Martin Pedard1, Céline Demougeot2, Clément Prati3, Christine Marie4. 1. INSERM U1093, Univ. Bourgogne Franche-Comté, F-21000 Dijon, France; Service de Neurologie, CHRU, Dijon, France. 2. EA4267 PEPITE, FHU INCREASE, Univ. Bourgogne Franche-Comté, F-25030 Besançon, France. 3. EA4267 PEPITE, FHU INCREASE, Univ. Bourgogne Franche-Comté, F-25030 Besançon, France; Service de Rhumatologie, CHRU, Besançon, France. 4. INSERM U1093, Univ. Bourgogne Franche-Comté, F-21000 Dijon, France. Electronic address: chmarie@u-bourgogne.fr.
Abstract
OBJECTIVES: Both peripheral and central brain-derived neurotrophic factor (BDNF) levels are decreased in depression and normalized by efficient anti-depressive therapies. While depression symptoms are frequent in rheumatoid arthritis, BDNF has been poorly investigated in this pathology. Therefore, the present study explored cerebral and peripheral BDNF in arthritis rats as well as the link between brain BDNF and the two factors recently involved in the pathogenesis of depression and present in rheumatoid arthritis namely inflammation and endothelial dysfunction. METHODS: The brain (hippocampus and frontal cortex) and blood (serum) were collected in rats subjected to adjuvant-induced arthritis (AIA) when inflammatory symptoms and endothelial dysfunction are fully developed. Anhedonia as a core symptom of depression symptom was assessed from preference for a saccharin drinking solution. Inflammation was assessed from the arthritis score and serum levels of TNFα and IL-1β. Treatment with the arginase inhibitor N(w)-hydroxy-nor-l-arginine (nor-NOHA) was used as a strategy to prevent endothelial dysfunction without improving inflammatory symptoms. RESULTS: As compared to controls, AIA rats displayed decreased brain BDNF levels that coexisted with anhedonia but contrasted with increased BDNF levels in serum. Brain BDNF deficiency correlated neither with arthritis score nor with pro-inflammatory cytokines levels, while it was mitigated by nor-NOHA treatment. A positive correlation was observed between serum BDNF and TNFα levels. CONCLUSIONS: Our study reveals that arthritis decreases BDNF levels in the brain and that endothelial dysfunction rather than inflammation contributes to the decrease. It also identifies a disconnection between serum and brain BDNF levels in arthritis.
OBJECTIVES: Both peripheral and central brain-derived neurotrophic factor (BDNF) levels are decreased in depression and normalized by efficient anti-depressive therapies. While depression symptoms are frequent in rheumatoid arthritis, BDNF has been poorly investigated in this pathology. Therefore, the present study explored cerebral and peripheral BDNF in arthritisrats as well as the link between brain BDNF and the two factors recently involved in the pathogenesis of depression and present in rheumatoid arthritis namely inflammation and endothelial dysfunction. METHODS: The brain (hippocampus and frontal cortex) and blood (serum) were collected in rats subjected to adjuvant-induced arthritis (AIA) when inflammatory symptoms and endothelial dysfunction are fully developed. Anhedonia as a core symptom of depression symptom was assessed from preference for a saccharin drinking solution. Inflammation was assessed from the arthritis score and serum levels of TNFα and IL-1β. Treatment with the arginase inhibitor N(w)-hydroxy-nor-l-arginine (nor-NOHA) was used as a strategy to prevent endothelial dysfunction without improving inflammatory symptoms. RESULTS: As compared to controls, AIA rats displayed decreased brain BDNF levels that coexisted with anhedonia but contrasted with increased BDNF levels in serum. Brain BDNF deficiency correlated neither with arthritis score nor with pro-inflammatory cytokines levels, while it was mitigated by nor-NOHA treatment. A positive correlation was observed between serum BDNF and TNFα levels. CONCLUSIONS: Our study reveals that arthritis decreasesBDNF levels in the brain and that endothelial dysfunction rather than inflammation contributes to the decrease. It also identifies a disconnection between serum and brain BDNF levels in arthritis.
Authors: Martin Pedard; Aurore Quirié; Philippe Garnier; Anne Tessier; Céline Demougeot; Christine Marie Journal: Front Physiol Date: 2018-01-09 Impact factor: 4.566