M Quigg1, M Straume, T Smith, M Menaker, E H Bertram. 1. Comprehensive Epilepsy Program, Department of Neurology, University of Virginia, Box 394, Health Sciences Center, Charlottesville, VA 22908, USA. quigg@virginia.edu
Abstract
RATIONALE: Epileptic seizures may alter neuroendocrinological cycles. Light pulses induce phase shifts in circadian rhythms. Using hippocampal-kindled rats to ensure maximal clinical expression, we determined if seizures likewise induce phase shifts. METHODS: We monitored the circadian rhythm of temperature (CRT) with intraperitoneal radiotelemetry in rats (n=21) isolated from time cues and light for 3-week trials. Seizures were triggered with hippocampal electrical stimulation at different circadian phases. Optimized, least-error phase shifts were calculated from preictal and postictal CRTs. Induced seizures were referenced to CRT (t(max)=00:00, 24-h circadian cycle). RESULTS: Phase shifts (individual responses=57) differed across the circadian cycle. Rather than forming a clear phase-response curve, phase shifts were especially variable between 00:00 and 06:00 h. CONCLUSIONS: This study demonstrates that electrically-induced seizures induce advances and delays in CRT in a phase-dependent fashion but in a pattern different from typical light-induced phase shifts. Disorders of circadian regulation may contribute to some of the altered endogenous cycles associated with epilepsy.
RATIONALE: Epileptic seizures may alter neuroendocrinological cycles. Light pulses induce phase shifts in circadian rhythms. Using hippocampal-kindled rats to ensure maximal clinical expression, we determined if seizures likewise induce phase shifts. METHODS: We monitored the circadian rhythm of temperature (CRT) with intraperitoneal radiotelemetry in rats (n=21) isolated from time cues and light for 3-week trials. Seizures were triggered with hippocampal electrical stimulation at different circadian phases. Optimized, least-error phase shifts were calculated from preictal and postictal CRTs. Induced seizures were referenced to CRT (t(max)=00:00, 24-h circadian cycle). RESULTS: Phase shifts (individual responses=57) differed across the circadian cycle. Rather than forming a clear phase-response curve, phase shifts were especially variable between 00:00 and 06:00 h. CONCLUSIONS: This study demonstrates that electrically-induced seizures induce advances and delays in CRT in a phase-dependent fashion but in a pattern different from typical light-induced phase shifts. Disorders of circadian regulation may contribute to some of the altered endogenous cycles associated with epilepsy.
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