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Behav Brain Res ; 369: 111922, 2019 09 02.
Article in English | MEDLINE | ID: mdl-31039378

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.


Subject(s)
Cognitive Dysfunction/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Seizures/etiology , Animals , Central Nervous System/metabolism , Cognition/physiology , Cognition Disorders/genetics , Cognitive Dysfunction/metabolism , Emotions/physiology , Gene Knockout Techniques/methods , Intracellular Signaling Peptides and Proteins/genetics , Kindling, Neurologic/physiology , Male , Maze Learning/physiology , PHD Zinc Fingers/genetics , Rats , Rats, Inbred F344 , Receptors, GABA-B/genetics , Seizures/genetics , Seizures/metabolism
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