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Brain-derived neurotrophic factor of the cerebral microvasculature: a forgotten and nitric oxide-dependent contributor of brain-derived neurotrophic factor in the brain
- Source :
- Acta Physiologica, Acta Physiologica, Wiley, 2016, 〈http://onlinelibrary.wiley.com/doi/10.1111/apha.12743/full〉. 〈10.1111/apha.12743〉, Acta Physiologica, Wiley, 2017, 219 (4), pp.790-802. ⟨10.1111/apha.12743⟩
- Publication Year :
- 2016
- Publisher :
- HAL CCSD, 2016.
-
Abstract
- International audience; AIM: Evidence that brain-derived neurotrophic factor (BDNF), a neurotrophin largely involved in cognition, is expressed by cerebral endothelial cells led us to explore in rats the contribution of the cerebral microvasculature to BDNF found in brain tissue and the link between cerebrovascular nitric oxide (NO) and BDNF production.METHODS: Brain BDNF protein levels were measured before and after in situ removal of the cerebral endothelium that was achieved by brain perfusion with a 0.2% CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propane sulphonate) solution. BDNF protein and mRNA levels as well as levels of endothelial NO synthase phosphorylated at serine 1177 (P-eNOSser1177 ) were measured in cerebral microvessel-enriched fractions. These fractions were also exposed to glycerol trinitrate. Hypertension (spontaneously hypertensive rats) and physical exercise training were used as experimental approaches to modulate cerebrovascular endothelial NO production.RESULTS: CHAPS perfusion resulted in a marked decrease in brain BDNF levels. Hypertension decreased and exercise increased P-eNOSser1177 and BDNF protein levels. However, BDNF mRNA levels that were increased by exercise did not change after hypertension. Finally, in vitro exposure of cerebral microvessel-enriched fractions to glycerol trinitrate enhanced BDNF production.CONCLUSION: These data reveal that BDNF levels measured in brain homogenates correspond for a large part to BDNF present in cerebral endothelial cells and that cerebrovascular BDNF production is dependent on cerebrovascular endothelial eNOS activity. They provide a paradigm shift in the cellular source of brain BDNF and suggest a new approach to improve our understanding of the link between endothelial function and cognition.
- Subjects :
- medicine.medical_specialty
hypertension
Physiology
Blotting, Western
Physical exercise
030204 cardiovascular system & hematology
Nitric Oxide
Polymerase Chain Reaction
Nitric oxide
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Chaps
Enos
Neurotrophic factors
Internal medicine
Rats, Inbred SHR
medicine
Animals
Rats, Wistar
Brain-derived neurotrophic factor
cerebral endothelium
biology
exercise
business.industry
brain-derived neurotrophic factor
Brain
Endothelial Cells
biology.organism_classification
Immunohistochemistry
Rats
Endocrinology
chemistry
nervous system
[ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Microvessels
biology.protein
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
business
Neuroscience
Perfusion
030217 neurology & neurosurgery
Neurotrophin
Subjects
Details
- Language :
- English
- ISSN :
- 17481708 and 17481716
- Database :
- OpenAIRE
- Journal :
- Acta Physiologica, Acta Physiologica, Wiley, 2016, 〈http://onlinelibrary.wiley.com/doi/10.1111/apha.12743/full〉. 〈10.1111/apha.12743〉, Acta Physiologica, Wiley, 2017, 219 (4), pp.790-802. ⟨10.1111/apha.12743⟩
- Accession number :
- edsair.doi.dedup.....1fedff8a631604e0e2cf0e8f16ff773f