Suprachiasmatic regulation of circadian rhythms of gene expression in hamster peripheral organs: effects of transplanting the pacemaker.
Neurotransplantation of the suprachiasmatic nucleus (SCN) was used to assess communication between the central circadian pacemaker and peripheral oscillators in Syrian hamsters. Free-running rhythms of haPer1, haPer2, and Bmal1 expression were documented in liver, kidney, spleen, heart, skeletal muscle, and adrenal medulla after 3 d or 11 weeks of exposure to constant darkness. Ablation of the SCN of heterozygote tau mutants eliminated not only rhythms of locomotor activity but also rhythmic expression of these genes in all peripheral organs studied. The Per:Bmal ratio suggests that this effect was attributable not to asynchronous rhythmicity between SCN-lesioned individuals but to arrhythmicity within individuals. Grafts of wild-type SCN to heterozygous, SCN-lesioned tau mutant hamsters not only restored locomotor rhythms with the period of the donor but also led to recovery of rhythmic expression of haPer1, haPer2, and haBmal1 in liver and kidney. The phase of these rhythms most closely resembled that of intact wild-type hamsters. Rhythmic gene expression was also restored in skeletal muscle, but the phase was altered. Behaviorally effective SCN transplants failed to reinstate rhythms of clock gene expression in heart, spleen, or adrenal medulla. These findings confirm that peripheral organs differ in their response to SCN-dependent cues. Furthermore, the results indicate that conventional models of internal entrainment may need to be revised to explain control of the periphery by the pacemaker.
Guo
Hongnian
H
Department of Biology and Program in Neuroscience and Behavior, University of Massachusetts, Amherst, Massachusetts 01003, USA.
Guo
Hongian
H
Brewer
Judy McKinley
JM
Lehman
Michael N
MN
Bittman
Eric L
EL
D056930:ARNTL Transcription Factors; D000313:Adrenal Medulla / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000502:physiology*; D006224:Cricetinae; D004622:Embryo, Mammalian; D015870:Gene Expression / Q000502:physiology*; D006321:Heart / Q000502:physiology; D017403:In Situ Hybridization / Q000379:methods; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008647:Mesocricetus; D009043:Motor Activity / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056950:Period Circadian Proteins; D010507:Periodicity; D012333:RNA, Messenger / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000502:physiology* / Q000637:transplantation*; D013997:Time Factors; D016378:Tissue Transplantation / Q000379:methods; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014667:Vasopressins / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D014667:Vasopressins; D016875:tau Proteins; C538961:Bmal1 protein, mouse; C513312:Per2 protein, mouse