Faculty Profile:

Douglas O. Frost, Ph.D.
Professor

Department of Pharmacology and Experimental Therapeutics<br>Department of Anesthesiology
School of Medicine

410-706-0413

dfrost@umaryland.edu

Research

The group's principal interest is in studying the cellular and molecular mechanisms underlying normal neural development and the perturbation of these mechanisms in disease states or by drugs. We also study how these mechanisms can be harnessed for brain repair.

Current research in the laboratory is focused in several areas:

Effects of drugs on the developing nervous system. Therapeutic and illicit drugs are taken by pregnant women, children and adolescents. We investigate the effects of these drugs on the development of neural circuitry in rodent models. The endpoints studied include gene expression profiling (real time PCR and in situ hybridization), endocrine assays (HPA stress axis activation), behavior (measures of activity, motor skill, affect, cognition, learning and memory) and neuroanatomical and receptor binding measures. We also study how the effects of early drug exposure interact with those of the psychiatric disease and the early life environment. Our work in this little-studied area promotes understanding of the behavioral effects of fetal drug exposure in humans and the development of new therapeutic strategies. We are beginning collaborative studies of antidepressant drug metabolism in humans.

Human disease states. We are using human post-mortem tissue to study alterations of neurotrophin expression and signaling in schizophrenia.

Neurotrophins. We study the role of neurotrophins in regulating the structural and functional development of neural circuitry. We manipulate neurotrophin signaling in vivo using a variety of technologies, then assay the effects on the survival of immature neurons, neuronal connectivity patterns, synaptic physiology and network function.

Brain repair. We have developed a technique that allows us to "rewire" the eye to abnormal brain targets The resulting neural circuits can take over the neurophysiologic and behavioral function of natural visual circuits that are damaged. We are now studying how rewiring alters patterns of cerebral gene expression and downstream connectivity.

Collaborators:

Prof. Bryan Kolb (University of Lethbridge, Alberta, Canada) – long-term effects on brain development of fetal exposure to antidepressant and antipsychotic drugs.
Prof. Todd Gould (University of Maryland School of Medicine) – effects of fetal antidepressant exposure on brain development.
Prof Margaret Fahnestock (McMaster Universtiy, Hamilton, Ontario, Canada - Altered neurotrophin signaling in schizophrenia. Neurotrophin signaling in visual system development.
Prof. Carol Tamminga (University of Texas Southwestern Medical Center) - Altered neurotrophin signaling in schizophrenia.
Prof. Jean-Francois Bouchard (Université de Montréal, Montreal, Quebec, Canada) - Netrin signaling in CNS development.

Lab Techniques

Techniques used in the lab:

Molecular (in situ hybridization, PCR, real time PCR)
Neuroanatomical pathway tracing (cholera toxin, HRP, Di-I, diamidino yellow, etc.),
Protein measurement (by ELISA, immunoprecipitation/immunoblotting).
Immunohistochemistry.
Confocal microscopy.
Computerized neuronal reconstruction and morphometry.
Radio immunoassays of stress hormones.
In vitro receptor binding.
Behavioral testing of live animals

Publications

Marchese, M., Garzon, D., Roberts, R., Fahnestock, M. and Frost, D.O., Transcript-specific alteration of hippocampal BDNF mRNA expression in schizophrenia, Manuscript preparation.

Ghose, S., Gao, X.-M., Roberts, R.C., Tamminga, C.A., Frost, D.O., Schizophrenia-associated increases in BDNF mRNA in specific populations of hippocampal dendrites, Manuscript in preparation.

Frost, D.O., Gibb,R. and Kolb, B., Trick or treat? Neurodevelopmental consequences of pharmacotherapy for affective disorders, Neuropsychopharmacology, in press, 2009.

Frost, D.O., Cercio, S., Carroll, C. and Kolb, B., Early exposure to haloperidol or olanzapine induces long-term alterations of dendritic form, Synapse, in press, 2009.

Halliwell, C., Comeau, W., Gibb, R., Frost, D.O. and Kolb, B., Factors influencing frontal cortex development and recovery from early frontal injury, Dev. Neurorehab., in press, 2009.

Rodger, J. and Frost, D.O., TrkB Signaling Modulates Topography But Not Ocular Segregation of Retinal Projections, 2009, 195, 35-44.

Turner, C.A., Calvo, N., Frost, D.O., Akil, H. and Watson, S.J., The fibroblast growth factor system is down regulated following social defeat, Neurosci. Lett., 2008, 430, 147-150.

Frost, D.O., Tamminga, C.A., Medoff, D.R., Caviness, V.S. Jr., Innocenti, G.M. and Carpenter,W.T. Jr., Neuroplasticity and schizophrenia, Biol. Psychiatr., 2004, 56, 540-543.

Pollock, G.S., Robichon, R., Boyd, K., Kerkel, K.A., Kramer, M., Lyles, J., Ambalavanar, R., Khan, A., Kaplan, D.R., Williams, R.W. and Frost, D.O. TrkB receptor signaling regulates developmental death dynamics, but not final number, of retinal ganglion cells, J. Neurosci., 2003, 23, 10137-10145.

Pollock, G.S. and Frost, D.O., Complexity in the modulation of neurotrophic factor mRNAs by early visual experience, Dev. Br. Res., 2003, 143, 225-232.

Tamminga, C.A. and Frost, D.O., Changing concepts in the neurochemistry of schizophrenia, Am. J. Psychiatr., 2001, 158, 1365-1366.

Frost, D.O., Ma, Y.-T., Hsieh, T., Forbes, M.E. and Johnson, J.E., Developmental changes in BDNF protein levels in the hamster retina and superior colliculus. J. Neurobiol., 2001, 49, 173-187.

Pollock, G.S., Vernon, E., Forbes, M.E., Yan, Q., Ma, Y.-T., Hsieh, T., Robichon, R., Frost, D.O., Johnson, J.E., Modulation of BDNF mRNA and protein levels by early visual experience and diurnal rhythms. J. Neurosci., 2001, 21, 3923-3931.

Frost, D.O. BDNF/trkB signaling in the developmental sculpting of visual connections, Prog. Br. Res., 2001 134, 35-49.

Frost, D.O., Boire, D., Gingras, G. and Ptito, M., Surgically-created neural pathways mediate visual pattern discrimination. Proc. Natl Acad. Sci., 97, 11068-11073, 2000.

Frost, D.O. and Cadet, J.L. Effects of drug-induced neurotoxicity on development of neural circuitry: A hypothesis. Br. Res. Rev., 34 (3), 103-118, (2000).

Bhide, P.G. & Frost, D.O., Intrinsic heterogeneity of retinal ganglion cells in their potential to form thalamic connections. J Comp Neurol. 1999, 411, 119-129.

Ma, Y.-T., Hsieh, T., Forbes, M.E., Johnson, J.E. and Frost, D.O., BDNF injected into the superior colliculus reduces developmental retinal ganglion cell death. J. Neurosci., 1998, 18, 2097-2107.

Boire, D., Morris, R., Ptito, M., LePore, F., and Frost, D.O. Effects of neonatal splitting of the optic chiasm on the development of feline visual callosal connections. Exp. Br. Res., 1995, 104, 275-286.

Bhide, P.G. & Frost, D.O., Axon substitution in the reorganization of developing neural connections. Proc. Nat. Acad. Sci., 1992, 89, 11847-11851.

Bhide, P.G. & Frost, D.O., Stages of growth of hamster retinofugal axons: Implications for developing axonal pathways with multiple targets. J. Neurosci., 1991, 11, 485-504.

Frost, D.O. Visual processing by novel, surgically created neural circuits. In: D. M.-K. Lam and G.M. Bray (Eds.), Regeneration and plasticity in the mammalian visual system, 1992, MIT Press, Cambridge, MA, pp. 197-219.

Métin, C. and Frost, D.O., Visual responses of neurons in somatosensory cortex of hamsters with experimentally induced retinal projections to somatosensory thalamus. Proc. Nat. Acad. Sci., 1989, 86, 357-361.

Personal History

BS and MS in electrical engineering, PhD in Neuroscience, all from the Massachusetts Institute of Technology.

Faculty member at:

University of Maryland Medical School (1993-Present)

Visiting Professor at the Molecular and Behavioral Neuroscience Institute, University of Michigan Medical School in 2006.

Visiting Professor at the University of Western Australia, Perth, Australia (2003)

Harvard Medical School (1988-1993)

Yale Medical School (1980-1988)

Faculty of Medicine, University of Lausanne (Switzerland; 1975-1980)

Laboratory Personnel

Jennie Milstein - Post-doctoral fellow

Monika Vinish - Post-doctoral fellow

Jenn Enos - Research Assistant

Back to All Faculty

School of Medicine | Dental School | Graduate School | University of Maryland, Baltimore
Center of Marine Biotechnology (COMB) | Medical Biotechnology Center (MBC)

Please read the disclaimer concerning use of this University of Maryland School of Medicine site.

® University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore MD 21201
site maintained by moderntymes.com