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Persistent expression of Fas/FasL mRNA in the mouse hippocampus after a single NMDA injection
1Department of Immunology, School of Medicine, Keimyung University, Taegu, Korea.
Abstract:
Synaptic reorganization plays a very important role in brain adaptations to environmental stimuli, diseases, and aging processes. The NMDA model of excitotoxic injury was used to investigate the long-term molecular changes in the surviving neural cells in the mouse hippocampus. We demonstrated that a single intraperitoneal injection of NMDA produces persistent expression of c-fos, c-jun, Fas, and Fas ligand (FasL) mRNA in the hippocampus for 5 months. To determine the cellular origin of those gene transcripts in our in vivo model, a glial cell line and primary fetal neuronal culture were used to investigate the inducibility of the c-fos, c-jun, Fas, and FasL mRNA by NMDA. Both c-fos and Fas mRNA expression was observed in the NMDA-treated glial or neuronal cultures; however, c-jun and FasL mRNA was undetectable in this study. In our in vivo model, mossy fiber sprouting and apoptosis were also observed up to 40 days after the NMDA injection. Therefore, we hypothesize that the observed long-term expression of c-fos, c-jun, Fas, and FasL mRNAs may reflect the ongoing synaptic reorganization.
Insights
This study shows N-methyl-D-aspartate (NMDA) induced persistent gene expression in mouse hippocampus for five months, suggesting ongoing synaptic reorganization after excitotoxic injury.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Synaptic plasticity is crucial for brain adaptation to various stimuli.
- Excitotoxic injury, modeled using NMDA, can induce long-term changes in neural cells.
Purpose of the Study:
- To investigate long-term molecular changes in mouse hippocampus following NMDA-induced excitotoxic injury.
- To determine the cellular origin of specific gene transcripts (c-fos, c-jun, Fas, FasL) after NMDA treatment.
Main Methods:
- Utilized an NMDA model of excitotoxic injury in mice.
- Analyzed persistent gene expression (c-fos, c-jun, Fas, FasL mRNA) in the hippocampus.
- Investigated gene inducibility in glial and primary neuronal cultures exposed to NMDA.
Main Results:
- NMDA injection led to persistent expression of c-fos, c-jun, Fas, and Fas ligand (FasL) mRNA in the hippocampus for up to 5 months.
- c-fos and Fas mRNA were inducible in both glial and neuronal cultures.
- c-jun and FasL mRNA were not detected in the cultured cells.
- Mossy fiber sprouting and apoptosis were observed up to 40 days post-NMDA injection.
Conclusions:
- Long-term expression of c-fos, c-jun, Fas, and FasL mRNAs in the hippocampus may indicate ongoing synaptic reorganization after excitotoxic injury.
- The cellular origins of these transcripts in vivo are likely a combination of neuronal and glial responses.