Astrocytes interact intimately with degenerating motor neurons in mouse amyotrophic lateral sclerosis (ALS)

UMMS Affiliation

Department of Psychiatry; Department of Pharmacology and Molecular Toxicology; Department of Cell Biology; Neuroscience Program

Publication Date


Document Type



Amyotrophic Lateral Sclerosis; Animals; Astrocytes; Gliosis; Humans; Image Processing, Computer-Assisted; Mice; Mice, Transgenic; Mitochondria; Motor Neurons; Mutation; *Nerve Degeneration; Reference Values; Superoxide Dismutase; Vacuoles


Cell Biology | Nervous System Diseases | Neurology | Neuroscience and Neurobiology | Psychiatry


Astrocytic proliferation and hypertrophy (astrogliosis) are associated with neuronal injury. However, neither the temporal nor the spatial relationship between astrocytes and injured neurons is clear, especially in neurodegenerative diseases. We investigated these questions in a mouse amyotrophic lateral sclerosis (ALS) model. The initial increase in astrogliosis coincided with the onset of clinical disease and massive mitochondrial vacuolation in motor neurons. After disease onset, astrogliosis increased further in parallel with the number of degenerating motor neurons. Examination of individual astrocytes by three-dimensional reconstruction revealed that astrocytes extended their processes toward, wrapped around, and sometimes penetrated vacuoles derived from neuronal mitochondria. These results show a close temporal correlation between the onset of neuronal degeneration and the beginning of astrogliosis in this neurodegenerative disease and reveal a novel spatial relationship that is consistent with the view that astrocytes play an active role in the neuronal degeneration process.

DOI of Published Version



Glia. 1999 Dec;28(3):215-24. DOI: 10.1002/(SICI)1098-1136(199912)28:3<215::AID-GLIA5>3.0.CO;2-C Link to article on publisher's site

Journal/Book/Conference Title



Medical student John B. Levine participated in this study as part of the Senior Scholars research program at the University of Massachusetts Medical School.

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Link to Article in PubMed

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