Department of Hygiene and Ecology, Faculty of Medical Sciences, University of Kragujevac, Serbia; Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Serbia.
Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Serbia.
Brain Behav Immun. 2019 May;78:177-187. doi: 10.1016/j.bbi.2019.01.019. Epub 2019 Jan 23.
Galectin-3 (Gal-3), a member of lectin family that binds to oligosaccharides, is involved in several biological processes, including maturation and function of nervous system. It had been reported that Gal-3 regulates oligodendrocytes differentiation and that Gal-3/Toll-like receptor-4 (TLR4) axis is involved in neuroinflammation. As both, central nervous system (CNS) maturation and neuroinflammation may affect behavior, the principle aim of this study was to examine the effects of Gal-3 gene deletion on behavior. Here we provide the evidence that Gal-3 deficiency shows clear anxiogenic effect in mature untreated animals (basal conditions). This was accompanied with lower interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) relative gene expression and hippocampal content, with no effect on TLR4 expression. Gal-3 deficiency was also accompanied with lower brain-derived neurotrophic factor (BDNF) relative gene expression and immunoreactivity in hippocampus (predominantly in CA1 region). Besides, the Gal-3 gene deletion resulted in attenuation of the hippocampal relative gene expression of GABA-A receptor subunits 2 and 5 (GABA-AR2S and GABA-AR5S), On the other hand, Gal-3 deficiency attenuates LPS-induced neuroinflammation. The anxiogenic effect of acute neuroinflammation was accompanied with increased hippocampal IL-6, TNF-α and TLR4 gene expression, as well as decreased gene and immunohistochemical BDNF expression in hippocampus, with significant decline in GABA-AR2S in wild type (WT) mice in comparison to basal conditions. Gal-3 gene deletion prevented the increase in IL-6, the decline in BDNF gene expression and immunoreactivity, and reduction in hippocampal GABA-AR2S, and therefore attenuated the anxiogenic effect of neuroinflammation. In summary, our data demonstrate that apparently opposite effects of Gal-3 deficiency on anxiety levels (anxiogenic effect under basal conditions and anxiolytic action during neuroinflammation) seem to be related to the shift in IL-6, TNF-α and hippocampal BDNF.
半乳糖凝集素-3（Gal-3）是凝集素家族的成员，可与寡糖结合，参与多种生物学过程，包括神经系统的成熟和功能。据报道，Gal-3 调节少突胶质细胞分化，Gal-3/Toll 样受体-4（TLR4）轴参与神经炎症。由于中枢神经系统（CNS）成熟和神经炎症都可能影响行为，本研究的主要目的是研究 Gal-3 基因缺失对行为的影响。本研究提供的证据表明，Gal-3 缺乏症在成熟的未处理动物（基础条件）中表现出明显的焦虑症效应。这伴随着白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）相对基因表达和海马含量降低，但对 TLR4 表达没有影响。Gal-3 缺乏症还伴随着海马（主要在 CA1 区）中脑源性神经营养因子（BDNF）相对基因表达和免疫反应性降低。此外，Gal-3 基因缺失导致 GABA-A 受体亚基 2 和 5（GABA-AR2S 和 GABA-AR5S）的海马相对基因表达减弱。另一方面，Gal-3 缺乏症可减轻 LPS 诱导的神经炎症。急性神经炎症的焦虑症效应伴随着海马 IL-6、TNF-α 和 TLR4 基因表达增加，以及海马 BDNF 基因和免疫组织化学表达降低，与基础条件相比，野生型（WT）小鼠的 GABA-AR2S 显著下降。Gal-3 基因缺失可防止 IL-6 增加、BDNF 基因表达和免疫反应性降低，以及减少海马 GABA-AR2S，从而减轻神经炎症的焦虑症效应。总之，我们的数据表明，Gal-3 缺乏症对焦虑水平的明显相反影响（基础条件下的焦虑症效应和神经炎症期间的抗焦虑作用）似乎与 IL-6、TNF-α 和海马 BDNF 的变化有关。
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