Abstract

Pathways by which inflammatory stimuli influence behaviors can involve changes in neuronal plasticity, however, the evidence for this is still insufficient. This study aimed to evaluate the effects of chronic lipopolysaccharide (LPS) injected alone or together with tetracycline antibiotic doxycycline (Dox) on the levels of Iba-1, BDNF, Bcl-xL and MMP-9 in brain regions in relation to stress-induced behaviors in the elevated plus-maze (EPM). LPS injected to adult rats every 2 days for a total of 7 injections reduced body weight gain, increased spleen and adrenal weights, decreased locomotor activity, and increased anxiety-like behavior. These effects were associated with increased expression of Iba-1, a well-known marker for activated microglia, in most brain regions investigated. Co-treatment of LPS with Dox attenuated LPS-induced microglial activation and behavioral changes, supporting their relation to the neuroinflammation. LPS administration also produced pro-apoptotic changes in the brain. In the hypothalamus and striatum, the levels of anti-apoptotic protein Bcl-xL were decreased, whereas in the amygdala, a significant increase in MMP-9 protein levels was observed. The levels of Iba-1 as well as MMP-9 in the amygdala positively correlated with the numbers of defecation. The data suggest that mechanisms of anxiety associated with neuroinflammation may involve the increase in MMP-9 levels in the amygdala.

摘要

炎性刺激影响行为的途径可能涉及神经元可塑性的变化，但是，其证据仍然不足。这项研究旨在评估单独或与四环素类抗生素多西环素（Dox）一起注射的慢性脂多糖（LPS）对与应激诱导有关的大脑区域Iba-1，BDNF，Bcl-xL和MMP-9水平的影响高迷宫（EPM）中的行为。每2天向成年大鼠注射LPS，共7次注射减少了体重增加，增加了脾脏和肾上腺的重量，降低了运动能力，并增加了类似焦虑的行为。这些影响与在研究的大多数大脑区域中活化小胶质细胞的众所周知的标志物Iba-1的表达增加有关。与Dox共同治疗LPS会减弱LPS诱导的小胶质细胞激活和行为改变，支持它们与神经炎症的关系。LPS给药还可以在大脑中产生促凋亡变化。在下丘脑和纹状体中，抗凋亡蛋白Bcl-xL的水平降低，而在杏仁核中，观察到MMP-9蛋白水平显着增加。杏仁核中Iba-1和MMP-9的水平与排便次数呈正相关。数据表明与神经炎症相关的焦虑机制可能涉及杏仁核中MMP-9水平的升高。抗凋亡蛋白Bcl-xL的水平降低，而在杏仁核中，观察到MMP-9蛋白水平显着增加。杏仁核中Iba-1和MMP-9的水平与排便次数呈正相关。数据表明与神经炎症相关的焦虑机制可能涉及杏仁核中MMP-9水平的升高。抗凋亡蛋白Bcl-xL的水平降低，而在杏仁核中，观察到MMP-9蛋白水平显着增加。杏仁核中Iba-1和MMP-9的水平与排便次数呈正相关。数据表明与神经炎症相关的焦虑机制可能涉及杏仁核中MMP-9水平的升高。