Serotonin hyperinnervation abolishes seizure susceptibility in Otx2 conditional mutant mice (Articolo in rivista)

Type
Label
  • Serotonin hyperinnervation abolishes seizure susceptibility in Otx2 conditional mutant mice (Articolo in rivista) (literal)
Anno
  • 2008-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1523/JNEUROSCI.2208-08.2008 (literal)
Alternative label
  • Tripathi PP, Di Giovannantonio LG, Viegi A, Wurst W, Simeone A, Bozzi Y. Tripathi PP, Di Giovannantonio LG, Viegi A, Wurst W, Simeone A, Bozzi Y (2008)
    Serotonin hyperinnervation abolishes seizure susceptibility in Otx2 conditional mutant mice
    in The Journal of neuroscience
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Tripathi PP, Di Giovannantonio LG, Viegi A, Wurst W, Simeone A, Bozzi Y. Tripathi PP, Di Giovannantonio LG, Viegi A, Wurst W, Simeone A, Bozzi Y (literal)
Pagina inizio
  • 9271 (literal)
Pagina fine
  • 9276 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 37 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • INCNR PISA (literal)
Titolo
  • Serotonin hyperinnervation abolishes seizure susceptibility in Otx2 conditional mutant mice (literal)
Abstract
  • The homeobox-containing transcription factor Otx2 is crucially involved in fate determination of midbrain neurons. Mutant mice, in which Otx2 was conditionally inactivated by a Cre recombinase expressed under the transcriptional control of the Engrailed1 (En1) gene (En1(cre/+); Otx2(flox/flox)), show a reduced number of dopaminergic neurons and an increased number of serotonergic neurons in the ventral midbrain. Despite these developmental anatomical alterations, En1(cre/+); Otx2(flox/flox) adult mice display normal motor function. Here, we further investigated the neurological consequences of Otx2 inactivation in adult En1(cre/+); Otx2(flox/flox) mice. Adult En1(cre/+); Otx2(flox/flox) mice showed increased serotonin (5-HT) levels in the pons, ventral midbrain, hippocampus (CA3 subfield), and cerebral cortex, as indicated by HPLC and immunohistochemistry. Conversely, SERT (5-HT transporter) levels were decreased in conditional mutant brains. As a consequence of this increased 5-HT hyperinnervation, En1(cre/+); Otx2(flox/flox) mice were resistant to generalized seizures induced by the glutamate agonist kainic acid (KA). Indeed, prolonged pretreatment of En1(cre/+); Otx2(flox/flox) mice with the 5- HT synthesis inhibitor para- chlorophenylalanine (pCPA) restored brain 5-HT content to control levels, fully reestablishing KA seizure susceptibility. Accordingly, c- fos mRNA induction after KA was restricted to the hippocampus in En1(Cre/+); Otx2(flox/flox) mice, whereas a widespread c- fos mRNA labeling was observed throughout the brain of En1(Cre/+); Otx2(flox/flox) mice pretreated with pCPA. These results clearly show that increased brain 5- HT levels are responsible for seizure resistance in En1(cre/+); Otx2(flox/flox) mice and confirm the important role of 5-HT in the control of seizure spread. (literal)
Prodotto di
Autore CNR

Incoming links:


Autore CNR di
Prodotto
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi
data.CNR.it