Научная статья на тему 'Embryonic proteoglycans potential means of prophylactics of neurodegenerative diseases'

Embryonic proteoglycans potential means of prophylactics of neurodegenerative diseases Текст научной статьи по специальности «Фармакология»

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Текст научной работы на тему «Embryonic proteoglycans potential means of prophylactics of neurodegenerative diseases»


Conference of Biological Psychiatry

«Stress and Behavior»

Proceedings of the 9th International Multidisciplinary Conference «Stress and behavior» Saint-Petersburg, Russia, 16-19 May 2005 Editor: Allan V. Kalueff, PhD





L.N. Mkrtchyan, M.I. Aghajanov

Yerevan State Medical University, Center of Extreme Dangerous Infections HM RA, Armenia

The interest to the fetal therapy of neurodegenerative (Alzheimer’s, Parkinson, and Kreuzfeld-Jacob) diseases rises from year to year. It was established that transplantation of stem cells improved memory and eliminated behavioral defects (Hadges et al., 2000). The embryonic hippocampal cells were used also during prion diseases, particularly at the scrappy model. Jeffery et al. (2000) succeeded in preventing progressive loss of nerve cells and thereby to preserve more than 50% of pyramidal and hippocampal neurons. The most effective result was obtained during the injection of stem cells 10 days before the beginning of the neuron destruction (Brown et al., 2001). This prophylactic aspect of the problem appears for us to be rather preferable. It was not in vain that Vice-President of the International Association of Alzheimer’s disease Brian Moss suggests that «in the nearest 10 years we will not be able to talk about the treatment of AD, but only of its prevention» (Global Perspective, 2004). Therefore, we have studied the preventive role of the humoral (proteoglycan) component of humoral substances (Mkrtchyan, 1994) in the model of neurodegeneration induced by aluminum chloride, as well as by the fragment of beta-amyloid. Hence the main attention was concentrated to the utilization of such methods of preparative biochemistry, allowing us to isolate the indicated substance in the condition maximally close to native states (patent RF N2240810, 2004). The EP composition was studied by gel-filtrational chromatography, HPLC, immunoenzyme and radioimmune analysis, and EPR. EP possessed an antimutagenous, interferonogenous, immunomodulatory activity simultaneously at therapeutical dose lacking acute and chronic toxicity. In the prophylactic series of our experiments (injection of EP 5 days prior to induction of neurodegeneration) the carried out morphological studies (Niessle coloring, silver impregnation, amyloid reaction, endothelial cell alkaline phosphatase, DNA and RNA, acid and neutral polysaccharides, polarization microscopy) confirmed protective properties of EP. Positive shifts are registered for neurons, astrocytes and microcirculatory vessels. In some cases, 60% preservation of pyramidal and hippocampal cells was observed. In the experimental animals in the state of aluminum neurotoxicosis, we studied free radical lipid per oxidation (POL). In the blood plasma and erythrocyte membranes, a significant change in lipid per oxidation (including the content of acylhydroperoxides, malone dialdehyde, shiff bases, NADPH- and ascorbate-dependent POL), was observed, with breaches of membrane function by increasing integral peroxidase activity, and the presence of intoxication by the elevation of the content of middle-chain molecules. Preliminary administration of EP prevents all these impairments. Similar picture is observed in various regions of the brain (cerebral cortex, hippocampus, and hypothalamus) and liver. The effect of EP was tested also on the cell culture of human neuroblastoma SHSY5Y. The nerve cells appear to be susceptible to alternative effect of aluminum chloride. At 96-h monolayer, a marked destruction of tissue, 5-fold inhibition of mitotic indices (0.4 ± 0.1 vs. 2.0 ± 0.5 in control) was observed. Notably, the absence of EP toxicity and its ability to evoke prolonged immunomodulatory effect at small doses (0.03 mg/kg). Temporary Pharmacopoeia abstract (TPA N13-52-98) of AMMT permitted to carry out clinical trials on the limited contingent of severely suffering patients. Interestingly, there were 4 volunteers under observation with neurogerontosis and

Psychopharmacol. Biol. Narcol. 2005. Vol. 5, N 2. P. 912—913

Psyhopharmacology & biological narcology

ISSN 1606-8181

Parkinson disease. It is possible to expect that in near future it will be possible to utilize EP to treat patients with high risk of development of neurodegenerative pathology.

Psychopharmacol. Biol. Narcol. 2005. Vol. 5, N 2. P. 912-913 ISSN 1606-8181

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Psyhopharmacology & biological narcology