Evaluation of the effects of new peptide compounds in experimental animals with a toxic model of Alzheimer’s disease

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Abstract

Development of new approaches to the treatment of Alzheimer’s disease (AD) is an actual problem of modern neurology owing to high prevalence of AD in the population and severe irreversible disability resulting from this disease. We investigated the effects of new peptide compounds, β-casomorphin-7 and colostrinin, in two complementary AD models in rats (with injection of β-amyloid into the nucleus basalis of Meynert and injection of streptozocin in the ventricles of the brain). Peptides were injected intranasally within 10 days after the onset of AD symptoms induced by neurotoxins. Injection of β-casomorphin-7 and colostrinin had similar effect on the behavior and cognitive function of rats with both amyloid and streptozocin AD model: there was statistically significant increase in locomotor activity and orienting responses, as well as improvement of animals’ cognitive functions. Colostrinin had stronger positive effect on the behavior of rats with induced AD, whereas β-casomorphin-7 had an effect on both sham-operated and model animals, which is indicative of the general neurotropic potential of this peptide. The proposed experimental approaches improve the capabilitiesof investigation of novel biologically active compounds aimed at prevention and treatment of neurodegenerative diseases.

About the authors

Alla V. Stavrovskaya

Research Center of Neurology

Email: snillario@gmail.com
Russian Federation, Moscow

Nina G. Yamshchikova

Research Center of Neurology

Email: snillario@gmail.com
Russian Federation, Moscow

A. S. Ольшанский

Research Center of Neurology

Email: snillario@gmail.com
Russian Federation, Moscow

G. A. Babkin

LLC Laktokor

Email: snillario@gmail.com
Russian Federation, Moscow

Sergey N. Illarioshkin

Research Center of Neurology

Author for correspondence.
Email: snillario@gmail.com
ORCID iD: 0000-0002-2704-6282

D. Sci. (Med.), Prof., Corr. Member of the Russian Academy of Sciences, Deputy Director, Head, Department for brain research

Russian Federation, Moscow

References

  1. Дубынин В.А., Каменский А.А. Бета-казоморфины и их роль в регуляции поведения. М.: КМК, 2010.
  2. Иллариошкин С.Н. Конформационные болезни мозга. М.:Янус-К, 2003.
  3. Иллариошкин С.Н. Возрастные расстройства памяти и внимания: механизмы развития и возможности нейротрансмиттерной терапии. Неврол. журн. 2007; 2: 34–40.
  4. Иллариошкин С.Н. Ранние (додементные) формы когнитивных расстройств. Consilium Med. 2007; 2: 107–111.
  5. Маклакова А.С., Дубынин В.А., Левицкая Н.Г. и др. Поведенческие эффекты бета-казоморфина-7 и его дез-Tyr аналогов. Бюл. эксперимент. биол. мед. 1993; 8: 155–158.
  6. Островская Р.У., Цаплина А.П., Вахитова Ю.В и др. Эффективность ноотропного и нейропротективного дипептида ноопепт на стрептозоциновой модели болезни Альцгеймера у крыс. Эксперим. и клинич. фармакол. 2009.
  7. Ставровская А.В., Конорова И.Л., Иллариошкин С.Н. и др. Технологии моделирования заболеваний нервной системы. В кн.:Неврология XXI века: диагностические, лечебные и исследовательские технологии. Руководство для врачей. В 3-х т. (под ред. М.А. Пирадова, С.Н. Иллариошкина, М.М. Танашян). Т. III. Современные исследовательские технологии в экспериментальной неврологии. М.: АТМО, 2015: 73–133.
  8. Суслина З.А., Иллариошкин С.Н., Пирадов М.А. Неврология и нейронауки – прогноз развития. Анн. клин. и эксперим. неврол. 2007; 1: 5–9.
  9. Яхно Н.Н., Захаров В.В., Локшина А.Б. и др. Деменции. Руководство для врачей. М.: МЕДпресс-информ, 2010.
  10. Януш М., Лисовски Ю., Дубовска-Инглот А. Колостринин и его применение. Патент РФ № 2217152 от 27.11.2003.
  11. Chen S.-Y, Wright J.W., Barres C.D. The neurochemical and behavioral effects of β-amyloid peptide (25-35). Brain Res. 1996; 720: 54–60.
  12. Chen Y., Liang Z., Blanchard J. et al. A non-transgenic mouse model (icv-STZ mouse) of Alzheimer’s disease: Similarities to and differences from the transgenic model (3xTg-AD mouse). Mol. Neurobiol. 2013;47: 711–725.
  13. Citron M. Strategies for disease modification in Alzheimer’s disease. Nat. Rev. Neurosci. 2004; 5: 677–685.
  14. Demetrius L., Magistretti P., Pellerin L. Alzheimer’s disease: the amyloid hypothesis and the inverse Warburg test. Front. Physiol. 2015; 5: 2–20.
  15. Freude S., Schilbach K., Schubert M. The role of IGF-1 receptor and insulin receptor signaling for the pathogenesis of Alzheimer’s disease: from model organisms to human disease. Curr. Alzheimer Res. 2009;6: 213–223.
  16. Giovannelli L., Casamenti F., Scali C. et al. Differential effects of amyloid peptides beta-(l-40) and beta-(25-35) injections into the rat nucleus basalis. Neuroscience. 1995; 66: 781–792.
  17. Gotz J., Lars M.I. Animal models of Alzheimer’s disease and frontotemporal dementia. Neuroscience. 2008; 9: 532–544.
  18. Iqbal K., Bolognin S., Wang X. et al. Animal models of the sporadic form of Alzheimer’s disease: focus on the disease and not just the lesions. J. Alzheimers dis. 2013; 37: 469–474.
  19. Ishrat T., Khan M.B., Hoda M.N., Yousuf S. Coenzyme Q10 modulates cognitive impairment against intracerebroventricular injection of streptozotocin in rats. Behav. Brain Res. 2006; 171: 9–16.
  20. Javed H., Khan M.M., Ahmad A., Vaibhav K. Rutin prevents cognitive impairments by ameliorating oxidative stress and neuroinflammation in rat model of sporadic dementia of Alzheimer type. Neuroscience. 2012; 210: 340–352.
  21. Lester-Coll N., Rivera E.J., Soscia S.J. et al. Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimer’s disease. J. Alzheimers Dis. 2006; 9: 13–33.
  22. Maurice T., Lockhart B., Privat A. Amnesia induced by centrally administered β-amyloid peptides involves cholinergic dysfunction. Brain Res. 1996; 706: 181–193.
  23. Maurice T., Su T.-P., Privat A. Sigmal (σ1) reseptor agonists and neurosteroids attenuates β25-35 amyloid-peptide-induced amnesia in mice through a common mechanism. Neuroscience. 1998; 83: 413–428.
  24. McDonald M.P., Dahl E.E., Overmier J.B. Effects of exogenous β-amyloid peptide on retention for special learning. Behav. Neural Biol. 1994; 62: 60–67.
  25. Paxinos G., Watson Ch. The rat brain in stereotaxic coordinates. 4th edition. Academic Press, 1998.
  26. Pepeu G., Giovannelli L., Casamenti F. et al. Amyloid β-peptides injection into the cholinergic nuclei: morphological, neurochemical and behavioural effects. Prog. Brain Res. 1996; 109: 273–282.
  27. Prickaerts J., Fahrig T., Blokland A. Cognitive performance and biochemical markers in septum hippocampus and striatum of rats after an i.c.v. injection of streptozotocin: a correlation analysis. Behav. Brain Res. 1999; 102: 73–88.
  28. Salkovic-Petrisic M., Hoyer S. Central insulin resistance as a trigger for sporadic Alzheimer-like pathology: an experimental approach. J. Neural Transm. 2007 (Suppl.): 217–233.
  29. Sienkiewicz-Szłapkaa E., Jarmołowskaa B., Krawczuka S. et al. Contents of agonistic and antagonistic opioid peptides in different cheese varieties. Int. Dairy J. 2009; 19: 258–263.
  30. Van Dam D., De Deyn P.-P. Animal models in the drug discovery pipeline for Alzheimer’s disease. Br. J. Pharmacol. 2011; 164: 1285–1300.
  31. Yamada K., Nabeshima T. Animal models of Alzheimer’s disease and evaluation of anti-dementia drugs. Pharmacology & Therapeutics.2000; 88: 93–163.
  32. Yamaguchi H., Sugihara S., Ogawa A. et al. Diffuse plaques associated with astroglial amyloid beta protein, possibly showing a disappearing stage of senile plaques. Acta Neuropathol. 1998; 95: 217–222.

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Copyright (c) 2016 Stavrovskaya A.V., Yamshchikova N.G., Ольшанский A.S., Babkin G.A., Illarioshkin S.N.

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