Journal
BRAIN BEHAVIOR AND IMMUNITY
Volume 78, Issue -, Pages 177-187Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2019.01.019
Keywords
Galectin-3 deficiency; Neuroinflammation; Cytokines; Toll-like receptor-4; Brain-derived neurotrophic factor; GABA-A receptor; Anxiety; Hippocampus; Mice
Categories
Funding
- Serbian Ministry of Science and Technological Development (Belgrade, Serbia) [175071, 175069]
- Swiss Science Foundation [IZ73Z0_152407]
- Faculty of Medical Sciences, University of Kragujevac, Serbia [JP 01/13, JP 07/17]
- Swiss National Science Foundation (SNF) [IZ73Z0_152407] Funding Source: Swiss National Science Foundation (SNF)
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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-alpha (TNF-alpha) 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-alpha 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-alpha and hippocampal BDNF.
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