Nicotinamide mononucleotide alleviates seizures via modulating SIRT1‐PGC ‐1α mediated mitochondrial fusion and fission

作者：Yahong Cheng, Puxin Huang, Qixian Zou, Hui Tian, Qingzhou Cheng, Hong Ding · 发表于：Journal of Neurochemistry · 年份：2024 · DOI：10.1111/jnc.16041 · 被引用次数：14 · 研究领域：Mitochondrial Function and Pathology、Sirtuins and Resveratrol in Medicine、Autophagy in Disease and Therapy

Abstract Both human and animal experiments have demonstrated that energy metabolism dysfunction in neurons after seizures is associated with an imbalance in mitochondrial fusion/fission dynamics. Effective neuronal mitochondrial dynamics regulation strategies remain elusive. Nicotinamide mononucleotide (NMN) can ameliorate mitochondrial functional and oxidative stress in age‐related diseases. But whether NMN improves mitochondrial energy metabolism to exert anti‐epileptic effects is unclear. This study aims to clarify if NMN can protect neurons from pentylenetetrazole (PTZ) or Mg 2+ ‐free‐induced mitochondrial disorder and apoptosis via animal and cell models. We established a continuous 30‐day PTZ (37 mg/kg) intraperitoneal injection‐induced epileptic mouse model and a cell model induced by Mg 2+ ‐free solution incubation to explore the neuroprotective effects of NMN. We found that NMN treatment significantly reduced the seizure intensity of PTZ‐induced epileptic mice, improved their learning and memory ability, and enhanced their motor activity and exploration desire. At the same time, in vitro and in vivo experiments showed that NMN can inhibit neuronal apoptosis and improve the mitochondrial energy metabolism function of neurons. In addition, NMN down‐regulated the expression of mitochondrial fission proteins (Drp1 and Fis1) and promoted the expression of mitochondrial fusion proteins (Mfn1 and Mfn2) by activating the SIRT1‐PGC‐1α pathway, thereby inhibiting PTZ or Mg 2+ ...