Abstracts

RATIONALE: Developmental treatment with AY-9944 (AY), leads to atypical absence epilepsy in waking adult rat and mice. AY induced spike and wave discharges (SWD) are recurrent and last life long. Whether abnormal EEG changes occur during sleep in AY treated subjects, remains to be determined. METHODS: Neonatal Long Evans hooded rats were either treated, every six days, with s.c. injection of AY (7.5 mg/Kg)(n=8)or saline to contros (n= 8), from postnatal day (P) 2 to P20. Chronic electrodes were implanted in AY treated and controls at P50 to perform ECoG and continuous video ECoG recordings from P55 onwards, to capture any abnormal behavior-electrical changes during awake and sleep in 12h-light-12h dark cycle with food and water ad libitum. RESULTS: During awake state, AY-9944 produced recurrent SWD lasting for 1447?303 sec/h,with a mean amplitude of 465?99uV associated with behavioral arrest, vibrissae twitching and facial myoclonia, and ability to move during seizures (n= 8)compared to SWD-like bursts lasting 26?25 sec/h and 142?70 uV in controls (n= 8). During sleep, AY induced SWD frequency increased from P50 to P120 and evolved into 5 Hz CSWSS associated with resting behavioral state and intermittent myclonic jerking movements by P150 to P250 (N= 4), compared to spontaneously intermittent sleep spindle (SS)like activity at 7- 9 Hz associated with resting state in controls (n= 4), (Mean CSWSS-SS% difference= -61, t= 18.12, df=6, two tailed p. < 0.0001 Unpaired t test). CONCLUSIONS: Cholesterol biosynthesis inhibition during rat development results in atypical absence seizures in awake state and continuous spike and wave with myoclonic jerking movements during slow wave sleep.