Gold-thioglucose-induced hypothalamic lesions inhibit metabolic modulation of light-induced circadian phase shifts in mice.
The circadian clock located in the suprachiasmatic nuclei is entrained by the 24-h variation in light intensity. The clock's responses to light can, however, be reduced when glucose availability is decreased. We tested the hypothesis that the ventromedial hypothalamus, a key area in the integration of metabolic and hormonal signals, mediates the metabolic modulation of circadian responses to light by injecting C57BL/6J mice with gold-thioglucose (0.6 g/kg) which damages glucose-receptive neurons, primarily located in the ventromedial hypothalamus. Light pulses applied during the mid-subjective night induce phase delays in the circadian rhythm of locomotor activity in mice kept in constant darkness. As previously observed, light-induced phase delays were significantly attenuated in fed mice pre-treated with 500 mg/kg i.p. 2-deoxy-D-glucose and in hypoglycemic mice fasted for 30 h, pre-treated with 5 IU/kg s.c. insulin or saline, compared to control mice fed ad libitum. In contrast, similar metabolic challenges in mice with gold-thioglucose-induced hypothalamic lesions did not significantly affect light-induced phase delays compared to mice treated with gold-thioglucose and fed ad libitum. These results indicate that destruction of gold-thioglucose-sensitive neurons in the ventromedial hypothalamus prevent metabolic regulation of circadian responses to light during shortage of glucose availability. Therefore, the ventromedial hypothalamus may be a central site coordinating the metabolic modulation of light-induced phase shifts of the circadian clock.
Challet
E
E
Center for Circadian Biology and Medicine, Department of Neurobiology and Physiology, Northwestern University, 2153 North Campus Drive, Evanston, IL 60208, USA.e-challet@nwu.edu
Bernard
D J
DJ
Turek
F W
FW
D000818:Animals; D006051:Aurothioglucose / Q000494:pharmacology*; D001522:Behavior, Animal / Q000528:radiation effects; D002940:Circadian Rhythm / Q000528:radiation effects*; D003847:Deoxyglucose / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D013493:Suprachiasmatic Nucleus / Q000378:metabolism; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism / Q000528:radiation effects
D005904:Glial Fibrillary Acidic Protein; D006051:Aurothioglucose; D003847:Deoxyglucose