Printed Poster | Session 1
063 – The role of Serine/Arginine-Rich Splicing Factor 3 (SRSF3) as a regulator of immune response after ischemic stroke: sexual dimorphism
Revathy Guruswamy (1) – Reza Rahimian (1) – Hajer Boutej (1) – Jasna Kriz (1)
CERVO Brain Research Centre and Department of Psychiatry and Neuroscience,, Laval University, Quebec, Canada (1)
Stroke constitutes a major cause of death and disability of the adults worldwide. Until now, there is no efficient therapy for stroke patients. Ischemic stroke induces rapid activation of microglia, and as the resident immune cells of the central nervous system, microglial activation is believed to play a central role in neuroinflammation and pathological progression of ischemic tissue. Microglial activation is known to be detrimental in the early phase of ischemia, whereas in the subacute and chronic phase they are involved in the brain repair mechanisms. Therefore, strategies aiming to modulate the immune response by delaying microglial activation in the early phase of Ischemia would be an important strategy to induce brain recovery following stroke. To date, there is no clear evidence of molecular signature of activated microglia after stroke and further, the extent to which sexual dimorphism is involved in their activation profile. We have recently discovered that, there is a novel ribosome-based check point mechanism involved in the control of innate immune response and microglial activation. Serine/Arginine-Rich Splicing Factor 3, a small RNA binding protein of serine and arginine-rich (SR) family, has been shown to suppress the translation of highly induced innate immune genes in activated microglia leading to the formation of divergent mRNA and protein immune networks after Lipopolysaccharide-induce immune response. Hence, we aimed to study the molecular signature of activated microglia after ischemic stroke. We have used transgenic mice CD11brGFP in which FLAG/EGFP is fused to the N terminus of the large subunit of ribosomal protein L10a and expressed under the transcriptional control of CD11b promoter. Using translating ribosome affinity purification (TRAP) method from brain homogenates, we pull-down the ribosome-attached (both) mRNAs and peptides, thereby obtaining the active dynamic translational state of microglial ribosomes. Our data shows that, after ischemic stroke SRSF3 is differentially regulated, and the top up-regulated mRNAs and peptides is completely different in microglia derived from male and female indicating that sexual dimorphism is crucial following ischemic stroke in microglia responses. Our findings suggest that by deregulating the SRSF3 activity in microglia in early phase of post-ischemic inflammation would be a promising therapeutic approach to control the ischemic damage due to inflammation.