Brain-derived neurotrophic factor in adjuvant-induced arthritis in rats. Relationship with inflammation and endothelial dysfunction

作者：Pedard Martin; Demougeot Celine; Prati Clement; Marie Christine^*

来源：Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2018, 82: 249-254.

DOI：10.1016/j.pnpbp.2017.11.006

• Adjuvant-induced arthritis
• Rheumatoid arthritis - depression
• Brain-derived neurotrophic factor - endothelial dysfunction

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 TNF alpha and IL-1 beta. 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 TNF alpha 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.

• 出版日期2018-3-2