RESEARCH SUMMARY

In my laboratory we apply electrophysiological techniques to brain slices and immortalized cultured cells to characterize normal brain electrophysiology and to learn how perturbations of that system may result in disease states. During normal active wakefulness, individual cortical neurons are firing independently as they process and transmit information. The scalp EEG during this time is relatively flat, since the independently firing neurons do not generate enough electrical potential to be detected. During sleep, regular discharges in the thalamocortical circuitry cause the cortical neurons to become synchronized. With millions of cells firing in synchrony, the EEG shows the classic slow waves of deep sleep.

Although much remains to be discovered, we do know quite a bit about the elegant and finely balanced system whereby the brain transitions from wakefulness to sleep. Input from the reticular activating system in the brainstem causes small changes in the activation of a calcium current and/or Ih, which are responsible for this transition. Relatively small perturbations of this system can switch neurons from the more-or-less synchronized firing of sleep to the time-locked firing seen during a generalized seizure. My primary clinical and research interest is to understand the interaction between normal sleep and its perversion in some forms of epilepsy.

A separate research interest involves exploring the role of steroid hormones in epilepsy. A common complaint among epileptic women is that seizures worsen at the time of their menses. This worsening may be related to natural brain chemicals known as “neurosteroids” and “neuroactive” steroids, compounds that may either increase or suppress the tendency toward seizures. Although there are several different classes of neurosteroids, one particularly well-studied group includes derivatives of pregnenolone. These compounds have powerful actions on GABA receptors, the predominant inhibitory neurotransmitter in the brain. In fact, one member of this family was previously used effectively for general anesthesia in surgery. My interest lies in determining how neurosteroids work at the GABA-A receptors and whether changing the subunit composition and/or phosphorylation state of those receptors might change the compounds’ effects.

RECENT PUBLICATIONS

Book Chapters/Invited Reviews

Neuroactive Steroids A. H. Lagrange and M. J. Kelly in H.L Henry and A.W. Norman (eds) Encyclopedia of Hormones Academic Press p8-19, 2004

GABA Receptors Gone Bad: The Wrong Place at the Wrong Time A.H. Lagrange Epilepsy Currents 5:91-95 2005

Retigabine: Bending Potassium Channels To Our Will Lagrange Epilepsy Currents 2005 (In Press)

Articles

Enhanced Desensitization In GABAA Receptors Containing The Alpha-4 Subunit. A. H. Lagrange, R. L. Macdonald (In Preparation)

Alpha-3 containing GABAA Receptors have low efficacy gating kinetics. A. H. Lagrange, R. L. Macdonald (In Preparation)

CONTACT INFORMATION

Department of Neurology, Vanderbilt University
6144 Medical Research Building III
Nashville, TN 37232-8552
Office: (615) 936-3918
E-mail: andre.lagrange@vanderbilt.edu

     
 
     

Faculty>
Andre Lagrange, Ph.D., M.D., Assistant Professor of Neurology

BIOGRAPHICAL SKETCH

Dr. Lagrange earned B.S. degrees is both Chemistry and Biology (with Honors) at the University of Washington in 1987. He earned a Ph.D. in Physiology and Pharmacology in 1996 and a M.D. in 1997, both at the Oregon Health Sciences University, while supported by a NIMH pre-doctoral NRSA fellowship. The next year he did an internal medicine internship at Saint Joseph Mercy Hospital in Ann Arbor, MI, followed by Neurology residency (1998-2001) and Clinical Neurophysiology Fellowship (2001-02) at the University of Michigan, Ann Arbor.

Dr. Lagrange was named Assistant Professor of Neurology at Vanderbilt University in 2002. In addition to his laboratory and clinical research activities, Dr. Lagrange is involved in the teaching and mentoring of residents, fellows, graduate and undergraduate students, and also serves as ad hoc reviewer for Epilepsy Research and Neuropharmacology. Dr. Lagrange’s honors include being the past recipient of a William Penry Epilepsy Minifellowship (2000) and the American Academy of Neurology Residents Scholarship (2001).


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