Charles K. Meshul
Research Biologist and Director, Electron Microscopy Facility, VAMC
Professor, Behavioral Neuroscience, Pathology, OHSU
e-mail: meshulc@ohsu.edu
Major Areas
Parkinson's disease, immuno-electron microscopy, drug abuse, antipsychotic drugs, in vivo microdialysis
Previous Positions
Postdoctoral Fellow, University of Maryland Medical Center
Associate Director, Office of Regeneration Research Programs, VAMC
Education
B.A. (1973) University of California, Los Angeles
Ph.D. (1982) University of Illinois Medical Center
Research Interests
My laboratory is mainly involved in investigating ultrastructural changes in synapses within the brain following various
drug treatment procedures or lesions of the nigrostriatal pathway and correlating these findings with functional changes using
in vivo microdialysis in both rats and mice. We have found that administration of the antipsychotic drug, haloperidol, or
following a lesion of the nigrostriatal pathway with the neurotoxins, 6-OHDA or MPTP, as a model for Parkinson's disease,
results in an increase in striatal asymmetric synapses containing discontinuous, or perforated, postsynaptic density and change
in the density of nerve terminal glutamate immunolabeling. These synaptic alterations may be related to the extrapyramidal side
effects and tardive dyskinesia associated with such antipsychotic drug treatment and in the movement disorders associated with
Parkinson's disease. We are currently investigating the effects of treadmill exercise on reversing the changes in striatal
glutamate function in the 6-OHDA model of Parkinson's disease. We have reported the nicotine or glutamate antagonists block the
induction of apomorphine-induced sensitization in 6-OHDA lesioned rats as a model for the dyskinesias that are observed in Parkinson's
patients on l-dopa therapy. In term of drug abuse research, we have recently found that cocaine and methamphetamine treatment result
in changes in glutamate immunoreactivity within various brain areas. We are currently investigating the effects on glutamate synapses
within the nucleus accumbens of mice, using both electron microscopy and in vivo microdialysis, following either systemic alcohol
administration or 2-bottle choice, 2-hour limited access.
Selected Recent Publications
Touchon JC, Moore C, Frederickson J, and Meshul CK: Lesion of subthalamic or motor thalamic nucleus in 6-hydroxydopamine
treated rats: affects of the striatal glutamate and apomorphine-induced contralateral rotations. Synapse, 51:287-298 (2004).
Fisher BE, Petzinger GM, Nixon K, Hogg E, Bremmer S, Meshul CK, and Jakowec MW: Exercise-induced behavioral recovery and neuroplasticity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse basal ganglia. J Neuroscience Research, 77:378-390 (2004).
Kozell LB, and Meshul CK: Nerve terminal glutamate immunoreactivity in the rat nucleus accumbens and ventral tegmental area after a short withdrawal from cocaine. Synapse, 51:224-232 (2004).
Dervan AG, Meshul CK, Beales M, McBean GJ, Moore C, Totterdell S, Snyder A, Meredith GE: Astrogial plasticity and glutamate function in a chronic mouse model of Parkinson's disease. Experimental Neurology, 190:145-156 (2004).
Bamford NA, Robinson S, Palmiter R, Joyce JA, Moore C, Meshul CK: Presynaptic modulation of corticostriatal terminals in a dopamine-deficiency. Journal of Neuroscience, 24:9541-9552 (2004).
McKee BL, and Meshul CK: Time-dependent changes in extracellular glutamate in the rat dorsolateral striatum following a single cocaine injection. Neuroscience, 133:605-613 (2005).
Touchon JC, Holmer HK, Moore C, McKee BL, Frederickson J, and Meshul CK: Apomorphine-induced alterations in striatal and substantia nigra glutamate following unilateral loss of striatal dopamine. Experimental Neurology, 193: 131-140 (2005).
Holmer HK, Keyghobadi M, Moore C, Menashe RA, and Meshul CK: Dietary restriction affects striatal glutamate in the MPTP-induced mouse model of nigrostriatal degeneration. Synapse, 57:100-112 (2005).
Holmer HK, Keyghobadi M, Moore C, and Meshul CK: L-Dopa-induced reversal in striatal glutamate following partial depletion of nigrostriatal dopamine with MPTP. Neuroscience, 136:333-341 (2005).
Shakil SS, Holmer HK, Moore C, Abernathy AT, Jakowec MW, Petzinger GM, and Meshul CK: High and low responders to novelty show differential effects in striatal glutamate. Synapse, 58:200-207 (2005).