Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental NeurologyАнналы клинической и экспериментальной неврологии2075-54732409-2533Eco-Vector56110.25692/ACEN.2018.5.6ReviewsОбзорыUnknownInfluence of genetic factors on neurophysiological mechanisms of neurodegenerative diseasesВлияние генетических факторов на нейрофизиологические механизмы нейродегенеративных заболеванийPonomarevaNatalia V.ПономареваНаталия Васильевна
Russian Federation
ponomare@yandex.ruFokinVitaliy F.ФокинВиталий Федорович
Russian Federation
ponomare@yandex.ruRogaevEvgeny I.РогаевЕвгений Иванович
Russian Federation
ponomare@yandex.ruIllarioshkinSergey N.ИллариошкинСергей Николаевич
Russian Federation
ponomare@yandex.ruResearch Center of NeurologyФГБНУ «Научный центр неврологии»Vavilov Institute of General Genetics, Russian Academy of SciencesФГБУН Институт общей генетики им. Н.И. Вавилова РАНLomonosov Moscow State University, Center of Genetic and Genetic TechnologiesМосковский государственный университет им. М.В.Ломоносова, Центр генетики и генетических технологийDepartment of Psychiatry, University of Massachusetts Medical SchoolНаучно-исследовательский психиатрический институт Брудника, Университет Массачусетской Медицинской Школы26122018125S465426122018Copyright ©; 2018, Ponomareva N.V., Fokin V.F., Rogaev E.I., Illarioshkin S.N.Copyright ©; 2018, Ponomareva N.V., Fokin V.F., Rogaev E.I., Illarioshkin S.N.2018Ponomareva N.V., Fokin V.F., Rogaev E.I., Illarioshkin S.N.Ponomareva N.V., Fokin V.F., Rogaev E.I., Illarioshkin S.N.https://creativecommons.org/licenses/by/4.0https://annaly-nevrologii.com/pathID/article/view/561

The review summarizes the main results of studies on the influence of genetic factors on neurophysiological changes in neurodegenerative age-related diseases – Alzheimer's (AD), Parkinson's (PD) and Huntington (HD) diseases. In some cases, neurophysiological methods make it possible to detect early changes already at the preclinical stage of neurodegenerative process. Such neurophysiological markers may be considered as endophenotypes and used for the early diagnosis of the diseases. The conducted studies are promising for clarifying which factors underlie the heterogeneity of diseases not only at the genetic level, but also at the neurophysiological level. At the same time, such an approach showed the presence of a number of neurophysiological alterations common to AD, PD, and HD. Disconnection of neural circuits, including interhemispheric disintegration, slowdown of information processes, disinhibition, hyperexcitability and epileptogenesis, as well as alterations in neurovascular coupling, are of great importance for the development of diseases. On the other hand, neurophysiological changes can directly affect the development of the disease, including the genetic level, as evidenced by experimental optogenetic studies, the results of deep brain stimulation and other neuromodulation methods. These data are valuable for a personalized approach to the prevention and treatment of age-dependent neurodegenerative diseases.

В обзоре суммированы основные результаты исследований, посвященных влиянию генетических факторов на нейрофизиологические изменения при нейродегенеративных возрастзависимых заболеваниях – болезнях Альцгеймера (БА), Паркинсона (БП) и Гентингтона (БГ). В ряде случаев нейрофизиологические методы дают возможность обнаружить изменения уже на доклинической стадии нейродегенеративного процесса. Такие нейрофизиологические маркёры обладают свойствами эндофенотипов и могут быть использованы для ранней диагностики болезней. Проведенные исследования позволяют выяснить, какие факторы лежат в основе гетерогенности заболеваний не только на молекулярно-генетическом, но и на нейрофизиологическом уровне. В то же время, такой подход показал наличие ряда общих для БА, БП и БГ нейрофизиологических нарушений. Наибольшее значение для развития заболеваний имеют изменения коннективности, включающие межполушарную дезинтеграцию, замедление информационных процессов,снижение торможения, гипервозбудимость и эпилептогенез, а также нарушения нейро-васкулярного сопряжения. С другой стороны, нейрофизиологические изменения могут прямо влиять на развитие болезни, в том числе и на генетическом уровне, о чем свидетельствует данные экспериментальных оптогенетических исследований, результаты глубокой стимуляции мозга и других методов нейромодуляции. Эти данные имеют большое значение для персонализированного подхода к профилактике и лечению возрастзависимых нейродегенеративных заболеваний.

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