Tyler Cox, Work done in lab of Dr. Scott Weber, Microbiology and Molecular Biology Department
Introduction
The immune system plays a role in protecting and maintaining the central nervous system (CNS). 1Dysfunctions within the immune system can affect the CNS and it is associated with diseases such as Multiple Sclerosis, Alzheimer’s and Parkinson’s disease. Having an imbalanced activation of immune cells within CNS results in cognitive impairments. CD5 is a protein on the surface of T cells and certain B cells that inhibits cellular activation and prevents immune cells from reacting too strongly to antigens and causing autoimmunity to our own tissues. Modulating CD5 and the immune system could affect the CNS and cognitive function. Observations in our lab suggest that mice deficient in CD5 (CD5 knock out; CD5KO) exhibit increased aggression and anxious behavior than wild type (WT) mice. Preliminary behavior tests indicate CD5 affects cognitive function. We hypothesize that in addition to its role in altering immune cell activation, the CD5 protein is a key factor that alters cognitive function.
Methods
We performed a series of behavior tests to analyze the role of CD5 in cognitive function. The Morris Water Maze test was used to examine memory and learning. Over the course of 7 days, we track pathways and record the time mice take to swim to a hidden platform. The Marble Burying test was used to examine anxiety and repetitive behavior. The Elevated Plus Maze test also examines anxiety by measuring time mice spend within closed-walled arms versus elevated open arms. 2 Knowing gut microbiome populations have been known to affect cognitive function, we also collected fecal samples with bacterial populations from CD5KO and WT mice and compared them.
The activation of T cells is known to effect cell metabolism. Since CD5 negatively regulates this activation, we measured the metabolic rates of CD5KO mouse T cells compared to WT T cells during both cell activation and non-activation periods.
Results
Behavior: The Water Maze tests showed no significant difference although we did observe that CD5KO mice found the platform faster than WT mice. The Marble Burying tests illustrated CD5KO mice burying significantly more marbles than WT mice, on average 17 marbles versus WT’s 12 out of 20 (Figure 1). Elevated Plus Maze resulted in CD5KO spending more time in the closed arms than WT mice, however, this change was not statistically significant. The Open Field tests resulted in CD5KO mice traveling an average of 38 meters versus 48 meters in WT mice during a 10-minute period (Figure 2). This suggests decreased locomotive activity that could be a result of altered cognitive function.
Microbiome: The bacterial populations collected from the guts of CD5KO and WT showed significantly different varieties of populations despite similar diets (Figure 3). This difference could be explained by the immune activation differences by CD5.
Metabolism: We found significant differences in naïve T cell mitochondrial respiration with CD5KO showing oxygen consumption rates as high as 100 pmoles/min/total cells higher than WT during pre-activation and post-activation stages (Figure 4).
Discussion and Conclusions
Significant differences observed in CD5KO and CD5WT mice suggests an important role of the CD5 protein in T cells and behavior. The higher marble burying rate of CD5KO mice indicates increased anxiety and compulsive behavior, as does their decreased locomotion and exploratory movement (Figures 1, 2). This decrease in movement may also be due to their decreased motivation to naturally explore environments. The microbiome populations were significantly different and could explain the interactions with cognition and behavior (Figure 3). The different T cell metabolic profiles in CD5KO and WT mice also indicate differences in immune activation that potentially alters the CNS and cognitive function (Figure 4). These results show important differences in immune and cognitive function, with future studies better illustrating CD5’s role within the immune system and its effects on cognitive function.
1 Mietelska-Porowska A and U. Wojda. 2017. T Lymphocytes and Inflammatory Mediators in the Interplay between Brain and Blood in Alzheimer’s Disease: Potential Pools of New Biomarkers. Journal of Immunology Research 2017: 1-17.
2 Vanessa de J.R. De-Paula. 2018. Relevance of gut microbiota in cognition, behaviour and Alzheimer’s disease. Pharmacological Research, Volume 136,2018, p. 29-34, ISSN 1043-6618, https://doi.org/10.1016/j.phrs.2018.07.007.