The Role of Neuroinflammation in Cognitive Functions and Social Interaction in Mice with Age-Dependent Neurodegeneration

Abstract—: Early activation of the compensatory mechanism, such as the innate immune response may result in pathological lesion of vessels and their dysfunction, cognitive decline, and impairments of cerebral microcirculation. These alterations create a condition for the development of age-related neurodegenerative diseases. NLRP3 inflammasomes play an important role as triggers of the inflammatory process in age-related neurodegenerative diseases. Here we studied development of social and cognitive impairments in aging NLRP3-knockout animals. The experimental group consisted of 12-month-old male NLRP3-knockout (NLRP3-/-) mice of B6.129S6-Nlrp3tm1Bhk/JJ strain (n = 10) and the control group consisted of 12рmonth-old male C57Bl/6×SJL mice (n = 10). Neurobehavioral study included “open field,” “elevated plus-maze,” “dark-light chamber,” three-chamber social, and five-trial social tests. After the placement of another subject into the “open field” NLRP3-/- mice spent less time in the center of the field as compared to C57Bl/6 mice (p = 0.013). In the “dark-light chamber” test, NLRP3-/- mice spent more time in the dark compartment compared to C57Bl/6 mice (p = 0.037). In the three-chamber social test, the time spent close to new or familiar subject did not differ in NLRP3-/- mice (p = 0.885). In the social five-trial test, there was no decrease in interest in a subject of opposite sex between trials 1 and 4. NLRP3-/- mice exhibit 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. © 2022, Pleiades Publishing, Inc.