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Metabolic Brain Disease

, Volume 33, Issue 2, pp 387–396 | Cite as

Poly-N-methylated Aβ-Peptide C-Terminal fragments (MEPTIDES) reverse the deleterious effects of amyloid-β in rats

  • Siya G. Sibiya
  • Musa V. Mbandla
  • Thavi Govender
  • Adeola Shobo
  • William M. U. Daniels
Original Article

Abstract

Alzheimer’s disease (AD) is characterized by extracellular deposition of amyloid-β (Aβ) plaques. These protein deposits impair synaptic plasticity thereby producing a progressive decline in cognitive function. Current therapies are merely palliative and only slow cognitive decline. Poly-N-methylated Aβ-Peptide C-Terminal Fragments (MEPTIDES) were recently shown to reduce Aβ toxicity in vitro and in Drosophila melanogaster, however whether these novel compounds are effective in inhibiting Aβ-induced toxicity in the mammalian brain remains unclear. We therefore investigated whether MEPTIDES have the ability to reduce the neurotoxic effects of Aβ in male Sprague-Dawley (SD) rats. Aβ42 (100 μg, 2 mM) or vehicle (0.15 M Tris buffer) was stereotaxically injected bilaterally into the dorsal hippocampus at a rate of 1 μl/min for 10 min. The effects on hippocampal-mediated learning were subsequently assessed using the Morris water maze (MWM). The presence of apoptotic activity was also assessed by determining the expression levels of active caspase-3 using real-time polymerase chain reaction and Western Blot techniques. In addition, half of the animals (n = 20) received an intraperitoneal (i.p.) injection of MEPTIDES (2 mg/kg) 48 h after intrahippocampal injection of Aβ42. Matrix-assisted laser desorption/ionization-time-of-flight (MALDI –TOF) mass spectrometry (MS) showed that MEPTIDES crossed the blood brain barrier (BBB) and revealed their distribution in the rat brain. Rats treated with Aβ42 displayed spatial learning deficits and increased hippocampal caspase-3 gene (CASP-3) expression which was reversed by subsequent injection of MEPTIDES. The present results show that MEPTIDES have the potential to reverse the toxic effects of Aβ42 in vivo.

Keywords

Alzheimer’s disease MEPTIDES Amyloid-β Learning Apoptosis 

Notes

Acknowledgements

The authors acknowledge the technical and editorial assistance by Miss Chloe Eliza Flinn.

This work was supported by the National Research Foundation of South Africa and the University of KwaZulu-Natal, College of Health Sciences.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted (ethical clearance no. 048/13/Animal).

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Siya G. Sibiya
    • 1
  • Musa V. Mbandla
    • 1
  • Thavi Govender
    • 2
  • Adeola Shobo
    • 2
  • William M. U. Daniels
    • 1
    • 3
  1. 1.College of Health Sciences, School of Laboratory Medicine and Medical SciencesUniversity of KwaZulu-NatalDurbanSouth Africa
  2. 2.Catalysis and Peptide Research Unit, School of Health SciencesUniversity of KwaZulu-NatalDurbanSouth Africa
  3. 3.School of Physiology, Faculty of Health SciencesUniversity of the WitwatersrandJohannesburgSouth Africa

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