Non-traumatic injury accounts for approximately half of clinical spinal cord injury, including chronic spinal cord compression. However, previous rodent spinal cord compression models are mainly designed for rats, few...Non-traumatic injury accounts for approximately half of clinical spinal cord injury, including chronic spinal cord compression. However, previous rodent spinal cord compression models are mainly designed for rats, few are available for mice. Our aim is to develop a thoracic progressive compression mice model of spinal cord injury. In this study, adult wild-type C57BL/6 mice were divided into two groups: in the surgery group, a screw was inserted at T9 lamina to compress the spinal cord, and the compression was increased by turning it further into the canal(0.2 mm) post-surgery every 2 weeks up to 8 weeks. In the control group, a hole was drilled into the lamina without inserting a screw. The results showed that Basso Mouse Scale scores were lower and gait worsened. In addition, the degree of hindlimb dysfunction in mice was consistent with the degree of spinal cord compression. The number of motor neurons in the anterior horn of the spinal cord was reduced in all groups of mice, whereas astrocytes and microglia were gradually activated and proliferated. In conclusion, this progressive compression of thoracic spinal cord injury in mice is a preferable model for chronic progressive spinal cord compression injury.展开更多
Dear Editor, mTORCI, as a center regulatory hub of metabolism, senses the cellular energy status, nutrition and extracellular stimuli and regulates cell growth, differentiation and functions of immune cells (Powell et...Dear Editor, mTORCI, as a center regulatory hub of metabolism, senses the cellular energy status, nutrition and extracellular stimuli and regulates cell growth, differentiation and functions of immune cells (Powell et al., 2012). Lysosomal localization of key signal comp orients is critical for mTORCI activati on: mTORCI activation requires co-localization of activated Rheb and mTORCI to the lysosome membrane (Buerger et al., 2006). Signals in eluding growth factors, cellular stresses and energy levels act on the disruption the formation of tuberous sclerosis complex (TSC) complex, comprised of TSC1, TSC2 and TBC1D7, which leads to the translocation and activation of Rheb on the lysosome membrane (Dibble et al., 2012). In response to nutrient levels, specifically the availability of amino acids and glucose (Efeyan et al., 2013), mTORCI is recruited to the lysosomal surface by Rag GTPases that are heterodimers of RagA or RagC bound to RagB or RagD. Multiple protein complexes have been implicated in regulation of mTORCI upon nutrient sensing including Ragulator, GATOR1, GATOR2, KICSTOR and vacuolar ATPases (Wolfson et al., 2017). Vacuolar ATPases are large multiple-protein complexes that acidify the lysosome and may mediate additional functions independent of their proton pump activity (Nishi and Forgac, 2002).展开更多
基金supported by the National Natural Science Foundation of China,No.31400824a grant from the Science and Technology Program of Jiangmen City of China,No.2015751the Scientific Research and Cultivating Foundation of the First Clinical Medical College of Jinan University of China,No.2013208
文摘Non-traumatic injury accounts for approximately half of clinical spinal cord injury, including chronic spinal cord compression. However, previous rodent spinal cord compression models are mainly designed for rats, few are available for mice. Our aim is to develop a thoracic progressive compression mice model of spinal cord injury. In this study, adult wild-type C57BL/6 mice were divided into two groups: in the surgery group, a screw was inserted at T9 lamina to compress the spinal cord, and the compression was increased by turning it further into the canal(0.2 mm) post-surgery every 2 weeks up to 8 weeks. In the control group, a hole was drilled into the lamina without inserting a screw. The results showed that Basso Mouse Scale scores were lower and gait worsened. In addition, the degree of hindlimb dysfunction in mice was consistent with the degree of spinal cord compression. The number of motor neurons in the anterior horn of the spinal cord was reduced in all groups of mice, whereas astrocytes and microglia were gradually activated and proliferated. In conclusion, this progressive compression of thoracic spinal cord injury in mice is a preferable model for chronic progressive spinal cord compression injury.
文摘Dear Editor, mTORCI, as a center regulatory hub of metabolism, senses the cellular energy status, nutrition and extracellular stimuli and regulates cell growth, differentiation and functions of immune cells (Powell et al., 2012). Lysosomal localization of key signal comp orients is critical for mTORCI activati on: mTORCI activation requires co-localization of activated Rheb and mTORCI to the lysosome membrane (Buerger et al., 2006). Signals in eluding growth factors, cellular stresses and energy levels act on the disruption the formation of tuberous sclerosis complex (TSC) complex, comprised of TSC1, TSC2 and TBC1D7, which leads to the translocation and activation of Rheb on the lysosome membrane (Dibble et al., 2012). In response to nutrient levels, specifically the availability of amino acids and glucose (Efeyan et al., 2013), mTORCI is recruited to the lysosomal surface by Rag GTPases that are heterodimers of RagA or RagC bound to RagB or RagD. Multiple protein complexes have been implicated in regulation of mTORCI upon nutrient sensing including Ragulator, GATOR1, GATOR2, KICSTOR and vacuolar ATPases (Wolfson et al., 2017). Vacuolar ATPases are large multiple-protein complexes that acidify the lysosome and may mediate additional functions independent of their proton pump activity (Nishi and Forgac, 2002).