myelin-basic-protein and Neurofibromatosis-1

Neonatal rat sciatic nerve Schwann cells in monolayer culture are stimulated to proliferate and to express a lipid and a protein characteristic of myelin by agents which raise intracellular cyclic adenosine 3',5'-monophosphate. Both glial growth factor and axolemmal fragments increase the rate of mitosis of cultured rat and human Schwann cells. Rat Schwann cell mitosis is enhanced by a soluble factor produced by concanavalin A-stimulated blood mononuclear cells and inhibited by lead salts. Schwann-like cells cultured from human dermal and plexiform neurofibromas resemble normal human Schwann cells in phenotype and response to mitogens.

Topics: Animals; Animals, Newborn; Axons; Cell Differentiation; Cell Division; Cell Separation; Cells, Cultured; Colforsin; Culture Media; Culture Techniques; Cyclic AMP; Fibronectins; Glia Maturation Factor; Humans; Laminin; Lead; Lymphokines; Myelin Basic Protein; Nerve Tissue Proteins; Neurofibromatosis 1; Rats; Schwann Cells; Sciatic Nerve

Neurofibromatosis type 1 (NF1) is a common neurogenetic disorder, in which affected individuals develop tumors of the nervous system. Children with NF1 are particularly prone to brain tumors (gliomas) involving the optic pathway that can result in impaired vision. Since tumor formation and expansion requires a cooperative tumor microenvironment, it is important to identify the cellular and acellular components associated with glioma development and growth. In this study, we used 3-D matrix assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) to measure the distributions of multiple molecular species throughout optic nerve tissue in mice with and without glioma, and to explore their spatial relationships within the 3-D volume of the optic nerve and chiasm. 3-D IMS studies often involve extensive workflows due to the high volume of sections required to generate high quality 3-D images. Herein, we present a workflow for 3-D data acquisition and volume reconstruction using mouse optic nerve tissue. The resulting 3-D IMS data yield both molecular similarities and differences between glioma-bearing and wild-type (WT) tissues, including protein distributions localizing to different anatomical subregions.. The current work addresses a number of challenges in 3-D MALDI IMS, driven by the small size of the mouse optic nerve and the need to maintain consistency across multiple 2-D IMS experiments. The 3-D IMS data yield both molecular similarities and differences between glioma-bearing and wild-type (WT) tissues, including protein distributions localizing to different anatomical subregions, which could then be targeted for identification and related back to the biology observed in gliomas of the optic nerve.

Topics: Animals; Brain Neoplasms; Diazepam Binding Inhibitor; Fiducial Markers; Imaging, Three-Dimensional; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Molecular Imaging; Myelin Basic Protein; Neurofibromatosis 1; Optic Chiasm; Optic Nerve Glioma; Optic Nerve Neoplasms; Proteomics; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization