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Characterization and changes in neurotrophin receptor p75‐expressing motor neurons in SOD1 G93A G1H mice
Author(s) -
Smith Kevin S.,
Rush Robert A.,
Rogers MaryLouise
Publication year - 2015
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.23763
Subject(s) - biology , motor neuron , amyotrophic lateral sclerosis , low affinity nerve growth factor receptor , choline acetyltransferase , soma , sod1 , neuron , neurotrophin , neuroscience , receptor , medicine , endocrinology , superoxide dismutase , oxidative stress , central nervous system , disease , spinal cord , biochemistry
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 µm 2 motor neurons increased, whereas the larger 600–900 µm 2 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. J. Comp. Neurol. 523:1664–1682, 2015. © 2015 Wiley Periodicals, Inc.