RRC ID 89281
Author Numakura Y, Tanaka M, Izawa T, Yamate J, Kuramoto T, Serikawa T, Kunisawa N, Shimizu S, Ohno Y, Kuwamura M.
Title Contrasting effects of PHD finger protein 24 (PHF24) on brain morphology of the spontaneous generalized tonic-clonic seizure model; Noda epileptic rat (NER) and Phf24-null rat.
Journal Exp Anim
Abstract Noda epileptic rat (NER) is a mutant model for epilepsy that exhibits spontaneous generalized tonic-clonic seizure. Epileptogenesis of NER remains to be elucidated; but it is detected an insertion of an endogenous retrovirus sequence in intron 2 of the PHD finger protein 24 (Phf24) gene. PHF24 is widely expressed in the soma of neurons and neuropil in the wild-type rat brain and spinal cord but significantly less expressed in NER. In addition, the characteristic PHF24 expressions were noted in the soma of specific populations of the inhibitory interneurons. Here, we first examined the morphology of the neurons and synapses in the brain of NER to evaluate the epileptogenesis of NER. In NER, the total number of neurons was decreased, but the inhibitory neurons were increased. Inhibitory synapses increased while excitatory synapses tended to decrease in NER. Secondary, we examined Phf24-null rat without symptom of seizures in the same manner and evaluate a contribution of PHF24 to the epileptogeneis of NER. Interestingly, the opposite trend was observed in Phf24-null rats, with a decrease in the inhibitory neurons and synapses, an increase trend in the excitatory synapses. PHF24 is considered to play an important role in maintaining of the inhibitory neurons in the rat brain. We conclude that the reduction of PHF24 might lead to impaired inhibitory signals and increase susceptibility to epilepsy in NER. The histopathological changes of NER in the present study may represent a secondary change to repeated seizures.
Published 2026-2-17
DOI 10.1538/expanim.25-0125
PMID 41708096
Resource
Rats NER/Kyo (StrainID=26) F344-Phf24em2Kyo (StrainID=131)