An early glycolysis burst in microglia regulates mitochondrial dysfunction in oligodendrocytes under neuroinflammation.
An early glycolysis burst in microglia regulates mitochondrial dysfunction in oligodendrocytes under neuroinflammation.
复制标题
DOI：
10.1016/j.isci.2023.107921
复制
发表时间：
2023-10-20
期刊：
影响因子：
5.8
通讯作者：
Giri, Shailendra
中科院分区：
文献类型：
--
作者：
Suhail, Hamid;Nematullah, Mohammad;Rashid, Faraz;Sajad, Mir;Fatma, Mena;Singh, Jaspreet;Zahoor, Insha;Cheung, Wing Lee;Tiwari, Nivedita;Ayasolla, Kameshwar;Kumar, Ashok;Hoda, Nasrul;Rattan, Ramandeep;Giri, Shailendra
在神经炎症疾病中，代谢和能量过程控制少突胶质细胞的功能是非常有趣的。然而，不同的细胞环境如何影响神经炎症期间少突胶质细胞的活性尚不清楚。我们证明激活的小胶质细胞能量代谢控制少突胶质细胞线粒体呼吸和活动。脂多糖/干扰素γ促进大鼠脑胶质细胞糖酵解，减少线粒体呼吸和髓磷脂蛋白合成。富集的小胶质细胞糖酵解早期破裂。在小胶质细胞条件培养基中，少突胶质细胞不呼吸，髓磷脂表达减少。SCENITH揭示了内毒素血症和实验性自身免疫性脑源性模型中小胶质细胞和o4阳性少突胶质细胞的代谢紊乱。小胶质细胞糖酵解的早期爆发是由PDPK1和蛋白激酶B/AKT信号介导的。我们发现小胶质细胞产生的一氧化氮和衣康酸（一种三羧酸分叉代谢物）可减少少突胶质细胞的线粒体呼吸。在炎症期间，我们在小胶质细胞中发现了一种信号通路，可以作为恢复少突胶质细胞线粒体功能和诱导髓鞘再生的治疗靶点。炎症诱导的小胶质细胞和少突胶质细胞代谢失调PDPK1-AKT信号通路促进激活的小胶质细胞早期糖酵解爆发，靶向小胶质细胞早期糖酵解恢复少突胶质细胞呼吸。细胞神经科学;免疫反应
Metabolism and energy processes governing oligodendrocyte function during neuroinflammatory disease are of great interest. However, how varied cellular environments affect oligodendrocyte activity during neuroinflammation is unknown. We demonstrate that activated microglial energy metabolism controls oligodendrocyte mitochondrial respiration and activity. Lipopolysaccharide/interferon gamma promote glycolysis and decrease mitochondrial respiration and myelin protein synthesis in rat brain glial cells. Enriched microglia showed an early burst in glycolysis. In microglia-conditioned medium, oligodendrocytes did not respire and expressed less myelin. SCENITH revealed metabolic derangement in microglia and O4-positive oligodendrocytes in endotoxemia and experimental autoimmune encephalitogenic models. The early burst of glycolysis in microglia was mediated by PDPK1 and protein kinase B/AKT signaling. We found that microglia-produced NO and itaconate, a tricarboxylic acid bifurcated metabolite, reduced mitochondrial respiration in oligodendrocytes. During inflammation, we discovered a signaling pathway in microglia that could be used as a therapeutic target to restore mitochondrial function in oligodendrocytes and induce remyelination. Inflammation induced metabolic dysregulation in microglia and oligodendrocytes PDPK1-AKT signaling facilitated the early burst of glycolysis in activated microglia Targeting early glycolysis in microglia restored respiration in oligodendrocyte Microglia-produced NO and itaconate, caused respiration failure in oligodendrocyte Neuroscience; Cellular neuroscience; Immune response
登录
查看更多内容
影响因子：
4.6
作者：
Dar S;Chhina J;Mert I;Chitale D;Buekers T;Kaur H;Giri S;Munkarah A;Rattan R
通讯作者：
Rattan R
影响因子：
6.1
作者：
Cintia Ferrari, Carina;Pott Godoy, Maria Clara;Juan Pitossi, Fernando
通讯作者：
Juan Pitossi, Fernando
影响因子：
6.5
作者：
de Barros, Jean-Paul Pais;Gautier, Thomas;Lagrost, Laurent
通讯作者：
Lagrost, Laurent
影响因子：
11.2
作者：
Dutta, R;McDonough, J;Trapp, BD
通讯作者：
Trapp, BD
影响因子：
2.1
作者：
Hannibal, Luciana
通讯作者：
Hannibal, Luciana