HORMONE ACTION IN THE CENTRAL NERVOUS SYSTEM
HORMONE ACTION IN THE CENTRAL NERVOUS SYSTEM
批准号:
2150967
负责人:
ALAN P FARWELL
金额:
$10.0万
依托单位国家:
美国
项目类别:
财政年份:
1995
资助国家:
美国
项目状态:
已结题
起止时间:
1995-09-01 至 1996-06-30
中文摘要
这是香农奖,为这项研究提供部分支持
英文摘要
This is a Shannon Award providing partial support for the research
projects that fall short of the assigned institute's funding range but
are in the margin of excellence. The Shannon Award is intended to
provide support to test the feasibility of the approach; develop further
tests and refine research techniques; perform secondary analysis of
available data sets; or conduct discrete projects that can demonstrate
the PI's research capabilities or lend additional weight to an already
meritorious application. The abstract below is taken from the original
document submitted by the principal investigator.
The absence of thyroid hormone during the period of active neurogenesis
is accompanied by multiple morphological alterations in the brain that
result in irreversible mental retardation (cretinism). These severe
morphological alterations in the cretinous brain can be attributed to
deficits in neuronal migration and axonal projection which lead to
attenuation of neural circuits. The goal of this proposal is the
characterization of mechanism(s) by which thyroid hormone can influence
neuronal migration in the developing brain by regulating the ability of
brain cells to interact with their extracellular environment. Previous
work in our laboratory has shown that thyroid hormone regulates
polymerization of the actin cytoskeleton in cultured astrocytes. Further
studies have shown that modulation of the microfilament organization by
thyroid hormone alters the ability of the cell to form attachments to
laminin, a major component of the extracellular matrix (ECM) in the
developing brain that provides key guidance cues to the elongating
neurite during migration. MY working hypothesis is that thyroid hormone
regulates interactions between the microfilaments, transmembrane
receptors known as integrins and the ECM in both astrocytes and neurons.
In the hypothyroid astrocyte, this would result in disorganized
patterning of ECM proteins on the cell surface that would disrupt spacial
cues essential to guide the migrating neurite to its target destination.
In the neurite, altered cytoskeletal-integrin interactions in the absence
of thyroid hormone would interfere with the ability of the neurite to
transduce these spatial cues. Indeed, microinjection of an antibody to
the integrin that recognizes both laminin and fibronectin, another
component of the brain ECM, blocks neural crest cell migration in chick
embryos. The first part of this proposal will characterize the effect
of thyroid hormone on the synthesis, secretion, and distribution of
laminin and fibronectin by astrocytes, both in vivo and in vitro. The
second part will examine the effect of altered integrin-ECM interactions
on neurite outgrowth. The final section will examine how thyroid hormone
can regulate ECM-derived cues by altering integrin-mediated activation
of intracellular signaling pathways. These studies will provide a
possible mechanism for the profound effects of thyroid hormone on the
developing brain. In addition, these studies will begin to address some
of the fundamental questions of how cells interact, respond and adapt to
their environment.
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HORMONE ACTION IN THE CENTRAL NERVOUS SYSTEM
-
批准号:2734201
-
项目类别:
-
资助金额:$18.11万
-
财政年份:1996
-
负责人:ALAN P FARWELL
-
依托单位:
HORMONE ACTION IN THE CENTRAL NERVOUS SYSTEM
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批准号:2150968
-
项目类别:
-
资助金额:$17.07万
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财政年份:1996
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负责人:ALAN P FARWELL
-
依托单位:
HORMONE ACTION IN THE CENTRAL NERVOUS SYSTEM
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批准号:2444149
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项目类别:
-
资助金额:$12.45万
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财政年份:1996
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负责人:ALAN P FARWELL
-
依托单位:
HORMONE ACTION IN THE CENTRAL NERVOUS SYSTEM
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批准号:2905759
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项目类别:
-
资助金额:$18.7万
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财政年份:1996
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负责人:ALAN P FARWELL
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依托单位:
HORMONE ACTION IN THE CENTRAL NERVOUS SYSTEM
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批准号:3080921
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项目类别:
-
资助金额:$7.66万
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财政年份:1990
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负责人:ALAN P FARWELL
-
依托单位:
HORMONE ACTION IN THE CENTRAL NERVOUS SYSTEM
-
批准号:3080924
-
项目类别:
-
资助金额:$9.37万
-
财政年份:1990
-
负责人:ALAN P FARWELL
-
依托单位:
HORMONE ACTION IN THE CENTRAL NERVOUS SYSTEM
-
批准号:3080922
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项目类别:
-
资助金额:$8.46万
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财政年份:1990
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负责人:ALAN P FARWELL
-
依托单位:
HORMONE ACTION IN THE CENTRAL NERVOUS SYSTEM
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批准号:3080923
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项目类别:
-
资助金额:$9.24万
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财政年份:1990
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负责人:ALAN P FARWELL
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依托单位:
HORMONE ACTION IN THE CENTRAL NERVOUS SYSTEM
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批准号:2133640
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项目类别:
-
资助金额:$9.79万
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财政年份:1990
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负责人:ALAN P FARWELL
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依托单位:
海外基金