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Department of Health and Human Services National Institutes of Health National Center for Research R

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Research at the National Primate Research Centers. Neurosciences, Neuroimaging, and ... Director, Yerkes National Primate Research Center ... – PowerPoint PPT presentation

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Title: Department of Health and Human Services National Institutes of Health National Center for Research R


1
Department 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

2
Brain Disorders Cause the Greatest Burden of
Disease Worldwide
Population
World Health Organization and Harvard Study, 2003
3
NPRCs Neuroscience, Neuroimaging,
Neurodegenerative Diseases
Autism
Obesity
Memory impairment
Post traumatic stress disorder
Comparative evolution
Neurodegeneration
Addiction
Emotion and Cognition
4
NPRCs Neuroscience, Neuroimaging,
Neurodegenerative Diseases
Autism
Obesity
Memory impairment
Post traumatic stress disorder
Comparative evolution
Neurodegeneration
Addiction
Emotion and Cognition
5
Recognition Memory in monkeys and humans
MTL Memory System
Neurodegenerative diseases
The Medial Temporal Lobe Memory System
Hippocampus
6
The 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
7
The 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
8
Eye Camera
Recognition memory task combined with Infrared
eye-tracking technology
Eye Camera Optics Module
Monocular Visor
9
2-min delay NC
10
2-min Delay MCI
11
Increased 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

13
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Longitudinal Studies Cognitive behavioral
testing Non-invasive imaging Genomic
profiling Metabolite profiling
14
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15
Additional 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
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