RRC ID 55777
Author Serikawa T, Kunisawa N, Shimizu S, Kato M, Alves Iha H, Kinboshi M, Nishikawa H, Shirakawa Y, Voigt B, Nakanishi S, Kuramoto T, Kaneko T, Yamamoto T, Mashimo T, Sasa M, Ohno Y.
Title Increased seizure sensitivity, emotional defects and cognitive impairment in PHD finger protein 24 (Phf24)-null rats.
Journal Behav Brain Res
Abstract Phf24 is known as Gαi-interacting protein (GINIP) and is associated with the GABAB receptor. To study the function of Phf24 protein in the central nervous system (CNS), we have newly developed Phf24-null rats and investigated their behavioral phenotypes, especially changes in seizure sensitivity, emotional responses and cognitive functions. Phf24-null rats did not exhibit any spontaneous seizures. However, they showed a higher sensitivity to pentylenetetrazol (PTZ)- or pilocarpine-induced convulsive seizures. Phf24-null rats also showed an elevated susceptibility to kindling development with repeated PTZ treatments, suggesting that Phf24 acts as an inhibitory modulator in epileptogenesis. Although young Phf24-null rats showed normal gross behaviors, elevated spontaneous locomotor activity, especially in terms of the circadian dark period, emotional hyper-reactivity, reduced anxiety behaviors in the elevated plus-maze (EPM) test, and cognitive deficits in the Morris water maze test were explicitly observed at older age (20-week-old). The present results suggest that Phf24 is essential for proper functioning of the CNS, especially in preventing epileptogenesis and controlling emotional and cognitive functions.
Volume 369
Pages 111922
Published 2019-9-2
DOI 10.1016/j.bbr.2019.111922
PII S0166-4328(19)30136-6
PMID 31039378
MeSH Animals Central Nervous System / metabolism Cognition / physiology Cognition Disorders / genetics Cognitive Dysfunction / genetics* Cognitive Dysfunction / metabolism Emotions / physiology Gene Knockout Techniques / methods Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism* Kindling, Neurologic / physiology Male Maze Learning / physiology PHD Zinc Fingers / genetics Rats Rats, Inbred F344 Receptors, GABA-B / genetics Seizures / etiology* Seizures / genetics Seizures / metabolism
IF 2.77
Times Cited 2
Rats F344/Stm (strainID=266)