title: Characterization and changes in neurotrophin receptor p75-Expressing motor neurons in SOD1(G93A) G1H mice [corrected].
abstract: Mice with high numbers of the Cu/Zn superoxide dismutase-1 G93A transgene (SOD1(G93A) G1H) have become the most commonly used animal model to study amyotrophic lateral sclerosis. This study investigated changes in size, numbers, and cell stress/death markers of motor neuron numbers in G1H mice that re-express the common p75 neurotrophin receptor (p75NTR). SOD1(G93A) G1H mice and age-matched C57BL/6J controls at 60, 80, 100, 120 days and end stage/140 days were analyzed for p75NTR, choline acetyltransferase (ChAT), activating transcription factor 3 (ATF3), and cleaved caspase-3. In addition, motor neuron counts and soma sizes were recorded. Motor neurons re-expressing p75NTR in SOD1(G93A) G1H mice were first observed at 80 days, and this continued to 140 days, peaking at 100-120 days at ∼5%. The soma area of motor neurons re-expressing p75NTR was always 600-800 µm(2) , suggesting that these are alpha motor neurons, which was confirmed after examination of somas post injection of a retrogradely transported antibody to p75NTR in 110-day-old SOD1(G93A) G1H mice. In motor neurons not re-expressing p75NTR, the frequency of small soma 200-400 µm2 motor neurons increased, whereas the larger 600-900 µm2 motor neurons decreased with progression, indicating that large motor neurons were dying off and shrinking in the process. There was minimal coexpression of p75NTR with ATF3, a marker for cell stress, but 85% coexpressed the apoptotic marker cleaved caspase-3. These findings indicate that in SOD1(G93A) G1H mice, p75NTR re-expression is detectable from 80 days in a small population of large motor neurons that represent 5% of the total motor neurons. Furthermore, p75NTR re-expression occurs in larger alpha motor neurons that express cleaved caspsase-3 and are destined to die.
authors.affiliation: Centre for Neuroscience, Department of Human Physiology, Flinders University, Adelaide, South Australia, Australia, 5001.
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Smith
authors.affiliation: Centre for Neuroscience, Department of Human Physiology, Flinders University, Adelaide, South Australia, Australia, 5001.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rush
authors.affiliation: Centre for Neuroscience, Department of Human Physiology, Flinders University, Adelaide, South Australia, Australia, 5001.
authors.forename: Mary-Louise
authors.initials: ML
authors.lastname: Rogers
mesh_terms: D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D048429:Cell Size; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D008159:Lumbar Vertebrae; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology*; D016501:Neurites / Q000378:metabolism / Q000473:pathology; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: D051700:Activating Transcription Factor 3; C103002:Atf3 protein, mouse; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D002795:Choline O-Acetyltransferase; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: RRID: AB_1852703; RRID: AB_2258513; RRID: AB_2314091; RRID: AB_2314176; RRID: AB_791009; RRID: IMSR_JAX:000664; RRID: IMSR_JAX:002300; RRID: nif-0000-30467; RRID: rid_000042; RRID: rid_000081; SOD1G93A; amyotrophic lateral sclerosis; p75NTR