Forkhead box P (foxP) mRNA expression in the rat hippocampus negatively correlates with performance in a spatial memory paradigm

The family of forkhead box (fox) proteins, including foxP and foxJ are highly conserved mammalian homologues of transcription factors known to regulate life span in Caenorhabditis elegans. Although a strong expression of foxP2 in the CNS, specifically in the hippocampus has been repeatedly documented, data on its functional properties are scarce. First evidence from genetic studies indicates its implication in neuropsychiatric disease including severe speech and language disorder and autism. In an animal knockout model, foxp2-null mice exhibit a behavioural phenotype characterized by severe motor abnormalities, reduced life-span, and an absence of ultrasonic vocalizations (“separation calls“), which play a major role in the proper interaction between mother and pup. Employing gene chip microarray analysis of hippocampal mRNA from the rat with subsequent validation by real-time PCR we were able to deliver first evidenced for a direct negative correlation between foxP mRNA levels with spatial memory, assessed by the y-maze spontaneous alterations paradigm, while no correlation with other cognitive and neurobehavioural markers included in our test battery could be observed. Interestingly, in an animal model based on NMDA receptor antagonism mimicking aspects of psychosis, foxJ, another member of the fox family was markedly up-regulated. Previously, foxJ has not been directly implicated in CNS function or neurobehavioural disorders. These preliminary data urgently require furthe