Mark S. LeDoux, M.D., Ph.D.

Professor, Department of Neurology
Professor, Anatomy and Neurobiology
Director, Dystonia and Huntington Disease Clinics
Director, Movement Disorders Research Laboratories

UT Medical Group

Education

B.S.	University of Louisiana, Lafayette	1983
M.D.	Louisiana State University School of Medicine	1988
Ph.D.	University of Alabama at Birmingham	1995

Post-Graduate Training

Fellow	Neuroanatomy/Neurophysiology, L.S.U. School of Medicine	1985-1986
Intern	General Surgery, University of Alabama at Birmingham	1988-1989
Resident	Neurosurgery, University of Alabama at Birmingham	1989-1992
Cushing Fellow	American Association of Neurological Surgeons	1992-1993
Resident	Neurology, University of Tennessee College of Medicine	1995-1997

Professional Certification and Licensing

Alabama Tennessee Diplomate-American Board of Psychiatry and Neurology

1989 1995

Clinical Subspecialty Expertise

Adult and Pediatric Movement Disorders, Botulinum Toxin for Dystonia and Spasticity

Research Interests

Broad, long-term goals are to understand the molecular and systems pathophysiology of dystonia, mechanisms of cell death in Parkinson's disease, molecular networks that participate in sensorimotor plasticity, and computational organization of motor systems.  We are also interested in cranial parasympathetic neurotransmission and gene expression profiles in the peripheral nervous system.  Three areas of recent focus are summarized below:    

1. The genetically dystonic (dt) rat is autosomal recessive mutant discovered in the Sprague-Dawley strain. The dt rat exhibits a movement disorder that closely resembles the generalized dystonias seen in humans. Even with supportive measures dt rats die before 40 days-of-age. Cerebellectomy eliminates the dt rat motor syndrome! After cerebellectomy, dt rats live into adulthood and are able to mate successfully. Electrophysiological investigations in awake, anesthetized, and slice preparations along with computational modeling and neuropharmacology are being used to determine the olivocerebellar defects in the dt rat and the effects of abnormal cerebellar output on motor control.  Recently, we identified the causal mutation in the dt rat as an IAP element insertion into Intron 1 of Atcay, the gene which encodes caytaxin.

2. The neural networks mediating suprasegmental control of the blink reflex and spontaneous blinking remain poorly understood. Viral transneuronal tracing is being used to define the integrated premotor cortical and subcortical control of levator palpebrae and orbicularis oculi motoneuron activity.

3.  Mutations in the gene TOR1A are associated with generalized dystonia in humans.  TOR1A codes for the AAA+ protein torsinA.  Via a dominant-negative effect, DYT1 mutations may impair the ability of torsinA to participate in processes critical to sensorimotor plasticity.  Current work will clarify the roles of normal and mutant torsinA in adaptive and maladaptive sensorimotor plasticity.

Representative Publications

LeDoux MS, Xu L, Xiao J, Ferrell B, Menkes DL, Homayouni R (2006) Murine central and peripheral nervous system transcriptomes: Comparative gene expression. Brain Research 2006 Jul 4; [Epub ahead of print]

Zhou FW, Xu JJ, Zhao Y, LeDoux MS, Zhou FM (2006) Opposite Functions of Histamine H1 and H2 Receptors and H3 Receptor in Substantia Nigra Pars Reticulata. Journal of Neurophysiology 2006 May 31; [Epub ahead of print]

Weller RE, LeDoux MS, Toll LM, Gould MK, Hicks RA, Cox JE (2006) Subdivisions of inferior temporal cortex in squirrel monkeys make dissociable contributions to visual learning and memory. Behavioral Neuroscience 120:423-446.

Xiao J, LeDoux MS (2005) Caytaxin deficiency causes generalized dystonia in rats. Molecular Brain Research 141:181-92

Jiao Y, Yan J, Zhao Y, Donahue LR, Beamer WG, Li X, Roe BA, LeDoux MS, Gu W (2005) Carbonic anhydrase-related protein VIII deficiency is associated with a distinctive lifelong gait disorder in waddles mice. Genetics 171:1239-1246.

Gong S, Y Zhao, M DeCuypere, LeDoux MS (2005) Cerebral cortical premotor control of primate orbicularis oculi motoneurons. Brain Research 1047:177-193.

Jinnah HA, Hess EJ, LeDoux MS, Sharma N, Baxter M, DeLong M (2005) Rodent models for dystonia research: characteristics, evaluation and utility. Movement Disorders. 20:283-292.

LeDoux MS (2005) Thermoregulatory dysfunction in Parkinson's disease. In: Parkinson's Disease and Nonmotor Dysfunction. RF Pfeiffer and I Bodis-Wollner (Eds). Humana Press.

LeDoux MS (2004) Animal Models of Movement Disorders (Ed). Elsevier. ISBN: 0120883821

LeDoux MS (2004) Tetrahydroisoquinolines and Parkinson's disease. In: Parkinson's Disease. M Ebadi and RF Pfeiffer (Eds). CRC Press.

LeDoux MS (2004) Animal models and the science of movement disorders. In: Animal Models of Movement Disorders. MS LeDoux (Ed). Elsevier.

LeDoux MS (2004) The genetically dystonic rat. In: Animal Models of Movement Disorders. MS LeDoux (Ed). Elsevier.

LeDoux MS (2004) Harmaline tremor. In: Animal Models of Movement Disorders. MS LeDoux (Ed). Elsevier.

Xiao J, Gong S, Zhao Y, LeDoux MS (2004) Developmental expression of torsinA. Developmental Brain Research 152:47-60.

Rahim F, Gupta D, Bertorini TE, LeDoux MS (2003) Dropped head presentation of mitochondrial myopathy. Journal of Clinical Neuromuscular Disease 5:108-114.

Xiao J, LeDoux MS (2003) Cloning, developmental regulation and neural localization of rat e-sarcoglycan. Molecular Brain Research 19:132-143.

Gong S, Zhou Q, LeDoux MS (2003) Blink-related eyelid sensorimotor anatomy in the rat. Anatomy and Embryology 207:193-208.

Cuthbertson S, LeDoux MS, Jones S, Zhou Q, Gong S, Ryan P, Reiner A (2003) Localization of preganglionic neurons that control choroidal blood flow via pterygopalatine ganglion. Investigative Ophthalmology and Visual Science 44:3713-3724.

Gong S, LeDoux MS (2003) Immunohistochemical detection of wheat germ agglutinin-horseradish peroxidase. Journal of Neuroscience Methods 126:25-34.

Cuthbertson S, LeDoux MS, Jones S, Zhou Q, Gong S, Ryan P, Reiner A (2003) Localization of preganglionic neurons that control choroidal blood flow via pterygopalatine ganglion. Investigative Ophthalmology and Visual Science 44:3713-3724.

LeDoux MS, Brady KA (2003) Secondary cervical dystonia associated with structural lesions of the central nervous system. Movement Disorders 18:60-69.

Al-Hayk K, LeDoux MS. (2003) Epilepsia partialis continua mistaken for Parkinson's disease. Movement Disorders 18:107.

LeDoux MS, Lorden JF (2002) Abnormal spontaneous and harmaline-stimulated Purkinje cell activity in the genetically dystonic rat. Experimental Brain Research 145: 457-467.

Ziefer P, Leung J, Razzano T, Shalish C, LeDoux MS, Lorden JF, Ozelius L, Breakefield XO, Standaert DG, Augood SJ (2002) Molecular cloning and expression of rat torsinA in the normal and genetically dystonic (dt) rat. Molecular Brain Research 101:132-135.

LeDoux MS, Zhou Q, Murphy RB, Greene ML, Ryan P (2001) Parasympathetic innervation of the meibomian glands in rats. Investigative Ophthalmology and Visual Science 42: 2434-2441.

Kim HS, Hong SJ, LeDoux MS, Kim KS (2001) Transcription factor AP-2 co-regulates the transcriptional activities of the tyrosine hydroxylase and dopamine ß-hydroxylase genes. Journal of Neurochemistry 76: 280-294.

LeDoux MS, Lorden JF, Smith JM, Mays LE. (1998) Serotonergic modulation of eye blinks in cat and monkey. Neuroscience Letters 253: 61-64.

LeDoux MS, Lorden JF. (1998) Abnormal cerebellar output in the genetically dystonic rat. Advances in Neurology: Dystonia 3. Edited by S Fahn, CD Marsden, M DeLong. Lippincott-Raven, Philadelphia, PA; pp. 63-78.

LeDoux MS, Hurst DC, Lorden JF. (1998) Single-unit activity of cerebellar nuclear cells in the awake genetically dystonic rat. Neuroscience 86: 533-545.

LeDoux MS, Lorden JF, Weir AD, Smith JM. (1997) Blink reflex to supraorbital nerve stimulation in the cat. Experimental Brain Research 116: 104-112.

LeDoux MS. (1997) Paroxysmal kinesigenic dystonia associated with a medullary hemorrhage. Movement Disorders 12: 819.

LeDoux MS, Lorden JF, Meinzen-Derr J. (1995) Selective elimination of cerebellar output in the genetically dystonic rat. Brain Research 696: 91-103.

LeDoux MS, Rutledge SL, Mountz JM, Darji JT. (1995) SPECT abnormalities in generalized dystonia. Pediatric Neurology 13: 5-10.

LeDoux MS, Lorden JF, Ervin JM. (1994) Inferior olive norepinephrine and serotonin levels during development in the genetically dystonic rat. Brain Reseach Bulletin 33: 299-305.

LeDoux MS, Lorden JF, Ervin JM. (1993) Cerebellectomy eliminates the motor syndrome of the genetically dystonic rat. Experimental Neurology 120: 302-310.

Whitworth RH Jr, LeDoux MS, Gould HJ III. (1991) Topographic distribution of connections from the primary motor cortex to the corpus striatum in Aotus trivirgatus. Journal of Comparative Neurology 307: 177-188.

LeDoux MS, Whitworth RH Jr, Gould HJ III. (1998) Interhemispheric connections of the somatosensory cortex in the rabbit. Journal of Comparative Neurology 258: 145-157.