Disentangling chemical and electrical effects of status epilepticus-induced dentate gyrus abnormalities
Daniela M S Moura1, Igor R P de Sales1, Juliana A Brandão1
1Brain Institute - UFRN, Natal, Brazil.
Abstract:
In rodents, status epilepticus (SE) triggered by chemoconvulsants can differently affect the proliferation and fate of adult-born dentate granule cells (DGCs). It is unknown whether abnormal neurogenesis results from intracellular signaling associated with drug-receptor interaction, paroxysmal activity, or both. To test the contribution of these factors, we systematically compared the effects of kainic acid (KA)- and pilocarpine (PL)-induced SE on the morphology and localization of DGCs generated before or after SE in the ipsi- and contralateral hippocampi of mice. Hippocampal insult was induced by unilateral intrahippocampal (ihpc) administration of KA or PL. We employed conditional doublecortin-dependent expression of the green fluorescent protein (GFP) to label adult-born cells committed to neuronal lineage either one month before (mature DGCs) or seven days after (immature DGCs) SE. Unilateral ihpc administration of KA and PL led to bilateral epileptiform discharges and focal and generalized behavioral seizures. However, drastic granule cell layer (GCL) dispersion occurred only in the ipsilateral side of KA injection, but not in PL-treated animals. Granule cell layer dispersion was accompanied by a significant reduction in neurogenesis after SE in the ipsilateral side of KA-treated animals, while neurogenesis increased in the contralateral side of KA-treated animals and both hippocampi of PL-treated animals. The ratio of ectopic neurons in the ipsilateral hippocampus was higher among immature as compared to mature neurons in the KA model (32.8% vs. 10.0%, respectively), while the occurrence of ectopic neurons in PL-treated animals was lower than 3% among both mature and immature DGCs. Collectively, our results suggest that KA- and PL-induced SE leads to distinct cellular alterations in mature and immature DGCs. We also show different local and secondary effects of KA or PL in the histological organization of the adult DG, suggesting that these unique epilepsy models may be complementary to our understanding of the disease. NEWroscience 2018.
Insights
Status epilepticus (SE) from kainic acid or pilocarpine affects adult neurogenesis differently. Kainic acid caused granule cell layer dispersion and reduced neurogenesis, while pilocarpine increased it, indicating distinct cellular alterations in the hippocampus.
Area of Science:
- Neuroscience
- Epilepsy Research
- Neurogenesis
Background:
- Status epilepticus (SE) impacts adult neurogenesis, but the specific mechanisms (drug-receptor interactions vs. seizure activity) remain unclear.
- Understanding how different chemoconvulsants induce SE and affect the brain is crucial for epilepsy research.
Purpose of the Study:
- To compare the effects of kainic acid (KA) and pilocarpine (PL)-induced SE on adult-born dentate granule cells (DGCs) in mice.
- To investigate whether SE-induced neurogenesis alterations stem from drug-receptor interactions or paroxysmal activity.
Main Methods:
- Induced unilateral SE using intrahippocampal KA or PL in mice.
- Utilized GFP to label mature and immature DGCs before and after SE.
- Analyzed DGC morphology, localization, and neurogenesis in ipsi- and contralateral hippocampi.
Main Results:
- KA-induced SE caused ipsilateral granule cell layer dispersion and reduced neurogenesis, with more ectopic immature neurons.
- PL-induced SE led to increased neurogenesis bilaterally, with minimal ectopic neurons.
- Both KA and PL induced bilateral epileptiform discharges and seizures.
Conclusions:
- KA- and PL-induced SE result in distinct cellular alterations in mature and immature DGCs.
- The findings highlight differential local and secondary effects of KA and PL on hippocampal organization.
- These distinct epilepsy models offer complementary insights into the disease.
