Title: Department of Health and Human Services National Institutes of Health National Center for Research R
1Department of Health and Human ServicesNational
Institutes of HealthNational Center for Research
Resources138th Meeting of theNational Advisory
Research Resources CouncilJanuary 30, 2008
- Research at the National Primate Research Centers
- Neurosciences, Neuroimaging, and
- Neurodegenerative Diseases
- Stuart Zola, Ph.D.
- Director, Yerkes National Primate Research Center
2Brain Disorders Cause the Greatest Burden of
Disease Worldwide
Population
World Health Organization and Harvard Study, 2003
3NPRCs Neuroscience, Neuroimaging,
Neurodegenerative Diseases
Autism
Obesity
Memory impairment
Post traumatic stress disorder
Comparative evolution
Neurodegeneration
Addiction
Emotion and Cognition
4NPRCs Neuroscience, Neuroimaging,
Neurodegenerative Diseases
Autism
Obesity
Memory impairment
Post traumatic stress disorder
Comparative evolution
Neurodegeneration
Addiction
Emotion and Cognition
5Recognition Memory in monkeys and humans
MTL Memory System
Neurodegenerative diseases
The Medial Temporal Lobe Memory System
Hippocampus
6The Perplexing Trajectories
Cognitive Ability
Primarily Memory
Additional Brain Regions
Neurodegenerative diseases, dementia, AD
Normal
MCI
Primarily Hippocampus
Other Cognitive Abilities
Neuropathology
MCI - Mild Cognitive Impairment
7The Perplexing Trajectories
Target area for early detection, translational
research
Cognitive Ability
Primarily Memory
Additional Brain Regions
Neurodegenerative diseases, dementia, AD
Normal
MCI
Primarily Hippocampus
Other Cognitive Abilities
Neuropathology
8Eye Camera
Recognition memory task combined with Infrared
eye-tracking technology
Eye Camera Optics Module
Monocular Visor
92-min delay NC
102-min Delay MCI
11Increased risk
12 Translational Research
Research With Nonhuman Primates
Clinical Research Applied to Patients
1950s Standardized memory tests for assessing
amnesia Amnesic case HM implicates the temporal
lobe
1960s-1990s Clarification of the role of the
hippocampus in memory Development of recognition
memory tasks for monkeys, including eye-tracking
2000 MCI identified as a precursor to AD
Determination that hippocampal pathology is
linked to MCI
2000 Discovery in monkeys of recognition memory
tasks specially sensitive to hippocampal damage
2006 Memory tasks developed in monkeys adapted
for early assessment of MCI Eye-tracking adapted
from work in monkeys
2008 Rehabilitation of memory impairment using
recognition memory tests and eye-tracking to
guide training and monitor success MCI, TBI, HIV
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Huntingtons disease
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Alzheimers disease
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Longitudinal Studies Cognitive behavioral
testing Non-invasive imaging Genomic
profiling Metabolite profiling
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15Additional notes
- Identification of a glycoaminoglycan (Hyaluronan,
HA) that inhibits remyelination following CNS
injury and accumulates in the aging primate brain
Developing agents to block, degrade, or
inhibit HA determine of HA influences white
matter damage and cognitive decline in nonhuman
primates. - Work in rodents and humans has revealed that
vasopressin plays important role in regulating
social cognition and behavior. Investigations of
the evolution of the primate vasopressin receptor
gene revealed the primate AVPR1 gene has a
repetitive element in the promoter that in humans
has been implicated in autism and social
cognition. There is considerable diversity in
chimpanzees many chimpanzees are missing this
behaviorally relevant region. Therefore,
chimpanzees may prove to be a critical model for
understanding how this element contributes to
social cognitive processes in humans and this has
important implications for understanding autism - Using conditioned fear paradigms with nonhuman
primates, researchers have developed a way to
measure the core symptoms of PTSD, namely the
inability to feel safe in an environment that
should make monkeys (or patients) feel safe.
Focus now is on what areas of the brain are
activated in the presence of safety cues and how
is this dysregulated in maternally separated
monkeys that cannot feel safe reversible brain
inactivation strategies - First in vivo evidence that stress (including
early life stressful experiences (maternal
separation, infant maltreatment by mothers) can
lead to increased activation of pro-inflammatory
signaling pathways, lead in turn to increased
release of pro-inflammatory cytokines that can
then cause alterations in brain serotonin,
subsequently linked to psychopathology