Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental NeurologyАнналы клинической и экспериментальной неврологии2075-54732409-2533Eco-Vector13710.17816/psaic137Original articlesОригинальные статьиUnknownExperience of experimental simulation of Huntington’s diseaseОпыт экспериментального моделирования болезни ГентингтонаStavrovskayaAlla V.СтавровскаяАлла Вадимовна
Russian Federation
alla_stav@mail.ruVoronkovDmitry N.ВоронковДмитрий Николаевич
Russian Federation
alla_stav@mail.ruYamshchikovaNina G.ЯмщиковаНина Гавриловна
Russian Federation
alla_stav@mail.ruOlshanskyArtem S.ОльшанскийАртем Сергеевич
Russian Federation
alla_stav@mail.ruKhudoerkovRudolf M.ХудоерковРудольф Михайлович
Russian Federation
alla_stav@mail.ruhttps://orcid.org/0000-0002-2704-6282IllarioshkinSergey N.ИллариошкинСергей Николаевич
Russian Federation

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

д.м.н., проф., член-корр. РАН, зам. директора по научной работе, рук. отдела исследований мозга

alla_stav@mail.ruResearch Center of NeurologyФГБНУ «Научный центр неврологии»0909201593495501022017Copyright ©; 2015, Stavrovskaya A.V., Voronkov D.N., Yamshchikova N.G., Ol’shanskiy A.S., Khudoerkov R.M., Illarioshkin S.N.Copyright ©; 2015, Stavrovskaya A.V., Voronkov D.N., Yamshchikova N.G., Ol’shanskiy A.S., Khudoerkov R.M., Illarioshkin S.N.2015Stavrovskaya A.V., Voronkov D.N., Yamshchikova N.G., Ol’shanskiy A.S., Khudoerkov R.M., Illarioshkin S.N.Stavrovskaya A.V., Voronkov D.N., Yamshchikova N.G., Ol’shanskiy A.S., Khudoerkov R.M., Illarioshkin S.N.https://creativecommons.org/licenses/by/4.0https://annaly-nevrologii.com/pathID/article/view/137

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease characterized by choreic hyperkinesia, cognitive decline, behavioral disorders, and progressive neuronal death affecting primarily the striatum. The fatal nature of HD makes searching for new effective methods of treatment topical, which requires the development of experimental models of the disease. This model can be created on the basis of 3-nitropropionic acid (3-NPA) that is a neurotoxin causing characteristic changes in motor skills and memory impairment in animals due to induction of oxidative stress, impaired glutathione defense, and destruction of striatal cells. HD in rats was simulated by chronic intraperitoneal administration of 3-NPA daily for 17 days. Systemic administration of a low dose of 3-NPA (10 mg/ kg) induced hyperactivity of the animals in the open field test (including movement redundancy as a hyperkinesia analogue) and had no effect on the behavior of the animals in the X-maze test. On the contrary, rats administered with a toxic dose of 3-NPA (20 mg/kg) demonstrated a significant decrease in the motor activity an cognitive decline in behavioral tests. Histopathological analysis revealed damage and loss of neurons and decreased expression of dopaminergic markers (tyrosine hydroxylases and plasma membrane dopamine transporter) in the striatum. Also, a gliotoxic effect of 3-NPA in the striatum was found, which was confirmed by immunohistochemical staining for astrocytic proteins: GFAP, glutamine synthetase, and aquaporin-4. This HD model may be helpful for testing new experimental therapies at various stages of neurodegeneration of the Huntington type, including those based on cell neurotransplantation.

Болезнь Гентингтона (БГ) является аутосомно-доминантным нейродегенеративным заболеванием и характеризуется хореическим гиперкинезом, снижением когнитивных функций, поведенческими расстройствами и прогрессирующей гибелью нейронов, поражающей, прежде всего, стриатум. В силу фатального характера БГ актуальным является поиск эффективных методов ее лечения, для чего требуется разработка экспериментальных моделей данного заболевания. Такая модель может быть создана с помощью 3-нитропропионовой кислоты (3-НПК) – нейротоксина, вызывающего характерные изменения моторики и ухудшение памяти у животных в результате индукции окислительного стресса, нарушения глутатионовой защиты и поражения клеток полосатого тела. БГ у крыс моделировалась хроническом введением 3-НПК внутрибрюшинно, ежедневно в течение 17 дней. Системное введение низкой дозы 3-НПК (10 мг/кг) вызывало гиперактивность животных в «открытом поле» (включая избыточность движений как аналог гиперкинезов) и не оказывало влияния на поведение животных в X-лабиринте. Напротив, при введении токсической дозы 3-НПК (20 мг/кг) крысы демонстрировали значительное снижение двигательной активности и ослабление когнитивных функций во время поведенческих исследований. Гистопатологический анализ выявил повреждение и гибель нейронов и снижение экспрессии дофаминергических маркеров (тирозингидроксилазы и мембранного переносчика дофамина) в стриатуме. Также обнаружили глиотоксическое действие 3-НПК в стриатуме, подтвержденное иммуно-гистохимическим окрашиванием на астроцитарные белки: GFAP, глутаминсинтетазу и аквапорин-4. Данная модель БГ может быть полезной для тестирования новых экспериментальных видов терапии на различных стадиях нейродегенерации «гентингтоновского» типа, в т.ч. основанных на клеточной нейротрансплантации.

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