Institute of Molecular Medicine, Department of Neurobiology, University of Southern Denmark, J.B. Winsløws Vej 25, DK-5000 Odense C, Denmark.
BRIDGE-Brain Research Inter-Disciplinary Guided Excellence, Department of Clinical Research, University of Southern Denmark, J.B. Winsløws Vej 19, DK-5000 Odense C, Denmark.
Cells. 2021 Mar 9;10(3):608. doi: 10.3390/cells10030608.
Increasing evidence demonstrates that inflammatory cytokines-such as tumor necrosis factor (TNF)-are produced at low levels in the brain under physiological conditions and may be crucial for synaptic plasticity, neurogenesis, learning and memory. Here, we examined the effects of developmental TNF deletion on spatial learning and memory using 11-13-month-old TNF knockout (KO) and C57BL6/J wild-type (WT) mice. The animals were tested in the Barnes maze (BM) arena under baseline conditions and 48 h following an injection of the endotoxin lipopolysaccharide (LPS), which was administered at a dose of 0.5 mg/kg. Vehicle-treated KO mice were impaired compared to WT mice during the acquisition and memory-probing phases of the BM test. No behavioral differences were observed between WT and TNF-KO mice after LPS treatment. Moreover, there were no differences in the hippocampal content of glutamate and noradrenaline between groups. The effects of TNF deletion on spatial learning and memory were observed in male, but not female mice, which were not different compared to WT mice under baseline conditions. These results indicate that TNF is required for spatial learning and memory in male mice under physiological, non-inflammatory conditions, however not following the administration of LPS. Inflammatory signalling can thereby modulate spatial cognition in male subjects, highlighting the importance of sex- and probably age-stratified analysis when examining the role of TNF in the brain.
越来越多的证据表明，炎症细胞因子（如肿瘤坏死因子（TNF））在生理条件下以低水平在大脑中产生，并且可能对突触可塑性、神经发生、学习和记忆至关重要。在这里，我们使用 11-13 个月大的 TNF 敲除（KO）和 C57BL6/J 野生型（WT）小鼠检查了 TNF 缺失对空间学习和记忆的影响。在基线条件下，将动物在 Barnes 迷宫（BM）竞技场中进行测试，并在注射内毒素脂多糖（LPS）后 48 小时进行测试，LPS 的剂量为 0.5mg/kg。与 WT 小鼠相比，在 BM 测试的获得和记忆探测阶段，接受载体处理的 KO 小鼠受损。在 LPS 处理后，WT 和 TNF-KO 小鼠之间没有观察到行为差异。此外，各组之间海马谷氨酸和去甲肾上腺素含量无差异。在生理、非炎症条件下，TNF 缺失对雄性小鼠的空间学习和记忆有影响，但对 LPS 处理后的雄性小鼠没有影响。这些结果表明，在生理条件下，TNF 在雄性小鼠的空间学习和记忆中是必需的，但在 LPS 给药后则不需要。炎症信号可以调节雄性受试者的空间认知，强调在检查 TNF 在大脑中的作用时，需要进行性别分层分析，可能还需要进行年龄分层分析。
