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Evaluation of Ago2 inhibition effects at damage length and functional recovery after spinal cord transection in rats

Grant number: 16/07716-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): October 01, 2016
Effective date (End): September 30, 2017
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Vera Paschon
Grantee:Giovanna Rossi Beltrame
Home Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

The spinal cord traumatic injury has devastating consequences, including autonomic deregulation, chronic pain, increased pain sensibility and often leads to more severe and debilitating conditions, such as paraplegia. Following the first insult, many processes take place in the organism, including cellular death, neuroinflammation, and glial scar formation, which worsen the patient's overall condition. Most of those processes are regulated by miRNAs, which plays important post-transcriptional roles in gene expression control. Distinct proteins regulate the function of miRNAs, argonaute 2 (AGO2) integrates RISC complex, mediating down-regulation of target mRNA due its catalytic activity which is responsible for "splicing" (Berezhna, Supekova et al. 2011). AGO2 specific roles in the lesion are not well understood, combining immunofluorescence, TUNEL assay, and behavioral tests the aim of this project is to evaluate the role of AGO2 in the functional recovery of forelimb movements and on the spread of secondary injury. To this end, rats will be submitted to spinal cord transection and pharmacological treatment with AGO2 inhibitor, aurintricarboxílic acid (ATA), directly in the lesion site. After 7 and 14 days, the motor and sensorial function recovery will be accessed by footprint analyzes, open field measures, and rotarod test. Moreover, we will analyze spinal cord after 1, 7 and 14 post-lesion employing molecular methods, as TUNEL assay and immunofluorescence. The approaches described above could contribute with future spinal cord therapies to restore the connectivity between brain and body.