MICROGLIA-DERIVED IL-6 IS REQUIRED FOR HIPPOCAMPUS-DEPENDENT LONG-TERM SPATIAL MEMORY FORMATION



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Abstract

The influence of the immune system on the functions of the central nervous system (CNS) and behavior is mainly studied in the context of inflammation and pathology. However, recent findings highlight the crucial role of cytokines in maintaining functional state of the CNS and participating in the formation of various aspects of cognitive functions. At the same time, the cellular sources of the cytokines that mediate these effects remain unclear. It is known that elevated production of IL-6 may be associated with the development of a condition accompanied by cognitive impairments. This study examines the role of IL-6, resident immune cells of the CNS, in maintaining behavioral function in homeostasis. To examine whether IL-6-mediated signaling plays a role in maintaining normal behavioral functions, mice with tamoxifen-dependent inactivation of IL-6 in CX3CR1+ microglia were used. It was found that deletion of IL-6 from microglia did not lead to changes in anxiety behavior in the "Black-White Box" test, indicating the absence of a connection between IL-6 production by tissue-resident macrophages and anxiety disorder. At the same time, "Barnes Maze" and "Morris Water Maze" tests revealed impaired long-term spatial memory formation, manifested by reduced time spent in target sector in mice with IL-6 deficiency in microglia. Impaired long-term spatial memory formation in mice with microglial genetic inactivation of Il6 also correlated with altered expression of C1qa and C1qb genes in the hippocampus, responsible for complement-dependent synaptic pruning. However, mice with IL-6 inactivation in microglia showed no impairments in spatial orientation or short-term memory. Thus, mice with IL-6 deficiency in microglia exhibited a phenotype of impaired hippocampus-dependent long-term spatial memory, but no impairments were observed in short-term memory and anxiety behavior.

About the authors

O. Namakanova

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation

Email: olga.namakanova@gmail.com
ORCID iD: 0000-0001-6423-5843

Junior research associate, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences,  Moscow, Russian Federation 

Russian Federation, 119334, Russian Federation , Moscow, 32, Vavilov st.

V. Gogoleva

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation

Email: violette.gogoleva@gmail.com

PhD, Junior research associate, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation

Russian Federation, 119334, Russian Federation, Moscow, 32, Vavilov st.

E. Tukhovskaya

Branch of M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Russia

Email: olga.namakanova@gmail.com

PhD, senior researcher, Branch of M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Russian Federation

Russian Federation, 142290, Russian Federation, Pushchino, Prospect Nauki, 6

E. Shaykhutdinova

Branch of M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Russia

Email: olga.namakanova@gmail.com

PhD, senior researcher, Branch of M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Russian Federation

Russian Federation, 142290, Russian Federation, Pushchino, Prospect Nauki, 6

G. Slashcheva

Branch of M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Russia

Email: olga.namakanova@gmail.com

PhD, senior researcher, Branch of M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Russian Federation

Russian Federation, 42290, Russian Federation, Pushchino, Prospect Nauki, 6

A. Ismailova

Branch of M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Russia

Email: olga.namakanova@gmail.com

Junior researcher, Branch of M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Russian Federation

Russian Federation, 142290, Russian Federation, Pushchino, Prospect Nauki, 6

N. Khotskin

Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk, Russian Federation

Email: olga.namakanova@gmail.com

Ph.D, Research Officer, Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russian Federation

Russian Federation, 630090, Russian Federation, Novosibirsk, Akademika Lavrentyeva Prospect, 10

M. Drutskaya

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation;
Sirius University of Science and Technology, Krasnodar Region, Russian Federation

Author for correspondence.
Email: marinadru@gmail.com

PhD, MD, Leading Research Associate, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow; Assistant Professor, Sirius University of Science and Technology, Krasnodar Region, Russian Federation 

Russian Federation, 119334, Russian Federation, Moscow, 32, Vavilov st. 354340, Russian Federation, Krasnodar Region, Federal Territory "Sirius", prospect Olimpiyskiy, 1

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Copyright (c) Namakanova O., Gogoleva V., Tukhovskaya E., Shaykhutdinova E., Slashcheva G., Ismailova A., Khotskin N., Drutskaya M.

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