Fasting-induced reduction in locomotor activity and reduced response of orexin neurons in carnitine-deficient mice

作者：Yoshida G; Li MX; Horiuchi M^*; Nakagawa S; Sakata M; Kuchiiwa S; Kuchiiwa T; Jalil MA; Begum L; Lu YB; Iijima M; Hanada T; Nakazato M; Huang ZL; Eguchi N; Kobayashi K; Saheki T

来源：Neuroscience Research, 2006, 55(1): 78-86.

DOI：10.1016/j.neures.2006.02.003

• body core temperature
• carnitine
• fasting
• fatty acid oxidation
• juvenile visceral steatosis (jvs)
• locomotor activity
• orexin
• sleep

We found reduced locomotor activity (LA) under fasting in systemic carnitine-deficient juvenile visceral steatosis (jvs(-/-)) mice. When food was withdrawn at 8:00 a.m. (lights-off at 7:00 p.m., 12 h/cycle), the nocturnal LA of jvs(-/-) mice was much less than the control (jvs(+/+) and jvs(+/-)) mice. LA recovered under carnitine or sucrose administration, but not under medium-chain triglyceride. In addition, fasted jvs(-/-) mice, without any energy supply, were activated by modafinil, a stimulator of the dopamine pathway. These results suggest that the reduced LA is not adequately explained by energy deficit. As the fasted jvs(-/-) mice showed lower body core temperature (BT), we examined the central nervous system regulating LA and BT. We found lower percentage of c-Fos positive orexin neurons in the lateral hypothalamus and reduced orexin-A concentration in the cerebrospinal fluid of fasted jvs(-/-) mice. Sleep analysis revealed that fasted jvs(-/-) mice had disruption of prolonged wakefulness, with a higher frequency of brief episodes of non-REM sleep during the dark period than fasted jvs(+/+) mice. These results strongly suggest that the reduced LA in fasted jvs(-/-) mice is related to the inhibition of orexin neuronal activity.

• 出版日期2006-5