Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental NeurologyАнналы клинической и экспериментальной неврологии2075-54732409-2533Eco-Vector61710.25692/ACEN.2019.4.5Original articlesОригинальные статьиUnknownMolecular expression of insulin signal transduction components in brain cells in an experimental model of Alzheimer’s diseaseЭкспрессия молекул — компонентов инсулин-опосредованной сигнальной трансдукции в клетках головного мозга при экспериментальной болезни АльцгеймераGorinaYana V.ГоринаЯна Валерьевна
Russian Federation
yana_20@bk.ruKomlevaYuliya K.КомлеваЮлия Константиновна
Russian Federation
yana_20@bk.ruLopatinaOlga L.ЛопатинаОльга Леонидовна
Russian Federation
yana_20@bk.ruChernykhAnatolii I.ЧерныхАнатолий Игоревич
Russian Federation
yana_20@bk.ruSalminaAlla B.СалминаАлла Борисовна
Russian Federation
yana_20@bk.ruVoyno-Yasenetsky Krasnoyarsk State Medical UniversityФГБОУ ВО «Красноярский государственный медицинский университет имени профессора В.Ф. Войно-Ясенецкого»Krasnoyarsk City Hospital No. 20 named after I.S. BerzonКрасноярская межрайонная клиническая больница № 20 им. И.С. Берзона26122019134283726122019Copyright ©; 2019, Gorina Y.V., Komleva Y.K., Lopatina O.L., Chernykh A.I., Salmina A.B.Copyright ©; 2019, Gorina Y.V., Komleva Y.K., Lopatina O.L., Chernykh A.I., Salmina A.B.2019Gorina Y.V., Komleva Y.K., Lopatina O.L., Chernykh A.I., Salmina A.B.Gorina Y.V., Komleva Y.K., Lopatina O.L., Chernykh A.I., Salmina A.B.https://creativecommons.org/licenses/by/4.0https://annaly-nevrologii.com/pathID/article/view/617

Introduction. The risk of Alzheimer’s disease (AD) is increased with cerebral insulin resistance, which may be caused by the impaired function of the cerebrovascular system, and may also have a direct effect on β-amyloid aggregation and Tau protein phosphorylation.

Aim. To study the molecular expression of insulin signal transduction components (IRS1, GSK3B and PKC) in the brain cells in an experimental model of AD.

Materials and methods. Experiments were conducted on 4-month-old C57BL/6 and B6.129S6-Nlrp3tm1Bhk/JJ male mice (NLRP3 knockout mice) with 5 animals in each group. AD was modelled in the experimental group of mice by administering β-amyloid; mice in the control group received sham surgery. IRS1, GSK3B and PKC expression in the amygdala was studied using immunohistochemistry methods.

Results. The C57BL/6 mice with AD had reduced IRS1 expression compared with the mice who received sham surgery (0.62±0.13 and 0.89±0.17; р=0.045), while the β-amyloid did not produce the same result in NLRP3 knockout mice. GSK3B expression was increased in C57BL/6 mice with AD (0.60±0.12) when compared with both the control group (0.20±0.02; p<0.0001) and the NLRP3 knockout mice with AD (0.27±0.08; p<0.0001). PKC expression in C57BL/6 mice with AD was reduced (0.52±0.14) when compared with the NLRP3 knockout mice with AD (0.89±0.18; p<0.05) and the control group (0.84±0.12; p<0.05).

Conclusion. The development of Alzheimer type-neurodegeneration is accompanied by disruptions in IRS1 and GSK3B expression, which is associated with impaired signal transmission along the PKC pathway. The suppression of neuroinflammation through NLRP3 inflammasome deletion has a protective effect in AD.

Введение. Риск развития болезни Альцгеймера (БА) повышается при наличии церебральной инсулинорезистентности, которая может быть вызвана нарушением функции сосудистой системы головного мозга, а также оказывать прямое влияние на агрегацию β-амилоида или гиперфосфорилирование тау-белка.

Цель исследования — изучение экспрессии молекул — компонентов инсулин-опосредованной сигнальной трансдукции (IRS1, GSK-3beta и PKC) в клетках головного мозга при экспериментальной БА.

Материалы и методы. Опыты проведены на 4-месячных мышах-самцах линий C57BL/6 и B6.129S6-Nlrp3tm1Bhk/JJ (NLRP3-нокаутных); по 5 особей в группе. У мышей опытных групп путем введения β-амилоидного пептида моделировали БА; мыши контрольных групп были ложнооперированными. Экспрессию IRS1, GSK-3beta и PKC в миндалевидном теле головного мозга изучали методом иммуногистохимии.

Результаты. У мышей линии C57BL/6 с БА экспрессия IRS1 была снижена по сравнению с ложнооперированными (0,62±0,13 и 0,89±0,17; р=0,045), тогда как у NLRP3-нокаутных животных такого действия β-амилоида не обнаружено. Экспрессия GSK3-beta увеличивалась у мышей линии C57BL/6 с БА (0,60±0,12) по сравнению как с контрольной группой (0,20±0,02; p<0,0001), так и с NLRP3-нокаутными мышами с БА (0,27±0,08; p<0,0001). Экспрессия PKC у мышей линии C57BL/6 с БА снижалась (0,52±0,14) по сравнению с NLRP3-нокаутными мышами с БА (0,89±0,18; p<0,05) и с контрольной группой (0,84±0,12; p<0,05).

Заключение. Развитие нейродегенерации альцгеймеровского типа сопровождается нарушением экспрессии IRS1 и GSK3-beta, что ассоциировано с нарушением передачи сигнала по PKC-пути. Подавление нейровоспаления за счет делеции инфламмасом NLRP3 имеет протективное значение при развитии БА.

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