We are analyzing https://link.springer.com/article/10.1007/s00018-023-04824-6.

Title:
Activity-dependent regulation of the BAX/BCL-2 pathway protects cortical neurons from apoptotic death during early development | Cellular and Molecular Life Sciences
Description:
During early brain development, homeostatic removal of cortical neurons is crucial and requires multiple control mechanisms. We investigated in the cerebral cortex of mice whether the BAX/BCL-2 pathway, an important regulator of apoptosis, is part of this machinery and how electrical activity might serve as a set point of regulation. Activity is known to be a pro-survival factor; however, how this effect is translated into enhanced survival chances on a neuronal level is not fully understood. In this study, we show that caspase activity is highest at the neonatal stage, while developmental cell death peaks at the end of the first postnatal week. During the first postnatal week, upregulation of BAX is accompanied by downregulation of BCL-2 protein, resulting in a high BAX/BCL-2 ratio when neuronal death rates are high. In cultured neurons, pharmacological blockade of activity leads to an acute upregulation of Bax, while elevated activity results in a lasting increase of BCL-2 expression. Spontaneously active neurons not only exhibit lower Bax levels than inactive neurons but also show almost exclusively BCL-2 expression. Disinhibition of network activity prevents the death of neurons overexpressing activated CASP3. This neuroprotective effect is not the result of reduced caspase activity but is associated with a downregulation of the BAX/BCL-2 ratio. Notably, increasing neuronal activity has a similar, non-additive effect as the blockade of BAX. Conclusively, high electrical activity modulates BAX/BCL-2 expression and leads to higher tolerance to CASP3 activity, increases survival, and presumably promotes non-apoptotic CASP3 functions in developing neurons.
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Keywords {🔍}

neurons, activity, cell, pubmed, bax, bcl, article, neurocre, expression, google, scholar, neuronal, baxbcl, death, cas, cortical, flexcasp, gbz, ratio, fig, cultures, active, cells, caspase, anova, oneway, survival, test, central, postnatal, div, control, regulation, cortex, development, mice, early, apoptosis, effect, casp, inactive, analysis, levels, electrical, developmental, compared, activitydependent, significantly, protein, network,

Topics {✒️}

poly-l-ornithine-coated glass coverslips neuro-cre + flex-casp3 + gbz + bax inh carrying paav-ef1a-mcherry-ires-cre neuro-cre + flex-casp3 + bax inh neuro-cre + flex-casp3 + bax inhibitor double-transduced neuro-cre + flex-casp3 paav-hdlx-mcherry-ires-cre paav-ef1a-mcherry-ires-cre neuro-cre + flex-casp3 cultures compared neuro-cre + flex-casp3 + gbz 05 neuro-cre + flex-casp3 + gbz camp/pka/creb signalling pathway long-term activity-dependent regulations gaba-cre + flex-casp3 + gbz double transgenic arccre/+/r26ai14/+ mice goat anti-rabbit igg fire-polished glass pipettes cre-recombinase-positive interneurons showed article download pdf neuro-cre + flex-casp3 neuro-cre+flex-casp3 single-transduced neuro-cre cultures paav-flex-tacasp3-tevp bmp4/tbx3/neurod1 cascade csu-w1 spinning disk arc-cre/tdtomato expression allowed quantitative real-time pcr pro-apoptotic bax/bcl-2 ratio gaba-cre + flex-casp3 goat anti-mouse igg tris-buffered saline solution stable mcherry-cre expression rabbit monoclonal anti-neun somatosensory cortical region rabbit monoclonal beta-actin high-throughput cre reporting fluorophore-conjugated secondary antibody achieve single-cell resolution rapid nucleus-scale reorganization fine-tuning neuronal populations cre-recombinase/mcherry expression gabaa-receptor antagonist gabazine somatic arc-cre tdtomato luminescent caspase-glo assay hdlx-driven cre construct 120mea100/30ir-ti-gr neocortical cajal-retzius cells double heterozygous arccreert/+/r26ai14/+ akt serine–threonine kinase 1 bax-inhibiting peptide derived

Schema {🗺️}

WebPage:
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         headline:Activity-dependent regulation of the BAX/BCL-2 pathway protects cortical neurons from apoptotic death during early development
         description:During early brain development, homeostatic removal of cortical neurons is crucial and requires multiple control mechanisms. We investigated in the cerebral cortex of mice whether the BAX/BCL-2 pathway, an important regulator of apoptosis, is part of this machinery and how electrical activity might serve as a set point of regulation. Activity is known to be a pro-survival factor; however, how this effect is translated into enhanced survival chances on a neuronal level is not fully understood. In this study, we show that caspase activity is highest at the neonatal stage, while developmental cell death peaks at the end of the first postnatal week. During the first postnatal week, upregulation of BAX is accompanied by downregulation of BCL-2 protein, resulting in a high BAX/BCL-2 ratio when neuronal death rates are high. In cultured neurons, pharmacological blockade of activity leads to an acute upregulation of Bax, while elevated activity results in a lasting increase of BCL-2 expression. Spontaneously active neurons not only exhibit lower Bax levels than inactive neurons but also show almost exclusively BCL-2 expression. Disinhibition of network activity prevents the death of neurons overexpressing activated CASP3. This neuroprotective effect is not the result of reduced caspase activity but is associated with a downregulation of the BAX/BCL-2 ratio. Notably, increasing neuronal activity has a similar, non-additive effect as the blockade of BAX. Conclusively, high electrical activity modulates BAX/BCL-2 expression and leads to higher tolerance to CASP3 activity, increases survival, and presumably promotes non-apoptotic CASP3 functions in developing neurons.
         datePublished:2023-06-03T00:00:00Z
         dateModified:2023-06-03T00:00:00Z
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            Somatosensory cortex
            Postnatal development
            BCL-2 family
            Executor caspases
            Neuronal firing
            Cell Biology
            Biomedicine
            general
            Life Sciences
            Biochemistry
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ScholarlyArticle:
      headline:Activity-dependent regulation of the BAX/BCL-2 pathway protects cortical neurons from apoptotic death during early development
      description:During early brain development, homeostatic removal of cortical neurons is crucial and requires multiple control mechanisms. We investigated in the cerebral cortex of mice whether the BAX/BCL-2 pathway, an important regulator of apoptosis, is part of this machinery and how electrical activity might serve as a set point of regulation. Activity is known to be a pro-survival factor; however, how this effect is translated into enhanced survival chances on a neuronal level is not fully understood. In this study, we show that caspase activity is highest at the neonatal stage, while developmental cell death peaks at the end of the first postnatal week. During the first postnatal week, upregulation of BAX is accompanied by downregulation of BCL-2 protein, resulting in a high BAX/BCL-2 ratio when neuronal death rates are high. In cultured neurons, pharmacological blockade of activity leads to an acute upregulation of Bax, while elevated activity results in a lasting increase of BCL-2 expression. Spontaneously active neurons not only exhibit lower Bax levels than inactive neurons but also show almost exclusively BCL-2 expression. Disinhibition of network activity prevents the death of neurons overexpressing activated CASP3. This neuroprotective effect is not the result of reduced caspase activity but is associated with a downregulation of the BAX/BCL-2 ratio. Notably, increasing neuronal activity has a similar, non-additive effect as the blockade of BAX. Conclusively, high electrical activity modulates BAX/BCL-2 expression and leads to higher tolerance to CASP3 activity, increases survival, and presumably promotes non-apoptotic CASP3 functions in developing neurons.
      datePublished:2023-06-03T00:00:00Z
      dateModified:2023-06-03T00:00:00Z
      pageStart:1
      pageEnd:20
      license:http://creativecommons.org/licenses/by/4.0/
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         Programmed cell death
         Somatosensory cortex
         Postnatal development
         BCL-2 family
         Executor caspases
         Neuronal firing
         Cell Biology
         Biomedicine
         general
         Life Sciences
         Biochemistry
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                  address:
                     name:Institute of Physiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
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               type:PostalAddress
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      name:Davide Warm
      affiliation:
            name:University Medical Center of the Johannes Gutenberg University
            address:
               name:Institute of Physiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
               type:PostalAddress
            type:Organization
      name:Federico De Rosa
      url:http://orcid.org/0000-0003-3678-5244
      affiliation:
            name:University Medical Center of the Johannes Gutenberg University
            address:
               name:Institute of Physiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
               type:PostalAddress
            type:Organization
      name:Heiko J. Luhmann
      url:http://orcid.org/0000-0002-7934-8661
      affiliation:
            name:University Medical Center of the Johannes Gutenberg University
            address:
               name:Institute of Physiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
               type:PostalAddress
            type:Organization
      name:Anne Sinning
      url:http://orcid.org/0000-0002-1518-7272
      affiliation:
            name:University Medical Center of the Johannes Gutenberg University
            address:
               name:Institute of Physiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
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      name:Institute of Physiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
      name:Institute of Physiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
      name:Institute of Physiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
      name:Institute of Physiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany

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