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

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.