Stage Dependent Effects of Progesterone on Motoneurons and Glial Cells of Wobbler Mouse Spinal Cord Degeneration
| Autor: | Laura Garay, Maria Meyer, Gisella Gargiulo Monachelli, Alejandro F. De Nicola, Analia Lima, Paulina Roig, Maria Claudia Gonzalez Deniselle, Rachida Guennoun, Michael Schumacher |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Genotype Cell Count Biology Spinal Cord Diseases Choline O-Acetyltransferase Andrology Mice Mice Neurologic Mutants Cellular and Molecular Neuroscience GAP-43 Protein Anterior Horn Cells Glutamate-Ammonia Ligase Glial Fibrillary Acidic Protein Image Processing Computer-Assisted medicine Animals RNA Messenger Gap-43 protein Progesterone Motor Neurons Glial fibrillary acidic protein Neurodegeneration Cell Biology General Medicine medicine.disease Spinal cord Choline acetyltransferase Astrogliosis Disease Models Animal medicine.anatomical_structure Gene Expression Regulation Spinal Cord nervous system Astrocytes Immunology biology.protein Neuroglia Female Wobbler disease |
| Zdroj: | Cellular and Molecular Neurobiology. 30:123-135 |
| ISSN: | 1573-6830 0272-4340 |
| DOI: | 10.1007/s10571-009-9437-8 |
| Popis: | In the Wobbler mouse, a mutation in the Vps54 gene is accompanied by motoneuron degeneration and astrogliosis in the cervical spinal cord. Previous work has shown that these abnormalities are greatly attenuated by progesterone treatment of clinically afflicted Wobblers. However, whether progesterone is effective at all disease stages has not yet been tested. The present work used genotyped (wr/wr) Wobbler mice at three periods of the disease: early progressive (1-2 months), established (5-8 months) or late stages (12 months) and age-matched wildtype controls (NFR/NFR), half of which were implanted with a progesterone pellet (20 mg) for 18 days. In untreated Wobblers, degenerating vacuolated motoneurons were initially abundant, experienced a slight reduction at the established stage and dramatically diminished during the late period. In motoneurons, the cholinergic marker choline acetyltransferase (ChAT) was reduced at all stages of the Wobbler disease, whereas hyperexpression of the growth-associated protein (GAP43) mRNA preferentially occurred at the early progressive and established stages. Progesterone therapy significantly reduced motoneuron vacuolation, enhanced ChAT immunoreactive perikarya and reduced the hyperexpression of GAP43 during the early progressive and established stages. At all stage periods, untreated Wobblers showed high density of glial fibrillary acidic protein (GFAP)+ astrocytes and decreased number of glutamine synthase (GS) immunostained cells. Progesterone treatment down-regulated GFAP+ astrocytes and up-regulated GS+ cell number. These data reinforced the usefulness of progesterone to improve motoneuron and glial cell abnormalities of Wobbler mice and further showed that therapeutic benefit seems more effective at the early progressive and established periods, rather than on advance stages of spinal cord neurodegeneration. |
| Databáze: | OpenAIRE |
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