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N-Acetyl Serotonin Protects Neural Progenitor Cells Against Oxidative Stress-Induced Apoptosis and Improves Neurogenesis in Adult Mouse Hippocampus Following Traumatic Brain Injury

  • Qingzhi Li
  • Pengcheng Wang
  • Chuixue Huang
  • Baozhi Chen
  • Jiabin Liu
  • Mingmei Zhao
  • Jiannong ZhaoEmail author
Article
  • 48 Downloads

Abstract

In this study, with primary mouse neural progenitor cells (NPCs), we investigated the neuroprotective effect of a tropomyosin-related kinase receptor B (TrkB) agonist, N-acetyl serotonin (NAS), against hydrogen peroxide (H2O2)-induced toxicity. We found that pre-incubation with NAS not only ameliorates H2O2-induced cell viability loss, lactate dehydrogenase (LDH) release, and proliferative and migratory capacity impairments, but counteracts H2O2-triggered production of nitric oxide (NO), reactive oxygen species (ROS), malondialdehyde (MDA), and 8-hydroxy-deoxyguanosine (8-OHdG) in a dose-dependent manner. Additionally, pre-treatment with NAS was able to attenuate H2O2-induced apoptosis in NPCs, evidenced by the decreased percentage of apoptotic cells and altered expression of apoptosis-related factors. Furthermore, in differentiated NPCs, NAS improves H2O2-induced reduction in neurite growth. Mechanistic studies revealed that the protective effects of NAS in NPCs may be mediated by the TrkB/PI3K/Akt/ cAMP response element binding protein (CREB) signaling cascades. In a mouse traumatic brain injury (TBI) model, we found that systemic administration of 30 mg/kg NAS could improve hippocampal neurogenesis, manifested by the increased number of SOX-2-positive cells and increased expression of phosphorylated CREB in the dentate gyrus (DG) area. Treatment with NAS also ameliorates cognitive impairments caused by TBI, as assessed by Y-maze and contextual and cued fear conditioning tests. Taken together, these results provide valuable insights into the neuroprotective and neuroregenerative effects of NAS, suggesting it may have therapeutic potential for the treatment of TBI.

Keywords

N-acetyl serotonin Neural progenitor cell Apoptosis Oxidative stress Hippocampal neurogenesis Traumatic brain injury 

Notes

Acknowledgments

All authors thank Dr. Jin Li for his kind assistance in data collection and analysis.

Compliance with Ethical Standards

Conflict of Interest

All authors declare that they have no conflict of interest related to this study.

Supplementary material

12031_2019_1263_MOESM1_ESM.docx (413 kb)
ESM 1 (DOCX 412 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of NeurosurgeryHainan General HospitalHaikouChina
  2. 2.Department of RadiotherapyNanfang Hospital of Southern Medical UniversityGuangzhouChina
  3. 3.Department of Neurosurgery, the Affiliated Hospital of Medical CollegeQingdao UniversityQingdaoChina

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