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Adipose-Derived Mesenchymal Stem Cells and Conditioned Medium Attenuate the Memory Retrieval Impairment During Sepsis in Rats

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Abstract

In this study, we hypothesized that sepsis induction impairs memory retrieval in rats while transplanted mesenchymal stem cells (MSCs) and MSC-conditioned medium (MSC-CM) application are capable of attenuating those complications. MSCs were obtained from adipose tissue of rats and at the second culture passage; MSCs and MSC–CM were collected. Rats were randomly divided into four experimental groups: sham, CLP, MSC, and MSC-CM. Sepsis was induced by cecal ligation and puncture (CLP) model in the CLP, MSC, and MSC-CM groups. The MSC group received 1 × 106 MSCs/rat (i.p., 2 h after CLP surgery); the MSC-CM rats received the conditioned medium (CM) from 1 × 106 MSCs intraperitoneally 2 h after sepsis induction. Novel object recognition test, sepsis score, and blood pressure measurement were performed 24 h after the treatments. The right hippocampus was taken for western blot analysis. CLP rats showed a significantly higher sepsis score and systolic blood pressure. They also had a significant increase in the phosphorylated form of CAMKII-α, cleaved caspase 3 and Bax/Bcl2 ratio, and a reduction in c-fos protein in the hippocampus tissue samples compared with the sham group. MSC transplantation and MSC-CM administration significantly decreased the mean sepsis score and prevented sepsis-induced attenuation of blood pressure compared with the CLP rats. Animals in the MSC and MSC-CM groups showed a better memory retrieval, attenuation in phosphorylated form of CAMKII-α, cleaved caspase 3 and Bax/Bcl2 ratio, and an increase in c-fos protein expression compared with the CLP group. It seems that CAMKII and c-fos are inversely involved in regulating memory processes in hippocampus. Phosphorylated form of CaMKII-α overexpression may impair the ability of object recognition. Our findings confirmed that MSC-CM application has more advantages compared with transplanted MSCs and may be offered as a promising therapy for inflammatory diseases such as severe sepsis.

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Data Availability

The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This research was supported by a grant (no = 41504) from Tehran University of Medical Sciences.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, 1417613151, Iran

    Fariba Akhondzadeh, Mehri Kadkhodaee, Behjat Seifi, Ghorbangol Ashabi, Farzaneh Kianian & Mina Ranjbaran

  2. Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Kamal Abdolmohammadi

  3. Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Maryam Izad

  4. MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

    Maryam Izad

  5. Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Maryam Adelipour

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  1. Fariba Akhondzadeh
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  6. Kamal Abdolmohammadi
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Fariba Akhondzadeh, Farzaneh Kianian, Ghorbongol Ashabi, and Kamal Abdolmohammadi. All authors read and approved the final manuscript.

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Correspondence to Mina Ranjbaran.

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Akhondzadeh, F., Kadkhodaee, M., Seifi, B. et al. Adipose-Derived Mesenchymal Stem Cells and Conditioned Medium Attenuate the Memory Retrieval Impairment During Sepsis in Rats. Mol Neurobiol 57, 3633–3645 (2020). https://doi.org/10.1007/s12035-020-01991-6

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