Hypothalamic neuronal loss and altered circadian rhythm of temperature in a rat model of mesial temporal lobe epilepsy.
OBJECTIVE
Numerous dysfunctions in endogenous hypothalamic function have been associated with mesial temporal lobe epilepsy (MTLE). One endogenous activity is the circadian rhythm of temperature (CRT). In this study we examined whether hypothalamically mediated function is altered in the electrically induced, self-sustained, limbic status epilepticus model of MTLE. We then wished to determine whether there was a structural basis for regulatory alterations.


METHODS
We measured CRT with peritoneal temperature telemetry obtained in light-entrained (LD) and in free-running, constant-dark (DD) conditions. CRT from epileptic and controls of normal animals and kindled animals were quantized by fast Fourier transform-nonlinear least squares analysis to determine rhythmic complexity.


RESULTS
The circadian component of CRT was preserved in all animals. In DD, CRTs of epileptic animals were more complex than those of normal animals. CRT of kindled animals showed no increased complexity after electrically induced seizures. Neuronal density was decreased in regions of the anterior and posterior hypothalamus but not in the suprachiasmatic nuclei from the epileptic rats.


CONCLUSIONS
Alterations in CRT due to the epileptic state were independent of isolated seizures. Altered circadian thermoregulation in epileptic rats corresponded to regional hypothalamic neuronal loss. Structural changes of the hypothalamus may explain alterations in endogenous rhythms in MTLE.
Quigg
M
M
Department of Neurology, University of Virginia, Charlottesville 22908, USA. quigg@virginia.edu
Clayburn
H
H
Straume
M
M
Menaker
M
M
Bertram
E H
EH
D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology*; D002452:Cell Count; D002940:Circadian Rhythm / Q000502:physiology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004833:Epilepsy, Temporal Lobe / Q000209:etiology / Q000503:physiopathology*; D006624:Hippocampus / Q000502:physiology / Q000503:physiopathology; D007031:Hypothalamus / Q000166:cytology / Q000503:physiopathology*; D007696:Kindling, Neurologic / Q000502:physiology; D008297:Male; D009474:Neurons / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley