The role of neuroinflammation in cognitive functions and social interaction in mice with age-dependent neurodegeneration

Abstract

Introduction. Early activation of the innate immune response as a compensatory mechanism can lead to the damage of vessels and their dysfunction. This enables the development and progression of cognitive dysfunction, alteration of cerebral microcirculation, thus makes the onset of age-related neurodegenerative diseases possible. Inflammasomes of NLRP3 play the important role as far as they are triggers of the inflammatory process in age-related chronic neurodegenerative diseases. Objectives. To study the development of social and cognitive impairments in aging NLRP3 knockout animals. Material and methods. The experimental group was NLRP3 knockout (NLRP3-/-) male mice of the line B6.129S6-Nlrp3tm1Bhk / JJ) aged 12 months (n=10); control group C57BL/6.SJL male mice aged 12 months (n=10). Neurobehavioral testing: open field test, X-maze test, light-dark box, three-chamber social test, and five-trial social memory test. Results. In the open field test, when the social object appeared, NLRP3-/- animals spent less time at the center of the field I in comparison with the animals of the C57BL/6 line (p=0.013). NLRP3-/- animals spent more time in the black chamber compared to the animals in the control group (p=0.037) in the light-dark box test. In the three-chamber social test NLRP3-/- animals spent the same time both with the new and the already familiar social object (p=0.885). In the five-trial social memory test NLRP3-/- animals did not demonstrate reduction of interest towards individuals of the opposite sex in the fourth attempt compared to the first attempt. Conclusion. NLRP3-/- mice have the increased levels of anxiety and inhibition, disruption of memory, and destructive changes in the field of social contacts and interactions. This indicates a disorder in the sphere of emotional behavior, as well as social memory

Keywords

• nlrp3-mice
• behavior
• cerebrovascular inflammation
• memory