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Faculty > Faculty Alphabetical > Robert Schmidt, MD, PhD

Professor, Pathology and Immunology
Head, Division of Neuropathology
Room 3720, West Building
Office: (314) 362-7429
Lab: (314) 362-7416
E-mail: reschmidt@pathology.wustl.edu
Publication List

Research

Disease of the peripheral autonomic nervous system is a significant complication of diabetes and aging with clinical presentations ranging from minor pupillary and sweating problems to significant disturbances in cardiovascular, alimentary and genitourinary function, resulting in significantly increased patient morbidity and mortality. My laboratory is interested in the neuropathology and pathogenesis of diabetic and age-associated sympathetic autonomic neuropathy. In order to develop insight into the early phases of these conditions, which presumably would be most amenable to therapy and would be most tightly coupled to pathogenetic mechanisms, we have developed and validated several rodent models which show close correspondence to human disease.

We have focused on the examination of alterations in synapses in sympathetic ganglia. Diabetes and aging result in the development of degenerating, regenerating, and pathologically distinctive dystrophic nerve terminals and post-synaptic dendritic elements in prevertebral sympathetic ganglia of streptozotocin (STZ)-induced diabetic and genetically diabetic rats and mice. Identical neuropathology characterizes aged humans, rats and mice which suggests shared mechanisms between diabetes and aging. Our long term goal of understanding the pathogenesis and treatment of diabetic and age-related autonomic neuropathy has resulted in the investigation of novel therapeutic agents and neurotrophic substances. IGF-I (insulin-like growth factor-I) treatment of diabetic rats with established ganglionic neuritic dystrophy results in nearly complete normalization of dystrophic pathology without altering the metabolic severity of diabetes. Since this result occurred without normalization of blood glucose levels, we have proposed that IGF-I acts directly as a neurotrophic substance to correct ganglionic deficiency of IGF-I and normalize deficits in its neuronal signaling cascade.

Thus, using relevant animal models which are faithful replicas of the human disease, characterized by dramatic and unambiguous neuropathology and reproducible over strain and species boundaries, our long term goal is to understand the pathogenesis and treatment of diabetic and age-related autonomic neuropathy

Editorial Responsibilities

2007 - PresentSenior EditorBrain Pathology
2001 - PresentEditorial BoardJournal of Neuropathology and Experimental Neurology
1991 - 1996Editorial BoardJournal of Neuropathology and Experimental Neurology

Service to the Department

2012 - PresentDirector, Clinical and Research Electron Microscopy Facility
2006 - PresentDirector, Research Electron Microscopy Core Facility
1992 - PresentDirector, Neuropathology Fellowship Program
1992 - PresentDirector, Neuropathology

Service to the University

2006 - PresentMember, Alumni Association Executive Council, Washington University School of Medicine

DBBS Graduate Program Affiliation

Neurosciences Program, Division of Biology and Biomedical Sciences

Diagnostic Expertise

Neuropathology, Autopsy and Surgical

Clinical Interest

Neuropathology - Neuropathology

Selected Publications

Espay AJ, MD, MSc, Paviour DC, PhD, MRCP, O'Sullivan JD, FRACP, Schmidt RE, MD, PhD, Revilla FJ, MD, Verhagen Metman L, MD. Juvenile levodopa-responsive parkinsonism with early orobuccolingual dyskinesias and cognitive impairment. Movement Disorders, in press, 2010

Pestronk A, Schmidt RE, Choksi R. Vascular pathology in dermatomyositis and anatomic relations to myopathology. Muscle Nerve, in press, 2010

Mancuso DJ, Kotzbauer P, Wozniak DF, Sims HF, Jenkins CM, Guan S, Han X, Yang K, Sun G, Malik I, Conyers S, Green KG, Schmidt RE, Gross RW. Genetic ablation of calcium-independent phospholipase A2 leads to alterations in hippocampal cardiolipin content and molecular species distribution, mitochondrial degeneration, autophagy and cognitive dysfunction. J Biol Chem 2009, 284:35632-35644, 2009 Abstract

Schmidt RE, Parvin CA, Green KG. Synaptic ultrastructural pathology anticipates the development of neuroaxonal dystrophy in the sympathetic ganglia of aged and diabetic mice. J Neuropathol Exp Neurol 2008, 67:1166-1186, 2008 Abstract

Malik I, Turk J, Mancuso DJ, Montier L, Wohltmann M, Wozniak D, Schmidt RE, Gross RW, Kotzbauer PT. Disrupted membrane homeostasis and accumulation of ubiquitinated proteins in a mouse model of infantile neuroaxonal dystrophy due to PLA2G6 Mutations. Am J Pathol 2008, 172:406-416, 2008 Abstract

McCandless EE, Piccio L, Woerner BM, Schmidt RE, Rubin JB, Cross AH, Klein RS. Pathologic expression of CXCL12 at the blood-brain barrier correlates with severity of multiple sclerosis. Am J Pathol 2008, 172:799-808, 2008 Abstract

Zhao Z, Fux B, Goodwin M, Dunay IR, Strong D, Miller BC, Cadwell K, Delgado-Vargas M, Ponpuak M, Green KG, Schmidt RE, Mizushima N, Deretic V, Sibley LD, Virgin HW. Atg5 is essential for cellular immunity in ivvo and recruitment of a p47 GTPase to the Toxoplasma gondii parasitophorous vacuole in macrophages. Cell Host Microbe 4: 458-469, 2008, 2008 Abstract

Schmidt RE, Green KG, Snipes LL, Feng D. Neuritic dystrophy and neuronopathy in Akita (Ins2Akita) diabetic mouse sympathetic ganglia. Exp Neurol, 2008, 216: 207-218, 2008 Abstract

Budde, M.D., Kim, J.H., Liang, H.F., Schmidt, R.E., Russell, J.H., Cross, A.H., Song, S.K. Toward Accurate Diagnosis of White Matter. Magn Reson Med 57 (4):688-95, 2007 Abstract

Schmidt RE, Dorsey DA, Parvin CA, Beaudet LN. Sympathetic neuroaxonal dystrophy in the aged rat pineal gland. Neurobiol Aging 27:1514-23, 2006 Abstract

Perry A, Schmidt RE. Cancer Therapy-Associated CNS Neuropathology: An Update and Review of the Literature. Acta Neuropathol 111:197-212, 2006 Abstract

Leone TC, Lehman JJ, Finck BN, Schaeffer PJ, Wende AR, Boudina S, Courtois M, Wozniak DF, Sambandam. The transcriptional co-activator PGC-1 as a critical transducer of postnatal growth and energy metabolic maturation programs. PLoS Biol 3:e101, 2005 Abstract

Schmidt RE, Dorsey DA, Beaudet LN, Parvin CA, Yarasheski KE, Smith SR, Williamson JR, Peterson RG, O. A potent sorbitol dehydrogenase inhibitor exacerbates autonomic neuropathy in rats with streptozotocin-induced diabetes. Exp Neurol 192:407-419, 2005 Abstract

Carroll SL, Byer SJ, Dorsey DA, Watson MA, Schmidt RE. Ganglion-specific patterns of diabetes-modulated gene expression are established in prevertebral and paravertebral sympathetic ganglia prior to the development of neuroaxonal dystrophy.. J Neuropathol Exp Neurol 63 (11): 1144-1154, 2004 Abstract

Schmidt RE, Dorsey DA, Beaudet LN, Peterson RG. Analysis of the Zucker diabetic fatty (ZDF) type 2 diabetic rat model suggests a neurotrophic role for insulin/IGF-I in diabetic autonomic neuropathy. Am J Pathol 163:21-28, 2003 Abstract

Schmidt RE, Dorsey DA, Beaudet LN, Frederick KE, Parvin CA, Plurad SB, Levisetti MG. Non-obese diabetic mice rapidly develop dramatic sympathetic neuritic dystrophy - A new experimental model of diabetic autonomic neuropathy. Am J Pathol 163:2077-2091, 2003 Abstract

Schmidt RE. Age-related sympathetic ganglionic neuropathology: Human pathology and animal models. Auton Neurosci 96:63-72, 2002 Abstract

Schmidt RE, Dorsey DA, Beaudet LN, Parvin CA, Escandon E. Effect of NGF and neurotrophin-3 on experimental diabetic autonomic neuropathy. J Neuropathol Exp Neurol 60:263-273, 2001 Abstract

Schmidt RE, Dorsey DA, Beaudet LN, Plurad SB, Parvin CA, Ohara S. Effect of IGF-I and neurotrophin-3 on gracile neuroaxonal dystrophy in diabetic and aging rats. Brain Res 876:88-94, 2000 Abstract

Schmidt RE, Dorsey DA, Roth KA, Parvin CA, Hounsom L, Tomlinson DR. Effect of streptozotocin-induced diabetes on NGF, P75(NTR) and Trk A content of prevertebral and paravertebral rat sympathetic ganglia. Brain Res 867:149-156, 2000 Abstract

Schmidt RE, Dorsey DA, Beaudet LN, Plurad SB, Parvin CA, Miller MS. Insulin-like growth factor I reverses experimental diabetic autonomic neuropathy. Am J Pathol 155:1651-1660, 1999 Abstract

Schmidt RE, Dorsey DA, Beaudet LN, Plurad SB, Williamson JR, Ido Y. Effect of sorbitol dehydrogenase inhibition on experimental diabetic autonomic neuropathy. J Neuropathol Exp Neurol 57:1175-1189, 1998 Abstract

Schmidt RE, Dorsey DA, Selznick LA, DiStefano PS, Carroll SL, Beaudet LN, Roth KA. Neurotrophin sensitivity of prevertebral and paravertebral rat sympathetic ganglia. J Neuropathol Exp Neurol 57:158-167, 1998 Abstract

Schmidt RE, Beaudet LN, Plurad SB, Snider WD, Ruit KG. Pathologic alterations in pre- and post-synaptic elements in aged mouse sympathetic ganglia. J. Neurocytol 24:189-206, 1995 Abstract

Zhang LI, Schmidt RE, Yan Q, Snider WD. NGF and NT-3 have differing effects on the growth of dorsal root axons in developing mammalian spinal cord. J Neurosci 14:5187-5201, 1994 Abstract

Ohara S, Roth KA, Beaudet LN, Schmidt RE. Transganglionic NPY response to sciatic nerve injury in young and aged rats. J Neuropathol Exp Neurol 53:646-662, 1994 Abstract

Schmidt RE, Plurad SB, Parvin CA, Roth KA. The effect of diabetes and aging on human sympathetic autonomic ganglia. Am J Pathol 143:143-153, 1993 Abstract

Schmidt RE, McAtee SJ, Plurad DA, Parvin CA, Cogswell BE, Roth KA. Differential susceptibility of prevertebral and paravertebral sympathetic ganglia to experimental injury. Brain Res 460:214-226, 1988 Abstract

Schmidt RE, Modert CW, Yip HK, Johnson EM Jr. Retrograde axonal transport of intravenously administered 125I-Nerve growth factor in rats with streptozotocin-induced diabetes. Diabetes 32:654-663, 1983 Abstract

Schmidt RE, Plurad SB, Olack BJ, Scharp DW. The effect of pancreatic islet transplantation and insulin therapy on experimental diabetic autonomic neuropathy. Diabetes 32:532-540, 1983 Abstract

Schmidt RE, Johnson EM Jr, Nelson JS. Experimental diabetic autonomic neuropathy. Am J Pathol 103:210-225, 1981 Abstract