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Nasal Cavity Administration of Melanin-Concentrating Hormone Improves Memory Impairment in Memory-Impaired and Alzheimer’s Disease Mouse Models

  • Seung Tack Oh
  • Quan Feng Liu
  • Ha Jin Jeong
  • Seongmi Lee
  • Manikandan Samidurai
  • Jihoon Jo
  • Sok Cheon Pak
  • Hi-Joon ParkEmail author
  • Jongpil KimEmail author
  • Songhee JeonEmail author
Article

Abstract

Melanin-concentrating hormone (MCH) is a highly conserved neuropeptide known to exhibit important functions in the brain. Some studies have reported that MCH improves memory by promoting memory retention. However, the precise molecular mechanisms by which MCH enhances memory impairment have yet to be fully elucidated. In this study, MCH was administered to the scopolamine-induced memory-impaired mice via the nasal cavity to examine the acute effects of MCH and Alzheimer’s disease (AD) mouse models to evaluate the chronic effects of MCH. MCH improved memory impairment in both models and reduced soluble amyloid beta in the cerebral cortex of APP/PS1 transgenic mice. In vitro assays also showed that MCH inhibits amyloid beta-induced cytotoxicity. Furthermore, MCH increased long-term potentiation (LTP) in the hippocampus of wild-type and 5XFAD AD mouse model. To further elucidate the mechanisms of the chronic effect of MCH, the levels of phosphorylated CREB and GSK3β, and the expression of BDNF, TrkB and PSD95 were examined in the cerebral cortex and hippocampus. Our findings indicate that MCH might have neuroprotective effects via downstream pathways associated with the enhancement of neuronal synapses and LTP. This suggests a therapeutic potential of MCH for the treatment of neurodegenerative diseases such as AD.

Keywords

Alzheimer’s disease (AD) Cognitive function Melanin-concentrating hormone (MCH) Scopolamine Long-term potentiation (LTP) 

Notes

Funding Information

This research was supported by grants from the National Research Foundation (2017R1A2B4009963) and the Korean Health Technology R&D Project founded by the Ministry of Health and Welfare (HI16C0405, HI18C1077) of the Republic of Korea.

Compliance with Ethical Standards

All animal experiments in this study followed the “Guide for Animal Experiments” provided by the Korean Academy of Medical Sciences. All animal protocols were approved by the Institutional Animal Care and Use Committee of Dongguk University, South Korea (IACUC-2016-1193), and Chonnam National University Medical School (CNU IACUC-H-2018-1).

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

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

Authors and Affiliations

  1. 1.Research InstituteDongkwang Pharmaceutical Company, Ltd.SeoulRepublic of Korea
  2. 2.Department of Neuropsychiatry, Graduate School of Oriental MedicineDongguk UniversityGyeongjuRepublic of Korea
  3. 3.Department of Child and Adolescent PsychiatryNational Center for Mental HealthSeoulRepublic of Korea
  4. 4.Department of Biomedical Sciences, BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University, Research Institute of Medical SciencesChonnam National University Medical SchoolGwangjuRepublic of Korea
  5. 5.NeuroMedical Convergence Lab, Biomedical Research InstituteChonnam National University HospitalGwangjuRepublic of Korea
  6. 6.School of Biomedical SciencesCharles Sturt UniversityBathurstAustralia
  7. 7.Department of Korean Medical Science, Graduate School of Korean MedicineKyung Hee UniversitySeoulRepublic of Korea
  8. 8.Integrative Parkinson’s Disease Research Group, Studies of Translational Acupuncture Research (STAR), Acupuncture & Meridian Science Research Center (AMSRC)Kyung Hee UniversitySeoulRepublic of Korea
  9. 9.Laboratory of Stem Cells & Cell Reprogramming, Department of ChemistryDongguk UniversitySeoulRepublic of Korea

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