Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Neurosci Res. 2021 Nov;172:99-109. doi: 10.1016/j.neures.2021.05.007. Epub 2021 May 21.
Within the brain, traumatic brain injury (TBI) alters synaptic plasticity and increases neuroinflammation and neuronal death. Yet, there lacks effective TBI treatments providing pleiotropic beneficial effects on these diverse cellular processes necessary for functional recovery. Here, we show the diabetes drug, metformin, significantly improves cognitive functions after controlled cortical impact (CCI) injury in mice, showing improved spatial learning and nest building. Furthermore, injured animals treated with metformin exhibit increased ramification of microglia processes, indicating reduced neuroinflammation. Finally, metformin treatment in vitro increased neuronal activation of partitioning defective 1 (Par1), a family of Ser/Thr kinases playing a key role in synaptic plasticity and neuroinflammation. These results suggest metformin is a promising therapeutic agent for targeting multiple cellular processes necessary for functional TBI recovery.
在大脑中，创伤性脑损伤 (TBI) 会改变突触可塑性，增加神经炎症和神经元死亡。然而，目前缺乏有效的 TBI 治疗方法，无法对这些对功能恢复至关重要的多种细胞过程产生多效有益的影响。在这里，我们展示了糖尿病药物二甲双胍，它能显著改善经皮质撞击（CCI）损伤后的小鼠认知功能，表现为空间学习和筑巢能力的提高。此外，用二甲双胍治疗的受伤动物表现出小胶质细胞过程分支增加，表明神经炎症减少。最后，二甲双胍在体外处理可增加分隔缺陷 1 (Par1) 的神经元激活，Par1 是丝氨酸/苏氨酸激酶家族，在突触可塑性和神经炎症中起着关键作用。这些结果表明，二甲双胍是一种有前途的治疗药物，可针对 TBI 恢复所需的多种细胞过程。
