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

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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.

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Funding

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.

Author information

Author notes

  1. Seung Tack Oh and Quan Feng Liu contributed equally to this work.

Authors and Affiliations

  1. Research Institute, Dongkwang Pharmaceutical Company, Ltd., Seoul, 04535, Republic of Korea

    Seung Tack Oh

  2. Department of Neuropsychiatry, Graduate School of Oriental Medicine, Dongguk University, Gyeongju, 38066, Republic of Korea

    Quan Feng Liu

  3. Department of Child and Adolescent Psychiatry, National Center for Mental Health, Seoul, 04933, Republic of Korea

    Ha Jin Jeong & Seongmi Lee

  4. Department of Biomedical Sciences, BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, 61469, Republic of Korea

    Manikandan Samidurai, Jihoon Jo & Songhee Jeon

  5. NeuroMedical Convergence Lab, Biomedical Research Institute, Chonnam National University Hospital, Gwangju, 61469, Republic of Korea

    Jihoon Jo

  6. School of Biomedical Sciences, Charles Sturt University, Bathurst, New South Wales, 2795, Australia

    Sok Cheon Pak

  7. Department of Korean Medical Science, Graduate School of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea

    Hi-Joon Park

  8. Integrative Parkinson’s Disease Research Group, Studies of Translational Acupuncture Research (STAR), Acupuncture & Meridian Science Research Center (AMSRC), Kyung Hee University, Seoul, 02447, Republic of Korea

    Hi-Joon Park

  9. Laboratory of Stem Cells & Cell Reprogramming, Department of Chemistry, Dongguk University, Seoul, 04620, Republic of Korea

    Jongpil Kim

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  1. Seung Tack Oh
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Corresponding authors

Correspondence to Hi-Joon Park, Jongpil Kim or Songhee Jeon.

Ethics declarations

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).

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Oh, S.T., Liu, Q.F., Jeong, H.J. et al. Nasal Cavity Administration of Melanin-Concentrating Hormone Improves Memory Impairment in Memory-Impaired and Alzheimer’s Disease Mouse Models. Mol Neurobiol 56, 8076–8086 (2019). https://doi.org/10.1007/s12035-019-01662-1

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