Ghosh Nabanita, Mitra Soham, Sinha Priyobrata, Chakrabarti Nilkanta, Bhattacharyya Arindam
Immunology Lab, Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, 700019, India.
Department of Physiology, University of Calcutta, 92, Acharya Prafulla Chandra Road, Kolkata, 700009, India.
Neurosci Res. 2018 Dec;137:36-42. doi: 10.1016/j.neures.2018.02.007. Epub 2018 Feb 23.
1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) -induced neuroinflammation and its impact in hippocampus remain elusive till date. Our present study includes the time dependent changes of inflammatory molecules in mouse hippocampus during MPTP treatment. MPTP treatment increased level of TNF-α, enhanced expression of TNFR2 along with PI3 kinase (PI3K) induced phosphorylation of Akt resulting in persistent nuclear factor-κB (NF-κB) activation. The expressions gradually increased from Day1 post-MPTP treatment, maximally at Day3 post-treatment. MPTP induced translocation of p65 and p52, two subunits of NF-κB family, to nucleus where they had been found to dimerize. Therefore, MPTP induced TNF-α signaling through TNFR2 mediated pathway and recruited p65-p52 dimer in hippocampal nucleus which is reported to have protective effect on hippocampal neurons indicated by unchanged neuronal count in hippocampus in treated groups with respect to control. Our finding suggests that this unique NF-κB dimer plays some role in providing inherent protection to hippocampus during MPTP-treatment.
1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的神经炎症及其对海马体的影响至今仍不清楚。我们目前的研究包括MPTP治疗期间小鼠海马体中炎症分子的时间依赖性变化。MPTP治疗增加了肿瘤坏死因子-α（TNF-α）的水平，增强了肿瘤坏死因子受体2（TNFR2）的表达，同时磷脂酰肌醇-3激酶（PI3K）诱导的蛋白激酶B（Akt）磷酸化导致核因子-κB（NF-κB）持续激活。这些表达在MPTP治疗后第1天开始逐渐增加，在治疗后第3天达到最大值。MPTP诱导NF-κB家族的两个亚基p65和p52易位至细胞核，在细胞核中它们被发现会二聚化。因此，MPTP通过TNFR2介导的途径诱导TNF-α信号传导，并在海马体细胞核中募集p65-p52二聚体，据报道该二聚体对海马体神经元具有保护作用，这在治疗组海马体中的神经元数量相对于对照组未发生变化中得到体现。我们的研究结果表明，这种独特的NF-κB二聚体在MPTP治疗期间为海马体提供内在保护方面发挥了一定作用。
