Biomedical subjects
Publications and source records attributed to W J Schwartz.
Quantitative values representing the length, girth, volume, shape, and cell counts of the suprachiasmatic nuclei (SCN) were measured in BALB/cByJ and C57BL/6J inbred mouse strains, which exhibit a large interstrain difference in the free-running period of their circadian locomotor rhythms. There were no differences in the gross architectural features of the SCN in these two strains.
BACKGROUND AND PURPOSE: Central nervous system complications of cardiac catheterization are most often attributed to embolic events that occur at the time of catheter manipulation. Nevertheless, the reason that over 50% of these events are localized to the posterior circulation remains unexplained. One potential explanation offered for this preponderance is the use of the brachial artery approach. In this report, we examined the relation between the route of catheterization and central nervous system complications. SUMMARY OF REPORT: We retrospectively analyzed all central nervous system complications that occurred after cardiac catheterization through a femoral route at our institution over a 3 1/2-year period. Thirteen patients were identified as having central nervous system complications. Using defined criteria, posterior circulatory events still accounted for at least 54% of central nervous system complications. CONCLUSIONS: The preponderance of posterior circulatory events is apparently independent of the route of catheterization. Furthermore, given the array of neurological symptoms and their often complete resolution, we feel it is unlikely that embolism is the sole pathophysiological mechanism involved in these events.
Cell bodies in the rat suprachiasmatic nucleus (SCN) were labeled with an antibody against a small domain of the period (per) protein, the product of a gene in Drosophila that regulates circadian rhythms. In immunoblots of SCN protein extracts, the antibody recognized a band of approximately 115 kD, as well as a heterogeneous antigen ranging from 160 kD to 170 kD. The antibody was found in previous studies to label putative circadian pacemaker neurons in Aplysia and Bulla, as well as the cellular sites of per expression in flies. Taken together, these results suggest that the region of the per protein recognized by this antibody may be widely conserved in neuronal circadian pacemakers.
Entrained and free-running rhythms of wheel-running activity were recorded in male BALB/cByJ mice with electrolytic lesions of the suprachiasmatic nucleus (SCN), site of a circadian pacemaker in mammals. Complete ablation of the nucleus abolished the circadian locomotor rhythm; in some cases, wheel-running was synchronized by a light-dark cycle, but the phase relationship of this activity to the cycle was often aberrant. Unilateral lesions or those missing the SCN did not eliminate rhythmicity.
We previously reported the results of an experimental paradigm in which tetrodotoxin (TTX) was chronically infused by miniosmotic pump into the rat suprachiasmatic nuclei (SCN) (Schwartz et al., 1987). Although TTX reversibly blocked photic entrainment and overt expression of the circadian drinking rhythm, the circadian pacemaker in the SCN continued to oscillate unperturbed by the toxin, and we concluded that Na(+)-dependent action potentials are not a part of the SCN pacemaker's internal timekeeping mechanism. In the research reported in the present paper, we used our paradigm to chronically infuse other agents, in order to evaluate the validity of this interpretation further. (1) Infusion of 50% procaine into the SCN of blinded rats resulted in a disorganized circadian drinking rhythm during the infusion, after which behavioral rhythmicity returned without apparent phase shift. In intact rats, procaine reduced the phase-resetting action of a reversed light-dark cycle imposed during the infusion. Thus, the effects of voltage-dependent Na+ channel blockade by a local anesthetic resemble those produced by TTX. (2) Infusion of high (20 mM) K+ or 100 microM veratridine into the SCN of blinded rats resulted in an apparent phase advance of the circadian drinking rhythm by over 4 hr. The phase-shifting effect of veratridine was blocked by simultaneous infusion of 1 microM TTX. Thus, membrane depolarization or direct activation of voltage-dependent Na+ channels can affect the pacemaker's oscillation. Our infusion paradigm can detect alterations of rhythm phase, and the lack of phase shift after TTX or procaine infusion is not an artifact of an insensitive method.
Mammalian circadian rhythmicity is endogenously generated by a pacemaker in the suprachiasmatic nuclei and precisely entrained to the 24-hr day/night cycle by periodic environmental light cues. We show that light alters the immunoreactive levels of a transcriptional regulatory protein, Fos, in the suprachiasmatic nuclei of albino rats. Photic regulation of Fos immunoreactivity does not occur in other retino-recipient brain areas except for the intergeniculate leaflet, which appears to be involved in mediating some of the complex effects of light on expressed circadian rhythms. Our results point to a promising new functional marker for the cellular effects of light and suggest that the expression of Fos or a related nuclear protein may be part of the mechanism for photic entrainment of the circadian clock to environmental light/dark cycles.
The 14C-labeled 2-deoxy-D-glucose technique was used to measure in vivo glucose utilization of the suprachiasmatic nuclei (SCN) of Turkish and golden hamsters during the middle hours of the light phase of the 12:12 h light-dark cycle. The nuclei were clearly visible on autoradiographs made from the brains of Turkish hamsters, and their rate of glucose utilization (69 +/- 6 mumol.100 g-1.min-1) was similar to that previously measured in other rodents, whereas the nuclei were hardly visible on autoradiographs from golden hamsters, and their rate (33 +/- 2 mumol.100 g-1.min-1) was less than half this value. Thus the high energy metabolism characteristic of the SCN of most species is not required for the circadian pacemaker in the nuclei to generate its oscillation.
Circadian rhythms of locomotion (wheel-running activity) in 12 inbred mouse strains were recorded for interstrain differences in tau DD, the endogenous (free-running) period of the circadian pacemaker measured in constant environmental darkness. The results indicate that 1 or more genetic loci influence the value of tau DD, and a large (50 min) difference in mean tau DD between 2 of the strains, BALB/cByJ and C57BL/6J, allowed further characterization of the origins and inheritance of the polymorphic expression of this circadian pacemaker property. The interstrain difference in mean tau DD was associated with an interstrain difference in light-induced shifts of the phase of the free-running locomotor rhythm; the BALB/c strain (with the shorter mean tau DD) displayed relatively fewer advance phase shifts. Neither the history of previous light exposure, albinism, nor elevated circulating testosterone levels could account for the interstrain difference in mean tau DD. The value of tau DD based on the circadian rhythm of drinking activity (with the running wheel removed) was longer than that based on locomotion; this discrepancy was significantly greater and more variable in BALB/c than in C57BL/6 mice, though the interstrain difference in mean tau DD could not be attributed entirely to this effect. Reciprocal F1 hybrids of BALB/c x C57BL/6 matings revealed dominance of the C57BL/6 genotype, no sex linkage, and a significant (but small) maternal effect. Examination of CXB recombinant inbred strains provided no support for the hypothesis of monogenic inheritance. Further study of inherited differences in the BALB/c and C57BL/6 strains may be a useful noninvasive experimental approach for investigation of the neurobiological substrates of circadian rhythmicity.
The mammalian suprachiasmatic nuclei contain an endogenous circadian pacemaker. A quantitative autoradiographic tracer method that measures L-[1-14C]leucine incorporation into protein was used to determine whether the overall rate of protein synthesis in the nuclei varies in a circadian fashion. Unlike the robust circadian rhythms of electrical activity and energy metabolism previously recorded from the nuclei at the two time points sampled, protein synthesis remained constant.
Physiological stimulation of the hypothalamo-neurohypophysial system by salt loading of rats resulted in a dramatically increased glucose utilization in the posterior pituitary but not in the paraventricular or supraoptic nuclei. The good correlation between glucose utilization and neural activity in the posterior pituitary (that is, nerve terminals) contrasted with the lack of correlation in the paraventricular and supraoptic nuclei (that is, the sites of the cell bodies of the same neurons). This difference in the metabolic response to functional activity between the two regions of these neurons can be explained by the differences in surface-to-volume ratios of these regions.
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The 2-deoxy-D-[14C]-glucose (2-DG) autoradiographic method for determining regional brain glucose consumption has been applied successfully by a number of workers for mapping the alterations of brain glucose consumption which occur in association with experimental alterations of brain functional activity. This paper provides a framework for the interpretation of these and further studies by presenting: (1) the pattern of regional brain glucose consumption in the normal, resting, awake rat; (2) the anatomical identities of brain structures which on autoradiographs appear only as regional variations of optical density. For this purpose, a series of 2-DG autoradiographs of coronal brain sections from an injected animal is compared with adjacent labeled Nissl sections.
We propose that the observed increases of both neuronal activity and cerebral blood flow seen throughout the brain during REM sleep may be effects of decreased central noradrenaline release.
Glucose consumption of the rat suprachiasmatic nuclei (SCN) was studied under various experimental conditions by means of the [14C]deoxyglucose (DG) technique. The results show that glucose consumption of the SCN, in contrast to other brain structures, is a function of both the time of day and environmental lighting conditions. These data are consistent with the hypothesis that the SCN have an essential role in circadian rhythm regulation and indicate that the DG technique may provide a novel approach for the study of the central neural mechanisms underlying circadian rhythm regulation.
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