2. Academic Validation
  3. Melatonin attenuates scopolamine-induced cognitive dysfunction through SIRT1/IRE1α/XBP1 pathway

Melatonin attenuates scopolamine-induced cognitive dysfunction through SIRT1/IRE1α/XBP1 pathway

  • CNS Neurosci Ther. 2024 Jul;30(7):e14891. doi: 10.1111/cns.14891.
Xiao-Qi Liu 1 2 3 4,  Shun Huang 5 6,  Jia-Yi Zheng 1 2 3 4,  Can Wan 1 2 3 4,  Tian Hu 1 2 3 4,  Ye-Feng Cai 1 2 3 4,  Qi Wang 7,  Shi-Jie Zhang 1 2 3 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
  • 2 Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
  • 3 Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
  • 4 Guangdong Provincial Key Laboratory of Research on Emergency in TCM Guangzhou, Guangzhou, China.
  • 5 Department of Nuclear Medicine, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, China.
  • 6 Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 7 Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China.
PMID: 39056330 DOI: 10.1111/cns.14891
Abstract

Background: The prevalence of dementia around the world is increasing, and these patients are more likely to have cognitive impairments, mood and anxiety disorders (depression, anxiety, and panic disorder), and attention deficit disorders over their lifetime. Previous studies have proven that melatonin could improve memory loss, but its specific mechanism is still confused.

Methods: In this study, we used in vivo and in vitro models to examine the neuroprotective effect of melatonin on scopolamine (SCOP)-induced cognitive dysfunction. The behavioral tests were performed. 18F-FDG PET imaging was used to assess the metabolism of the brain. Protein expressions were determined through kit detection, Western blot, and immunofluorescence. Nissl staining was conducted to reflect neurodegeneration. MTT assay and RNAi transfection were applied to perform the in vitro experiments.

Results: We found that melatonin could ameliorate SCOP-induced cognitive dysfunction and relieve anxious-like behaviors or HT22 cell damage. 18F-FDG PET-CT results showed that melatonin could improve cerebral glucose uptake in SCOP-treated mice. Melatonin restored the cholinergic function, increased the expressions of Neurotrophic Factors, and ameliorated oxidative stress in the brain of SCOP-treated mice. In addition, melatonin upregulated the expression of silent information regulator 1 (SIRT1), which further relieved endoplasmic reticulum (ER) stress by decreasing the expression of phosphorylate inositol-requiring Enzyme (p-IRE1α) and its downstream, X-box binding protein 1 (XBP1).

Conclusions: These results indicated that melatonin could ameliorate SCOP-induced cognitive dysfunction through the SIRT1/IRE1α/XBP1 pathway. SIRT1 might be the critical target of melatonin in the treatment of dementia.

Keywords

ER stress; SIRT1; cognitive impairment; melatonin; scopolamine.

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