CSPG-PTPσ blockade promote neurofilament growth and synaptic formation via regulating autophagy flux in spinal cord injury

Abstract

Abstract Chondroitin sulfate proteoglycans (CSPGs) play critical role in the pathology of spinal cord injury (SCI). CSPG can be induced by autophagy inhibition in astrocyte, however, CSPG impact on autophagy and its role in SCI was still unknown. We investigate intracellular sigma peptide (ISP) targeting protein tyrosine phosphatase σ (PTPσ), effect on autophagy and synaptic formation in SCI. We determined autophagy related protein light chain 3 (LC3) and p62, autophagosome-lysosome fusion related protein STX17 (syntaxin 17), and lysosome-associated membrane protein 2 (LAMP2), pre-synaptic marker synaptophysin (SYN) and postsynaptic density protein-95 (PSD-95) in vivo SCI and in vitro primary spinal neuron via western blot. The expression of LC3B and NeuN, LAMP2 and STX17, SYN and vesicular glutamate transporter 1(VGLUT1), neuronal growth-associated protein GAP-43 and neurofilament were determined via immunofluorescence (IF). The preserved neuron in the injured spinal cord were assessed via Nissl-staining and neurobehavioral function by Basso Mouse Scale (BMS) score. We found that ISP activated autophagy flux related level of LC3B and p62, autophagosome-lysosome fusion related LAMP2/STX17, excitatory synapse marker SYN/VGLUT1, axon growth related GAP-43/Neurofilament expression in SCI. ISP promote preserved number of motor neurons and improved neurobehavioral recovery after SCI. CSPG-PTPσ blockade restored autophagy flux, synaptic and neurofilament growth, and promote functional recovery in SCI. Our study extended CSPG-PTPσ role in autophagy flux regulation, synaptic function and functional recovery in SCI.