Altered expression and modulation of activity-regulated cytoskeletal associated protein (Arc) in serotonin transporter knockout rats.
A gene variant in the human serotonin transporter (SERT) can increase the vulnerability to mood disorders. SERT knockout animals show similarities to the human condition and represent an important tool to investigate the mechanisms underlying the pathologic condition in humans. Along this line of thinking, we used SERT KO rats (SERT(+/-) and SERT(-/-)) to investigate abnormalities in the expression and function of the activity-regulated gene Arc (Activity-regulated cytoskeletal associated protein) and the early inducible gene Zif-268, (zinc finger binding protein clone 268), which are important players in neuronal plasticity. We found lower basal Arc mRNA levels in hippocampus and prefrontal cortex of mutant rats in comparison with wild-type animals. Moreover SERT mutant rats show altered stress responsiveness. Indeed an acute swim stress significantly up-regulated the levels of Arc mRNA in hippocampus and prefrontal cortex, as well as of Zif-268 in frontal cortex, only in SERT(+/-) and SERT(-/-) rats. These alterations may be associated to behavioral traits linked to SERT and may contribute to the neuroplastic and morphological changes observed in depression.
Molteni
Raffaella
R
Center of Neuropharmacology, Department of Pharmacological Sciences, Universita' di Milano, Via Balzaretti 9, 20133 Milan, Italy.
Calabrese
Francesca
F
Maj
Paola F
PF
Olivier
Jocelien D A
JD
Racagni
Giorgio
G
Ellenbroek
Bart A
BA
Riva
Marco A
MA
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D055786:Gene Knockout Techniques; D006624:Hippocampus / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000172:deficiency* / Q000235:genetics; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013550:Swimming / Q000502:physiology / Q000523:psychology
D000199:Actins; D003598:Cytoskeletal Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; C092069:activity regulated cytoskeletal-associated protein