Journal of Neuroimmune Pharmacology

, Volume 14, Issue 2, pp 278–294 | Cite as

Melatonin Rescue Oxidative Stress-Mediated Neuroinflammation/ Neurodegeneration and Memory Impairment in Scopolamine-Induced Amnesia Mice Model

  • Tahir Muhammad
  • Tahir Ali
  • Muhammad Ikram
  • Amjad Khan
  • Sayed Ibrar Alam
  • Myeong Ok KimEmail author


Cognitive decline and memory impairment induced by oxidative brain damage are the critical pathological hallmarks of Alzheimer’s disease (AD). Based on the potential neuroprotective effects of melatonin, we here explored the possible underlying mechanisms of the protective effect of melatonin against scopolamine-induced oxidative stress-mediated c-Jun N-terminal kinase (JNK) activation, which ultimately results in synaptic dysfunction, neuroinflammation, and neurodegeneration. According to our findings, scopolamine administration resulted in LPO and ROS generation and decreased the protein levels of antioxidant proteins such as Nrf2 and HO-1; however, melatonin co-treatment mitigated the generation of oxidant factors while improving antioxidant protein levels. Similarly, melatonin ameliorated oxidative stress-mediated JNK activation, enhanced Akt/ERK/CREB signaling, promoted cell survival and proliferation, and promoted memory processes. Immunofluorescence and western blot analysis indicated that melatonin reduced activated gliosis via attenuation of Iba-1 and GFAP. We also found that scopolamine promoted neuronal loss by inducing Bax, Pro-Caspase-3, and Caspase-3 and reducing the levels of the antiapoptotic protein Bcl-2. In contrast, melatonin significantly decreased the levels of apoptotic markers and increased neuronal survival. We further found that scopolamine disrupted synaptic integrity and, conversely, that melatonin enhanced synaptic integrity as indicated by Syntaxin, PSD-95, and SNAP-23 expression levels. Furthermore, melatonin ameliorated scopolamine-induced impairments in spatial learning behavior and memory formation. On the whole, our findings revealed that melatonin attenuated scopolamine-induced synaptic dysfunction and memory impairments by ameliorating oxidative brain damage, stress kinase expression, neuroinflammation, and neurodegeneration.

Graphical Abstract

The proposed schematic diagram showing the neuroprotective effect of melatonin against scopolamine-induced oxidative stress-mediated synaptic dysfunction, memory impairment neuroinflammation and neurodegeneration.


Amnesia Reactive oxygen species (ROS) Brain-derived neurotrophic factor (BDNF) Cyclic AMP response element-binding protein (CREB) Scopolamine Melatonin 



This research was supported by the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT (2016M3C7A1904391).

Compliance with Ethical Standards

Conflict of Interest

The authors declared no competing financial interests.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Tahir Muhammad
    • 1
  • Tahir Ali
    • 1
  • Muhammad Ikram
    • 1
  • Amjad Khan
    • 1
  • Sayed Ibrar Alam
    • 1
  • Myeong Ok Kim
    • 1
    Email author
  1. 1.Division of Applied Life Science (BK 21), College of Natural SciencesGyeongsang National UniversityJinjuRepublic of Korea

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