Effects of single cyclosporin A pretreatment on pentylenetetrazol-induced convulsion and on TRE-binding activity in the rat brain

https://doi.org/10.1016/0169-328X(95)00102-XGet rights and content

Abstract

Using electrophoretic mobility-shift assay (EMSA), we examined changes in DNA-binding activities of transcriptional factor-activated protein-1 (AP-1), which is a Fos-Jun protein complex, onto its responsive element THE in the hippocampus and amygdaloid nucleus of rats stimulated with pentylenetetrazol (PTZ) injection, and also investigated the effects of a single administration of the immunosuppressant cyclosporin A (CsA). In EMSA with nuclear extracts from the rat brain, the TRE-binding activity of AP-1 in the hippocampus and amygdaloid nucleus markedly increased 2 h after the PTZ injection (75 mg/kg, i.p.). These PTZ-induced increases of the TRE-binding protein in these regions were completely suppressed by pretreatment with CsA (5 mg/kg, s.c.) 1 h before the PTZ injection. In addition, the administration of CsA significantly ameliorated PTZ-induced convulsion. This therapeutic effect of single CsA pretreatment may be based, in part, on the effects on the TRE-binding activity of AP-1 in the brain. Since single pretreatment of CsA in the present study had no effect on the PTZ-induced induction of c-fos mRNA, c-jun mRNA, Fos protein nor Jun protein, the inhibitory effects of single CsA administration on PTZ-induced TRE-binding activity in the brain may be related to the effects of CsA on AP-1 itself. These results suggest that an immune response via activation of transcriptional factor in the brain tissue is involved in the convulsion.

References (36)

  • AsanumaM. et al.

    Effects of repeated immunosuppressant treatment on rat pentylenetetrazol-induced convulsion

    Jpn. J. Psychiatr. Neurol

    (1994)
  • AsanumaM. et al.

    Opposite effects of rough and gentle handling with repeated saline administration on c-fos mRNA expression in the rat brain

    J. Neural. Transm.

    (1992)
  • AsanumaM. et al.

    Effects of repeated injection of cyclosporin A on pentylenetetrazol-induced convulsion and cyclophilin mRNA levels in rat brain

    Neurochem. Res.

    (1995)
  • NoumaP.A.

    Determining the prognosis of childhood epilepsies by establishing immune abnormalities

    Clin. Neurol. Neurosurg.

    (1992)
  • ClipstoneN.A. et al.

    Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation

    Nature

    (1992)
  • DowL.W. et al.

    Response to alpha-interferon in children with Philadelphia chromosome-positive chronic myelocytic leukemia

    Cancer

    (1991)
  • ElliotJ.F. et al.

    Induction of interleukin 2 mRNA inhibited by Cyclosporin A

    Science

    (1984)
  • EmmelE.A. et al.

    Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell activation

    Science

    (1989)
  • Cited by (26)

    • Different preparations, doses, and treatment regimens of cyclosporine a cause adverse effects but no robust changes in seizure thresholds in rats

      2015, Epilepsy Research
      Citation Excerpt :

      Indeed, contrary results are available from in vivo investigations in rodents regarding the modulation of seizure susceptibility by CsA. Some studies revealed proconvulsant effects (Asanuma et al., 1995b; Famiglio et al., 1989; Fujisaki et al., 2002; Racusen et al., 1988, 1990; Setkowicz et al., 2004; Shuto et al., 1999; Yamauchi et al., 2005), while others showed anticonvulsant effects by CsA treatment (Asanuma et al., 1995a; Homayoun et al., 2002; Jung et al., 2012; Moia et al., 1994; Setkowicz and Ciarach, 2007). Similarly, several in vitro studies also revealed either an initiation or increase (Gorji et al., 2002; Wong and Yamada, 2000) or a decrease (Jung et al., 2012) of epileptiform activity in brain slice recordings in response to CsA.

    View all citing articles on Scopus
    View full text