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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Publicado: 2010
Materias:
Mus
Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02724340_v30_n1_p123_Meyer
http://hdl.handle.net/20.500.12110/paper_02724340_v30_n1_p123_Meyer
Aporte de:
id paper:paper_02724340_v30_n1_p123_Meyer
record_format dspace
spelling paper:paper_02724340_v30_n1_p123_Meyer2023-06-08T15:25:06Z Stage dependent effects of progesterone on motoneurons and glial cells of wobbler mouse spinal cord degeneration 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. 2010 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02724340_v30_n1_p123_Meyer 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
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.
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
publishDate 2010
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02724340_v30_n1_p123_Meyer
http://hdl.handle.net/20.500.12110/paper_02724340_v30_n1_p123_Meyer
_version_ 1768542885267898368