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Publication

Lower susceptibility of insulin-regulated aminopeptidase knock-out mice to pentylenetetrazol-induced seizures.

Book Contribution - Book Chapter Conference Contribution

OBJECTIVES:

To study whether knock-out (KO) of insulin-regulated aminopeptidase (IRA P) can alter the seizure susceptibility in a pentylenetetrazol (PTZ) mouse seizure model.

BACKGROUND:

The peptide angiotensin IV (Ang IV ) is known to facilitate acquisition in spatial memory tasks and to influence seizure susceptibility. Ang IV has been shown to be antiepileptogenic in a mouse model of PTZ kindling. It is suggested that one of the mechanisms by which Ang IV exerts these effects is by inhibiting IRA P and consequently prolonging the half-life of neuropeptides in the brain. Indeed, Stragier et al. found that the Ang IV -mediated inhibition of pilocarpine induced seizures in rats was prevented by a somatostatin-2 receptor antagonist, suggesting the involvement of somatostatin-14. To unequivocally unravel the involvement of IRA P in seizure generation, IRA P mice were treated with PTZ to achieve acute generalized seizures.

RESULTS RESULTS:

Adult male and female IRA IRA IRA P wild-type (WT) and KO mice showed no differences in locomotor activity, as showed by an open field test. Basal EEG monitoring specified that WT and KO mice did not display spontaneous convulsions. Challenging these mice intravenously with PTZ resulted in an increased threshold in male IRA P KO mice in comparison with male IRA P WT mice. The PTZ thresholds were significantly higher for the myoclonic twitch, clonus without loss of reflexes and clonus with loss of reflexes. These behavioural data were confirmed by video-EEG monitoring. Female mice did not show any differences in PTZ thresholds.

CONCLUSIONS:

This study shows that male IRA P KO mice are less sensitive to the development of generalized seizures following PTZ administration and that IRA P is involved in seizure generation.
Book: Acta Neurologica Belgica, Supplement Volume 108
Series: Acta Neurologica Belgica, Supplement Volume 108
Publication year:2008
Keywords:IRAP, pentylenetetrazole, seizures, behaviour
  • ORCID: /0000-0002-0112-7471/work/82915162
  • ORCID: /0000-0003-2140-0751/work/62005124
  • ORCID: /0000-0002-6234-9908/work/61725336