Transgenic rats expressing dominant negative BMAL1 showed circadian clock amplitude reduction and rapid recovery from jet lag.

The circadian rhythms are endogenous rhythms of about 24 h, and are driven by the circadian clock. The clock centre locates in the suprachiasmatic nucleus. Light signals from the retina shift the circadian rhythm in the suprachiasmatic nucleus, but there is a robust part of the suprachiasmatic nucleus that causes jet lag after an abrupt shift of the environmental lighting condition. To examine the effect of attenuated circadian rhythm on the duration of jet lag, we established a transgenic rat expressing BMAL1 dominant negative form under control by mouse Prnp-based transcriptional regulation cassette [BMAL1 DN (+)]. The transgenic rats became active earlier than controls, just after light offset. Compared to control rats, BMAL1 DN (+) rats showed smaller circadian rhythm amplitudes in both behavioural and Per2 promoter driven luciferase activity rhythms. A light pulse during the night resulted in a larger phase shift of behavioural rhythm. Furthermore, at an abrupt shift of the light-dark cycle, BMAL1 DN (+) rat showed faster entrainment to the new light-dark cycle compared to controls. The circadian rhythm has been regarded as a limit cycle phenomenon, and our results support the hypothesis that modification of the amplitude of the circadian limit cycle leads to alteration in the length of the phase shift.

Transcutaneous cisternal puncture for sampling of cerebrospinal fluid in awake rat.

Reported cisternal puncture methods require the anesthetization and fixation of an animal within a stereotaxic frame. To determine the effect of anesthesia and animal fixation on the central nervous system (CNS), amino acid concentrations of cerebrospinal fluid (CSF) sampled by transcutaneous cisternal puncture were compared among awake rats, pentobarbital-anesthetized rats and pentobarbital-anesthetized rats fixed in a stereotaxic frame. Although the concentrations of many amino acids in the CSF of pentobarbital-anesthetized rats were lower than in awake rats, use of the stereotaxic frame resulted in significantly increased amino acid concentrations in the CSF. These data indicate that CSF sampling by transcutaneous cisternal puncture from awake rats is a suitable method for serial measurement of drug effects on the CNS.