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Dr.
Bill Griffith
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| Full Professor
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Research Interests |
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Over the past several years, my
lab has described age-related changes in ligand-gated, voltage-gated
calcium channels and calcium homeostasis in basal forebrain neurons.
These neurons are involved in attention, arousal, as well as some
forms of memory. The basal forebrain may also have relevance to
the clinical symptoms of Alzheimer’s disease in humans.
Our long-term goal is to identify the cellular and molecular mechanisms
responsible for age-related changes in cellular function. We utilize
a rodent model of aging coupled with a variety of techniques including,
patch-clamp electrophysiology, microfluorimetric measurements
of intracellular calcium concentration ([Ca2+]i), laser scanning
confocal fluorescent microscopy, and single-cell reverse transcription/polymerase
chain reaction (scRT-PCR). Our results support a model in which
basal forebrain neurons modify their physiological properties
during aging, and specific mechanisms of Ca2+ homeostasis are
changed to compensatory for age-related deterioration. The elucidation
of these compensatory mechanisms may be important sites for future
therapeutics design to alleviate age-related pathologies.
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Education |
| Ph.D., Department of Pharmacology and Toxicology,
University of Texas Medical Branch, Galveston, 1980
Research Associate, Department of Pharmacology, School of Pharmacy,
University of London.
Postdoctoral Fellow, Department of Neurology, Baylor College of
Medicine, Houston, Texas
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Recent Publications
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Dove, L.S., Abbott, L.C. and Griffith, W.H. (1998)
Whole-cell and single channel analysis of P-type calcium currents
in cerebellar Purkinje cells of leaner mutant mice J. Neuroscience
18:7687-7699.
Murchison, D. and Griffith, W.H. (1999) Age-related alterations
in caffeine-sensitive calcium stores and mitochondrial buffering
in rat basal forebrain. Cell Calcium 25:439-452.
Gallagher, J. P., Shinnick-Gallagher, P. and W.H. Griffith. (2000)
Cellular pharmacology at synapses within the septal complex. In:
The Behavioral Neuroscience of the Septal Region. Ed. Robert Numan.
Springer-Verlag. pp.48-70.
Murchison, D. and Griffith, W.H. (2000) Mitochondria buffer nontoxic
calcium loads and release calcium through the mitochondria permeability
transition pore and sodium/calcium exchanger in rat basal forebrain
neurons. Brain Research854:139-151.
Dove, L.S., Nahm, S-S., Murchison, D, Abbott, L.C. and Griffith,
W.H. (2000) Altered calcium homeostasis in cerebellar purkinje
cells of leaner mutant mice. J. Neurophysiol. 84:513-524.
Griffith, W.H., Jasek, M.C., Bain, S.H. and Murchison, D. (2000)
Modification of ion channels and calcium homeostasis of basal
forebrain neurons during aging. Behavioral Brain Res. 115:219-233.
Han, S-H., McCool, B.A., Murchison, D., Nahm, S-S., Parrish, A.R.
and Griffith, W.H. (2002) Single-cell RT-PCR detects shifts in
mRNA expression profiles of basal forebrain neurons during aging.
Brain Research 98:67-80.
Griffith, W.H. (2002) Commentary: Quest for ion channel
modulation by free radicals during brain aging. Neurobiology
of Aging 23:835-836
Murchison, D., Dove, L.S., Abbott, L.C., and Griffith, W.H. (2002)
Homeostatic compensation maintains Ca2+ signaling function in
Purkinje neurons in the leaner mutant mouse. The Cerebellum
1:119-127.
Murchison D, Zawieja DC , Griffith WH. Changes in mitochondrial
function affect calcium homeostasis in aged rat basal forebrain
neurons. Cell Calcium (in press)
Han S-H, Murchison D, Griffith WH. Low voltage-activated calcium
currents and fast tetrodotoxin-resistant sodium currents identify
cholinergic and noncholinergic cell types of the rat basal forebrain.
Submitted.
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Current Grants |
| NIH/National Institute of Aging,
RO1,(PI) Physiology of Cholinergic Basal Forebrain Neurons, 10/01/03-09/31/08,
$1,455,000.
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Link
to Vita |
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