Olivier H. Thibault, Ph.D.
Associate Professor
Bowman Gray School of Medicine, Wake Forest University, 1993.
Office: MS-320 Chandler Medical Center (0298)
Lab: MS-231; (859) 323-6259
Tel: (859) 323-4863
Calcium electrophysiology/imaging and brain aging correlates
Current Projects
Current lab interests include identifying underlying mechanisms through which individual components of peripheral metabolic dysregulation (particularly hyperinsulinemia and hypercholesterolemia) impact brain function. We focus on electrophysiological and imaging Ca2+-sensitive biomarkers known to be modified in aging in the hippocampus (recording of single L-type voltage-gated Calcium channels, the Ca2+-dependent AHP, and Ca2+ transients). Experiments use sharp and patch electrode techniques, calcium imaging and molecular techniques in models of aging and Alzheimer's disease, as well as primary hippocampal neurons. Other studies monitor Ca2+-induced Ca2+ release functions with aging and also monitor the impact of PPAR-Gamma agonists on neurons and astrocytes. We have also been using a new and alternative method for measuring glucose utilization in single live cells. Rather than measuring the uptake of a fluorescent glucose analog, this imaging technique uses disappearance of the indicator as evidence of utilization. Our combined efforts, including behavioral (Morris water maze, active avoidance, fear conditioning) and microarray approaches are aimed at identifying novel therapeutic targets that may contribute to prevention of cognitive decline with aging and/or Alzheimer's disease.
Selected Publications
Searcy J.L., Phelps J.T., Pancani T., Kadish I., Popovich J., Anderson K.L., Beckett T.L., Murphy M.P., Chen K.-C., Blalock E.M., Landfield P.W., Porter N.M., Thibault O. (2012) Long-term pioglitazone treatment improves learning and attenuates pathological markers in a mouse model of AD. In Press Journal of Alzheimer’s Disease.
Thibault O., Pancani T., Landfield P.W., Norris C.M. Reduction in neuronal L-type calcium channel activity in a double knock-in mouse model of Alzheimer’s disease (2011). Biochimica et Biophysica Acta – Molecular Basis of Disease 2012, 546–549.
Latimer C.S., Searcy J.L., Bridges M.T., Brewer L.D., Popović J., Blalock E.M., Landfield P.W., Thibault O., and Porter N.M. (2011). Reversal of glial and neurovascular markers of unhealthy brain aging by exercise in middle-aged female mice. PLoS ONE 6(10): e26812. doi:10.1371/journal.pone.0026812.
Pancani T., Anderson K.L., Porter N.M., Thibault O. (2011). Imaging of a glucose analog, calcium and NADH in neurons and astrocytes: dynamic responses to depolarization and sensitivity to pioglitazone. doi:10.1016/j.ceca.2011.09.002 Cell Calcium 50, 548-558.
Gant J.C., Chen K.-C., Norris C.M., Thibault O., Blalock E.M., Porter N.M., and Landfield P.W. (2011). Disrupting Function of FK506-Binding Protein 1b/12.6 Induces the Ca2+-Dysregulation Aging Phenotype in Hippocampal Neurons. J. Neurosci. 13(5):1693-1703. PMID:21289178
Blalock E.M.; Phelps J.T.; Pancani T.; Searcy J.L.; Anderson K.; Gant J.C.; Popovic J.; Avdiushko M.; Cohen D.A.; Chen K.-C.; Porter N.M.; Thibault O (2010). Effects of long-term Pioglitazone treatment on peripheral and central markers of Aging. PLoS ONE 5(4): e10405. Doi:101371/journal.pone0010405. PMC2861595.
Blalock EM, Grondin R, Chen KC, Thibault O, Thibault V, Pandya JD, Dowling A, Zhang Z, Sullivan P, Porter NM, Landfield PW. (2010) Aging-related gene expression in hippocampus proper compared with dentate gyrus is selectively associated with metabolic syndrome variables in rhesus monkeys. J Neurosci. 2010 Apr 28;30(17):6058-71.
Pancani T., Phelps J.T., Searcy J.L., Kilgore M.W., Porter N.M., and Thibault O. (2009). Distinct modulation of voltage-gated and ligand-gated Ca2+ currents by PPAR-γ agonists in cultured hippocampal neurons. J. Neurochem., 109:1800-1811.
Kadish I. , Thibault O., Blalock E.M., Chen, K.-C., Gant J.C., Porter N.M., and Landfield P.W. (2009). Onset of hippocampal and cognitive aging: Lifespan expression analyses identify associated changes in metabolism and cholesterol trafficking. J. Neurosci., 29:1805-1816.
Gant J.C., Thibault O., Blalock E.M., Yang J., Bachstetter A., Kotick J., Schauwecker P.E., Hauser K.F., Smith G.M., Mervis R., Li Y., and Barnes G.N. (2009). Decreased number of interneurons and increased seizures in neuropilin 2 deficient mice: implications for autism and epilepsy. Epilepsia. 2009 Apr;50(4):629-45. Epub 2008 Jul 24.
Norris C.M., Blalock E.M., Chen K.C., Porter N.M., Thibault O., Kraner S.D., and Landfield P.W. (2008). Hippocampal 'zipper' slice studies reveal a necessary role for calcineurin in the increased activity of L-type Ca(2+) channels with aging. Neurobiol Aging. 2008 May 7.
Gant J.C., and Thibault O. (2008). Action potential generation in aged rat hippocampal neurons: regulation by selective forms of hyperpolarization. Neurobiology of Aging 2008. Epub doi:10.1016/j.neurobiolaging.2008.02.006
Norris C.M., Blalock E.M., Chen K.-C., Porter N.M., Thibault O., Kraner S.D., and Landfield, P.W. Hippocampal "zipper" slice studies reveal a necessary role for calcineurin in the increased activity of L-type Ca2+ channels with aging. Neurobiology of Aging 2008. Epub doi:10.1016/j.neurobiolaging.2008.03.026
Thibault,O., Gant J.C. and Landfield P.W. (2007). Expansion of the Calcium hypothesis of brain aging and Alzheimer’s disease: minding the store. Aging Cell 6: 307-317.
Brewer L.D., Thibault O., Rogers J.T., Staton J., Thibault V., Kraner S., Landfield P.W., Porter N.M. (2007). Increased vulnerability of hippocampal neurons with age in culture: temporal association with increases in NMDA receptor current, NR2A subunit expression and recruitment of L-type Calcium channels. Brain Research 1151:20-31.
Rowe WB, Blalock EM, Chen KC, Kadish I, Wang D, Barrett JE, Thibault O, Porter NM, Rose GM, Landfield PW (2007). Hippocampal Expression Analyses Reveal Selective Association of Immediate-Early, Neuroenergetic, and Myelinogenic Pathways with Cognitive Impairment in Aged Rats. J Neurosci 27: 3098-3110.
Brewer L.D., Porter N.M., Kerr, S.D., Landfield P.W. and Thibault O. (2006). Chronic 1 alpha, 25-(OH)2vitamin D3 treatment reduces Ca2+-mediated hippocampal biomarkers of aging. Cell Calcium 40: 277-286.
Norris C.M., Blalock E.M., Thibault O., Porter N.M. and Landfield P.W. (2006). Electrophysiological mechanisms of delayed excitotoxicity: positive feed back loop between NMDA receptor current and depolarization-mediated glutamate release. J. Neurophysiol. 96(5): 2488-2500.
Kelly K., Nadon N., Morrison J., Thibault O., Barnes C.A., and Blalock E.M. (2006). The neurobiology of aging. Epilepsy Res. 68S: S5-S20.
Gant J.C., Sama M.A., Landfield P.W., Thibault O. (2006). Early and simultaneous emergence of multiple hippocampal biomarkers of aging is mediated by Ca2+-release. J. Neurosci. 26: 3482-3490.
Attucci S, Clodfelter GV, Thibault O, Staton J, Moroni F, Landfield PW, Porter NM.(2002). Group I metabotropic glutamate receptor inhibition selectively blocks a prolonged Ca(2+) elevation associated with age-dependent excitotoxicity. Neuroscience 112:183-194.
Thibault O, Hadley R, Landfield PW. (2001). Elevated postsynaptic [Ca2+]i and L-type calcium channel activity in aged hippocampal neurons: relationship to impaired synaptic plasticity. J Neurosci 21:9744-9756.
Chen K-C, Blalock EM, Thibault O, Kaminker P and Landfield PW. (2000). Expression of a1D subunit mRNA is correlated with L-type Ca2+ channel activity in single neurons of hippocampal "zipper" slices. PNAS 97(8):4357-4362.
Thibault O, Porter NM, Chen K-C, Kaminker PG, Blalock EM, Clodfelter GV, Brewer L and Landfield PW. (1998). Calcium dysregulation in neuronal aging and Alzheimer's disease: history and new directions. Cell Calcium, 24 (5/6): 417-433.
Porter NM, Thibault O, Thibault V, Chen K-C and Landfield PW (1997). Calcium channel density and hippocampal cell death with age in long-term culture. J Neurosci 17:5629-5639.
Thibault O and Landfield PW. (1996). Increase in single L-type calcium channels in hippocampal neurons during aging. Science 272:1017-1020.
Campbell LW, Hao S-Y, Thibault O, Blalock EM and Landfield PW. (1996). Aging changes in voltage-gated calcium currents in hippocampal CA1 neurons. J Neurosci 16: 6286-6295.
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