ACCUMULATION OF β-AMYLOID LEADS TO A DECREASE IN LYNX1 AND LYPD6B EXPRESSION IN THE HIPPOCAMPUS AND INCREASED EXPRESSION OF PRO-INFLAMMATORY CYTOKINES IN THE HIPPOCAMPUS AND BLOOD SERUM

M. L. Bychkov; Бычков М. Л.; A. V. Kirichenko; Кириченко А. В.; A. S. Paramonov; Парамонов А. С.; M. P. Kirpichnikov; Кирпичников М. П.; E. N. Lukmanova; Люкманова Е. Н.

doi:10.31857/S2686738922600881

ACCUMULATION OF β-AMYLOID LEADS TO A DECREASE IN LYNX1 AND LYPD6B EXPRESSION IN THE HIPPOCAMPUS AND INCREASED EXPRESSION OF PRO-INFLAMMATORY CYTOKINES IN THE HIPPOCAMPUS AND BLOOD SERUM

Authors: Bychkov M.L.¹, Kirichenko A.V.¹, Paramonov A.S.¹, Kirpichnikov M.P.¹^,2, Lukmanova E.N.¹^,2^,3
Affiliations:
1. Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
2. Interdisciplinary Scientific and Educational School “Molecular Technologies of Living Systems and Synthetic Biology”, Faculty of Biology, Lomonosov Moscow State University M.V. Lomonosov
3. Shenzhen MSU-BIT University
Issue: Vol 511, No 1 (2023)
Pages: 354-359
Section: Articles
URL: https://journals.rcsi.science/2686-7389/article/view/135647
DOI: https://doi.org/10.31857/S2686738922600881
EDN: https://elibrary.ru/IYLGDX
ID: 135647

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Abstract

Alzheimer’s disease is a rapidly progressive neurodegenerative disease, the development of which is associated with the accumulation of β-amyloid oligomers, dysfunction of the α7-nAChR nicotinic acetylcholine receptor, and activation of inflammation. Previously, we have shown that the neuromodulator Lynx1, which belongs to the Ly6/uPAR family, competes with β-amyloid(1–42) for binding to α7-nAChR. In the present work, we studied the expression and localization of Ly6/uPAR family proteins in the hippocampus of 2xTg-AD transgenic mice that model AD and demonstrate increased amyloidosis in the brain. Using real-time PCR, we showed a decrease in the expression of the genes encoding Lynx1, Lypd6b, and the postsynaptic marker PSD95, as well as an increase in the expression of the TNFα gene in the hippocampus of 2xTg-AD mice. Histochemical analysis revealed that, in the hippocampus of 2xTg-AD mice Lynx1 does not co-localize with α7-nAChR that can lead to the development of pathology when the receptor interacts with oligomeric β-amyloid. Also, in 2xTg-AD mice, activation of systemic inflammation was shown, which manifests itself in a decrease in the serum level of SLURP-1, a Ly6/uPAR family protein capable of regulating inflammatory processes, as well as an increase in the content of pro-inflammatory cytokines TNFα and TNFβ. Thus, α7-nAChR dysfunction and maintenance of the inflammatory microenvironment in the brain in Alzheimer’s disease may be associated with a decrease in the expression of Ly6/uPAR family proteins that regulate α7-nAChR activity and inflammation.

Keywords

Alzheimer’s disease, nicotinic acetylcholine receptor, Ly6/uPAR, Lynx1, SLURP-1, Lypd6b

About the authors

M. L. Bychkov

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: ekaterina-lyukmanova@yandex.ru
Russian Federation, Moscow

A. V. Kirichenko

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: ekaterina-lyukmanova@yandex.ru
Russian Federation, Moscow

A. S. Paramonov

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: ekaterina-lyukmanova@yandex.ru
Russian Federation, Moscow

M. P. Kirpichnikov

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; Interdisciplinary Scientific and Educational School “Molecular Technologies of Living Systems and Synthetic Biology”, Faculty of Biology, Lomonosov Moscow State University M.V. Lomonosov

Email: ekaterina-lyukmanova@yandex.ru
Russian Federation, Moscow; Russian Federation, Moscow

E. N. Lukmanova

Author for correspondence.
Email: ekaterina-lyukmanova@yandex.ru
Russian Federation, Moscow; Russian Federation, Moscow; China, Shenzhen

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