Related Experiment Video
Updated: Jul 17, 2026
Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
Published on: April 24, 2021
Inducible cAMP early repressor (ICER) isoforms and neuronal apoptosis in cortical in vitro culture
Agata Klejman1, Leszek Kaczmarek
1Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, Pasteura 3, 02-093 Warsaw, Poland.
Abstract:
CREB activation and CREB-dependent signaling pathways are crucial for neuronal survival. The term ICER (inducible cAMP early repressor) refers to four protein isoforms that are all endogenous, inducible antagonists of CREB. Jaworski and others (2003) have previously shown that one of those isoforms, ICER IIgamma, is highly expressed in apoptotic neurons in vitro and its overexpression evokes neuronal death. In this study we investigated the role of all four ICER isoforms in cortical neuronal culture, comparing their expression level in serum-deprived/MK-801-treated neurons and their pro-apoptotic properties towards transfected cortical neurons. We have found that all four isoforms are induced upon pro-apoptotic treatment, and also that each of them separately evokes neuronal cell death following cortical culture transfection with the genes. The most efficiently induced, as well as the most effective in evoking neuronal cell death, were both ICER Igamma and IIgamma isoforms.
Insights
All four inducible cAMP early repressor (ICER) isoforms are elevated in neurons undergoing apoptosis. ICER Igamma and IIgamma most potently induce neuronal cell death, highlighting their role in programmed neuronal death.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Death Research
Background:
- CREB activation is vital for neuronal survival.
- ICERs are endogenous antagonists of CREB, inhibiting its signaling.
- Previous work identified ICER IIgamma's pro-apoptotic role in specific neuronal contexts.
Purpose of the Study:
- To investigate the role of all four ICER isoforms in neuronal apoptosis.
- To compare the expression levels of ICER isoforms in apoptotic cortical neurons.
- To assess the pro-apoptotic potential of each ICER isoform in cortical neurons.
Main Methods:
- Utilized cortical neuronal cultures.
- Induced apoptosis using serum deprivation and MK-801 treatment.
- Quantified ICER isoform expression levels.
- Transfected neurons with genes encoding ICER isoforms to evaluate cell death induction.
Main Results:
- All four ICER isoforms were found to be induced upon pro-apoptotic treatment.
- Each of the four ICER isoforms, when overexpressed, induced neuronal cell death.
- ICER Igamma and ICER IIgamma showed the highest induction levels and strongest pro-apoptotic effects.
Conclusions:
- All four ICER isoforms play a role in programmed neuronal death.
- ICER Igamma and ICER IIgamma are key mediators of apoptosis in cortical neurons.
- These findings elucidate the function of ICER isoforms in neuronal survival and death pathways.
