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

Abstract

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. 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). 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. 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.