HUMAN TYROSINE HYDROXYLASE AND SCHIZOPHRENIA
HUMAN TYROSINE HYDROXYLASE AND SCHIZOPHRENIA
批准号:
6627574
负责人:
JOHN W HAYCOCK
金额:
$11.59万
依托单位国家:
美国
项目类别:
财政年份:
1992
资助国家:
美国
项目状态:
已结题
起止时间:
1992-03-01 至 2003-12-31
关键词:
aromatic L aminoacid decarboxylase caudate nucleus dopamine dopamine beta monooxygenase dopamine transporter enzyme mechanism human tissue immunochemistry immunoprecipitation molecular psychobiology neurochemistry neurotransmitter biosynthesis norepinephrine nucleus accumbens postmortem protein isoforms protein structure function putamen schizophrenia serotonin serotonin transporter tryptophan 5 monooxygenase tyrosine 3 monooxygenase western blottings
中文摘要
这是一份修订后的K02支持竞争续订申请
约翰·W·海考克博士这一奖项将使海科克博士能够继续他的
并继续他最近资助的研究
项目(MH55208)关于精神疾病中的大脑单胺类系统,
它是在本奖项的过程中发起和发展的。
研究与儿茶酚胺功能相关的临床问题的能力
与他之前建立的基础神经科学同时进行
研究计划(NS25134)已经实现了候选人的一个专业
长期目标。因此,候选人的短期目标是
通过招募更年轻的员工专注于实验室的发展
科学家参与实现这两个国家的科学目标
临床和基础研究项目。除了开发
他作为实验室主任的角色,候选人将继续他的
追求新颖的多学科方法实现科学发展
这是他最近开发的,使用不稳定表位的抗体
研究体内信号分子的调控。
拟议的研究计划侧重于酪氨酸羟化酶(TyrOH)和
色氨酸羟基酶(TrpOH),它催化初始和速度-
限制儿茶酚胺(多巴胺和去甲肾上腺素)的摄入量
5-羟色胺的生物合成。其中的每一个都有变化
系统与精神障碍有牵连,尤其是,
精神分裂症。酪氨酸高度调控--受蛋白质磷酸化
在短期和长期通过转录控制;以及,
选择性剪接(仅在猴子和人类中出现)
产生多种TyrOH亚型,可能还会产生额外水平的
监管。相比之下,人们对TrpOH知之甚少,
尽管它在进化和功能上与TyrOH很接近。尸检
将使用定量印迹分析人脑组织
免疫标记技术和为此开发的一系列抗体库
申请人的目的。酪氨酸和TrpOH蛋白水平,以及
酪氨酸异构体的相对丰度将在
从冷冻条件下解剖出的适合神经化学的脑区
横断面。多巴脱羧酶(紧接在TyrOH和
TrpOH)和多巴胺β-羟基酶(将多巴胺转化为
去甲肾上腺素)蛋白质水平也将被量化,以及类似的
已经为另一类突触前神经元开发了检测方法
单胺能标记物--囊泡单胺和质膜单胺
传送者。主要的学习小组将包括(a.)
确诊为精神分裂症的自杀/猝死受害者
及(B)年龄匹配的猝死对照受试者没有轴1
精神错乱。对主要抑郁症患者的平行、协作研究
将提供比较组,并允许识别潜在的
疾病特定的差异。
英文摘要
This is a revised application for competitive renewal of K02 support for
Dr. John W. Haycock. This award will enable Dr. Haycock to continue his
scientific development and to pursue his recently funded research
program (MH55208) on brain monoaminergic systems in mental illnesses,
which was initiated and developed over the course of the current award.
The ability to study clinical issues related to catecholamine function
concurrently with his previously established fundamental neuroscience
research program (NS25134) has realized one of the candidate's major
long-term goals. As a result, the candidate's short-term goals are
focused upon development of his laboratory by recruiting younger
scientists to participate in effecting the scientific goals of both the
clinical and fundamental research projects. In addition to developing
his role as a laboratory director, the candidate will continue his
scientific development by pursuing a novel, multidisciplinary approach
which he has recently developed, using antibodies to labile epitopes for
studying the regulation of signaling molecules in vivo.
The proposed research plan focuses upon tyrosine hydroxylase (TyrOH) and
tryptophan hydroxylase (TrpOH), which catalyze the initial and rate-
limiting steps in catecholamine (dopamine and norepinephrine) and
serotonin biosynthesis, respectively. Alterations in each of these
systems have been implicated in mental disorders and, in particular,
schizophrenia. TyrOH is highly regulated--by protein phosphorylation
in the short-term and by transcriptional control in the long-term; and,
alternative splicing (which occurs exclusively in monkeys and humans)
produces multiple TyrOH isoforms and perhaps, an additional level of
regulation. By contrast, comparatively little is known about TrpOH,
despite its evolutionary and functional proximity to TyrOH. Postmortem
human brain tissue will be analyzed using quantitative blot
immunolabeling techniques and a bank of antibodies developed for this
purpose by the applicant. TyrOH and TrpOH protein levels, as well as
the relative abundances of TyrOH isoforms, will be measured in
neurochemically appropriate brain regions dissected from cryostatic
sections. DOPA decarboxylase (immediately downstream of both TyrOH and
TrpOH) and dopamine beta-hydroxylase (which converts dopamine to
norepinephrine) protein levels will also be quantitated, and similar
assays have been developed for another class of presynaptic
monoaminergic markers--the vesicular and plasmalemmal monoamine
transporters. The primary study groups will consist of (a.)
suicide/sudden death victims having confirmed diagnoses of schizophrenia
and (b.) age-matched, sudden-death control subjects having no Axis 1
mental disorder. Parallel, collaborative studies of major depressives
will provide comparison groups and allow identification of potential
disease-specific differences.
期刊论文(12)
专著(0)
科研奖励(0)
会议论文
登录
查看更多内容
Lack of regulation of aromatic L-amino acid decarboxylase in intact bovine chromaffin cells.
完整牛嗜铬细胞中芳香族 L-氨基酸脱羧酶缺乏调节。
DOI:
10.1046/j.1471-4159.2002.00849.x
发表时间:
2002
期刊:
Journal of neurochemistry
影响因子:
4.7
作者:
[Waymire,JackC, Haycock,JohnW]
通讯作者:
Haycock,JohnW
Immunohistochemical studies on phosphorylation of tyrosine hydroxylase in central catecholamine neurons using site- and phosphorylation state-specific antibodies.
使用位点和磷酸化状态特异性抗体对中枢儿茶酚胺神经元中酪氨酸羟化酶的磷酸化进行免疫组织化学研究。
DOI:
10.1016/s0306-4522(97)00189-9
发表时间:
1998
期刊:
Neuroscience
影响因子:
3.3
作者:
[Xu,ZQ, Lew,JY, Harada,K, Aman,K, Goldstein,M, Deutch,A, Haycock,JW, Hökfelt,T]
通讯作者:
Hökfelt,T
Elevated tyrosine hydroxylase in the locus coeruleus of suicide victims.
自杀受害者蓝斑中酪氨酸羟化酶升高。
DOI:
10.1046/j.1471-4159.1994.62020680.x
发表时间:
1994
期刊:
Journal of neurochemistry
影响因子:
4.7
作者:
[Ordway,GA, Smith,KS, Haycock,JW]
通讯作者:
Haycock,JW
A DEVD-inhibited caspase other than CPP32 is involved in the commitment of cerebellar granule neurons to apoptosis induced by K+ deprivation.
除 CPP32 外,DEVD 抑制的 caspase 参与小脑颗粒神经元 K 剥夺诱导的细胞凋亡。
DOI:
10.1046/j.1471-4159.1998.70051809.x
发表时间:
1998
期刊:
Journal of neurochemistry
影响因子:
4.7
作者:
[D'Mello,SR, Aglieco,F, Roberts,MR, Borodezt,K, Haycock,JW]
通讯作者:
Haycock,JW
MONOAMINERGIC ENZYMES IN SCHIZOPHRENIA
-
批准号:2675431
-
项目类别:
-
资助金额:$10.72万
-
财政年份:1996
-
负责人:JOHN W HAYCOCK
-
依托单位:
MONOAMINERGIC ENZYMES IN SCHIZOPHRENIA
-
批准号:2255642
-
项目类别:
-
资助金额:$8.65万
-
财政年份:1996
-
负责人:JOHN W HAYCOCK
-
依托单位:
MONOAMINERGIC ENZYMES IN SCHIZOPHRENIA
-
批准号:2890753
-
项目类别:
-
资助金额:$6.16万
-
财政年份:1996
-
负责人:JOHN W HAYCOCK
-
依托单位:
MONOAMINERGIC ENZYMES IN SCHIZOPHRENIA
-
批准号:2416150
-
项目类别:
-
资助金额:$8.4万
-
财政年份:1996
-
负责人:JOHN W HAYCOCK
-
依托单位:
HUMAN TYROSINE HYDROXYLASE AND SCHIZOPHRENIA
-
批准号:3070325
-
项目类别:
-
资助金额:$7.48万
-
财政年份:1992
-
负责人:JOHN W HAYCOCK
-
依托单位:
TYROSINE HYDROXYLASE AND SCHIZOPHRENIA
-
批准号:2240239
-
项目类别:
-
资助金额:$9.83万
-
财政年份:1992
-
负责人:JOHN W HAYCOCK
-
依托单位:
HUMAN TYROSINE HYDROXYLASE AND SCHIZOPHRENIA
-
批准号:6490776
-
项目类别:
-
资助金额:$11.25万
-
财政年份:1992
-
负责人:JOHN W HAYCOCK
-
依托单位:
HUMAN TYROSINE HYDROXYLASE AND SCHIZOPHRENIA
-
批准号:6343671
-
项目类别:
-
资助金额:$10.92万
-
财政年份:1992
-
负责人:JOHN W HAYCOCK
-
依托单位:
HUMAN TYROSINE HYDROXYLASE AND SCHIZOPHRENIA
-
批准号:3070326
-
项目类别:
-
资助金额:$8.5万
-
财政年份:1992
-
负责人:JOHN W HAYCOCK
-
依托单位:
TYROSINE HYDROXYLASE AND SCHIZOPHRENIA
-
批准号:2240237
-
项目类别:
-
资助金额:$8.39万
-
财政年份:1992
-
负责人:JOHN W HAYCOCK
-
依托单位:
HUMAN TYROSINE HYDROXYLASE AND SCHIZOPHRENIA
-
批准号:6139329
-
项目类别:
-
资助金额:$10.6万
-
财政年份:1992
-
负责人:JOHN W HAYCOCK
-
依托单位:
HUMAN TYROSINE HYDROXYLASE AND SCHIZOPHRENIA
-
批准号:2766331
-
项目类别:
-
资助金额:$10.3万
-
财政年份:1992
-
负责人:JOHN W HAYCOCK
-
依托单位:
TYROSINE HYDROXYLASE AND SCHIZOPHRENIA
-
批准号:2240238
-
项目类别:
-
资助金额:$9.41万
-
财政年份:1992
-
负责人:JOHN W HAYCOCK
-
依托单位:
MULTIPLE FORMS OF HUMAN TYROSINE HYDROXYLASE
-
批准号:2247163
-
项目类别:
-
资助金额:$7.0万
-
财政年份:1991
-
负责人:JOHN W HAYCOCK
-
依托单位:
MULTIPLE FORMS OF HUMAN TYROSINE HYDROXYLASE
-
批准号:3429406
-
项目类别:
-
资助金额:$6.87万
-
财政年份:1991
-
负责人:JOHN W HAYCOCK
-
依托单位:
SMALL INSTRUMENTATION PROGRAM
-
批准号:3526131
-
项目类别:
-
资助金额:$1.4万
-
财政年份:1989
-
负责人:JOHN W HAYCOCK
-
依托单位:
CELLULAR REGULATION OF TYROSINE HYDROXYLASE
-
批准号:6126212
-
项目类别:
-
资助金额:$20.73万
-
财政年份:1987
-
负责人:JOHN W HAYCOCK
-
依托单位:
CELLULAR REGULATION OF TYROSINE HYDROXYLASE
-
批准号:2265470
-
项目类别:
-
资助金额:$13.77万
-
财政年份:1987
-
负责人:JOHN W HAYCOCK
-
依托单位:
CELLULAR REGULATION OF TYROSINE HYDROXYLASE
-
批准号:3477007
-
项目类别:
-
资助金额:$8.15万
-
财政年份:1987
-
负责人:JOHN W HAYCOCK
-
依托单位:
CELLULAR REGULATION OF TYROSINE HYDROXYLASE
-
批准号:3477006
-
项目类别:
-
资助金额:$9.38万
-
财政年份:1987
-
负责人:JOHN W HAYCOCK
-
依托单位:
海外基金