Stage dependent effects of progesterone on motoneurons and glial cells of wobbler mouse spinal cord degeneration
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...
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todo:paper_02724340_v30_n1_p123_Meyer2023-10-03T15:15:01Z Stage dependent effects of progesterone on motoneurons and glial cells of wobbler mouse spinal cord degeneration Meyer, M. Gonzalez Deniselle, M.C. Garay, L.I. Monachelli, G.G. Lima, A. Roig, P. Guennoun, R. Schumacher, M. De Nicola, A.F. Glial fibrillary acidic protein Glutamine synthetase Neurodegeneration Neuroprotection Progesterone Wobbler choline acetyltransferase glial fibrillary acidic protein glutamate ammonia ligase messenger RNA neuromodulin progesterone animal cell animal experiment animal model animal tissue article cell degeneration chronotherapy controlled study disease course drug efficacy female genotype glia cell male mouse mouse mutant neuroprotection nonhuman priority journal protein expression spinal cord atrophy spinal cord motoneuron wild type wobbler mouse Animals Anterior Horn Cells Astrocytes Cell Count Choline O-Acetyltransferase Disease Models, Animal Female GAP-43 Protein Gene Expression Regulation Genotype Glial Fibrillary Acidic Protein Glutamate-Ammonia Ligase Image Processing, Computer-Assisted Male Mice Mice, Neurologic Mutants Motor Neurons Neuroglia Progesterone RNA, Messenger Spinal Cord Spinal Cord Diseases Mus 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. © 2009 Springer Science+Business Media, LLC. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_02724340_v30_n1_p123_Meyer |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Glial fibrillary acidic protein Glutamine synthetase Neurodegeneration Neuroprotection Progesterone Wobbler choline acetyltransferase glial fibrillary acidic protein glutamate ammonia ligase messenger RNA neuromodulin progesterone animal cell animal experiment animal model animal tissue article cell degeneration chronotherapy controlled study disease course drug efficacy female genotype glia cell male mouse mouse mutant neuroprotection nonhuman priority journal protein expression spinal cord atrophy spinal cord motoneuron wild type wobbler mouse Animals Anterior Horn Cells Astrocytes Cell Count Choline O-Acetyltransferase Disease Models, Animal Female GAP-43 Protein Gene Expression Regulation Genotype Glial Fibrillary Acidic Protein Glutamate-Ammonia Ligase Image Processing, Computer-Assisted Male Mice Mice, Neurologic Mutants Motor Neurons Neuroglia Progesterone RNA, Messenger Spinal Cord Spinal Cord Diseases Mus |
| spellingShingle |
Glial fibrillary acidic protein Glutamine synthetase Neurodegeneration Neuroprotection Progesterone Wobbler choline acetyltransferase glial fibrillary acidic protein glutamate ammonia ligase messenger RNA neuromodulin progesterone animal cell animal experiment animal model animal tissue article cell degeneration chronotherapy controlled study disease course drug efficacy female genotype glia cell male mouse mouse mutant neuroprotection nonhuman priority journal protein expression spinal cord atrophy spinal cord motoneuron wild type wobbler mouse Animals Anterior Horn Cells Astrocytes Cell Count Choline O-Acetyltransferase Disease Models, Animal Female GAP-43 Protein Gene Expression Regulation Genotype Glial Fibrillary Acidic Protein Glutamate-Ammonia Ligase Image Processing, Computer-Assisted Male Mice Mice, Neurologic Mutants Motor Neurons Neuroglia Progesterone RNA, Messenger Spinal Cord Spinal Cord Diseases Mus Meyer, M. Gonzalez Deniselle, M.C. Garay, L.I. Monachelli, G.G. Lima, A. Roig, P. Guennoun, R. Schumacher, M. De Nicola, A.F. Stage dependent effects of progesterone on motoneurons and glial cells of wobbler mouse spinal cord degeneration |
| topic_facet |
Glial fibrillary acidic protein Glutamine synthetase Neurodegeneration Neuroprotection Progesterone Wobbler choline acetyltransferase glial fibrillary acidic protein glutamate ammonia ligase messenger RNA neuromodulin progesterone animal cell animal experiment animal model animal tissue article cell degeneration chronotherapy controlled study disease course drug efficacy female genotype glia cell male mouse mouse mutant neuroprotection nonhuman priority journal protein expression spinal cord atrophy spinal cord motoneuron wild type wobbler mouse Animals Anterior Horn Cells Astrocytes Cell Count Choline O-Acetyltransferase Disease Models, Animal Female GAP-43 Protein Gene Expression Regulation Genotype Glial Fibrillary Acidic Protein Glutamate-Ammonia Ligase Image Processing, Computer-Assisted Male Mice Mice, Neurologic Mutants Motor Neurons Neuroglia Progesterone RNA, Messenger Spinal Cord Spinal Cord Diseases Mus |
| description |
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. © 2009 Springer Science+Business Media, LLC. |
| format |
JOUR |
| author |
Meyer, M. Gonzalez Deniselle, M.C. Garay, L.I. Monachelli, G.G. Lima, A. Roig, P. Guennoun, R. Schumacher, M. De Nicola, A.F. |
| author_facet |
Meyer, M. Gonzalez Deniselle, M.C. Garay, L.I. Monachelli, G.G. Lima, A. Roig, P. Guennoun, R. Schumacher, M. De Nicola, A.F. |
| author_sort |
Meyer, M. |
| title |
Stage dependent effects of progesterone on motoneurons and glial cells of wobbler mouse spinal cord degeneration |
| title_short |
Stage dependent effects of progesterone on motoneurons and glial cells of wobbler mouse spinal cord degeneration |
| title_full |
Stage dependent effects of progesterone on motoneurons and glial cells of wobbler mouse spinal cord degeneration |
| title_fullStr |
Stage dependent effects of progesterone on motoneurons and glial cells of wobbler mouse spinal cord degeneration |
| title_full_unstemmed |
Stage dependent effects of progesterone on motoneurons and glial cells of wobbler mouse spinal cord degeneration |
| title_sort |
stage dependent effects of progesterone on motoneurons and glial cells of wobbler mouse spinal cord degeneration |
| url |
http://hdl.handle.net/20.500.12110/paper_02724340_v30_n1_p123_Meyer |
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