Increased Expression of GAP43 in Interneurons in a Rat Model of Experimental Polymicrogyria

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.

Overlapping cortical malformations in patients with pathogenic variants inGRIN1andGRIN2B

“…Alternatively, it has been noted that MCD-associated NMDAR variants tend to have GOF effects 13. This is consistent with animal models of NMDAR agonist-induced polymicrogyria 34–36…”

De novo mutations in GRIN1 cause extensive bilateral polymicrogyria

“…Ibotenate is an agonist of both NMDA and glutamatergic metabotropic receptors. Intracerebral ibotenate injection in newborn mice ( Marret et al , 1995 ), hamsters ( Marret et al , 1996 ; Takano et al , 2004 ) and rats ( Takano and Matsui, 2015 ) causes a range of grey and white matter changes, including polymicrogyria-like lesions, similar to those seen following perinatal hypoxic/ischaemic insults. Over-stimulation of NMDA receptors is thought to lead to excitotoxicity due to excess calcium influx through the receptor channel ( Choi et al , 1988 ; Zhou et al , 2013 ).…”

Polymicrogyria in a miniature poodle dog: Clinical and MRI findings

“…These include a total of nine dogs, all of them standard poodles, and mention a single case of a golden retriever 6 . PMG has also been reported in laboratory rats, 7 calves, 6 and as an uncommon manifestation of Akabane viral infection in sheep 8 …”