Exacerbation of absence seizures by central prolactin in female taiep rats: An animal model of epilepsy-prone leukodystrophy

Abstract

Absence seizures are a type of generalized epilepsy characterized by spike-wave discharges (SWDs) in the electroencephalogram (EEG). This condition affects girls more frequently than boys and has a worse prognosis in women during puberty and adulthood. These characteristics of sexual dimorphism and age predominance could be attributed to changes in plasma hormone levels during development, particularly during puberty, which can modulate the cortico-thalamic circuit responsible for generating and sustaining SWDs. Prolactin is a peptide hormone secreted by adenohypophysis, exhibits sexual dimorphism and undergoes an increase during puberty. In this study, we employed female taiep rats, a well-validated animal model of leukodystrophy known as hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC). This model has a sexually dimorphic pattern of SWDs, with males exhibiting greater susceptibility to the condition. The rats were ovariectomized and electrodes were implanted for EEGs and a stainless-steel cannula for administration of rat prolactin via intracerebroventricular (i.c.v.) injection. Five 12-hour EEGs were performed with fixed 48-hour start intervals: the control EEG followed by i.c.v. prolactin administration at doses of 0.5, 1, 2, or 4 μg/2 μL. The frequency of SWDs increased significantly with the 2 and 4 μg/2 μL doses of prolactin. The mean duration of SWDs increased significantly with all doses evaluated, with the greatest effect observed 6 h after 4 μg/2 μL of prolactin, which doubled the mean duration obtained in control conditions. Additionally, prolactin 4 μg/2 μL significantly decreased the latency to the first SWDs. We propose that prolactin is capable of neuromodulating the thalamo-cortical circuit responsible for spike-wave discharges.