Neuroprotective dobutamine treatment upregulates superoxide dismutase 3, anti-oxidant and survival genes and attenuates genes mediating inflammation
(2018) In BMC Neuroscience 19(1).- Abstract
Background: Labor subjects the fetus to an hypoxic episode and concomitant adrenomodullary catecholamine surge that may provide protection against the hypoxic insult. The beta1-adrenergic agonist dobutamine protects against hypoxia/aglycemia induced neuronal damage. We aimed to identify the associated protective biological processes involved. Results: Hippocampal slices from 6 days old mice showed significant changes of gene expression comparing slices with or without dobutamine (50 mM) in the following two experimental paradigms: (1) control conditions versus lipopolysacharide (LPS) stimulation and (2) oxygen-glucose deprivation (OGD), versus combined LPS/OGD. Dobutamine depressed the inflammatory response by modifying the toll-like... (More)
Background: Labor subjects the fetus to an hypoxic episode and concomitant adrenomodullary catecholamine surge that may provide protection against the hypoxic insult. The beta1-adrenergic agonist dobutamine protects against hypoxia/aglycemia induced neuronal damage. We aimed to identify the associated protective biological processes involved. Results: Hippocampal slices from 6 days old mice showed significant changes of gene expression comparing slices with or without dobutamine (50 mM) in the following two experimental paradigms: (1) control conditions versus lipopolysacharide (LPS) stimulation and (2) oxygen-glucose deprivation (OGD), versus combined LPS/OGD. Dobutamine depressed the inflammatory response by modifying the toll-like receptor-4 signalling pathways, including interferon regulatory factors and nuclear factor Κ B activation in experimental paradigm 1. The anti-oxidant defense genes superoxide dismutase 3 showed an upregulation in the OGD paradigm while thioredoxin reductase was upregulated in LPS paradigm. The survival genes Bag-3, Tinf2, and TMBIM-1, were up-regulated in paradigm 1. Moreover, increased levels of SOD3 were verified on the protein level 24 h after OGD and control stimulation in cultures with or without preconditioning with LPS and dobutamine, respectively. Conclusions: Neuroprotective treatment with dobutamine depresses expression of inflammatory mediators and promotes the defense against oxidative stress and depresses apoptotic genes in a model of neonatal brain hypoxia/ischemia interpreted as pharmacological preconditioning. We conclude that beta1-adrenoceptor activation might be an efficient strategy for identifying novel pharmacological targets for protection of the neonatal brain.
(Less)
- author
- Markus, Tina LU ; Ley, David LU ; Hansson, Stefan R. LU ; Wieloch, Tadeusz LU and Ruscher, Karsten LU
- organization
- publishing date
- 2018-03-09
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Dobutamine, Gene array, Hippocampal slice cultures, Hypoxia, Lipopolysaccharide, Preconditioning, Superoxide dismutase 3
- in
- BMC Neuroscience
- volume
- 19
- issue
- 1
- article number
- 9
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:29523072
- scopus:85043449352
- ISSN
- 1471-2202
- DOI
- 10.1186/s12868-018-0415-2
- language
- English
- LU publication?
- yes
- id
- a9f254ac-45a8-4273-b0bd-b626337621c2
- date added to LUP
- 2018-03-20 07:56:13
- date last changed
- 2024-06-24 11:42:14
@article{a9f254ac-45a8-4273-b0bd-b626337621c2, abstract = {{<p>Background: Labor subjects the fetus to an hypoxic episode and concomitant adrenomodullary catecholamine surge that may provide protection against the hypoxic insult. The beta1-adrenergic agonist dobutamine protects against hypoxia/aglycemia induced neuronal damage. We aimed to identify the associated protective biological processes involved. Results: Hippocampal slices from 6 days old mice showed significant changes of gene expression comparing slices with or without dobutamine (50 mM) in the following two experimental paradigms: (1) control conditions versus lipopolysacharide (LPS) stimulation and (2) oxygen-glucose deprivation (OGD), versus combined LPS/OGD. Dobutamine depressed the inflammatory response by modifying the toll-like receptor-4 signalling pathways, including interferon regulatory factors and nuclear factor Κ B activation in experimental paradigm 1. The anti-oxidant defense genes superoxide dismutase 3 showed an upregulation in the OGD paradigm while thioredoxin reductase was upregulated in LPS paradigm. The survival genes Bag-3, Tinf2, and TMBIM-1, were up-regulated in paradigm 1. Moreover, increased levels of SOD3 were verified on the protein level 24 h after OGD and control stimulation in cultures with or without preconditioning with LPS and dobutamine, respectively. Conclusions: Neuroprotective treatment with dobutamine depresses expression of inflammatory mediators and promotes the defense against oxidative stress and depresses apoptotic genes in a model of neonatal brain hypoxia/ischemia interpreted as pharmacological preconditioning. We conclude that beta1-adrenoceptor activation might be an efficient strategy for identifying novel pharmacological targets for protection of the neonatal brain.</p>}}, author = {{Markus, Tina and Ley, David and Hansson, Stefan R. and Wieloch, Tadeusz and Ruscher, Karsten}}, issn = {{1471-2202}}, keywords = {{Dobutamine; Gene array; Hippocampal slice cultures; Hypoxia; Lipopolysaccharide; Preconditioning; Superoxide dismutase 3}}, language = {{eng}}, month = {{03}}, number = {{1}}, publisher = {{BioMed Central (BMC)}}, series = {{BMC Neuroscience}}, title = {{Neuroprotective dobutamine treatment upregulates superoxide dismutase 3, anti-oxidant and survival genes and attenuates genes mediating inflammation}}, url = {{http://dx.doi.org/10.1186/s12868-018-0415-2}}, doi = {{10.1186/s12868-018-0415-2}}, volume = {{19}}, year = {{2018}}, }