ABSTRACT
Glycogen synthase kinase 3 (GSK3), a prominent enzyme in carbohydrate metabolism, also has a major role in brain function. It is physiologically regulated by the kinase Akt, which phosphorylates GSK3 to inhibit catalytic activity. Inositol hexakisphosphate-1 (IP6K1) generates the inositol pyrophosphate diphosphoinositol pentakisphosphate (IP7), which physiologically inhibits Akt leading to enhanced GSK3 activity. We report that IP6K1 binds and stimulates GSK3 enzymatic activity in a non-catalytic fashion. Physiological relevance is evident in the inhibition of GSK3 activity in the brains of IP6K1-deleted mice. Behavioral alterations of IP6K1 knockout mice resemble those of GSK3 mutants. Accordingly, modulation of IP6K1-GSK3ß interaction may exert beneficial effects in psychiatric disorders involving GSK3.
Subject(s)
Glycogen Synthase Kinase 3/metabolism , Motor Activity/physiology , Phosphotransferases (Phosphate Group Acceptor)/physiology , Signal Transduction , Social Behavior , Amphetamine/pharmacology , Animals , Male , Mice , Mice, Knockout , Motor Activity/drug effects , Motor Activity/genetics , Phosphotransferases (Phosphate Group Acceptor)/genetics , Phosphotransferases (Phosphate Group Acceptor)/metabolism , Protein Binding , Rotarod Performance TestABSTRACT
BACKGROUND: Screening cytomegalovirus infection in pregnant women is still controversial in 2004 in France. In this context, we evaluated the interest of such a screening in 2004 in France. This paper was designed to describe trends in CMV prenatal screening practices in 2000-2003 in France. METHODS: This retrospective study, describes the prescription of CMV screening in HIV-negative pregnant women giving birth in the private care sector, according to their occupational category and geographical area. Data were provided by the "Caisse d'Assurance-maladie des Travailleurs Indépendants" (independent workers health insurance fund). RESULTS: The study included 34.347 women, delivering in 2001-2004 (beginning of pregnancy in 2000-2003). The number of pregnant women screened for CMV increased significantly between 2000 (5.8%, 301/5.177), 2001 (11.1%, 1.130/10.139) and 2002 (22.1%, 2.701/12.223), (p<0.001), then was stable in 2003 (22.0%, 1.496/6.808). The percentage of women screened for CMV, at least once during pregnancy, doubled between 2001 and 2002 (p<0.001) in each occupational category and geographical area. It was significantly different between occupational categories (p<0.01), with a higher percentage of women in the self-employed and commercial agent occupational categories than in the craftsman category. There was also a significant difference between geographical areas (p<0.001), with a higher rate in Paris. CONCLUSION: This study providing baseline information on CMV practices showed: 1- a significant increase in the frequency of CMV screening among pregnant women over the period 2000-2002 with a stabilization in 2003; 2- a similar trend observed in each occupation category and geographical area but with a markedly higher frequency of screening practices in the Paris area and among self-employed women. A study measuring the effect of the 2004 ANAES recommendation suggesting not to screen for CMV during pregnancy should be conducted.
