Gene, cell, and axon changes in the familial amyotrophic lateral sclerosis mouse sensorimotor cortex.
Lower motoneuron abnormalities have been extensively documented in the murine model of familial amyotrophic lateral sclerosis, whereas information on corticospinal neurons in these mice is very limited. We investigated 1) mRNA levels of inflammation-related molecules in the deep layers in which corticospinal neurons reside, 2) corticospinal neurons labeled from tracer injections in the corticospinal tract at the cervical level, 3) axonal damage revealed by beta-amyloid precursor protein accumulation, and 4) glial cell activation in the sensorimotor cortex of presymptomatic and end-stage superoxide dismutase (SOD)-1 (G93A) mice. We demonstrated induction of inflammatory gene transcripts in the deep layers, early and progressive shrinkage of corticospinal cell bodies and activation of surrounding astrocytes and microglia with upregulation of major histocompatibility complex class I antigen. Accumulation of beta-amyloid precursor protein in proximal axonal swellings indicating axonal injury was also evident at the terminal stage in the motor cortex and internal capsule. Glial and axon changes were not observed elsewhere in the cortex. These data reveal that the entire motor circuit is affected in this murine amyotrophic lateral sclerosis model as it is in human amyotrophic lateral sclerosis. Sensorimotor cortical inflammation and progressive corticospinal cell body and fiber damage may reflect transsynaptic signaling of damage from lower motoneurons.
Kassa
Roman M
RM
Department of Morphological and Biomedical Sciences, University of Verona, Verona, Italy. roman@anatomy.univr.it
Mariotti
Raffaella
R
Bonaconsa
Marta
M
Bertini
Giuseppe
G
Bentivoglio
Marina
M
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001369:Axons / Q000473:pathology*; D039481:CD11b Antigen / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression / Q000235:genetics*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D011712:Pyramidal Tracts / Q000473:pathology; D013003:Somatosensory Cortex / Q000473:pathology*; D013266:Stilbamidines / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D016564:Amyloid beta-Protein Precursor; D039481:CD11b Antigen; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; C000606290:SOD1 protein, human; D013266:Stilbamidines; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1