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Aerobic exercise training improves memory function through modulation of brain-derived neurotrophic factor and synaptic proteins in the hippocampus and prefrontal cortex of type 2 diabetic rats

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Abstract

Aims/Introduction

Defective insulin signaling in the brain may disrupt hippocampal neuroplasticity resulting in learning and memory impairments. Thus, this study investigated the effect of aerobic exercise training on cognitive function and synaptic protein markers in diabetic rats.

Materials and methods

Twenty male Wistar rats (200–250 g), were fed on high-fat diet and received a low dose of streptozotocin (35 mg/kg, i.p) to induce type 2 diabetes. Then diabetic animals were randomly divided into sedentary and training groups. The exercise training program was treadmill running at 27 m/min for 60 min/day for 8 weeks. One day after the last training session, Morris Water Maze (MWM) task was performed to evaluate spatial learning and memory. Then, the hippocamp and prefrontal cortex tissues were instantly dissected for immunoblotting assay of BDNF, GSK-3β, p-GSK-3β, P38, p-P38, ERK1/2, p-ERK1/2, heat shock protein-27 (HSP27), SNAP-25, synaptophysin, and PSD-95. Independent t-test analysis and two-way ANOVA was used to determine the differences under significance level of 0.05 using the 26th version of IBM SPSS statistical software.

Results

The results showed that aerobic exercise improved memory as assessed in the MWM task. Moreover, aerobic exercise up-regulated HSP27 and BDNF protein levels in the prefrontal cortex, and hippocampus coincided with robust elevations in SNAP25 and PSD-95 levels. Moreover, exercise reduced phosphorylated P38, while increased p-ERK1/2 and p-GSK-3β (p).

Conclusion

Our findings suggest that aerobic exercise may debilitate the harmful effects of diabetes on the cognitive function possibly through enhancing synaptic protein markers.

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Acknowledgements

We are grateful to the Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, especially Dr. Farhoudi for their laboratory equipment, exercise facilities, and technical support.

Funding

The fund for this study was provided by Dr. Iraj Sadri. This fund was used to purchase the necessary supplies. Authors also declare that no funds, grants, or other support were received during the preparation of this manuscript from other organizations or institutes.

Author information

Author notes

  1. Iraj Sadri and Mostafa Khani contributed equally to this work.

Authors and Affiliations

  1. Department of Physical Education and Sports Sciences, Islamic Azad University, Shabestar Branch, Shabestar, 5381637181, Iran

    Iraj Sadri

  2. Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Tabriz, 29 Bahman Blvd, Tabriz, 5166616471, Iran

    Saeid Dabbagh Nikookheslat & Mostafa Khani

  3. Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Pouran Karimi

  4. Department of Chemistry and Biochemistry, Faculty of Science, University of Windsor, Windsor, ON, Canada

    Sanaz Nadimi

Authors
  1. Iraj Sadri
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  4. Mostafa Khani
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  5. Sanaz Nadimi
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Contributions

I.S. designed and performed research, analyzed data, and wrote the manuscript. S.D.N. contributed new reagents, and analytical tools and analyzed data and reviewed and edited the manuscript. P.K. analyzed data, and contributed to the discussion and reviewed and edited the manuscript. M.K. designed research, analyzed data, contributed to the discussion, and reviewed and edited the manuscript. S.N. Cooperated in running exercise protocol and data extraction, analyzed data, and wrote the manuscript I.S. is the sponsor of this work and has full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding authors

Correspondence to Iraj Sadri or Mostafa Khani.

Ethics declarations

Ethics approval

This study was approved by the research ethics committee (REC) of Tabriz University of Medical Sciences (TUOMS) (IR.TBZMED.REC.1395.1225).

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Not applicable.

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All the participants gave their consent for the publication of identifiable details, which can include photograph(s) and/or videos and/or case history and/or details within the text (“Material”) to be published in the Journal of diabetes and metabolic disorders and the present article.

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There are no competing conflicts of interest to declare. 

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Sadri, I., Nikookheslat, S.D., Karimi, P. et al. Aerobic exercise training improves memory function through modulation of brain-derived neurotrophic factor and synaptic proteins in the hippocampus and prefrontal cortex of type 2 diabetic rats. J Diabetes Metab Disord (2023). https://doi.org/10.1007/s40200-023-01360-9

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