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Neurobehavioral protective effects of Japanese sake yeast supplement against chronic stress-induced anxiety and depression-like symptoms in mice: Possible role of central adenosine receptors

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Abstract

Rationale

Using routine synthetic drugs in the treatment of psychiatric disorders may have some restrictions due to serious side effects and pharmacoresistance. Some natural agents may be promising alternatives in this case. The neuroprotective activity of the neuromodulator adenosine and its receptor, A1 receptor (A1R) in the central nervous system has been mentioned in different studies.

Objective

We aimed to determine the anxiolytic, antidepressant and sedative effects of Japanese sake yeast as the first report.

Method

Mice were subjected to a one-week stress protocol and concomitantly treated orally with sake yeast at the dose levels of 100, 200 and 300 mg kg-1 once daily for a week. The anxiolytic, antidepressant, and sedative actions of sake yeast were evaluated with the related tests.

Results

In all dose regiments, sake yeast significantly improved functions in the EPM and FST. 200 and 300 mg/kg of sake yeast significantly increased sleep duration and reduced sleep latency. Anxiolytic and antidepressant-like activities of sake yeast were maintained by the injection of ZM241385 (15 mg kg−1), a selective adenosine A2AR antagonist but completely counteracted by the injection of 8-cyclopentyltheophylline (10 mg kg−1), a selective adenosine A1R antagonist. 300 mg/kg of the yeast significantly increased the BDNF levels. Amygdala corticosterone levels did not show any significant changes at any dosage. Amygdala TNF-α, IL-6 and IL-1β levels also decreased significantly with all the sake regiments compared to the control group.

Conclusions

We conclude that oral sake yeast supplement exerts a neurobehavioral protective effect predominantly by activating central A1Rs.

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The authors are grateful to the Iran National Science Foundation (INSF) and the Research Center of Physiology of Semnan University of Medical Sciences for their cooperation and also Prof. Dr. Thomas Budde for providing the supplement (medicine) for the present study.

Funding statement

This study was funded by Iran National Science Foundation (INSF), Tehran, Iran [grant number 98012571].

Data availabilitty statement

Raw data were originated from the Research Center of Physiology, Semnan University of Medical Sciences, Semnan. Supporting and analyzed data for results of this study are available from the corresponding authors Nasrollah Moradikor or Ali Rashidy-Pour on request.

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Authors and Affiliations

  1. Research Center of Physiology, Department of Pharmacology, Semnan University of Medical Sciences, Semnan, Iran

    Hooman Bozorgi

  2. Research Center of Physiology, Department of Physiology, Semnan University of Medical Sciences, Semnan, Iran

    Ali Rashidy-Pour

  3. International Center for Neuroscience Research, Institute for Intelligent Research, Tbilisi, Georgia

    Nasrollah Moradikor

  4. Rooyan Darou Pharmaceutical Company, Semnan, Iran

    Melika Zamani

  5. Neurosciences Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Ehsan Motaghi

  6. Department of Physiology and Pharmacology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Ehsan Motaghi

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  1. Hooman Bozorgi
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Corresponding authors

Correspondence to Nasrollah Moradikor or Ehsan Motaghi.

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The experiments of the present study were approved by the Ethical Reviews Committee of Semnan University of Medical Sciences and Health Services (approval ID: IR.SEMUMS.REC.1398.275).

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Bozorgi, H., Rashidy-Pour, A., Moradikor, N. et al. Neurobehavioral protective effects of Japanese sake yeast supplement against chronic stress-induced anxiety and depression-like symptoms in mice: Possible role of central adenosine receptors. Psychopharmacology 241, 401–416 (2024). https://doi.org/10.1007/s00213-023-06496-3

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