SUPRACHIASMATIC NUCLEI/NEUROBIOLOGY OF A CIRCADIAN CLOCK
SUPRACHIASMATIC NUCLEI/NEUROBIOLOGY OF A CIRCADIAN CLOCK
批准号:
2891700
负责人:
William J Schwartz
金额:
$28.55万
依托单位国家:
美国
项目类别:
财政年份:
1986
资助国家:
美国
项目状态:
已结题
起止时间:
1986-08-01 至 2001-03-31
关键词:
DNA methylation affinity chromatography biological clocks biological signal transduction circadian rhythms dark adaptation environmental adaptation gel mobility shift assay gene expression genetic regulatory element laboratory rat neuropharmacology photoactivation photobiology photostimulus posttranscriptional RNA processing protooncogene suprachiasmatic nucleus transcription factor
中文摘要
昼夜节律是先天计时能力的明显表现
英文摘要
Circadian rhythms are the overt manifestation of an innate timekeeping
system, i.e., a "circadian clock," that is synchronized (entrained) to
the 24-hr day-night cycle by environmental light. The clinical and
practical significance of the human clock is now well recognized. The
overall objective of this research program is to understand the
endogenous oscillatory mechanism of the circadian pacemaker in the
suprachiasmatic nuclei (SCN) of mammals. During the current grant
period, we began to study whether an alteration of gene expression might
be involved in the entraining effect of light. We found that light
regulates the expression of c-Fos and Fos-related transcriptional
regulatory proteins in the ventrolateral SCN and in the intergeniculate
leaflet (IGL) of rats. In this competing continuation application,
experimental results are presented that lead to the hypothesis that
events at the transcriptional level are part of the mechanism for photic
entrainment of the circadian pacemaker to the light-dark cycle, and, more
specifically, that Fos expression in the SCN may be a link in the
entrainment mechanism. Protocols are proposed to study four questions
directed to this hypothesis.
(1) What are the effects of light and circadian phase on the expression
of Fos, on its interaction with Jun, and on their binding to DNA?
Patterns of Fos/Jun expression will be evaluated by immunohistochemistry
and in situ hybridization, identification of the immunoreactive and mRNA
species by Western and Northern blot analysis, and detection of
sequence-specific DNA binding by mobility shift (gel retardation) assay.
(2) What are the implications of the localization of Fos to the
retino-recipient ventrolateral SCN and IGL? The possible colocalization
of Fos to neurons that synthesize known neuropeptides and the dependence
of light-induced Fos activation in the SCN on visual input from the IGL
will be assessed.
(3) Do stimuli that affect pacemaker entrainment modify Fos expression in
the SCN? Changes of Fos expression will be investigated after injection
of the N-methyl-D-aspartate antagonist MK-801, after daily injections of
melatonin, and in the fetal SCN.
(4) Will experimental reduction of intracellular Fos levels in the SCN
inhibit the entraining action of light? An antisense oligonucleotide
complementary to the 5' end of rat c-fos mRNA will be introduced by
stereotaxic infusion in to the SCN via mini-osmotic pump, and its effects
on light-induced phase shifts of overt behavioral rhythmicity will be
measured.
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Compositional changes of AP-1 DNA-binding proteins are regulated by light in a mammalian circadian clock.
AP-1 DNA 结合蛋白的组成变化受哺乳动物生物钟中光的调节。
DOI:
10.1016/0896-6273(93)90112-5
发表时间:
1993
期刊:
Neuron
影响因子:
16.2
作者:
[Takeuchi,J, Shannon,W, Aronin,N, Schwartz,WJ]
通讯作者:
Schwartz,WJ
Understanding circadian clocks: from c-fos to fly balls.
了解生物钟:从 c-fos 到飞球。
DOI:
10.1002/ana.410410303
发表时间:
1997
期刊:
Annals of neurology.
影响因子:
--
作者:
[Schwartz,WJ]
通讯作者:
Schwartz,WJ
Further evaluation of the tetrodotoxin-resistant circadian pacemaker in the suprachiasmatic nuclei.
进一步评估视交叉上核中的抗河豚毒素昼夜节律起搏器。
DOI:
10.1177/074873049100600205
发表时间:
1991
期刊:
Journal of biological rhythms
影响因子:
3.5
作者:
[Schwartz,WJ]
通讯作者:
Schwartz,WJ
In vivo metabolic activity of hamster suprachiasmatic nuclei: use of anesthesia.
仓鼠视交叉上核的体内代谢活动:使用麻醉。
DOI:
10.1152/ajpregu.1987.252.2.r419
发表时间:
1987
期刊:
The American journal of physiology
影响因子:
--
作者:
[Schwartz,WJ]
通讯作者:
Schwartz,WJ
An antibody to the Drosophila period protein labels antigens in the suprachiasmatic nucleus of the rat.
果蝇周期蛋白的抗体标记大鼠视交叉上核中的抗原。
DOI:
10.3109/01677069209167270
发表时间:
1992
期刊:
Journal of neurogenetics
影响因子:
1.9
作者:
[Siwicki,KK, Schwartz,WJ, Hall,JC]
通讯作者:
Hall,JC
共 13 条
Circadian Biology at the Supra-Organismal Level
-
批准号:8420539
-
项目类别:
-
资助金额:$37.32万
-
财政年份:2010
-
负责人:William J Schwartz
-
依托单位:
Circadian Biology at the Supra-Organismal Level
-
批准号:7779841
-
项目类别:
-
资助金额:$39.03万
-
财政年份:2010
-
负责人:William J Schwartz
-
依托单位:
Circadian Biology at the Supra-Organismal Level
-
批准号:8225275
-
项目类别:
-
资助金额:$38.68万
-
财政年份:2010
-
负责人:William J Schwartz
-
依托单位:
Circadian Biology at the Supra-Organismal Level
-
批准号:8052728
-
项目类别:
-
资助金额:$38.68万
-
财政年份:2010
-
负责人:William J Schwartz
-
依托单位:
Neurobiology of Circadian Dysrhythmias
-
批准号:7065710
-
项目类别:
-
资助金额:$28.72万
-
财政年份:2004
-
负责人:William J Schwartz
-
依托单位:
Neurobiology of Circadian Dysrhythmias
-
批准号:7219377
-
项目类别:
-
资助金额:$27.89万
-
财政年份:2004
-
负责人:William J Schwartz
-
依托单位:
Neurobiology of Circadian Dysrhythmias
-
批准号:6853576
-
项目类别:
-
资助金额:$29.42万
-
财政年份:2004
-
负责人:William J Schwartz
-
依托单位:
Neurobiology of Circadian Dysrhythmias
-
批准号:6780169
-
项目类别:
-
资助金额:$29.42万
-
财政年份:2004
-
负责人:William J Schwartz
-
依托单位:
HYPOTHALAMIC RECONSTRUCTION USING NEURAL PRECURSOR CELLS
-
批准号:6229027
-
项目类别:
-
资助金额:$23.37万
-
财政年份:2000
-
负责人:William J Schwartz
-
依托单位:
HYPOTHALAMIC RECONSTRUCTION USING NEURAL PRECURSOR CELLS
-
批准号:6477196
-
项目类别:
-
资助金额:$21.92万
-
财政年份:2000
-
负责人:William J Schwartz
-
依托单位:
HYPOTHALAMIC RECONSTRUCTION USING NEURAL PRECURSOR CELLS
-
批准号:6625500
-
项目类别:
-
资助金额:$21.88万
-
财政年份:2000
-
负责人:William J Schwartz
-
依托单位:
SUPRACHIASMATIC NUCLEI-NEUROBIOLOGY OF A CIRCADIAN CLOCK
-
批准号:3409253
-
项目类别:
-
资助金额:$20.9万
-
财政年份:1986
-
负责人:William J Schwartz
-
依托单位:
SUPRACHIASMATIC NUCLEI-NEUROBIOLOGY OF A CIRCADIAN CLOCK
-
批准号:3409252
-
项目类别:
-
资助金额:$20.07万
-
财政年份:1986
-
负责人:William J Schwartz
-
依托单位:
SUPRACHIASMATIC NUCLEI-NEUROBIOLOGY OF A CIRCADIAN CLOCK
-
批准号:3406003
-
项目类别:
-
资助金额:$1.95万
-
财政年份:1986
-
负责人:William J Schwartz
-
依托单位:
SUPRACHIASMATIC NUCLEI-NEUROBIOLOGY OF A CIRCADIAN CLOCK
-
批准号:3409248
-
项目类别:
-
资助金额:$0.25万
-
财政年份:1986
-
负责人:William J Schwartz
-
依托单位:
SUPRACHIASMATIC NUCLEI-NEUROBIOLOGY OF A CIRCADIAN CLOCK
-
批准号:3409246
-
项目类别:
-
资助金额:$25.34万
-
财政年份:1986
-
负责人:William J Schwartz
-
依托单位:
SUPRACHIASMATIC NUCLEI-NEUROBIOLOGY OF A CIRCADIAN CLOCK
-
批准号:3409247
-
项目类别:
-
资助金额:$0.23万
-
财政年份:1986
-
负责人:William J Schwartz
-
依托单位:
SUPRACHIASMATIC NUCLEI-NEUROBIOLOGY OF A CIRCADIAN CLOCK
-
批准号:3409255
-
项目类别:
-
资助金额:$4.61万
-
财政年份:1986
-
负责人:William J Schwartz
-
依托单位:
SUPRACHIASMATIC NUCLEI-NEUROBIOLOGY OF A CIRCADIAN CLOCK
-
批准号:3409251
-
项目类别:
-
资助金额:$11.52万
-
财政年份:1986
-
负责人:William J Schwartz
-
依托单位:
SUPRACHIASMATIC NUCLEI/NEUROBIOLOGY OF A CIRCADIAN CLOCK
-
批准号:2265275
-
项目类别:
-
资助金额:$25.41万
-
财政年份:1986
-
负责人:William J Schwartz
-
依托单位:
海外基金