|
 ZHIMING
ZHANG, M.D.
Current
position is a Research Associate Professor of Anatomy and
Neurobiology, College of Medicine University of Kentucky. Capital
University
of
Medical
Science
1983,
Postdoctoral training at the
University
of
Rochester
1989-1993.
Research Assistant professor 1994-1999,
and Research Associate professor 1999 to present.
Research
and Development
website
I am currently studying the neurorestorative
and neuroprotective trophic
actions of GDNF on midbrain dopamine neurons as a promising
therapeutic approach for the treatment of Parkinson’s disease.
My major role in these studies is to quantify the changes
inside the brain accompanying chronic GDNF infusion into the lateral
ventricle and the putamen and to utilize functional magnetic
resonance imaging (MRI to noninvasively
follow functional changes in the nigrostriatal dopamine system in
animals showing behavioral recovery from chronic GDNF infusion.
I am also studying aging of central dopaminergic pathways in
nonhuman primates. The
central hypothesis of the study is that age-related declines in
motor functions result from functional changes in the nigrostriatal
dopaminergic system in animals and human.
To address this issue, I have developed techniques to measure
pharmacologically evoked blood oxygen level-dependent changes in the
basal ganglia of MRI-adapted, awake rhesus monkeys using functional
MRI. In the study, I
use fMRI to measure age-related changes
in the basal ganglia in response to various dopamine agonists and
antagonists such as SKF-81297 (D1 agonist) and LY17155 (D1 agonist).
This technique will provide unique and important insights
into parkinsonian brain activity and age-associated changes.
University of Kentucky
Chandler Medical Center
Department of Anatomy & Neurobiology
48A Davis Mills Bldg (MRISC)
Lexington, KY 40536-0098
Phone: (859) 257-6032
Fax: (859) 323-3625
E-mail:zzhan01@pop.uky.edu
RECENT PUBLICATIONS
Gash,
D. M., Z. Zhang, et al. (1996). "Functional recovery in
parkinsonian monkeys treated with GDNF." Nature 380(6571):
252-5.
Ovadia,
A., Z. Zhang, et al. (1995). "Increased
susceptibility to MPTP toxicity in middle-aged rhesus monkeys."
Neurobiol Aging 16(6): 931-7.
Zhang, Z., Y. Miyoshi, et al. (1997). "Dose
response to intraventricular glial cell
line-derived neurotrophic factor
administration in parkinsonian monkeys." J Pharmacol
Exp Ther 282(3): 1396-401.
Gash,
D. M., Z. Zhang, et al. (1998).
"Neuroprotective
and neurorestorative properties of GDNF."
Ann Neurol 44(3 Suppl
1): S121-5.
Zhang, Z., M. Zhang, et al. (1999).
"MPTP-Induced pallidal lesions in rhesus monkeys."
Exp Neurol 155(1): 140-9.
Duan,
W., Z. Zhang, et al. (1999).
"Participation of prostate apoptosis
response-4 in degeneration of dopaminergic neurons in models of
Parkinson's disease." Ann Neurol
46(4): 587-97.
Zhang, Z., A. Andersen, et al. (2000). "Motor slowing and parkinsonian
signs in aging rhesus monkeys mirror human aging." J Gerontol
A Biol Sci
Med Sci 55(10): B473-80.
Zhang, Z., A. H. Andersen, et al. (2000).
"Functional MRI of apomorphine activation of the basal ganglia
in awake rhesus monkeys."
Brain Res 852(2): 290-6.
Zhang, Z., A. Andersen, et al. (2001). "Pharmacological
MRI mapping of age-associated changes in basal ganglia circuitry of
awake rhesus monkeys." Neuroimage
14(5): 1159-67.
Anders
Andersen, Zhiming Zhang
et al., (2002). MRI compatible chamber and training protocol for parharmarcological
MRI study in awake rhesus monkeys. J Neurosci
Methods 118(2):
141-52.
Richard
Grondin, Zhiming Zhang, Yi Ai et al., (2002).
Chronic, controlled GDNF infusion promotes structural and
functional recovery in advanced parkinsonian monkeys. Brain 125(Pt
10): 2191-201.
Maswood, N., Grondin, R., Zhang, Z.,
Stanford, J. A., Surgener, S. P., Gash, D. M. and Gerhardt, G. A.
2002. Effects of chronic intraputamenal infusion of glial cell
line-derived neurotrophic factor (GDNF) in aged Rhesus monkeys.
Neurobiol Aging 23, 881-9.
Ai, Y., Markesbery, W., Zhang, Z., Grondin,
R., Elseberry, D., Gerhardt, G. A. and Gash, D. M. 2003.
Intraputamenal infusion of GDNF in aged rhesus monkeys: distribution
and dopaminergic effects. J Comp Neurol 461, 250-61.
Grondin, R., Zhang, Z., Ai, Y., Gash, D.
M. and Gerhardt, G. A. 2003. Intracranial delivery of proteins and
peptides as a therapy for neurodegenerative diseases. Prog Drug Res
61, 101-23.
Grondin, R., Cass, W. A., Zhang, Z.,
Stanford, J. A., Gash, D. M. and Gerhardt, G. A. 2003. Glial cell
line-derived neurotrophic factor increases stimulus-evoked dopamine
release and motor speed in aged rhesus monkeys. J Neurosci 23,
1974-80.
Maswood, N., Young, J., Tilmont, E., Zhang, Z.,
Gash, D. M., Gerhardt, G. A., Grondin, R., Roth, G. S., Mattison,
J., Lane, M. A., Carson, R. E., Cohen, R. M., Mouton, P. R.,
Quigley, C., Mattson, M. P. and Ingram, D. K. 2004. Caloric
restriction increases neurotrophic factor levels and attenuates
neurochemical and behavioral deficits in a primate model of
Parkinson's disease. Proc Natl Acad Sci U S A 101, 18171-6.
Gash, D. M., Zhang, Z., Ai, Y., Grondin,
R., Coffey, R. and Gerhardt, G. A. 2005. Trophic factor distribution
predicts functional recovery in parkinsonian monkeys. Ann Neurol 58,
224-33.
Hardy, P. A., Gash, D., Yokel, R.,
Andersen, A., Ai, Y. and Zhang, Z. 2005. Correlation of R2 with
total iron concentration in the brains of rhesus monkeys. J Magn
Reson Imaging 21, 118-27.
Zhang, J.,
Stanton
, D. M., Nguyen, X. V., Liu, M., Zhang, Z., Gash, D. and
Bing
, G. 2005. Intrapallidal
lipopolysaccharide injection increases iron and ferritin levels in
glia of the rat substantia nigra and induces locomotor deficits.
Neuroscience 135, 829-38.
Cass, W. A., Grondin, R., Andersen, A. H.,
Zhang, Z., Hardy, P. A., Hussey-Andersen, L. K., Rayens, W. S.,
Gerhardt, G. A. and Gash, D. M. 2006. Iron accumulation in the
striatum predicts aging-related decline in motor function in rhesus
monkeys. Neurobiol Aging.
Joseph, J. E., Powell, D. K., Andersen, A. H., Bhatt, R. S., Dunlap,
M. K., Foldes, S. T., Forman, E., Hardy, P. A., Steinmetz, N. A. and
Zhang, Z. 2006. fMRI in alert, behaving monkeys: An adaptation of
the human infant familiarization novelty preference procedure. J
Neurosci Methods. 2006 Oct 15;157(1):10-24. Epub 2006 May 3.
Zhang Z, Andersen
AH, Ai Y, Loveland A, Hardy PA, Gerhardt GA, Gash DM. Assessing
nigrostriatal dysfunctions by pharmacological MRI in parkinsonian
rhesus macaques. Neuroimage. 2006 Nov 1;33(2):636-43. Epub 2006 Sep
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