EFFECT OF NANOCARRIERS WITH ANTISENSE OLIGONUCLEOTIDES ON HISTOLOGICAL STRUCTURE OF ORGANS SYNTHESIZING PRION-PROTEIN

: 22 September 2016; Hits: 1174

Bìol. Tvarin, 2016, Volume 18, Issue 3, pp. 91–96

http://dx.doi.org/10.15407/animbiol18.03.091

EFFECT OF NANOCARRIERS WITH ANTISENSE OLIGONUCLEOTIDES ON HISTOLOGICAL STRUCTURE OF ORGANS SYNTHESIZING PRION-PROTEIN

N. Yu. Susol, Yu. V. Martyn, N. V. Kuzmina, V. V. Vlizlo

This email address is being protected from spambots. You need JavaScript enabled to view it.

Institute of animal biology NAAS,
38 V.Stus str., Lviv 79034, Ukraine

Polymer compounds serves as a perspective carriers for medicinal preparations and engages antisense therapy against diseases with diverse etiology. However, the problem is in toxic effect of polymers on the animal organism. Of particular relevance acquire research on developing effective carriers of nucleotides, which could be used for prevention and treatment for disease of pathological protein synthesis.

We have been investigated the transportation and delivery of complexes of oligonucleotides with three newly polymer carriers based on dymetylaminoetylmethakrylate — MP-27, MP-2 and MP-3. The research was conducted by the example of action complexes polymer carriers with antisense oligonucleotides on cellular prion expressions. Nanocarriers influence on the structure of organs of white rats (Rattus norvegicus var. alba, Wistar line) was showed.

The complexes with polymers MP-2 and MP-3 caused the minor changes in the microstructure of the brain, small intestine and spleen. In particular, in histological structure of brain, reducing the number of neurons in sight was seen on the 7^th day after injection. In the small intestine serous membrane sprawling and Peyer plaques swelling have been detected. Histological preparations spleen revealed an increase in the size of individual follicles.

However, the effect of carrier MR-27 does not cause pathological changes in the structure of the small intestine, spleen and brain both separately and in combination with antisense oligonucleotides. So, polymeric carrier MY-27 can be used to transport of medicines.

Keywords: RATS, BRAIN, SPLEEN, INTESTINE, POLIMERIC CARRIERS, ANTISENSE OLIGONUCLEOTIDES, CELLULAR PRION

1. Schlachetzki F., Boado J. Gene therapy of the brain: the trans-vascular approach. Neurology, 2004, vol. 62, no. 8, pp. 75–81. https://doi.org/10.1212/01.WNL.0000120551.38463.D9

2. Yamamoto T., Nakatani M., Narukawa K. Antisense drug discovery and development. Future Med. Chem., 2011, vol. 3, pp. 59–65. https://doi.org/10.4155/fmc.11.2

3. Vlizlo V. V., Stadnyk V. V., Mayor Ch. Ya., Verbitsky P. I. Physiological prion and its role in the functioning of the cell. The Animal Biology, 2008, vol. 10, no. 1–2, pp. 9–23. (in Ukrainian)

4. Trevitt C., Collinge J. A systematic review of prion therapeutics in experimental models. Brain, 2006, no. 129, pp. 2241–2265. https://doi.org/10.1093/brain/awl150

5. White M. D. Therapy for prion diseases: Insights from the use of RNA interference. Prion, 2009, vol. 3, no. 3, pp. 121–128. https://doi.org/10.4161/pri.3.3.9289

6. Verbitsky P. I. Spongioform encephalopathy in cattle and other prion infections. Kyiv, Vetinform, 2005, 240 p. (in Ukrainian)

7. Pardridge W., Miller F., Weiss N. The blood-brain barrier in brain homeostasis and neurological diseases. Biochim Biophys Acta, 2009, vol. 1788, no. 4, pp. 842‒857. https://doi.org/10.1016/j.bbamem.2008.10.022

8. Mironov A. Jr., Latawiec D., Wille H. Cytosolic prion protein in neurons. Neuroscience, 2003, vol. 23, pp. 1183–1193.

9. Mabbott N. A., Bruce M. E. Prion pathogenesis and secondary lymphoid organs. Prion, 2012, vol. 1, no. 6, pp. 322–333. https://doi.org/10.4161/pri.20676

10. Chen L. N., Zhang B. Y. Proteomic Analyses for the Global S-Nitrosylated Proteins in the Brain Tissues of Different Human Prion Diseases. Prion, 2015, vol. 11, no. 1–2, pp. 15–23.

11. Kushkevych M. V., Vlizlo V. V. Localization and level of the cellular prion in the jejunum of the rats Wistar line of different age groups. Biological systems, 2013, vol. 3, pp. 325–329.

12. European convention for the protection of vertebrate animals used for experimental and scientific purposes. Strasburg, Council of Europe, 1986, pp. 52–53.

download full text in PDF

Search