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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-wright14647134862021-08-03T06:36:52Z SK Channel Clustering in SOD1-G93A Motoneurons Dukkipati, Saihari Shekar Neurobiology Physiology Neurosciences ALS amyotrophic lateral sclerosis SK channels motoneurons motor neurons SOD1 potassium channels Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease that currently has no cure and extremely limited treatment options. The specific mechanisms that underlie motoneuron degeneration and death, which are classical features of this disease, are mostly unknown. This thesis tests the hypothesis that small-conductance calcium-activated potassium channels (SK) may be downregulated in ALS motoneurons, as suggested by computational modelling. SK channel expression was measured in spinal alpha-motoneuron cell bodies or somata of wildtype (WT) and mutant (mt) SOD1-G93A mice, a transgenic animal model of ALS. Quantitative immunohistochemical analysis of the developmental expression of SK channel isoforms SK2 and SK3 at various postnatal time points was performed to assess the effects of motoneuron degeneration on the level and/or pattern of protein expression on the somata of lower lumbar motor nuclei. Results indicate that the selective expression of SK3 may be gradually reduced over development in WT and mutant SOD1 mice but is affected by disease pathogenesis. In addition, SK channels appear to be clustered in both WT and mutant SOD1 motoneurons throughout development. However, SK clusters appear to be significantly smaller in mutant SOD1 motoneurons compared to their WT littermates. These changes indicate that the activity of SK channels, which regulate the firing rate of motoneurons, may be affected in ALS. 2016-05-31 English text Wright State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=wright1464713486 http://rave.ohiolink.edu/etdc/view?acc_num=wright1464713486 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Neurobiology
Physiology
Neurosciences
ALS
amyotrophic lateral sclerosis
SK channels
motoneurons
motor neurons
SOD1
potassium channels
spellingShingle Neurobiology
Physiology
Neurosciences
ALS
amyotrophic lateral sclerosis
SK channels
motoneurons
motor neurons
SOD1
potassium channels
Dukkipati, Saihari Shekar
SK Channel Clustering in SOD1-G93A Motoneurons
author Dukkipati, Saihari Shekar
author_facet Dukkipati, Saihari Shekar
author_sort Dukkipati, Saihari Shekar
title SK Channel Clustering in SOD1-G93A Motoneurons
title_short SK Channel Clustering in SOD1-G93A Motoneurons
title_full SK Channel Clustering in SOD1-G93A Motoneurons
title_fullStr SK Channel Clustering in SOD1-G93A Motoneurons
title_full_unstemmed SK Channel Clustering in SOD1-G93A Motoneurons
title_sort sk channel clustering in sod1-g93a motoneurons
publisher Wright State University / OhioLINK
publishDate 2016
url http://rave.ohiolink.edu/etdc/view?acc_num=wright1464713486
work_keys_str_mv AT dukkipatisaiharishekar skchannelclusteringinsod1g93amotoneurons
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