Early Life Seizures Differentially Activate c-Fos in Hippocampal CA1 Cell Populations

Early life seizures (ELS) are quite different from those in adults and can be associated with longlasting deficits in cognitive and behavioral function. A majority of the epileptic syndromes that occur in childhood indicate that the developing brain has a great capability to generate seizures. The m...

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Autores principales: Bergan Babrowicz, Bo Xing, Frances Jensen
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Lenguaje:EN
Publicado: Appalachian State University Honors College 2021
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spelling oai:doaj.org-article:0c2f35eb4e0b420887096641b53ec77c2021-11-11T16:10:35ZEarly Life Seizures Differentially Activate c-Fos in Hippocampal CA1 Cell Populations1934-3361https://doaj.org/article/0c2f35eb4e0b420887096641b53ec77c2021-11-01T00:00:00Zhttps://impulse.appstate.edu/articles/2021/early-life-seizures-differentially-activate-c-fos-hippocampal-ca1-cell-populationshttps://doaj.org/toc/1934-3361Early life seizures (ELS) are quite different from those in adults and can be associated with longlasting deficits in cognitive and behavioral function. A majority of the epileptic syndromes that occur in childhood indicate that the developing brain has a great capability to generate seizures. The mechanisms of ELS include multiple molecular and cellular processes in the activitydependent subpopulation of neurons with the expression of immediate-early genes (IEGs, such as c-Fos). This present study used a transgenic mouse model, in which CreER and following tdTomato expression was driven by Fos promoter (FosTRAP1), to permanently label the ELSassociated cells in the CA1 region of the hippocampus. CreER is Cre recombinase to promote high-level expression. TdTomato is a red fluorescent protein to permanently label CreER recombination. We measured tdTomato expression in the hippocampus in brain sections from FosTRAP1 mice with and without seizures. The chemoconvulsant kainate (KA) induced seizures was associated with a statistically significant increase of c-Fos expression shown by permanent tdTomato fluorophore labeling. Video analysis determined that there was a statistically significant correlation between tonic-clonic seizure duration and c-Fos expression in FosTRAP1 mice. In immunohistochemistry (IHC) experiments, brain sections were stained with different neuronal markers (NeuN, Iba-2, GFAP, and GAD-67) to confirm cell identity. Image analysis revealed that the vast majority of stained cells were pyramidal neurons, based on colocalization of the NeuN labeled and tdTomato+ cells. IHC staining also determined there was minimal colocalization of tdTomato+ cells and neuronal markers in glial cells, astrocytes, and GABAergic inhibitory interneurons. Given the prevalence of intellectual disability and social deficits following seizures in early life, identification of cells activated by seizures will allow further studies to examine their structure and function after seizures, in order to identify new therapeutic targets for potential clinical use.Bergan Babrowicz,Bo XingFrances JensenAppalachian State University Honors Collegearticleearly life seizuresfostrapimmunohistochemistryhippocampusNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENImpulse: The Premier Undergraduate Neuroscience Journal (2021)
institution DOAJ
collection DOAJ
language EN
topic early life seizures
fostrap
immunohistochemistry
hippocampus
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
spellingShingle early life seizures
fostrap
immunohistochemistry
hippocampus
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Bergan Babrowicz,
Bo Xing
Frances Jensen
Early Life Seizures Differentially Activate c-Fos in Hippocampal CA1 Cell Populations
description Early life seizures (ELS) are quite different from those in adults and can be associated with longlasting deficits in cognitive and behavioral function. A majority of the epileptic syndromes that occur in childhood indicate that the developing brain has a great capability to generate seizures. The mechanisms of ELS include multiple molecular and cellular processes in the activitydependent subpopulation of neurons with the expression of immediate-early genes (IEGs, such as c-Fos). This present study used a transgenic mouse model, in which CreER and following tdTomato expression was driven by Fos promoter (FosTRAP1), to permanently label the ELSassociated cells in the CA1 region of the hippocampus. CreER is Cre recombinase to promote high-level expression. TdTomato is a red fluorescent protein to permanently label CreER recombination. We measured tdTomato expression in the hippocampus in brain sections from FosTRAP1 mice with and without seizures. The chemoconvulsant kainate (KA) induced seizures was associated with a statistically significant increase of c-Fos expression shown by permanent tdTomato fluorophore labeling. Video analysis determined that there was a statistically significant correlation between tonic-clonic seizure duration and c-Fos expression in FosTRAP1 mice. In immunohistochemistry (IHC) experiments, brain sections were stained with different neuronal markers (NeuN, Iba-2, GFAP, and GAD-67) to confirm cell identity. Image analysis revealed that the vast majority of stained cells were pyramidal neurons, based on colocalization of the NeuN labeled and tdTomato+ cells. IHC staining also determined there was minimal colocalization of tdTomato+ cells and neuronal markers in glial cells, astrocytes, and GABAergic inhibitory interneurons. Given the prevalence of intellectual disability and social deficits following seizures in early life, identification of cells activated by seizures will allow further studies to examine their structure and function after seizures, in order to identify new therapeutic targets for potential clinical use.
format article
author Bergan Babrowicz,
Bo Xing
Frances Jensen
author_facet Bergan Babrowicz,
Bo Xing
Frances Jensen
author_sort Bergan Babrowicz,
title Early Life Seizures Differentially Activate c-Fos in Hippocampal CA1 Cell Populations
title_short Early Life Seizures Differentially Activate c-Fos in Hippocampal CA1 Cell Populations
title_full Early Life Seizures Differentially Activate c-Fos in Hippocampal CA1 Cell Populations
title_fullStr Early Life Seizures Differentially Activate c-Fos in Hippocampal CA1 Cell Populations
title_full_unstemmed Early Life Seizures Differentially Activate c-Fos in Hippocampal CA1 Cell Populations
title_sort early life seizures differentially activate c-fos in hippocampal ca1 cell populations
publisher Appalachian State University Honors College
publishDate 2021
url https://doaj.org/article/0c2f35eb4e0b420887096641b53ec77c
work_keys_str_mv AT berganbabrowicz earlylifeseizuresdifferentiallyactivatecfosinhippocampalca1cellpopulations
AT boxing earlylifeseizuresdifferentiallyactivatecfosinhippocampalca1cellpopulations
AT francesjensen earlylifeseizuresdifferentiallyactivatecfosinhippocampalca1cellpopulations
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