Use of pregabalin to study Central and Peripheral Nervous System and Muscular System in the MDX Mice

• Grant number: 15/14385-7
• Support type: Regular Research Grants
• Duration: February 01, 2017 - January 31, 2019
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Gustavo Ferreira Simoes
• Grantee: Gustavo Ferreira Simoes
• Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Assoc. researchers: Alexandre Leite Rodrigues de Oliveira ; Taize Machado Augusto

Abstract

Currently, much is known about muscle involvement in DMD, but few studies have focused on the effects on the central nervous system (CNS), specifically in the motor and sensory neuron on the spinal cord microenvironment and spinal ganglion. It is known that during the course of the disease, the axon terminal,in the neuromuscular junction, enter a denervation cycle and reinnervation simulating that way, a peripheral nerve injury that can directly influence the motor and sensory neurons. he pregabalin (Lyrica, Pfizer) is a drug similar to GABA (gamma-aminobutyric acid) used as an anticonvulsant. Pregabalin binds the ±2´ subunit (type1) of voltage-gated calcium channels attenuating the calcium influx into the neuronal cell. Among its neuroprotective effects we can mention the reduction of neurotransmitter release after inflammation, modulation of excitatory synaptic transmission, anti-apoptotic and anti-inflammatory effects, inducing the improvement of motor function, reduction in the levels of caspase-3, increase the expression of GFAP (GlialFibrilaryAcidProtein) and microglia after spinal cord injury. The aims of this work are promote a favorable microenvironment for the central and peripheral nerve regeneration as well as in skeletal muscle system MDX mice (animal models for the study of Duchenne Muscular Dystrophy) showing degeneration processes / muscle regeneration already in the first weeks life. So, we allowed the improvement of disease symptoms and improved quality of life and survival of the studied model.At the same time of muscle degenerative process we will promote peripheral nerve injury, with the purpose of enhancing the damage at the spinal cord microenvironment , in the sciatic nerve, spinal ganglia and skeletal muscle fibers in order to better understand the mechanisms of the treatment level morphological, molecular and functional both with analysis in vivo and in vitro. Preliminary studies in our laboratory have shown that pregabalin is presented as a neuroprotective potential to neuromuscular diseases, especially Duchenne Muscular Dystrophy. The MDX mice treated with pregabalin showed increase synaptic circuits in the alpha motor neuron microenvironment after sciatic nerve lesion (around 31% compared to the untreated group). We can see also that the glial reactivity presented is reduced in the group treated with pregabalin (around 64% compared to the untreated group). We believe that, from the results obtained in this project may provide information for better understanding of the mechanisms involved in the processes related to the CNS and PNS during muscle degeneration processes. (AU)