BACKGROUND： Cortical motor neurons, also known as upper motor neurons, are large projection neurons whose axons convey signals to lower motor neurons to control the muscle movements. Degeneration of cortical motor ne...BACKGROUND： Cortical motor neurons, also known as upper motor neurons, are large projection neurons whose axons convey signals to lower motor neurons to control the muscle movements. Degeneration of cortical motor neuron axons is implicated in several debilitating disorders including hereditary spastic paraplegia （HSP）. Since the discovery of the first HSP gene, SPASTthat encodes spastin, over 70 distinct genetic loci associated with HSP have been identified. How the mutations of these functionally diverse genes result in axonal degeneration and why certain axons are affected in HSP remain largely unknown. The development of induced pluripotent stem cell （iPSC） technology has provided researchers an excellent resource to generate patient-specific human neurons to model human neuropathological processes including axonal defects. METHODS： In this article, we will first review the pathology and pathways affected in the common forms of liSP subtypes by searching the PubMed database. We will then summarize the findings and insights gained from studies using iPSC-based models, and discuss challenges and future directions. RESULTS： HSPs, a heterogeneous group of genetic neurodegenerative disorders, exhibit similar pathological changes that result from retrograde axonal degeneration of cortical motor neurons. Recently, iPSCs have been generated from several common forms of HSP including SPG4, SPG3A, and SPG11 patients. Neurons derived from HSP iPSCs exhibit impaired neurite outgrowth, increased axonal swellings, and reduced axonal transport, recapitulating disease-specific axonal defects. CONCLUSIONS： These patient-derived neurons offer a unique tool to study the pathogenic mechanisms and explore the treatments for rescuing axonal defects in HSP, as well as other diseases involving axonopathy.展开更多
In order to determine how nociceptive input conveyed by the C-fibers terminating in superficial lam-inae of the spinal cord reaches the wide dynamic range (WDR) cells in deeper dorsal horn, which functions as ascend-i...In order to determine how nociceptive input conveyed by the C-fibers terminating in superficial lam-inae of the spinal cord reaches the wide dynamic range (WDR) cells in deeper dorsal horn, which functions as ascend-ing projection pathway, the morphological features of some WDR cells in the deeper dorsal horn of the cat lumbar spinal cord were studied by intracellular injection of horseradish peroxidase and physiological characterization. One of the fully stained neurons with somata in lamina V and dendrites that entered lamina Ⅱ were examined by electron mi-croscopy. Immunogold staining of ultrathin sections through the labeled proximal dendrites in lamina Ⅱ revealed that these dendrites received numerous synapses from substance P and glutamate immunoreactive (IR) axons, which were considered originating from C-fibers. In addition, many GABA-IR terminals were found presynaptic to the labeled dendrites. The results, therefore, suggest that the information carried by primary afferent can be sent from the super-ficial dorsal horn to the deeper laminae through monosynaptic contacts between C-fiber terminals and the long dorsal dendrites of some WDR cells in the deeper laminae, and that GABAergic system is involved in postsynaptic control to modulate the transmission of nociceptive sensory information.展开更多
文摘BACKGROUND： Cortical motor neurons, also known as upper motor neurons, are large projection neurons whose axons convey signals to lower motor neurons to control the muscle movements. Degeneration of cortical motor neuron axons is implicated in several debilitating disorders including hereditary spastic paraplegia （HSP）. Since the discovery of the first HSP gene, SPASTthat encodes spastin, over 70 distinct genetic loci associated with HSP have been identified. How the mutations of these functionally diverse genes result in axonal degeneration and why certain axons are affected in HSP remain largely unknown. The development of induced pluripotent stem cell （iPSC） technology has provided researchers an excellent resource to generate patient-specific human neurons to model human neuropathological processes including axonal defects. METHODS： In this article, we will first review the pathology and pathways affected in the common forms of liSP subtypes by searching the PubMed database. We will then summarize the findings and insights gained from studies using iPSC-based models, and discuss challenges and future directions. RESULTS： HSPs, a heterogeneous group of genetic neurodegenerative disorders, exhibit similar pathological changes that result from retrograde axonal degeneration of cortical motor neurons. Recently, iPSCs have been generated from several common forms of HSP including SPG4, SPG3A, and SPG11 patients. Neurons derived from HSP iPSCs exhibit impaired neurite outgrowth, increased axonal swellings, and reduced axonal transport, recapitulating disease-specific axonal defects. CONCLUSIONS： These patient-derived neurons offer a unique tool to study the pathogenic mechanisms and explore the treatments for rescuing axonal defects in HSP, as well as other diseases involving axonopathy.
基金Project supported by the State Science and Technology Commission and the National Natural Science Foundation of China.
文摘In order to determine how nociceptive input conveyed by the C-fibers terminating in superficial lam-inae of the spinal cord reaches the wide dynamic range (WDR) cells in deeper dorsal horn, which functions as ascend-ing projection pathway, the morphological features of some WDR cells in the deeper dorsal horn of the cat lumbar spinal cord were studied by intracellular injection of horseradish peroxidase and physiological characterization. One of the fully stained neurons with somata in lamina V and dendrites that entered lamina Ⅱ were examined by electron mi-croscopy. Immunogold staining of ultrathin sections through the labeled proximal dendrites in lamina Ⅱ revealed that these dendrites received numerous synapses from substance P and glutamate immunoreactive (IR) axons, which were considered originating from C-fibers. In addition, many GABA-IR terminals were found presynaptic to the labeled dendrites. The results, therefore, suggest that the information carried by primary afferent can be sent from the super-ficial dorsal horn to the deeper laminae through monosynaptic contacts between C-fiber terminals and the long dorsal dendrites of some WDR cells in the deeper laminae, and that GABAergic system is involved in postsynaptic control to modulate the transmission of nociceptive sensory information.
