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High-Intensity Interval Training Ameliorates Molecular Changes in the Hippocampus of Male Rats with the Diabetic Brain: the Role of Adiponectin

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Abstract

Alzheimer’s disease (AD) is closely related to type 2 diabetes (T2D). This study investigated the impact of high-intensity interval training (HIIT) on diabetes-induced disturbances in AD-related factors (including AMP-activated protein kinase (AMPK), glycogen synthase kinase-3β (GSK3β), and tau protein) in the hippocampus, with the main focus on adiponectin signaling.

In total, 28 male Wistar rats at the age of 8 weeks were randomly assigned to four groups (n = 7 in each group): control (Con), type 2 diabetes (T2D), HIIT (Ex), and type 2 diabetes + HIIT (T2D + Ex). T2D was induced by a high-fat diet plus a single dose of streptozotocin (STZ). Rats in Ex and T2D + Ex groups performed 8 weeks of HIIT (running at 8–95% of Vmax, 4–10 intervals). Insulin and adiponectin levels in serum and hippocampus were measured along with hippocampal expression of insulin and adiponectin receptors, phosphorylated AMPK, dephosphorylated GSK3β, and phosphorylated tau. Homeostasis model assessment for insulin resistance (HOMA-IR), homeostasis model assessment for insulin resistance beta (HOMA-β), and quantitative insulin sensitivity check index (QUICKI) were calculated to assess insulin resistance and sensitivity. T2D decreased insulin and adiponectin levels in serum and hippocampus, as well as the hippocampal levels of insulin and adiponectin receptors and AMPK, but increased GSK3β and tau in the hippocampus. HIIT reversed diabetes-induced impairments and consequently decreased tau accumulation in the hippocampus of diabetic rats. HOMA-IR, HOMA-β, and QUICKI were improved in Ex and T2D + Ex groups. Overall, our results confirmed that T2D has undesirable effects on the levels of some Alzheimer’s-related factors in the hippocampus, and HIIT could ameliorate these impairments in the hippocampus.

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Data Availability

All data and material is available at https://kmu.ac.ir/en by request.

Materials Availability

All data and material is available at https://kmu.ac.ir/en by request.

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Acknowledgements

We would like to thank the Physiology Research Center and Neuroscience Research Center of Kerman University of Medical sciences for their financial help.

Funding

This study was funded by Physiology Research Center and Neuroscience Research Center of Kerman University of Medical Sciences (grants No. 99000443 and 99–42).

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Authors and Affiliations

  1. Physiology Research Center, Institute of Neuropharmacology and Department of Physiology and Pharmacology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

    Kayvan Khoramipour, Mohammad Abbas Bejeshk & Mohammad Amin Rajizadeh

  2. Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran

    Hamid Najafipour

  3. Department of Alternative Medicine, Resalat Hospital, Tehran, Iran

    Padideh Dehghan

  4. School of Human Kinetics and Recreation, Memorial University of Newfoundland, St. John’s, NL, Canada

    Fattaneh Farahmand

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  1. Kayvan Khoramipour
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  4. Hamid Najafipour
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Contributions

All authors contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by Kayvan Khoramipour, Mohammad Abbas Bejeshk, and Mohammad Amin Rajizadeh. The first draft of the manuscript was written by Kayvan Khoramipour, Mohammad Abbas Bejeshk, and Mohammad Amin Rajizadeh. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Kayvan Khoramipour.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the ethics committee of KUMS (ethics approval code: IR.KMU.REC.1399.503).

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Khoramipour, K., Bejeshk, M.A., Rajizadeh, M.A. et al. High-Intensity Interval Training Ameliorates Molecular Changes in the Hippocampus of Male Rats with the Diabetic Brain: the Role of Adiponectin. Mol Neurobiol 60, 3486–3495 (2023). https://doi.org/10.1007/s12035-023-03285-z

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