Experiments in macaque monkeys provide critical insights into age-associated changes in cognitive and sensory function

The use of animal models in brain aging research has led to numerous fundamental insights into the neurobiological processes that underlie changes in brain function associated with normative aging. Macaque monkeys have become the predominant nonhuman primate model system in brain aging research due to their striking similarities to humans in their behavioral capacities, sensory processing abilities, and brain architecture. Recent public concern about nonhuman primate research has made it imperative to attempt to clearly articulate the potential benefits to human health that this model enables. The present review will highlight how nonhuman primates provide a critical bridge between experiments conducted in rodents and development of therapeutics for humans. Several studies discussed here exemplify how nonhuman primate research has enriched our understanding of cognitive and sensory decline in the aging brain, as well as how this work has been important for translating mechanistic implications derived from experiments conducted in rodents to human brain aging research.

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Age affects procedural paired-associates learning in the grey mouse lemur (Microcebus murinus)

Scientific Reports ◽

10.1038/s41598-021-80960-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Daniel Schmidtke

Keyword(s):

Nonhuman Primate ◽

Animal Studies ◽

Brain Aging ◽

Mouse Lemur ◽

Microcebus Murinus ◽

Primate Model ◽

Aging Research ◽

Paired Associates ◽

Age Related ◽

Grey Mouse Lemur

AbstractThe ability to associate memorized objects with their location in space gradually declines during normal aging and can drastically be affected by neurodegenerative diseases. This study investigates object-location paired-associates learning (PAL) in the grey mouse lemur (Microcebus murinus), a nonhuman primate model of brain aging. Touchscreen-based testing of 6 young adults (1–5 years) and 6 old adults (> 7 years) in the procedural rodent dPAL-task revealed significant age-related performance decline, evident in group differences in the percentage of correct decision during learning and the number of sessions needed to reach a predefined criterion. Response pattern analyses suggest decreased susceptibility to relative stimulus-position biases in young animals, facilitating PAL. Additional data from a subset of “overtrained” individuals (n = 7) and challenge sessions using a modified protocol (sPAL) further suggest that learning criteria routinely used in animal studies on PAL can underestimate the endpoint at which a stable performance is reached and that more conservative criteria are needed to improve construct validity of the task. To conclude, this is the first report of an age effect on dPAL and corroborates the role of mouse lemurs as valuable natural nonhuman primate models in aging research.

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Social Psychobiologic Dysfunction Associated with Anabolic Steroid Abuse: A Review

The Sport Psychologist ◽

10.1123/tsp.4.3.275 ◽

1990 ◽

Vol 4 (3) ◽

pp. 275-284 ◽

Cited By ~ 4

Author(s):

Edward Gregg ◽

W. Jack Rejeski

Keyword(s):

Nonhuman Primate ◽

Social Withdrawal ◽

Primate Research ◽

Primate Model ◽

Psychological States ◽

Steroid Abuse ◽

Overt Behavior ◽

Descriptive Research ◽

The Social ◽

Androgenic Steroids

This article reviews both human and nonhuman primate research dealing with the social psychobiologic effects of anabolic/androgenic steroids (AS). Descriptive research and anecdotal reports within the realm of sport suggest that AS may have a variety of psychological and behavioral effects including psychotic episodes and increased aggression. Recent investigations with a nonhuman primate model confirm that the effects of AS on psychological states and overt behavior can be quite varied, ranging from those that can be characterized as active (e.g., mania and aggression) to more passive states (e.g., depression and social withdrawal). There are also profound physiological effects of a biobehavioral origin that constitute a risk for cardiovascular disease. The most striking aspect of AS is that the effects of this drug are due to an interaction between its pharmacologic properties and the social milieu.

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Brain aging research at the close of the 20th century: from bench to bedside

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2001.3.3/ccmeltzer ◽

2001 ◽

Vol 3 (3) ◽

pp. 167-180

Keyword(s):

Brain Function ◽

Brain Aging ◽

Aging Brain ◽

Aging Research ◽

Fertile Ground ◽

Biological Substrate ◽

Dementing Illness ◽

And Function ◽

And Behavior

Remarkable and continued growth in the field of brain aging research has been fueled by a confluence of factors. Developments in molecular biology, imaging, and genetics coupled with the imperative caused by the aging of the population has created fertile ground for improved understanding of the interaction between brain function and behavior. Aging changes in neurochemical systems may account for the spectrum of cognitive and behavioral states of successfully aged pen sons, but may also contribute to enhanced vulnerability to depressive or dementing illness. In particular, the refinement of in vivo imaging approaches to investigating the structure and function of the aging brain has provided the opportunity to strengthen our knowledge of the biological substrate of the aging brain and neuropsychiatrie disorders, and translate these into therapeutics.

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Tacrolimus, a Potential Neuroprotective Agent, Ameliorates Ischemic Brain Damage and Neurologic Deficits after Focal Cerebral Ischemia in Nonhuman Primates

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/01.wcb.0000088761.02615.eb ◽

2003 ◽

Vol 23 (10) ◽

pp. 1183-1194 ◽

Cited By ~ 22

Author(s):

Yasuhisa Furuichi ◽

Masashi Maeda ◽

Akira Moriguchi ◽

Taiji Sawamoto ◽

Akio Kawamura ◽

...

Keyword(s):

Cerebral Infarction ◽

Nonhuman Primate ◽

Focal Cerebral Ischemia ◽

Sensory Function ◽

Neuroprotective Activity ◽

Nonhuman Primate Model ◽

Primate Model ◽

Neurologic Deficits ◽

Infarction Volume

Tacrolimus (FK506), an immunosuppressive drug, is known to have potent neuroprotective activity and attenuate cerebral infarction in experimental models of stroke. Here we assess the neuroprotective efficacy of tacrolimus in a nonhuman primate model of stroke, photochemically induced thrombotic occlusion of the middle cerebral artery (MCA) in cynomolgus monkeys. In the first experiment, tacrolimus (0.01, 0.032, or 0.1 mg/kg) was intravenously administered immediately after MCA occlusion, and neurologic deficits and cerebral infarction volumes were assessed 24 hours after the ischemic insult. Tacrolimus dose-dependently reduced neurologic deficits and infarction volume in the cerebral cortex, with statistically significant amelioration of neurologic deficits at 0.032 and 0.1 mg/kg and significant reduction of infarction at 0.1 mg/kg. In the second experiment, the long-term efficacy of tacrolimus on neurologic deficits and cerebral infarction was assessed. Vehicle-treated monkeys exhibited persistent and severe deficits in motor and sensory function for up to 28 days. A single intravenous bolus injection of tacrolimus (0.1 or 0.2 mg/kg) produced long-lasting amelioration of neurologic deficits and significant reduction of infarction volume. In conclusion, we have provided compelling evidence that a single dose of tacrolimus not only reduces brain infarction but also ameliorates long-term neurologic deficits in a nonhuman primate model of stroke, strengthening the view that tacrolimus might be beneficial in treating stroke patients.

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Normal Cognitive and Brain Aging

The Oxford Handbook of Adult Cognitive Disorders ◽

10.1093/oxfordhb/9780190664121.013.2 ◽

2019 ◽

pp. 4-24

Author(s):

Stephanie L. Leal ◽

Michael A. Yassa

Keyword(s):

Individual Differences ◽

Brain Aging ◽

Integrative Approach ◽

Aging Brain ◽

Aging Research ◽

Factors Associated ◽

Biological Phenomena ◽

Neurocognitive Aging ◽

Process Factors ◽

The Individual

Normal cognitive and brain aging are a set of interconnected and complex biological phenomena that can be understood from a multidisciplinary and integrative approach combining studies in animals and humans. This chapter summarizes some of the key facets involved in these phenomena from an individual differences approach and highlights episodic memory as a key area of rich investigation. Cognitive and biological changes with age are discussed with specific emphasis on the factors associated with selective vulnerabilities and resiliencies to the aging process. Factors associated with modifiable risk are discussed alongside strategies to reduce such risk and maintain intact cognitive function in older adulthood. The power of the individual differences approach as well as caveats and methodological limitations to neurocognitive aging research are discussed with the goal of delineating key gaps in understanding the aging brain and paving the path for future investigations.

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Phenotypic outcomes in CNS serotonin and serotonin-mediated behavior are modulated by gene X environment interactions: A nonhuman primate model

PsycEXTRA Dataset ◽

10.1037/e552512012-012 ◽

2006 ◽

Author(s):

J. Dee Higley ◽

Tim K. Newman

Keyword(s):

Nonhuman Primate ◽

Nonhuman Primate Model ◽

Primate Model ◽

Gene X Environment Interactions

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Maternal High-Fat Diet Persistently Alters Bone Marrow Immune Cell Proportions and Function in a Nonhuman Primate Model

Diabetes ◽

10.2337/db18-222-or ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 222-OR

Author(s):

MICHAEL J. NASH ◽

TAYLOR K. SODERBORG ◽

RACHEL C. JANSSEN ◽

ERIC M. PIETRAS ◽

JACOB E. FRIEDMAN

Keyword(s):

Bone Marrow ◽

Nonhuman Primate ◽

High Fat Diet ◽

Immune Cell ◽

High Fat ◽

Nonhuman Primate Model ◽

Primate Model ◽

And Function

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Reperfusion plus Selective Intra-arterial Cooling (SI-AC) Improve Recovery in a Nonhuman Primate Model of Stroke

Neurotherapeutics ◽

10.1007/s13311-020-00895-6 ◽

2020 ◽

Author(s):

Di Wu ◽

Yongjuan Fu ◽

Longfei Wu ◽

Mitchell Huber ◽

Jian Chen ◽

...

Keyword(s):

Nonhuman Primate ◽

Nonhuman Primate Model ◽

Primate Model

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Chromosome Instability, Aging and Brain Diseases

Cells ◽

10.3390/cells10051256 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1256

Author(s):

Ivan Y. Iourov ◽

Yuri B. Yurov ◽

Svetlana G. Vorsanova ◽

Sergei I. Kutsev

Keyword(s):

Brain Aging ◽

Chromosome Instability ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Accelerated Aging ◽

Brain Diseases ◽

Aging Brain ◽

Ontogenetic Changes ◽

Health And Disease

Chromosome instability (CIN) has been repeatedly associated with aging and progeroid phenotypes. Moreover, brain-specific CIN seems to be an important element of pathogenic cascades leading to neurodegeneration in late adulthood. Alternatively, CIN and aneuploidy (chromosomal loss/gain) syndromes exhibit accelerated aging phenotypes. Molecularly, cellular senescence, which seems to be mediated by CIN and aneuploidy, is likely to contribute to brain aging in health and disease. However, there is no consensus about the occurrence of CIN in the aging brain. As a result, the role of CIN/somatic aneuploidy in normal and pathological brain aging is a matter of debate. Still, taking into account the effects of CIN on cellular homeostasis, the possibility of involvement in brain aging is highly likely. More importantly, the CIN contribution to neuronal cell death may be responsible for neurodegeneration and the aging-related deterioration of the brain. The loss of CIN-affected neurons probably underlies the contradiction between reports addressing ontogenetic changes of karyotypes within the aged brain. In future studies, the combination of single-cell visualization and whole-genome techniques with systems biology methods would certainly define the intrinsic role of CIN in the aging of the normal and diseased brain.

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