Progesterone up-regulates neuronal brain-derived neurotrophic factor expression in the injured spinal cord
Progesterone (PROG) provides neuroprotection to the injured central and peripheral nervous system. These effects may be due to regulation of myelin synthesis in glial cells and also to direct actions on neuronal function. Recent studies point to neurotrophins as possible mediators of hormone action....
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todo:paper_03064522_v125_n3_p605_Gonzalez2023-10-03T15:22:21Z Progesterone up-regulates neuronal brain-derived neurotrophic factor expression in the injured spinal cord González, S.L. Labombarda, F. González Deniselle, M.C. Guennoun, R. Schumacher, M. De Nicola, A.F. Analysis of variance ANOVA BDNF Brain-derived neurotrophic factor Control CTL ILIGV/area Immunohistochemistry In situ hybridization Inverse logarithm of grain intensity per area ISH Neuroprotection Neurotrophins Steroid hormones brain derived neurotrophic factor messenger RNA progesterone animal cell animal experiment animal model animal tissue article cell density controlled study density gene expression gene expression regulation grain immunoreactivity in situ hybridization male motoneuron neuroprotection nonhuman priority journal protein blood level rat spinal cord atrophy spinal cord injury spinal cord lesion spinal cord nerve cell spinal cord ventral horn upregulation Animals Brain-Derived Neurotrophic Factor Disease Models, Animal Immunohistochemistry Male Motor Neurons Nerve Degeneration Neuroprotective Agents Progesterone Rats Rats, Sprague-Dawley RNA, Messenger Spinal Cord Spinal Cord Injuries Up-Regulation Progesterone (PROG) provides neuroprotection to the injured central and peripheral nervous system. These effects may be due to regulation of myelin synthesis in glial cells and also to direct actions on neuronal function. Recent studies point to neurotrophins as possible mediators of hormone action. Here, we show that the expression of brain-derived neurotrophic factor (BDNF) at both the mRNA and protein levels was increased by PROG treatment in ventral horn motoneurons from rats with spinal cord injury (SCI). Semiquantitative in situ hybridization revealed that SCI reduced BDNF mRNA levels by 50% in spinal motoneurons (control: 53.5±7.5 grains/mm2 vs. SCI: 27.5±1.2, P<0.05), while PROG administration to injured rats (4 mg/kg/day during 3 days, s.c.) elicited a three-fold increase in grain density (SCI+PROG: 77.8±8.3 grains/mm2, P<0.001 vs. SCI). In addition, PROG enhanced BDNF immunoreactivity in motoneurons of the lesioned spinal cord. Analysis of the frequency distribution of immunoreactive densities (χ2: 812.73, P<0.0001) showed that 70% of SCI+PROG motoneurons scored as dark stained whereas only 6% of neurons in the SCI group belonged to this density score category (P<0.001). PROG also prevented the lesion-induced chromatolytic degeneration of spinal cord motoneurons as determined by Nissl staining. In the normal intact spinal cord, PROG significantly increased BDNF inmunoreactivity in ventral horn neurons, without changes in mRNA levels. Our findings suggest that PROG enhancement of endogenous neuronal BDNF could provide a trophic environment within the lesioned spinal cord and might be part of the PROG activated-pathways to provide neuroprotection. © 2004 IBRO. Published by Elsevier Ltd. All rights reserved. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_03064522_v125_n3_p605_Gonzalez |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
Analysis of variance ANOVA BDNF Brain-derived neurotrophic factor Control CTL ILIGV/area Immunohistochemistry In situ hybridization Inverse logarithm of grain intensity per area ISH Neuroprotection Neurotrophins Steroid hormones brain derived neurotrophic factor messenger RNA progesterone animal cell animal experiment animal model animal tissue article cell density controlled study density gene expression gene expression regulation grain immunoreactivity in situ hybridization male motoneuron neuroprotection nonhuman priority journal protein blood level rat spinal cord atrophy spinal cord injury spinal cord lesion spinal cord nerve cell spinal cord ventral horn upregulation Animals Brain-Derived Neurotrophic Factor Disease Models, Animal Immunohistochemistry Male Motor Neurons Nerve Degeneration Neuroprotective Agents Progesterone Rats Rats, Sprague-Dawley RNA, Messenger Spinal Cord Spinal Cord Injuries Up-Regulation |
spellingShingle |
Analysis of variance ANOVA BDNF Brain-derived neurotrophic factor Control CTL ILIGV/area Immunohistochemistry In situ hybridization Inverse logarithm of grain intensity per area ISH Neuroprotection Neurotrophins Steroid hormones brain derived neurotrophic factor messenger RNA progesterone animal cell animal experiment animal model animal tissue article cell density controlled study density gene expression gene expression regulation grain immunoreactivity in situ hybridization male motoneuron neuroprotection nonhuman priority journal protein blood level rat spinal cord atrophy spinal cord injury spinal cord lesion spinal cord nerve cell spinal cord ventral horn upregulation Animals Brain-Derived Neurotrophic Factor Disease Models, Animal Immunohistochemistry Male Motor Neurons Nerve Degeneration Neuroprotective Agents Progesterone Rats Rats, Sprague-Dawley RNA, Messenger Spinal Cord Spinal Cord Injuries Up-Regulation González, S.L. Labombarda, F. González Deniselle, M.C. Guennoun, R. Schumacher, M. De Nicola, A.F. Progesterone up-regulates neuronal brain-derived neurotrophic factor expression in the injured spinal cord |
topic_facet |
Analysis of variance ANOVA BDNF Brain-derived neurotrophic factor Control CTL ILIGV/area Immunohistochemistry In situ hybridization Inverse logarithm of grain intensity per area ISH Neuroprotection Neurotrophins Steroid hormones brain derived neurotrophic factor messenger RNA progesterone animal cell animal experiment animal model animal tissue article cell density controlled study density gene expression gene expression regulation grain immunoreactivity in situ hybridization male motoneuron neuroprotection nonhuman priority journal protein blood level rat spinal cord atrophy spinal cord injury spinal cord lesion spinal cord nerve cell spinal cord ventral horn upregulation Animals Brain-Derived Neurotrophic Factor Disease Models, Animal Immunohistochemistry Male Motor Neurons Nerve Degeneration Neuroprotective Agents Progesterone Rats Rats, Sprague-Dawley RNA, Messenger Spinal Cord Spinal Cord Injuries Up-Regulation |
description |
Progesterone (PROG) provides neuroprotection to the injured central and peripheral nervous system. These effects may be due to regulation of myelin synthesis in glial cells and also to direct actions on neuronal function. Recent studies point to neurotrophins as possible mediators of hormone action. Here, we show that the expression of brain-derived neurotrophic factor (BDNF) at both the mRNA and protein levels was increased by PROG treatment in ventral horn motoneurons from rats with spinal cord injury (SCI). Semiquantitative in situ hybridization revealed that SCI reduced BDNF mRNA levels by 50% in spinal motoneurons (control: 53.5±7.5 grains/mm2 vs. SCI: 27.5±1.2, P<0.05), while PROG administration to injured rats (4 mg/kg/day during 3 days, s.c.) elicited a three-fold increase in grain density (SCI+PROG: 77.8±8.3 grains/mm2, P<0.001 vs. SCI). In addition, PROG enhanced BDNF immunoreactivity in motoneurons of the lesioned spinal cord. Analysis of the frequency distribution of immunoreactive densities (χ2: 812.73, P<0.0001) showed that 70% of SCI+PROG motoneurons scored as dark stained whereas only 6% of neurons in the SCI group belonged to this density score category (P<0.001). PROG also prevented the lesion-induced chromatolytic degeneration of spinal cord motoneurons as determined by Nissl staining. In the normal intact spinal cord, PROG significantly increased BDNF inmunoreactivity in ventral horn neurons, without changes in mRNA levels. Our findings suggest that PROG enhancement of endogenous neuronal BDNF could provide a trophic environment within the lesioned spinal cord and might be part of the PROG activated-pathways to provide neuroprotection. © 2004 IBRO. Published by Elsevier Ltd. All rights reserved. |
format |
JOUR |
author |
González, S.L. Labombarda, F. González Deniselle, M.C. Guennoun, R. Schumacher, M. De Nicola, A.F. |
author_facet |
González, S.L. Labombarda, F. González Deniselle, M.C. Guennoun, R. Schumacher, M. De Nicola, A.F. |
author_sort |
González, S.L. |
title |
Progesterone up-regulates neuronal brain-derived neurotrophic factor expression in the injured spinal cord |
title_short |
Progesterone up-regulates neuronal brain-derived neurotrophic factor expression in the injured spinal cord |
title_full |
Progesterone up-regulates neuronal brain-derived neurotrophic factor expression in the injured spinal cord |
title_fullStr |
Progesterone up-regulates neuronal brain-derived neurotrophic factor expression in the injured spinal cord |
title_full_unstemmed |
Progesterone up-regulates neuronal brain-derived neurotrophic factor expression in the injured spinal cord |
title_sort |
progesterone up-regulates neuronal brain-derived neurotrophic factor expression in the injured spinal cord |
url |
http://hdl.handle.net/20.500.12110/paper_03064522_v125_n3_p605_Gonzalez |
work_keys_str_mv |
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