Testicular androgens determining the incidence of spike-wave discharges in taiep rats: A model of H-ABC leukodystrophy

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Abstracto

  • Absence seizures are characterized as a generalized type of epilepsy that occurs during childhood. Importantly, absence seizures in children often discontinue after puberty. There is limited availability of animal models in which electroencephalography (EEG) can be performed in the long term; however, two absence seizure models, GAERS and WAG/Rij albino rats, are available. The taiep rat is a myelin mutant rat with tubulinopathy due to a tubulin β 4A gene mutation and characteristic spike-wave discharges (SWDs) that mimic absence seizure epilepsy in humans and the above rat models. This study aimed to analyze spike-wave discharges after an orchiectomy was performed on postnatal day (PND) 2 or PND 90 in adult rats; and SWDs was recorded in both groups on PND 104. The results suggest that androgens play a critical role in susceptibility to SWDs. In fact, orchiectomy during the neonatal period significantly reduced the frequency of spike-wave discharges. However, if an orchiectomy was performed in adulthood, then SWDs were significantly increased. The mean duration of spike-wave discharges did not differ among the groups tested. Acute administration of testosterone (1 mg/kg) did not change the frequency or duration of spike-wave discharges in the control group or both orchiectomized groups. Overall, this study is the first to show a dichotomic influence of testicular androgens on spike-wave discharges. These findings will have implications in children with this type of generalized epilepsy and may explain the disappearance of absence epilepsy in two-thirds of patients after puberty.

fecha de publicación

  • 2022

Palabras clave

  • Androgens
  • Demyelination
  • Leukodystrophy
  • Myelin
  • Seizures
  • Tubulinopathy

Volumen

  • Vol.782