and Purkinje cells of the cerebellum following exposure to sarin ...

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Cerebral amyloid angiopathy and plaques, and visceral amyloidosis in aged macaques

Cited by 64 publications

References 14 publications

Age-related decreases in SYN levels associated with increases in MAP-2, apoE, and GFAP levels in the rhesus macaque prefrontal cortex and hippocampus

Age-related decreases in SYN levels associated with increases in MAP-2, apoE, and GFAP levels in the rhesus macaque prefrontal cortex and hippocampus

Aging in Rhesus Monkeys: Relevance to Human Health Interventions

Long-term effects of subchronic exposure to sarin, alone and with stress or other chemicals

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