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Diphtheria toxoid nanoparticles improve learning and memory impairment in animal model of Alzheimer’s disease

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Abstract

Background

Alzheimer’s disease (AD) is a neurodegenerative disorder involving memory. The present study aimed at evaluating the effects of encapsulated diphtheria toxoid (DT) on behavioral learning impairment, and XBP1 mRNA splicing in AD.

Methods

A DT-loaded nanoparticle (NP) carrier was prepared using the ionic gelation method. Sixty-three rats were divided into nine groups: (1) healthy, (2–4) sham, and (5–9) AD models: (5) AD was induced by intracerebroventricular injection of amyloid beta (Aβ) 1-42. (6) The rats received a subcutaneous diphtheria vaccine only 28 days before Aβ injection. (7) The rats received an intranasal diphtheria vaccine, in group 8, induced by administering empty chitosan NPs. 9) it was induced by administering chitosan NPs carrying DT. Morris water maze (MWM) test was used to examine the animals’ learning and memory. Also, X-box binding protein 1 (XBP-1) mRNA gene splicing was studied in the hippocampus by reverse-transcription polymerase chain reaction (RT-PCR).

Results

For the first time, chitosan NPs were prepared with an average diameter size of 40 nm and the effectiveness of approximately 70% during DT encapsulation. In comparison with the healthy group, the AD models exhibited significant impairment of learning and memory (P < 0.05), while DT-administrated animals showed significant improvements in learning and memory impairment (P < 0.05). XBP-1 mRNA gene splicing was only detected in an untreated AD group, while encapsulated DT completely inhibited splicing.

Conclusion

The therapeutic effects of DT chitosan NPs against learning and memory impairment were observed in this study, and XBP1 mRNA splicing was reported in the animal models.

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Funding

This study was supported by research deputy of Guilan University of Medical Sciences (GUMS) (96022305).

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Authors and Affiliations

  1. Medical Biotechnology Research Center, School of Nursing, Midwifery and Paramedicine, Guilan University of Medical Sciences, Rasht, Iran

    Samane Heydari, Mahmood Abedinzade & Iraj Nikokar

  2. Department of Microbiology, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran

    Mojtaba Hedayati Ch

  3. Department of Microbiology, Parasitology, and Immunology, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran

    Farshid Saadat

  4. Department of Pharmaceutics, School of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran

    Ehsan Aboutaleb

  5. Quality Control of Bacterial and Parasitic Vaccine Department, Quality Control Management, Razi Vaccine and Serum Research Institute, Agricultural Research Education and Extension Organization (AREEO), Karaj, Iran

    Abolfazl Khafri & Ali Rezaei Mokarram

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  1. Samane Heydari
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Contributions

SH, MHC, FS, and MA designed the study, wrote the protocol, performed the interpretation of data, and wrote the first draft of the manuscript. SH, MHC, FS, MA, IN, and EA managed the acquisition of data. MHC, FS, MA, IN, EA, AK, and ARM performed critical revision of the manuscript and managed the literature searches. SH, MHC, and MA performed analysis and administrative, technical and material support. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Mahmood Abedinzade.

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The authors declare no conflict of interest.

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All authors hereby declare that all experiments have been examined and approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. I look forward to hearing you.

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Heydari, S., Hedayati Ch, M., Saadat, F. et al. Diphtheria toxoid nanoparticles improve learning and memory impairment in animal model of Alzheimer’s disease. Pharmacol. Rep 72, 814–826 (2020). https://doi.org/10.1007/s43440-019-00017-w

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