Establishment and characterization of adenoviral E1A immortalized cell lines derived from the rat suprachiasmatic nucleus

Earnest, David J.; Liang, Feng; DiGiorgio, Susan; Gallagher, Mary E.; Harvey, Brandon K.; Earnest, Barbara J.; Seigel, Gail M.

doi:10.1002/(sici)1097-4695(199904)39:1<1::aid-neu1>3.0.co;2-f

Cited by 35 publications

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“…Immortalized rat SCN2.2 cells retain the endogenous oscillatory and pacemaker properties of the SCN in situ 88 , and can generate self-sustained rhythms of gene expression and glucose metabolism. They also restore behavioural rhythmicity when transplanted into SCN-lesioned hosts 89,90 .…”

Section: The Circadian Clock In Mammalsmentioning

confidence: 99%

Circadian rhythms from multiple oscillators: lessons from diverse organisms

et al. 2005

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The organization of biological activities into daily cycles is universal in organisms as diverse as cyanobacteria, fungi, algae, plants, flies, birds and man. Comparisons of circadian clocks in unicellular and multicellular organisms using molecular genetics and genomics have provided new insights into the mechanisms and complexity of clock systems. Whereas unicellular organisms require stand-alone clocks that can generate 24-hour rhythms for diverse processes, organisms with differentiated tissues can partition clock function to generate and coordinate different rhythms. In both cases, the temporal coordination of a multi-oscillator system is essential for producing robust circadian rhythms of gene expression and biological activity.The temporal coordination of internal biological processes, both among these processes and with external environmental cycles, is crucial to the health and survival of diverse organisms, from bacteria to humans. Central to this coordination is an internal CLOCK that controls CIRCADIAN RHYTHMS of gene expression and the resulting biological activity (BOX 1). Despite disparate phylogenetic origins and vast differences in complexity among the species that show circadian rhythmicity, at the core of all circadian clocks is at least one internal autonomous circadian OSCILLATOR. These oscillators contain positive and negative elements that form autoregulatory feedback loops, and in many cases these loops are used to generate 24-hour timing circuits 1, 2 . Components of these loops can directly or indirectly receive environmental input to allow ENTRAINMENT of the clock to environmental time and transfer temporal information through output Competing interests statementThe authors declare no competing financial interests. NIH Public Access Author ManuscriptNat Rev Genet. Author manuscript; available in PMC 2009 September 1. Published in final edited form as:Nat Rev Genet. 2005 July ; 6(7): 544-556. doi:10.1038/nrg1633. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript pathways to regulate rhythmic clock-controlled gene (CCG) expression and rhythmic biological activity.Whereas a self-contained clock in single-celled organisms programmes 24-hour rhythms in diverse processes, multicellular organisms with differentiated tissues can partition clock function among different cell types to coordinate tissue-specific rhythms and maintain precision. Now that individual molecular circadian oscillators have been sufficiently described, it has become possible to go beyond single oscillators to try and understand how multiple oscillators are integrated into circadian systems. Evidence accumulated in recent years indicates that the intracellular oscillator systems of single-celled organisms might be more complex than those of higher eukaryotes, whereas the complexity of circadian outputs in multicellular organisms is an emergent property of intercellular interactions. In this review, we discuss the complexity of the circadian clocks on the basis of molecular genetic and geno...

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Section: The Circadian Clock In Mammalsmentioning

confidence: 99%

Circadian rhythms from multiple oscillators: lessons from diverse organisms

et al. 2005

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“…The strength of the restored rhythm positively correlates with SCN 2.2 cell survival in the graft. Grafts of immortalized mesencephalic cells or of NIH/3T3 fibroblasts both fail to rescue circadian rhythmicity in SCNlesioned animals (7). Of particular interest is the recent finding that SCN 2.2 cells act as central pace-makers in driving circadian oscillations in NIH/3T3 co-cultures (6).…”

Section: Central Clocks Peripheral Oscillators and Cell Linesmentioning

confidence: 99%

“…However, there is no published evidence that these lines express spontaneous, self-sustained rhythms or rescue rhythms in SCNlesioned animals (5,6). In contrast, another cell line derived from fetal rat SCN, the SCN 2.2 cell line, exhibits endogenous spontaneous circadian rhythmicity in vitro (5,7). We have focused on the SCN 2.2 line to further assess its usefulness as a model system for studying the mammalian central circadian pacemaker.…”

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“…The SCN 2.2 cell line is a pluripotent and immortalized line of SCN progenitor cells from fetal rat hypothalamic tissue that exhibits both neuronal and glial morphologies in culture (5,7). Neuronal cell types express several peptide neurotransmitters found in the SCN.…”

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“…These include vasoactive peptide (VIP), argininevasopressin (AVP), and somatostatin (SMT). Additionally, the line lacks oxytocin-(OXY) and corticotropinreleasing factor-(CRF) staining, which are found in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus but not in the nearby SCN (7). Like the SCN in situ, SCN 2.2 cultures generate robust twenty-four hour rhythms in brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) content as well as 2-deoxyglucose (2-DG) uptake.…”

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Immortalized Suprachiasmatic Nucleus Cells Express Components of Multiple Circadian Regulatory Pathways

Hurst

Earnest

Gillette

2002

Biochemical and Biophysical Research Communications

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We undertook an extensive antigenic characterization of the SCN 2.2 cell line in order to further evaluate whether the line expresses components of circadian regulatory pathways common to the hypothalamic suprachiasmatic nucleus (SCN), the central circadian clock in mammals. We found that differentiated SCN 2.2 cultures expressed a broad range of putative clock genes, as well as components of daytime, nighttime, and crepuscular circadian regulatory pathways found within the SCN in vivo. The line also exhibits several antigens that are highly expressed in a circadian pattern and/or differentially localized in the SCN relative to other hypothalamic regions. Expression of a broad complement of circadian regulatory proteins and putative clock genes further support growing evidence in recent reports that the SCN 2.2 cell line is an appropriate model for investigating the regulation of central mammalian pacemaker. © 2002 Elsevier Science (USA) Key Words: period; cryptochrome; casein kinase; PACAP; PKA; PKC; PKG; NOS; I1; VGF.The central biological pacemaker in mammals lies in the hypothalamic suprachiasmatic nucleus (SCN). The SCN drives circadian behavior, expresses rhythmic gene expression and integrates external stimuli in order to synchronize molecular timekeeping mechanisms with changing environmental conditions. Receptivity to phase shifting stimuli is gated by the circadian state of the central pacemaker. This gating behavior is most clearly demonstrated by the sensitivity of the SCN to light during the night phase, but not during the day phase. All photic, social and hormonal influences on the circadian clock are integrated at the cellular level through multiple signaling pathways within the SCN.The complexity of interacting signaling pathways involved in regulation of the SCN has encouraged researchers to seek cell culture systems to complement in vivo analysis of the mammalian circadian clock. Whether a cell line exhibits central or peripheral circadian clock characteristics complicates selection of an appropriate model system. To provide useful applications for central mammalian pacemaker research, cell line models must exhibit persistent self-sustained oscillations in circadian gene products, restore animal circadian rhythms in SCN-lesioned hosts and exhibit time-dependent responses to stimuli through regulatory pathways that characterize SCN function. Rhythmic gene expression has been demonstrated in NIH/ 3T3 fibroblasts, Rat-1 fibroblasts and spontaneously immortalized embryonic mouse fibroblasts after synchronizing signals (1-5). However, there is no published evidence that these lines express spontaneous, self-sustained rhythms or rescue rhythms in SCNlesioned animals (5, 6). In contrast, another cell line derived from fetal rat SCN, the SCN 2.2 cell line, exhibits endogenous spontaneous circadian rhythmicity in vitro (5, 7). We have focused on the SCN 2.2 line to further assess its usefulness as a model system for studying the mammalian central circadian pacemaker.The SCN 2.2 cell line is a pluripoten...

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Melatonin Receptors in Central Nervous System

Dubocovich

2007

Handbook of Contemporary Neuropharmacology

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The functional role of melatonin receptors in the mammalian central nervous system and their therapeutic potential is discussed. Melatonin, dubbed the “hormone of darkness,” is produced primarily in the pineal gland and retina following circadian rhythms with high levels of night. The chapter describes the structure, molecular pharmacology, signaling, and function of the MT1 and MT2 mammalian melatonin receptors. This is followed by discussion of recent advances in the regulation of melatonin receptor sensitivity and its role in circadian rhythm modulation by the circadian timing system. Recent advances in the discovery and development of therapeutic agents targeting melatonin receptors for the treatment of insomnia, circadian rhythm dysfunctions, and depression are also highlighted.

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Establishment and characterization of adenoviral E1A immortalized cell lines derived from the rat suprachiasmatic nucleus

Cited by 35 publications

References 36 publications

Circadian rhythms from multiple oscillators: lessons from diverse organisms

Circadian rhythms from multiple oscillators: lessons from diverse organisms

Immortalized Suprachiasmatic Nucleus Cells Express Components of Multiple Circadian Regulatory Pathways

Melatonin Receptors in Central Nervous System

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