INSERM U1093, Univ. Bourgogne Franche-Comté, F-21000 Dijon, France; Service de Neurologie, CHRU, Dijon, France.
EA4267 PEPITE, FHU INCREASE, Univ. Bourgogne Franche-Comté, F-25030 Besançon, France.
Prog Neuropsychopharmacol Biol Psychiatry. 2018 Mar 2;82:249-254. doi: 10.1016/j.pnpbp.2017.11.006. Epub 2017 Nov 7.
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.
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.
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.
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.
外周和中枢脑源性神经营养因子（BDNF）水平在抑郁症中降低，并通过有效的抗抑郁治疗得到正常化。虽然在类风湿关节炎中经常出现抑郁症状，但 BDNF 在该病理中的研究甚少。因此，本研究探讨了关节炎大鼠的脑和外周 BDNF 以及脑 BDNF 与最近参与抑郁症发病机制且存在于类风湿关节炎中的两个因素（炎症和内皮功能障碍）之间的联系。
在炎症症状和内皮功能障碍充分发展时，收集接受佐剂诱导关节炎（AIA）的大鼠的大脑（海马体和前额皮质）和血液（血清）。通过偏爱蔗糖溶液来评估作为抑郁症状核心症状的快感缺失。通过关节炎评分以及血清 TNFα 和 IL-1β 水平来评估炎症。使用精氨酸酶抑制剂 N（w）-羟基-nor-l-精氨酸（nor-NOHA）作为一种预防内皮功能障碍而不改善炎症症状的策略。
与对照组相比，AIA 大鼠的脑 BDNF 水平降低，同时伴有快感缺失，但血清 BDNF 水平升高。脑 BDNF 缺乏既与关节炎评分无关，也与促炎细胞因子水平无关，但 nor-NOHA 治疗可减轻其缺乏。血清 BDNF 与 TNFα 水平呈正相关。
本研究表明关节炎降低了大脑中的 BDNF 水平，而内皮功能障碍而不是炎症导致了 BDNF 水平的降低。它还确定了关节炎中血清和脑 BDNF 水平之间的脱节。
