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Published on: October 6, 2017
Increased expression of GAP43 in interneurons in a rat model of experimental polymicrogyria
Tomoyuki Takano1, Katsuyuki Matsui2
1Department of Pediatrics, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Japan tmyktkn@belle.shiga-med.ac.jp.
Insights
Polymicrogyria in rats lowers seizure threshold due to damage to inhibitory interneurons. This study found increased growth-associated protein GAP43 expression and vulnerable interneurons in affected brains, explaining seizure susceptibility.
Area of Science:
- Neuroscience
- Developmental Neuroscience
Background:
- Polymicrogyria is a cortical malformation associated with epilepsy.
- The underlying mechanisms contributing to seizure susceptibility in polymicrogyria remain unclear.
Purpose of the Study:
- To investigate seizure susceptibility in a rat model of polymicrogyria.
- To analyze seizure threshold and growth-associated protein GAP43 expression in this model.
Main Methods:
- Polymicrogyria was induced in rat neonates via intracerebral ibotenate injection.
- Seizure threshold was assessed using pentylenetetrazole injection.
- Interneuron and pyramidal cell populations were analyzed using immunofluorescence for GAP43 and parvalbumin.
Main Results:
- Polymicrogyria rats exhibited variable seizure severity after pentylenetetrazole administration, unlike control rats.
- Degenerating interneurons (Fluoro-Jade B-positive) were identified in polymicrogyria brains.
- Significantly higher GAP43 expression was observed in polymicrogyria brains, particularly in parvalbumin-positive interneurons.
Conclusions:
- The study identifies a selective vulnerability of inhibitory interneurons in polymicrogyria.
- This interneuron vulnerability is proposed as the basis for the decreased seizure threshold in this experimental model.
Abstract:
To investigate seizure susceptibility in polymicrogyria, the seizure threshold and growth-associated protein GAP43 expression were analyzed in a rat experimental model of polymicrogyria induced by intracerebral injection of ibotenate. A total of 72 neonates from 9 pregnant rats were used. Intraperitoneal pentylenetetrazole injection did not induce any seizure activity in the control rats, although it elicited seizures of variable severity in the polymicrogyria rats. Fluoro-Jade B-positive degenerating interneurons were found in the polymicrogyria brains; however, no such neurons were detected in the control brains. In the polymicrogyria rats, the GAP43 expression was significantly and widely distributed in the brain, and the percentage of parvalbumin-positive interneurons in the GAP43-positive cells was significantly higher than that observed in the nonphosphorylated neurofilament-positive pyramidal cells. We conclude that the relatively selective vulnerability of inhibitory interneurons constitutes the basis for the decreased seizure threshold observed in this model of polymicrogyria.
