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Research Highlights:I. The Adult Spinal Cord Contains Multipotent Neural Stem CellsII. Spinal Cord-Derived Progenitor Cells are Prevalent and ActiveIII. Fate Choice of Adult Neural Progenitor Cells can be Modulated after Spinal Cord InjuryIV. NT-3 Stimulates limited regeneration of the cortico-spinal tract following spinal contusion injury |
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Lab Members: |
| - Drew Sellers |
| - Martha McGaughy |
| - Don Maris |
| - Eric Huebner |
| - Mary Nivison |
NIH R21:
Dr Philip Horner and Dr. Denise Inman have received a 2 year $275,000 NIH R21 award
to develop a "Murine Model for Regulation of Gliosis in Glaucoma".
Abstract:
Our knowledge of CNS glial cells now reveals that glia are much more than support cells for neurons. Glia provide structure to CNS tissue, guide migrating cells, regulate neurotransmitters in the extracellular milieu, produce signaling molecules, maintain synaptic connections, form the blood-brain barrier, monitor the environment and respond in myriad ways to injury and disease. Glial response to injury is called gliosis, and involves upregulation of intermediate filaments within the cell, changes in the complement of ion channels, secretion of signaling molecules and can also include proliferation. Gliosis occurs early in the chronic mouse model of glaucoma, and the magnitude of the response in all glial populations is significant. As of yet, the positive or negative impact of gliosis on RGC health and the progression of glaucoma has not been studied. This research will study the role gliosis plays in glaucoma by tempering the glial response in an animal model.
NIH R01:
"Regulation of Adult Progenitor Cells and Neural Repair".
Abstract:
Injury to the adult mammalian CNS leads to cell death and the severing of axonal connections that exhibit limited regeneration. Following spinal cord injury the functions of severed pathways, including locomotion, sensation and autonomic function are permanently lost leaving patients with a devastating level of disability. The failure to regenerate spinal pathways is due, in part, to the formation of physical and molecular barriers to axonal regrowth. This project seeks to define the plasticity of the NG2-expressing progenitor cell, its growth factor responsiveness and function in repair of the adult spinal cord. In addition, direct modification of endogenous progenitor cells using epidermal growth factor (EGF) is proposed to maintain NG2-expressing cells in a proliferative state and increase recovery from spinal cord injury. Direct activation of the endogenous NG2-cells with EGF will be used to increase the period of plasticity following injury and improve the regeneration of motor pathways. Overall, these experiments will better define the role and regulation of progenitor cells in the injured adult spinal cord and explore a novel approach to increase functional plasticity by regulation of endogenous proliferation.
SELECTED PUBLISHED AND ACCEPTED ARTICLES IN REFEREED JOURNALS:
Drew L. Sellers, Don O. Maris, and P.J. Horner. 2009. Post-injury niches direct temporal shifts in progenitor fate-choice to direct niche succession and repair after spinal cord injury. Journal of Neuroscience, 29(20):6722-33
Lasiene J, Matsui A, Sawa Y, Wong F, and P.J. Horner. Age-related myelin dynamicsrevealed by increased oligodendrogenesis and short internodes. Aging Cell. 2009. Apr;8(2):201-13.
Rhee, W. S. Ray, H. Yokoo, M.E. Hoane, C. C. Lee, A. M. Mikheev, P.J. Horner, R.C. Rostomily. 2009. Quantitative analysis of mitotic Olig2 cells in adult human brain and gliomas: implications for glioma histogenesis and biology. Glia, 2009 Apr 1;57(5):510-23
Calkins D, Horner PJ, Roberts R, Gradianu M, Berkowitz BA. 2008. Manganese-enhanced MRI of the DBA/2J Mouse Model of Hereditary Glaucoma. Invest Ophthalmol Vis Sci. 49(11):5083-8
Bosco, A., D.M.Inman, M.R.Steele, G.Wu, N.Marsh-Armstrong, D.J. Calkins, P.J. Horner, M.L.Vetter. 2008. Reduced retina microglial activation and improved optic nerve integrity with minocycline treatment in the DBA/2J mouse model of glaucoma. IOVS, 49(4):1437-46
Lasiene, J., L. Shupe, S. Perlmutter, P.J. Horner. 2008. No evidence for chronic demyelination in spared axons following spinal cord injury in a mouse. Journal of Neuroscience, 9;28(15):3887-96
Buckingham, B., D. Inman, W. Lambert, E. Oglesby, D.J. Calkins, M. Steele, M. Vetter, N. Marsh-Armstrong and P.J. Horner. 2008. Progressive Ganglion Cell Degeneration Precedes Neuronal Loss in a Mouse Model of Glaucoma. Journal of Neuroscience, 28(11):2735-44
Soto., I., E. Oglesby, B.P. Buckingham, J.L. Son, E.D.O. Roberson, M.R. Steele, D.M. Inman, M.L. Vetter, P.J. Horner and N. Marsh-Armstrong. 2007. Retinal Ganglion Cells Down-regulate Gene Expression and Lose their Axons within the Optic Nerve Head in a Mouse Glaucoma Model. Journal of Neuroscience, 9;28(2):548-61.
Petit, A., D.L. Sellers, D. J. Liebl, M. Tessier-Lavigne, T.E. Kennedy, P.J. Horner. 2007. Adult Spinal Cord Progenitor Cells are repelled by netrin-1 in the embryonic and injured adult spinal cord. Proc Natl Acad Sci U S A. Nov 6;104(45):17837-42.
Inman, D.M. and P.J. Horner. 2007. Reactive Non-Proliferative Gliosis Predominates in a Chronic Model of Glaucoma. Glia, 55(9):942-53
Park, I., J. Lasiene, S-H. Chou, P.J. Horner, S. H. Pun. 2007. Neuron-specific delivery of nucleic acids mediated by Tet1-modified poly(ethylenimine). Journal of Gene Medicine, 9(8):691-702
Bergen, J.M., I. Park, P.J. Horner, S. H. Pun. 2007. Nonviral Approaches for Neuronal Delivery of Nucleic Acids. Pharm Res. Oct 12
Horky, L.L., F. Galimi, F.H. Gage and P.J. Horner. 2006. Fate of Endogenous Stem/Progenitor Cells Following Spinal Cord Injury. J. Comp. Neurol. 498(4):525-538
Inman, D.M, R.M. Sappington, P.J. Horner and D.J. Calkins. 2005.Quantitative Correlation of Optic Nerve Pathology with Ocular Pressure and Corneal Thickness in the DBA/2J Mouse Model of Glaucoma. IOVS 47(3):986-96
Steele, M.R., D.M. Inman, D.J. Calkins, P.J. Horner, M.L. Vetter. 2005. Microarray Analysis of Retinal Gene Expression in the DBA/2J Model of Glaucoma. IOVS 47(3):977-85
Arvanian, V.L., W.J. Bowers, A.J. Anderson, P.J. Horner, H.J. Federoff, L.M. Mendell. 2005. Combined delivery of neurotrophin-3 and NMDA receptors 2D subunit strengthens synaptic transmission in contused and staggered double hemisected spinal cord of neonatal rat
Exp. Neurol. 197(2):347-52
Sellers D.L. and P.J. Horner. 2005. Instructive Niches: Environmental Instructions that Confound NG2 Proteoglycan Expression and the Fate-Restriction of CNS Progenitors. Journal of Anatomy. 207:727–734
Gaulke, L.J., P.J. Horner, A.J. Fink, C.L. McNamara and R.R. Hicks. 2005. Environmental Enrichment Increases Progenitor Cell Survival in the Dentate Gyrus following Lateral Fluid Percussion Injury in Rats. Mol. Brain Research. 141(2):138-50
Horner, P.J. and T.D. Palmer. 2003. La vida loca! The nightlife of an astrocyte. Trends in Neuroscience. 26(11): 597-603
Milatovic, D., S. Zala-Milatovic, K.S. Montine, P.J. Horner, and T.J. Montine. 2003. Pharmacologic suppression of neuronal oxidative damage and dendritic degeneration following direct activation of glial innate immunity in mouse cerebrum. Journal of Neurochemistry. 87(6): 1518-26
Arvanian, V.L., P.J. Horner, F.H.Gage and L.M.Mendell. 2003. Chronic neurotrophin-3 strengthens synaptic connections to motoneurons in the neonatal rat. J. Neurosci. 23:8706-8712
South, S., T. Kohno, B.K. Kaspar, D. Hegarty, B. Vissel, C. Drake, M. Ohata, S. Jenab, A. Sailer, S. Malkmus, T. Masuyama, P.J. Horner, J. Bogulavsky, S. Tonegawa, F.H. Gage, T.L.Yaksh, C.J.Woolf, S.F. Heinemann, and C.E. Inturrisi. 2003. A Conditional Deletion of the NMDAR1 Subunit in Adult Spinal Cord Dorsal Horn Reduces NMDA Currents and Injury-Induced Pain. J. Neurosci. 23(12):5031-5040
Horner, P.J., M. Thallmair and F.H. Gage. 2003. Defining the NG2 cell of the adult central nervous system. Journal of Neurocytology. 31(6/7):469-480.
Moore, E.M., S. Presnell, U Garrigues, A. Guibot, E. LeGuern, D. Smith, L. Yao, T.E. Whitmore, T. Gilbert, T.D. Palmer, P.J. Horner, R.E. Kuestner. 2002. Expression of IL-17B in neurons and evaluation of its possible role in the chromosome 5q-linked form of Charcot-Marie-Tooth disease. Neuromuscular Disorders. 12(2):141-50
Lipson, A.C. and P.J. Horner. 2002. Potent possibilities: Endogenous stem cells in the adult spinal cord. Progress in Brain Research. 137:283-297
Horner, P.J. and F.H. Gage. 2002. Regeneration in the adult and aging brain. Archives of Neurology. 59(11):1717-1720
Horner, P.J. and F.H.Gage. 2000. Regenerating the damaged central nervous system. Nature. 407:963-970
Shihabuddin, L., P.J. Horner, J. Ray and F.H.Gage. 2000. Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus. J.Neurosci. 20(23):8727-8735
Horner, P.J., A.E.Power, G.Kempermann, H.G.Kuhn, T.D.Palmer, J. Winkler, L.J.Thal, and F.H. Gage. 2000. Existence of progenitor cells throughout the intact adult rat spinal cord. J.Neurosci. 20(6): 2218-2228
McTigue, D. M., P. J. Horner, B. T. Stokes, and F. H. Gage.1998. Neurotrophin-3 and brain-derived neurotrophic factor induce oligodendrocyte proliferation, migration, and myelination in the contused adult rat spinal cord. J.Neurosci. 18(14):5354-5365
Popovich, P.G., P.J. Horner, B.B. Mullin, and B.T. Stokes. 1996. A Quantitative Spatial Analysis of the Blood-Spinal Cord Barrier I. Permeability after Spinal Contusion Injury. Exp. Neurol. 142:258-275
Horner, P.J., P.G. Popovich, B.B. Mullin, and B.T. Stokes. 1996. A Quantitative Spatial Analysis of the Blood-Spinal Cord Barrier II. Permeability after Intraspinal Fetal Transplantation. Exp. Neurol. 142:226-243
Horner, P.J., P.J. Reier, and B.T. Stokes. 1996. Quantitative Analysis of Vascularization and Cytochrome Oxidase Following Fetal Transplantation in the Contused Rat Spinal Cord. J. Comp. Neurol. 364(4):690-703
Horner, P.J. and B.T. Stokes. 1995. Fetal Transplantation Following Spinal Contusion Injury Results in Chronic Alterations in CNS Glucose Metabolism. Exp. Neurol.133(2):231-243
BOOK CHAPTERS:
Jacobson, B.E. and P.J. Horner. 2008. Gliogenesis in the Adult Spinal Cord. Postnatal and Adult Neurogenesis, Research Signpost, L. Bonfanti editor, Ch 6, pg 83-100.
McDonald, J.W. and the APA Spinal Cord Injury Consortium. 1999. Spinal Cord Injury: New Insights for Novel Treatments. Scientific American. August, pg65-73.
Senut, M-C., I. Aubert, P.J. Horner, and F.H. Gage. 1997. Gene Transfer for Adult CNS Regeneration and Aging. Gene Transfer and Therapy for Neurobiological Disorders, Umana Press, E.A. Choicca and X.O. Brakefield editors, Ch 17, pg 341-371.
Stokes, B.T., P.J. Horner, and M. Akino. 1996. Spinal Cord Injury Modeling and Functional Assessment. Central Nervous System Trauma: Research Techniques, CRC Press, S.T. Ohnishi and T. Ohnishi editors, Ch 20.
Stokes, B.T. and P.J. Horner. 1996. Spinal Cord Injury Modeling and Outcome Assessment. Neurotrauma: A Comprehensive Textbook on Head and Spinal Injury, McGraw-Hill, Inc., R.K. Narayan, J.E. Wilberger, and J.T. Povlishock editors, Ch 103, pg 1395-1402.
Horner, P.J., P.G. Popovich, P.J. Reier and B.T. Stokes. 1994. Fetal Spinal Transplant Vascularity: Metabolic and Immunologic Mechanisms. Neural Transplantation, CNS Neuronal Injury, and Regeneration - Recent Advances , CRC press, Joe Marwah, Herman Teitelbaum, and Kedar N. Prasad editors, ch 9, pg 119-140.
Stokes, B.T., M. Kim-Lee and P.J. Horner. 1993. Calcium Paradox: A Novel Mode of Secondary CNS Injury. Neurosurgical Topics Series, 14 Spinal Trauma: Current Evaluation and Management, Gary Rea and Carole Miller editors, ch 13, pg 207-212.
OTHER PUBLICATIONS:
Horner, P.J. and F.H. Gage. 1997. Experimental Spinal Cord Regeneration: Promising New Approaches. Brain Work Vol. 7 No. 2.