PLEIOTROPHIN INDUCES CHANGES IN THE GENE EXPRESSION OF MICE CEREBRAL CORTICES FOLLOWING ISCHEMIC STROKES
University of Alberta
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Date TBA
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Poster Board
PS04-08PM-069
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An emerging approach in ischemic stroke research involves modulating neuroplasticity to heighten the central nervous system’s (CNS) ability to recover following an injury. One method to achieve this involves counteracting the inhibitory environment induced by chondroitin sulfate proteoglycans (CSPGs) in the CNS’s extracellular matrix (ECM). A multifunctional growth factor called pleiotrophin (PTN) has been shown to interact with CSPGs to promote pro-growth processes without requiring CSPG degradation. Previous studies have outlined PTN’s neurotrophic effects; however, its exact role and downstream effectors post-stroke have yet to be fully explored.
In this study, we used RNA sequencing to characterize the changes in gene expression following PTN administration in mice cortices post-stroke and when anaplastic lymphoma kinase (ALK), a downstream effector of PTN, is blocked via alectinib. Photothrombosis was used to induce strokes on the right sensorimotor cortex of adult C57BL6/J mice, which were then given cortical PTN microinjections the following day. Mice in the experimental alectinib group were fed a daily diet of an alectinib/jelly mixture. The brains were extracted one week post-stroke, and RNA was isolated for sequencing. We found that PTN causes differential expression in stroke animals specifically, with an overrepresentation of developmental and proteoglycan ECM components among the upregulated genes – such as igf2, nrp2, vcan, and sdc3 – and a downregulation in genes related to synaptic integrity – such as psd95, sap90, camk2a, and shank1. Postulating that a downregulating synaptic integrity facilitates synaptogenesis, we provide evidence that PTN may have a beneficial effect after stroke by promoting neuroplasticity.Recommended posters
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