Graduate Studies Faculty
Charles K. Meshul, Ph.D.
Neuroscience Graduate Program
Research Interests:Parkinson's disease, drugs of abuse, electron/light microscopy, immunocytochemistry, in vivo microdialysis, synaptic plasticity, neuroleptic drugs, treadmill exercise, neuroanatomy, cellular » PubMed Listing
Preceptor RotationsAcademic Term Available Fall 2015 Yes Winter 2015 Yes Summer 2016 Yes Fall 2016 Yes Winter 2016 Yes Spring 2016 Yes Summer 2017 Yes Fall 2017 Yes Winter 2017 Yes Spring 2017 Yes
Faculty MentorshipDr. Meshul is not available as a mentor for 2016-2017. Dr. Meshul is not available as a mentor for 2015-2016.
My laboratory is mainly involved in investigating electron microscopic/immunocytochemical changes in synapses within the brain following various drug treatment procedures or lesions of the nigrostriatal pathway, as a model for Parkinson’s disease (PD), and correlating these findings with functional/protein changes using in vivo microdialysis/westerns and motor behaviors in mice. Using a new progressive mouse model of PD developed in my lab, by administering increased doses of the toxin, MPTP, we have found that exposure of mice to a socially enriched environment can, after the initiation of the loss of dopamine, slow down or block the neurochemical and motor behavioral deficits due to continued treatment with MPTP. We are currently investigating 1.) the therapeutic affects of exercise in this same progressive MPTP model of PD in both young and aged mice, 2.) the effect of MPTP in a double floxed line of mice (lox-P-Vgat; lox-P-Vglut2) in which either the motor cortex is activated or the subthalamic nucleus is inactivated by infusion of AAV-cre. Either treatment results in neuroprotection from dopamine loss in the striatum and substantia nigira, and 3.) the effect of a flavinoid derivative, which specifically activates the brain derived neurotrophic factor receptor, TrkB, on blocking the further loss of dopamine during continued MPTP treatment.
B.A. (1973) University of California, Los Angeles
Ph.D. (1982) University of Illinois Medical Center
Selected Recent Publications
GoldbergNRS, Fields V, Pflibsen L, Salvatore MF, Meshul CK: Social enrichment attenuates nigrostriatal lesioning and reverses motor impairment in a progressive 1-methyl-2-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. Neurobiology of Disease, 45:1051-1067 (2012).
Walker RH, MooreC, DaviesG, DirlingLB, KochRJ, MeshulCK: Effects of subthalamic nucleus lesions and stimulation upon corticostriatal afferents in the 6-hydroxydopamine-lesioned rat. PLoS One, 7(3):e32919 (2012).
Baptista, M, DaveK, FrasierM, ShererT, BeckM, VarshoJ, GreeleyM, ParkerG,MooreC, ChurchillMJ, MeshulCK, FiskeB: Leucine-Rich Repeat Kinase 2 (LRRK2) Knockout Rats Display an Abnormal Kidney Phenotype that Progresses with Age. PLoS One. 2013 Nov 14;8(11):e80705. doi: 10.1371/journal.pone.0080705.
Spinelli KJ, Taylor JK, Osterberg VR, Churchill MJ, Pollock E, Moore C, MeshulCK, Unni VK: Alpha-synuclein aggregation begins at presynaptic terminals. Journal of Neuroscience, 34:2037-50, (2014).
Sconce MD, Churchill MJ, Moore C, Meshul CK: Intervention with 7,8-dihyroxyflavone blocks further stiratal terminal loss and restores motor deficits in a progressive mouse model of Parkinson’s disease. Neuroscience, 290:454-471 (2015).
BenteaE, SconceMD, Churchill MJ, Liefferinge JV, SatoH, MeshulCK, MassieA: MPTP-induced parkinsonism in mice alters striatal and nigral xCT expression but is unaffected by the genetic loss of xCT. Neuroscience Letters, 593:1-6 (2015).
PingP, EshaqRS, MeshulCK, MooreC, Hood RL, Leidenheimer NJ: Neuronal Gamma-Aminobutyric Acid (GABA) type A receptors undergo cognate ligand chaperoning in the endoplasmic reticulum by endogenous GABA. Frontiers in Cellular Neuroscience, 9:188. doi: 10.3389/fncel.2015.00188 (2015).
Sconce MD, ChurchillMJ, GreeneRE, Meshul CK: Intervention with exercise restores motor deficits but not nigrostriatal loss in a progressive MPTP mouse model of Parkinson’s disease. Neuroscience, 299:156-174(2015).
Jimenez VA, Helms CM, Cornea A, Meshul CK, Grant KA: An ultrastructural analysis of the effects of ethanol self-administration on the hypothalamic paraventricular nucleus in rhesus macaques. Frontiers in Cellular Neuroscience, 9:260:doi: 10.3389/fncel.2015.00260 (2015).
PflibsenL, StangKA, Sconce MD, Wilson VB, Hood RL, Meshul CK, MitchellSH: Executive function deficits and glutamatergic alterations in a progressive MPTP mouse model of Parkinson’s disease. Journal of Neuroscience Research, in press (2015).