Persisting Rhythmicity

Much controversy has revolved around the circadian rhythm alteration after lesioning of the suprachiasmatic nuclei (SCN). Several investigators have claimed that all circadian rhythms are obliterated after bilateral lesioning of the SCN; others including ourselves have shown rhythm alteration to a differing extent for different variables rather than an overall obliteration after such intervention. Figures 13-15 provide evidence supporting the persistence of rhythms after bilateral lesioning of the SCN and illustrate the merits of chronobiometric analyses to obtain a valid interpretation of the data. Figure 13 shows the circadian temperature patterns in Fischer rats, without or with unilateral or bilateral lesions of the SCN. A visual inspection of the data (Figure 13/IIA) may erroneously convey the impression that rhythmicity is abolished. The use of chronobiologic techniques such as a plexogram (that is, the stacking of the data over an idealized anticipated cycle of 24 hours) shows that there is a persisting circadian pattern, albeit an altered one, with a reduced amplitude and an advanced phase, Figure 13/IIIB and C. This is also shown in curves obtained from several different animals (Figure 13/I). Whereas the circadian temperature amplitude of rats with a histologically validated bilateral lesioning of the SCN is much reduced, it is noteworthy that in rats with a unilateral lesion of the SCN, the amplitude is actually larger than that of sham-operated rats. Further evidence supporting the influence of planetary-interplanetary phenomena is provided by the fact that sham-operated rats and rats with a unilateral lesion of the SCN kept in continuous light of low intensity have a circadian period of core temperature that is desynchronized from 24 hours, with an average period close to the "lunar" day; this is not the case for rats with a bilateral lesioning of the SCN which can have either a shortened or lengthened circadian period (Figure 13/III).

Persistence of the circadian rhythmicity of the ³H-TdR incorporation into DNA of different organs and of the mitotic index of the corneal epithelium of BD₂F₁ female mice after bilateral lesioning of the SCN has also been extensively demonstrated by Scheving (Figure 14/I-VI). For animals with a bilateral lesion of the SCN, Pasley could not validate a circadian rhythm in the drinking of water, but demonstrated it (P=0.002) for the drinking of 5% ethanol (Figure 14/VII and VII). The SCN is not the sole or primary pacemaker of the entire circadian system.

Circadians have been shown to persist even during transient cortical (Figure 15/I) or lasting functional (Figure 15/II) brain ablation. Rectal temperature and blood eosinophils have been measured longitudinally on three patients with emotional disease (one catatonic and two paranoid schizophrenic adult women). In data from these patients, periodograms show the major peak at a trial period of 24 hours before treatment and near 24 hours rather than at 12 hours during 12-hourly electroshock, regression, and post-regression (Figure 15/IB and C).

A circadian rhythm in systolic and diastolic blood pressure, urinary excretion of sodium and potassium, as well as urine volume, is also shown to persist in a 4-year-old comatose girl (Figure 15/II), indicating that even the brain as a whole may not be necessary for the persistence of a circadian system in some physiologic variables.

The adrenal glands are also an important source of circadian rhythmicity. For instance, a circadian component of variation in the circulating eosinophil count cannot be demonstrated for patients with adrenocortical insufficiency (Figure 16/I, bottom), whereas in healthy people with either restricted or unrestricted activity, this rhythmicity is not only demonstrable, but amplified by enhanced motor activity. Whereas for patients with Addison's disease a circadian rhythm in eosinophil counts cannot be statistically validated, circadians persist, however, for serum iron (P<0.001). Whereas in intact rats a circadian rhythm can invariably be detected for pregenenolone, corticosterone and dehydroepiandrosterone, in adrenalectomized and orchidectomized rats, a circadian rhythm remains demonstrable for plasma pregnenolone and for brain dehydroepiandrosterone (Figure 16/II). Circadians of adrenal corticosterone also persist on the day after stepwise cerebral ablation (Figure 16/III).

Figures 13-16 indicate that both the adrenals and the brain are important organs for maintaining an unimpaired and coordinated circadian system, yet some circadian rhythmicity persists even after removal of either one of these organs, adding support to the concept of a cellular circadian component in the genetically anchored chronome.