Reduced food anticipatory activity in genetically orexin (hypocretin) neuron-ablated mice.
Daily restricted feeding (RF) produces an anticipatory locomotor activity rhythm and entrains the peripheral molecular oscillator independently of the central pacemaker located in the suprachiasmatic nucleus (SCN). As orexins (hypocretins) are neuropeptides that coordinate sleep/wake patterns and motivated behaviours, such as food seeking, we studied the involvement of orexin in the food anticipatory activity (FAA) induced by RF. Daily RF shifted the mRNA rhythm of a clock-controlled gene mDbp in the cerebral cortex and caudate putamen but not in the SCN. Under these experimental conditions, prepro-orexin mRNA and orexin A immunoreactivity in the lateral hypothalamic area (LHA) did not show daily variation. Fasting increased the number of orexin A-ir cells, while RF did not. However, RF shifted the peak of Fos expression of the orexin neurons from night to day. Genetic ablation of orexin neurons in orexin/ataxin-3 transgenic mice severely reduced the formation of FAA under RF conditions. The expression of mNpas2 mRNA, a transcription factor thought to be involved in regulation of the food entrainable oscillator as well as mPer1 and mBmal1 mRNA, was reduced in the forebrain of orexin/ataxin-3 mice. Based on these results, we suggest that activity of the orexin neuron in the LHA contributes to the promotion and maintenance of FAA.
Akiyama
Masashi
M
Department of Pharmacology, School of Science and Engineering, Waseda University, 2-7-5 Higashifushimi, Nishitokyo, 202-0021, Japan.
Yuasa
Tomoyo
T
Hayasaka
Naomi
N
Horikawa
Kazumasa
K
Sakurai
Takeshi
T
Shibata
Shigenobu
S
D056930:ARNTL Transcription Factors; D000818:Animals; D000067699:Ataxin-3; D051792:Basic Helix-Loop-Helix Proteins; D001522:Behavior, Animal; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002940:Circadian Rhythm / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004435:Eating / Q000502:physiology; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005247:Feeding Behavior / Q000502:physiology*; D005508:Food Deprivation / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics; D009479:Neuropeptides / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D000068797:Orexins; D056950:Period Circadian Proteins; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D056930:ARNTL Transcription Factors; D000067699:Ataxin-3; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; D000068797:Orexins; D056950:Period Circadian Proteins; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; C538960:BMAL1 protein, human; C538961:Bmal1 protein, mouse; C498260:Dbp protein, mouse; C000596229:HCRT protein, human; C539022:PER1 protein, human; C539023:Per1 protein, mouse; C092341:ATXN3 protein, human; C511594:Atxn3 protein, mouse