Neuroscience 2003 Abstract
| Presentation Number: | 284.2 |
|---|---|
| Abstract Title: | Molecular circadian rhythms in rat-1 fibroblasts II: pharmacological manipulation of period and phase. |
| Authors: |
Harnish, S.*1
; Hurst, W. J.1
; Camacho, F.1
; Vielhaber, E.1
; Lozada, A.2
; Friedman, E.1
; Errico, M.1
; Lenox, R. H.1
; Giovanni, A.1
1Dept. of CNS Res., Aventis Pharmaceut., Bridgewater, NJ 2HTS Assay Develop., Aventis Pharmaceut., Bridgewater, NJ |
| Primary Theme and Topics |
Autonomic, Neuroendocrine and Other Homeostatic Systems - Biological Rhythms and Sleep -- Molecular biology and physiology of clocks |
| Session: |
284. Biological Rhythms: Molecular Biology & Physiology Poster |
| Presentation Time: | Sunday, November 9, 2003 2:00 PM-3:00 PM |
| Location: | Morial Convention Center - Hall F-I, Board # H58 |
| Keywords: | Cellular, SCN, Assay, Clock |
The hypothalamic suprachiasmatic nucleus (SCN) is the primary modulator of circadian rhythms in mammals. This central pacemaker endogenously generates near-24h oscillations and integrates varied environmental, neuronal and humoral signals to adjust the phase of circadian rhythms throughout an organism. Many of these input/output pathways have been thoroughly mapped utilizing a broad spectrum of experimental approaches. These include analysis of behavior, biochemistry, electrophysiology and more recently, real-time in vivo reporting systems. However, many of these systems, while integral to mammalian circadian research, are laborious and relatively low-throughput. Nevertheless, the more recent discovery of peripheral circadian oscillators has uncovered an opportunity to utilize cellular systems that provide an additional perspective of molecular clock mechanism.
In these studies, a high-throughput cellular circadian system in Rat-1 fibroblasts (see Hurst et al., 2003 SFN abstract) was employed to determine the direct effects of pharmacological agents on molecular clock mechanism. Several classes of pharmacological agents were evaluated for acute phase-response as well as chronic effects on circadian period. Among the compounds tested were classic synchronization and phase-shifting agents, general inhibitors of transcription and translation as well as specific inhibitors of varied proteases and kinases. Circadian period of cultures was determined by Fourier analysis. For each compound, dose-response curves were constructed and effective concentrations for a 1-hour lengthening or shortening of circadian period (ECΔτ+1h or ECΔτ-1h, respectively) were determined.
In these studies, a high-throughput cellular circadian system in Rat-1 fibroblasts (see Hurst et al., 2003 SFN abstract) was employed to determine the direct effects of pharmacological agents on molecular clock mechanism. Several classes of pharmacological agents were evaluated for acute phase-response as well as chronic effects on circadian period. Among the compounds tested were classic synchronization and phase-shifting agents, general inhibitors of transcription and translation as well as specific inhibitors of varied proteases and kinases. Circadian period of cultures was determined by Fourier analysis. For each compound, dose-response curves were constructed and effective concentrations for a 1-hour lengthening or shortening of circadian period (ECΔτ+1h or ECΔτ-1h, respectively) were determined.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2003 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2003. Online.
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