Increasing problems with rigidity, bradykinesia, tremor and gait disturbances are seen with advancing age. These movement dysfunctions are associated with a significant increase in morbidity and mortality in the elderly. Our studies in rhesus monkeys will initially focus on delineating the relationship between age-associated changes in the nigrostriatal system and the decline in motor functions during normal aging processes. Our research program project has been designed to critically test four hypotheses. Hypothesis 1: that rhesus monkeys undergo declines in motor functions which closely model those seen in humans. Hypothesis 2: that there is a gradual, continuous change in nigrostriatal dopaminergic function in rhesus monkeys with age. Hypothesis 3: that there is a gradual continuous loss of midbrain dopamine neurons in rhesus monkeys in aging. Hypothesis 4: that upregulation of the nigrostriatal dopaminergic system in older rhesus monkeys by intracerebral administrations of the potent dopaminergic trophic factor GDNF improve motor function. The program project is organized into three research projects which are supported by two core units. Project 1-3 are carefully integrated and coordinated to analyze motor functions and the nigrostriatal dopaminergic system in rhesus monkeys. An Administrative Core supports all three project, coordinating collection, pooling and analysis of data. A Primate Core Facility supervises and coordinates the use of all rhesus monkeys in these studies.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
1P01AG013494-01A1
Application #
2001731
Study Section
Special Emphasis Panel (ZAG1-PCR-5 (O1))
Project Start
1997-02-18
Project End
2002-01-31
Budget Start
1997-02-18
Budget End
1998-01-31
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Kentucky
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
832127323
City
Lexington
State
KY
Country
United States
Zip Code
40506
Stenslik, M J; Evans, A; Pomerleau, F et al. (2018) Methodology and effects of repeated intranasal delivery of DNSP-11 in awake Rhesus macaques. J Neurosci Methods 303:30-40
Miller, Erin M; Quintero, Jorge E; Pomerleau, Fran├žois et al. (2015) Simultaneous glutamate recordings in the frontal cortex network with multisite biomorphic microelectrodes: New tools for ADHD research. J Neurosci Methods 252:75-9
Stenslik, Mallory J; Potts, Lisa F; Sonne, James W H et al. (2015) Methodology and effects of repeated intranasal delivery of DNSP-11 in a rat model of Parkinson's disease. J Neurosci Methods 251:120-9
Fuqua, Joshua L; Littrell, Ofelia M; Lundblad, Martin et al. (2014) Dynamic changes in dopamine neuron function after DNSP-11 treatment: effects in vivo and increased ERK 1/2 phosphorylation in vitro. Peptides 54:1-8
Stephens, Michelle L; Williamson, Anne; Deel, Megan E et al. (2014) Tonic glutamate in CA1 of aging rats correlates with phasic glutamate dysregulation during seizure. Epilepsia 55:1817-25
Littrell, O M; Fuqua, J L; Richardson, A D et al. (2013) A synthetic five amino acid propeptide increases dopamine neuron differentiation and neurochemical function. Neuropeptides 47:43-9
Miller, Erin M; Pomerleau, Francois; Huettl, Peter et al. (2012) The spontaneously hypertensive and Wistar Kyoto rat models of ADHD exhibit sub-regional differences in dopamine release and uptake in the striatum and nucleus accumbens. Neuropharmacology 63:1327-34
Littrell, Ofelia M; Pomerleau, Francois; Huettl, Peter et al. (2012) Enhanced dopamine transporter activity in middle-aged Gdnf heterozygous mice. Neurobiol Aging 33:427.e1-14
Hinzman, Jason M; Thomas, Theresa Currier; Quintero, Jorge E et al. (2012) Disruptions in the regulation of extracellular glutamate by neurons and glia in the rat striatum two days after diffuse brain injury. J Neurotrauma 29:1197-208
Stephens, Michelle L; Quintero, Jorge E; Pomerleau, Francois et al. (2011) Age-related changes in glutamate release in the CA3 and dentate gyrus of the rat hippocampus. Neurobiol Aging 32:811-20

Showing the most recent 10 out of 65 publications