PMID- 29375397
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 8
DP  - 2017
TI  - The Cerebral Brain-Derived Neurotrophic Factor Pathway, Either Neuronal or 
      Endothelial, Is Impaired in Rats with Adjuvant-Induced Arthritis. Connection with 
      Endothelial Dysfunction.
PG  - 1125
LID - 10.3389/fphys.2017.01125 [doi]
LID - 1125
AB  - Cognitive abilities are largely dependent on activation of cerebral 
      tropomyosin-related kinase B receptors (TrkB) by brain-derived neurotrophic 
      factor (BDNF) that is secreted under a bioactive form by both neurons and 
      endothelial cells. In addition, there is mounting evidence for a link between 
      endothelial function and cognition even though the underlying mechanisms are not 
      well known. Therefore, we investigated the cerebral BDNF pathway, either neuronal 
      or endothelial, in rheumatoid arthritis (RA) that combines both endothelial 
      dysfunction (ED) and impaired cognition. Adjuvant-induced arthritis (AIA) in rats 
      was used as a model of RA. Clinical inflammatory symptoms were evaluated from an 
      arthritis score and brains were collected at day 31 +/- 2 post-immunization. 
      Neuronal expression of BDNF and TrkB phosphorylated at tyrosine 816 (p-TrkB) was 
      examined in brain slices. Endothelial BDNF and p-TrkB expression was examined on 
      both brain slices (hippocampal arterioles) and isolated cerebral 
      microvessels-enriched fractions (vessels downstream to arterioles). The 
      connection between endothelial nitric oxide (NO) and BDNF production was explored 
      on the cerebrovascular fractions using endothelial NO synthase (eNOS) levels as a 
      marker of NO production, N(omega)-Nitro-L-arginine methyl ester hydrochloride 
      (L-NAME) as a NOS inhibitor and glyceryl-trinitrate as a slow releasing NO donor. 
      Brain slices displayed lower BDNF and p-TrkB staining in both neurons and 
      arteriolar endothelial cells in AIA than in control rats. For endothelial cells 
      but not neurons, a strong correlation was observed between BDNF and p-TrkB 
      staining. Of note, a strong correlation was also observed between neuronal p-TrkB 
      and endothelial BDNF staining. In cerebral microvessels-enriched fractions, AIA 
      led to decreased BDNF and eNOS levels with a positive association between the 2 
      parameters. These effects coincided with decreased BDNF and p-TrkB staining in 
      endothelial cells. The exposure of AIA cerebrovascular fractions to GTN increased 
      BDNF levels while the exposure of control fractions to L-NAME decreased BDNF 
      levels. Changes in the cerebral BDNF pathway were not associated with arthritis 
      score. The present study reveals that AIA impairs the endothelial and neuronal 
      BDNF/TrkB pathway, irrespective of the severity of inflammatory symptoms but 
      dependent on endothelial NO production. These results open new perspectives for 
      the understanding of the link between ED and impaired cognition.
FAU - Pedard, Martin
AU  - Pedard M
AD  - INSERM UMR1093-CAPS, Universite Bourgogne Franche-Comte, UFR des Sciences de 
      Sante, Dijon, France.
AD  - Service de Neurologie, CHRU Dijon, Dijon, France.
FAU - Quirie, Aurore
AU  - Quirie A
AD  - INSERM UMR1093-CAPS, Universite Bourgogne Franche-Comte, UFR des Sciences de 
      Sante, Dijon, France.
FAU - Garnier, Philippe
AU  - Garnier P
AD  - INSERM UMR1093-CAPS, Universite Bourgogne Franche-Comte, UFR des Sciences de 
      Sante, Dijon, France.
FAU - Tessier, Anne
AU  - Tessier A
AD  - INSERM UMR1093-CAPS, Universite Bourgogne Franche-Comte, UFR des Sciences de 
      Sante, Dijon, France.
FAU - Demougeot, Celine
AU  - Demougeot C
AD  - EA4267 PEPITE, FHU INCREASE, University of Bourgogne Franche-Comte, Besancon, 
      France.
FAU - Marie, Christine
AU  - Marie C
AD  - INSERM UMR1093-CAPS, Universite Bourgogne Franche-Comte, UFR des Sciences de 
      Sante, Dijon, France.
LA  - eng
PT  - Journal Article
DEP - 20180109
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC5767301
OTO - NOTNLM
OT  - BDNF
OT  - NO
OT  - TrkB
OT  - cognition
OT  - endothelium
EDAT- 2018/01/30 06:00
MHDA- 2018/01/30 06:01
PMCR- 2018/01/09
CRDT- 2018/01/30 06:00
PHST- 2017/10/26 00:00 [received]
PHST- 2017/12/20 00:00 [accepted]
PHST- 2018/01/30 06:00 [entrez]
PHST- 2018/01/30 06:00 [pubmed]
PHST- 2018/01/30 06:01 [medline]
PHST- 2018/01/09 00:00 [pmc-release]
AID - 10.3389/fphys.2017.01125 [doi]
PST - epublish
SO  - Front Physiol. 2018 Jan 9;8:1125. doi: 10.3389/fphys.2017.01125. eCollection 
      2017.