慢性肾病的血脑屏障通透性：与大鼠炎症、认知和情绪障碍有关

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research Pub Date : 2025-06-11 DOI:10.1016/j.bbr.2025.115693

Mickaël Bobot , Amandine Bruyat , Laurent Thomas , Samantha Fernandez , Alexandre Brodovitch , José Boucraut , Stéphane Burtey , Vincent Nail , Benjamin Guillet , Guillaume Hache

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引用次数: 0

摘要

慢性肾脏疾病（CKD）与认知障碍有关。CKD与血脑屏障（BBB）通透性增加有关，导致动物和人类认知障碍增加。本研究的目的是描述富腺嘌呤饮食（ARD）诱导的大鼠CKD模型中血液和脑脊液（CSF）中的炎症谱，与血脑屏障通透性的关系，并探讨认知和情绪障碍表型。脑99 mTc-DTPA SPECT/CT同位素成像显示，ARD大鼠血脑屏障通透性增加5倍，脑灌注无改变。CKD与脑脊液PDGFRß水平升高相关（445 ± 85.6 vs. 303 ± 104.9 pg/mL, p = 0.03），提示周细胞功能障碍，但与脑脊液炎症因子水平无关，尽管全身炎症增加。神经行为学评价结果显示，ARD大鼠存在短期空间记忆、社会记忆和抑郁特征的损害，但不存在焦虑。总之，CKD诱导全身炎症和血脑屏障通透性与大鼠周细胞功能障碍、记忆和抑郁特征的改变有关。血脑屏障破坏似乎是CKD期间认知和情绪损害的关键机制。

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Blood-brain barrier permeability in CKD: Link with inflammation and cognitive and mood impairment in rats

Chronic kidney disease (CKD) is associated with cognitive impairment. CKD is associated with increased permeability of the blood-brain barrier (BBB), resulting in increased cognitive impairment in animals and in humans. The aim of this study is to describe the inflammatory profile in blood and cerebro-spinal fluid (CSF) during a CKD model induced by adenine rich diet (ARD) in rats, in relation to BBB permeability and to explore the cognitive and mood impairment phenotypes. ARD rats displayed a 5-fold increase in BBB permeability, quantified with brain ^99 mTc-DTPA SPECT/CT isotopic imaging, without alteration of brain perfusion. CKD is associated with increased PDGFRß levels in CSF (445 ± 85.6 vs. 303 ± 104.9 pg/mL, p = 0.03), suggesting pericyte dysfunction, but not with CSF levels of inflammatory cytokines, despite increased systemic inflammation. Neurobehavioural evaluation highlighted that ARD rats had impairment of short-term spatial memory, social memory and depressive features but not anxiety. In conclusion, CKD induces systemic inflammation and BBB permeability associated with pericyte dysfunction and alteration of memory and depressive features in rats. BBB disruption seems to be a crucial mechanism involved in cognitive and mood impairment during CKD.

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来源期刊

Behavioural Brain Research 医学-行为科学

CiteScore

5.60

自引率

0.00%

发文量

383

审稿时长

61 days

期刊介绍： Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.