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Noradrenergic innervation of the cerebellar cortex in normal and in Purkinje cell degeneration mutant mice: evidence for long term survival following loss of the two major cerebellar cortical neuronal populations
Authors:D L Felten  S Y Felten  K W Perry  R W Fuller  J I Nurnberger  B Ghetti
Affiliation:1. Department of Neurobiology and Anatomy, University of Rochester School of Medicine, Rochester, NY 14642 U.S.A.;2. The Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46227 U.S.A.;3. Department of Psychiatry Indiana University School of Medicine, Indianapolis, IN 46223, U.S.A.;4. Department of Pathology, Division of Neuropathology, Indiana University School of Medicine, Indianapolis, IN 46223, U.S.A.;1. Department of Neurobiology, Gifu University Graduate School of Medicine, Gifu, Japan;2. Department of Molecular Design and Synthesis, Gifu University Graduate School of Medicine, Gifu, Japan;3. Department of Embryology, Institute for Developmental Research, Aichi Human Service Center, Aichi, Japan;1. Neuroscience Institute, National Research Council, Padua Section, 35121, Padua, Italy;2. Foundation for Advanced Biomedical Research, Veneto Institute of Molecular Medicine, Padua, Italy;3. Department of Biology, University of Padua, 35121, Padua, Italy;4. West Midlands Regional Genetics Laboratory, Birmingham Women''s and Children''s Hospital, Mindelsohn Way, Birmingham, B15 2TG, United Kingdom;5. Department of Biomedical Sciences, University of Padua, 35121, Padua, Italy;1. Department of Obstetrics and Maternal-Fetal Medicine, Necker-Enfants Malades Hospital, AP-HP and Paris Descartes University;2. Department of Histology-Embryology and Cytogenetics, Unit of Embryo & Fetal Pathology, Necker-Enfants Malades Hospital, AP-HP and Paris Descartes University;3. Department of Pathology, Necker-Enfants Malades Hospital, AP-HP and Paris Descartes University;4. Department of Pediatric Neurosurgery, Necker-Enfants Malades Hospital, AP-HP and Paris Descartes University;5. EHU FETUS, Université de Paris and IMAGINE Institute;6. Department of Pathology, Poissy Saint Germain-en-Laye Hospital, Versailles Saint-Quentin-en-Yvelines University;7. Department of Neuropathology, Lariboisière Hospital, AP-HP and Paris Diderot University;8. Institute of Psychiatry and Neuroscience of Paris, INSERM U1266, & IMAGINE Institute;9. INSERM UMR 1163, IMAGINE Institute
Abstract:Purkinje cell degeneration mutant mice were examined during the course of Purkinje cell death (26 and 35 days old) and at 3, 5, 9 and 12 months of age. Glyoxylic acid fluorescence histochemistry for catecholamines was used to investigate possible alterations or reorganization of the noradrenergic fibers from the coeruleo-cerebellar system in response to the degeneration of two major cell types in the cerebellar cortex, of which one, the Purkinje cell, is reported to be the major target neuron. In control mice, noradrenergic fibers traveled in linear and tortuous profiles through the granule cell layer, formed pericellular arrays alongside Purkinje cell somata, and branched profusely into both radially oriented and longitudinally oriented chains. The density of noradrenergic varicosities diminished in the molecular layer, there was with age. In the mutants, concomitant with the progressive shrinkage of the molecular layer, there was a progressive increase in the density of noradrenergic varicosities. This was most conspicuous at 9 and 12 months of age, at which time the molecular layer has been depleted not only of Purkinje cell dendrites, but also of parallel fibers. Noradrenergic fibers in these zones formed dense parallel bundles of varicose profiles whose density reached 621.3 +/- 122.8% (mean +/- SD, n = 4) at 9-12 months of age, compared with age-matched controls. Neurochemical measurement of norepinephrine content in whole cerebellum of the Purkinje cell degeneration mutants revealed no change compared with age-matched controls. We conclude that noradrenergic innervation persists in the cerebellar cortex despite the death of Purkinje cells and most of the granule cells. Although we found an increased density of varicosities in the molecular layer of mutant mice, progressing with age, we believe that this can be explained on the basis of the resultant geometry of the altered cerebellar cortex. It appears that the health of the environment surrounding the noradrenergic fibers in cerebellar cortex has little influence on their anatomical integrity.
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