Sporadic ALS Astrocytes Induce Neuronal Degeneration In Vivo. 2017

Kun Qian, and Hailong Huang, and Andrew Peterson, and Baoyang Hu, and Nicholas J Maragakis, and Guo-Li Ming, and Hong Chen, and Su-Chun Zhang
Department of Reproductive Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Astrocytes from familial amyotrophic lateral sclerosis (ALS) patients or transgenic mice are toxic specifically to motor neurons (MNs). It is not known if astrocytes from sporadic ALS (sALS) patients cause MN degeneration in vivo and whether the effect is specific to MNs. By transplanting spinal neural progenitors, derived from sALS and healthy induced pluripotent stem cells (iPSCs), into the cervical spinal cord of adult SCID mice for 9 months, we found that differentiated human astrocytes were present in large areas of the spinal cord, replaced endogenous astrocytes, and contacted neurons to a similar extent. Mice with sALS but not non-ALS cells showed reduced non-MNs numbers followed by MNs in the host spinal cord. The surviving MNs showed reduced inputs from inhibitory neurons and exhibited disorganized neurofilaments and aggregated ubiquitin. Correspondingly, mice with sALS but not non-ALS cells showed declined movement deficits. Thus, sALS iPSC-derived astrocytes cause ALS-like degeneration in both MNs and non-MNs.

UI MeSH Term Description Entries
D008297 Male Males
D009046 Motor Neurons Neurons which activate MUSCLE CELLS. Neurons, Motor,Alpha Motorneurons,Motoneurons,Motor Neurons, Alpha,Neurons, Alpha Motor,Alpha Motor Neuron,Alpha Motor Neurons,Alpha Motorneuron,Motoneuron,Motor Neuron,Motor Neuron, Alpha,Motorneuron, Alpha,Motorneurons, Alpha,Neuron, Alpha Motor,Neuron, Motor
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000690 Amyotrophic Lateral Sclerosis A degenerative disorder affecting upper MOTOR NEURONS in the brain and lower motor neurons in the brain stem and SPINAL CORD. Disease onset is usually after the age of 50 and the process is usually fatal within 3 to 6 years. Clinical manifestations include progressive weakness, atrophy, FASCICULATION, hyperreflexia, DYSARTHRIA, dysphagia, and eventual paralysis of respiratory function. Pathologic features include the replacement of motor neurons with fibrous ASTROCYTES and atrophy of anterior SPINAL NERVE ROOTS and corticospinal tracts. (From Adams et al., Principles of Neurology, 6th ed, pp1089-94) ALS - Amyotrophic Lateral Sclerosis,Lou Gehrig Disease,Motor Neuron Disease, Amyotrophic Lateral Sclerosis,Amyotrophic Lateral Sclerosis With Dementia,Amyotrophic Lateral Sclerosis, Guam Form,Amyotrophic Lateral Sclerosis, Parkinsonism-Dementia Complex of Guam,Amyotrophic Lateral Sclerosis-Parkinsonism-Dementia Complex 1,Charcot Disease,Dementia With Amyotrophic Lateral Sclerosis,Gehrig's Disease,Guam Disease,Guam Form of Amyotrophic Lateral Sclerosis,Lou Gehrig's Disease,Lou-Gehrigs Disease,ALS Amyotrophic Lateral Sclerosis,Amyotrophic Lateral Sclerosis Parkinsonism Dementia Complex 1,Amyotrophic Lateral Sclerosis, Parkinsonism Dementia Complex of Guam,Disease, Guam,Disease, Lou-Gehrigs,Gehrig Disease,Gehrigs Disease,Sclerosis, Amyotrophic Lateral
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001253 Astrocytes A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with MICROGLIA) respond to injury. Astroglia,Astroglia Cells,Astroglial Cells,Astrocyte,Astroglia Cell,Astroglial Cell,Astroglias,Cell, Astroglia,Cell, Astroglial
D013116 Spinal Cord A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER. Coccygeal Cord,Conus Medullaris,Conus Terminalis,Lumbar Cord,Medulla Spinalis,Myelon,Sacral Cord,Thoracic Cord,Coccygeal Cords,Conus Medullari,Conus Terminali,Cord, Coccygeal,Cord, Lumbar,Cord, Sacral,Cord, Spinal,Cord, Thoracic,Cords, Coccygeal,Cords, Lumbar,Cords, Sacral,Cords, Spinal,Cords, Thoracic,Lumbar Cords,Medulla Spinali,Medullari, Conus,Medullaris, Conus,Myelons,Sacral Cords,Spinal Cords,Spinali, Medulla,Spinalis, Medulla,Terminali, Conus,Terminalis, Conus,Thoracic Cords
D013569 Synapses Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions. Synapse

Related Publications

Kun Qian, and Hailong Huang, and Andrew Peterson, and Baoyang Hu, and Nicholas J Maragakis, and Guo-Li Ming, and Hong Chen, and Su-Chun Zhang
April 2010, Neuropathology : official journal of the Japanese Society of Neuropathology,
Kun Qian, and Hailong Huang, and Andrew Peterson, and Baoyang Hu, and Nicholas J Maragakis, and Guo-Li Ming, and Hong Chen, and Su-Chun Zhang
January 2014, Medecine sciences : M/S,
Kun Qian, and Hailong Huang, and Andrew Peterson, and Baoyang Hu, and Nicholas J Maragakis, and Guo-Li Ming, and Hong Chen, and Su-Chun Zhang
August 2011, Journal of neurology, neurosurgery, and psychiatry,
Kun Qian, and Hailong Huang, and Andrew Peterson, and Baoyang Hu, and Nicholas J Maragakis, and Guo-Li Ming, and Hong Chen, and Su-Chun Zhang
January 2022, Oxidative medicine and cellular longevity,
Kun Qian, and Hailong Huang, and Andrew Peterson, and Baoyang Hu, and Nicholas J Maragakis, and Guo-Li Ming, and Hong Chen, and Su-Chun Zhang
January 1999, Ryoikibetsu shokogun shirizu,
Kun Qian, and Hailong Huang, and Andrew Peterson, and Baoyang Hu, and Nicholas J Maragakis, and Guo-Li Ming, and Hong Chen, and Su-Chun Zhang
August 2011, Nature biotechnology,
Kun Qian, and Hailong Huang, and Andrew Peterson, and Baoyang Hu, and Nicholas J Maragakis, and Guo-Li Ming, and Hong Chen, and Su-Chun Zhang
October 2011, Proceedings of the National Academy of Sciences of the United States of America,
Kun Qian, and Hailong Huang, and Andrew Peterson, and Baoyang Hu, and Nicholas J Maragakis, and Guo-Li Ming, and Hong Chen, and Su-Chun Zhang
December 2015, Glia,
Kun Qian, and Hailong Huang, and Andrew Peterson, and Baoyang Hu, and Nicholas J Maragakis, and Guo-Li Ming, and Hong Chen, and Su-Chun Zhang
January 1996, Cold Spring Harbor symposia on quantitative biology,
Kun Qian, and Hailong Huang, and Andrew Peterson, and Baoyang Hu, and Nicholas J Maragakis, and Guo-Li Ming, and Hong Chen, and Su-Chun Zhang
September 2022, Cell metabolism,
Copied contents to your clipboard!