Establishing the Neurostructural and Clinical Impact of Brain Iron Dysregulation in Cocaine Use Disorder
Establishing the Neurostructural and Clinical Impact of Brain Iron Dysregulation in Cocaine Use Disorder
批准号:
10208844
负责人:
JENS H JENSEN
金额:
$18.69万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-07-15 至 2023-06-30
关键词:
AccountingAdultAgeAgingAnimalsArousalBasal GangliaBehavioralBiologicalBlood - brain barrier anatomyBrainCell DeathCell physiologyCellsChronicClinicalCocaineCognitiveCognitive deficitsCorpus striatum structureCross-Sectional StudiesCuesDecision MakingDepressed moodDiffusionDiseaseDisease modelExecutive DysfunctionFree RadicalsFrequenciesFutureGenderGoalsHomeostasisHumanHyperactivityImageImpaired cognitionImpulsivityIn VitroIndividualInvestigationIronKnowledgeLiteratureLongitudinal StudiesMagnetic Resonance ImagingMeasuresMethodsNerve DegenerationNeurobiologyNeurodegenerative DisordersNeurosciencesPharmacotherapyReportingResearchResponse to stimulus physiologyRewardsRiskScienceSeveritiesSeverity of illnessSourceSpecificityStructureSubstance Use DisorderTestingTissuesTreatment outcomeWorkaddictionbasebehavioral phenotypingcatalystclinically relevantcocaine exposurecocaine useexecutive functionmagnetic fieldneural networkneuroimagingnew therapeutic targetoxidative damagepre-clinicalpreclinical studyrelating to nervous systemresponsetherapeutic targetvirtual
中文摘要
项目总结
可卡因使用障碍(Cud)是为数不多的没有有效治疗方法的药物使用障碍之一。
药物疗法。导致CUD不妥协的一个假设机制是监管失调
脑铁稳态的影响。铁稳态是一个关键的生物学机制,但在很大程度上被忽视了
在成瘾研究方面。证实了之前的一份报告,我们的团队最近证明了大脑铁是
在未寻求治疗的CUD患者中显著升高。然而,虽然升高的脑铁有
与衰老中的认知衰退和神经退行性疾病的疾病严重性有关,
CUD的神经生物学和临床相关性仍不清楚。这个项目的目标是建立影响
CUD患者的脑铁代谢失调。
我们建议研究慢性阻塞性肺病患者脑内铁含量升高是否与疾病的严重程度有关。
通过与不良治疗结果相关的措施:脑内异常的神经微结构
执行控制和边缘觉醒神经网络以及行为和认知缺陷。我们将完成
这利用了先进的定量MRI方法,这些方法对脑铁和神经具有敏感性和特异性
微观结构,我们小组在这方面有特殊的专业知识,专注于认知测量,一直发现
在CUD中是异常的。这个项目的总体假设是,通过增加氧化损伤的风险和
细胞死亡,脑内铁过量积聚导致脑内神经微结构受损
网络与这种障碍有关,并与执行控制中的行为和认知缺陷有关
以及以奖励为基础的决策。证明脑铁升高对CUD的不利影响
建立脑铁失调作为未来CUD研究的有前景的治疗靶点。
英文摘要
PROJECT SUMMARY
Cocaine use disorder (CUD) is among the few substance use disorders without an effective
pharmacotherapy. One hypothesized mechanism contributing to the intransigence of CUD is the dysregulation
of brain iron homeostasis. Iron homeostasis is a critical biological mechanism that has been largely overlooked
in addiction research. Corroborating a previous report, our group recently demonstrated that brain iron is
significantly elevated in non-treatment seeking individuals with CUD. However, while elevated brain iron has
been associated with cognitive decline in aging and disease severity in neurodegenerative diseases, the
neurobiological and clinical relevance in CUD remain unknown. The goal of this project is to establish the impact
of brain iron dysregulation in CUD.
We propose to investigate whether elevated brain iron in CUD contributes to disease severity as defined
by measures that have been associated with poor treatment outcome: aberrant neural microstructure within the
executive control and limbic arousal neural networks and behavioral and cognitive deficits. We will accomplish
this utilizing advanced, quantitative MRI methods that are sensitive and specific for brain iron and neural
microstructure, in which our group has particular expertise, focusing on cognitive measures consistently found
as aberrant in CUD. The overall hypothesis of this project is that, by increasing the risk of oxidative damage and
cell death, excess buildup of brain iron in CUD contributes to compromised neural microstructure within brain
networks implicated in the disorder and are associated with behavioral and cognitive deficits in executive control
and reward-based decision making. Demonstrating the adverse impact of elevated brain iron in CUD would
establish brain iron dysregulation as a promising therapeutic target for future studies of CUD.
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会议论文
Establishing the Neurostructural and Clinical Impact of Brain Iron Dysregulation in Cocaine Use Disorder
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批准号:10056480
-
项目类别:
-
资助金额:$22.43万
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财政年份:2020
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负责人:JENS H JENSEN
-
依托单位:
Neuroimaging Core (NI)
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批准号:10621737
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项目类别:
-
资助金额:$22.22万
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财政年份:2014
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负责人:JENS H JENSEN
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依托单位:
MRI Method for In Vivo Iron Quantification
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批准号:6850423
-
项目类别:
-
资助金额:$27.97万
-
财政年份:2005
-
负责人:JENS H JENSEN
-
依托单位:
MRI Method for In Vivo Iron Quantification
-
批准号:7097389
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项目类别:
-
资助金额:$25.93万
-
财政年份:2005
-
负责人:JENS H JENSEN
-
依托单位:
MRI Method for In Vivo Iron Quantification
-
批准号:7282086
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项目类别:
-
资助金额:$25.18万
-
财政年份:2005
-
负责人:JENS H JENSEN
-
依托单位:
MR Method for Determining Magnetic Field Correlation
-
批准号:6778291
-
项目类别:
-
资助金额:$16.45万
-
财政年份:2003
-
负责人:JENS H JENSEN
-
依托单位:
MR Method for Determining Magnetic Field Correlation
-
批准号:6930105
-
项目类别:
-
资助金额:$21.02万
-
财政年份:2003
-
负责人:JENS H JENSEN
-
依托单位:
MR Method for Determining Magnetic Field Correlation
-
批准号:6670517
-
项目类别:
-
资助金额:$15.96万
-
财政年份:2003
-
负责人:JENS H JENSEN
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依托单位:
海外基金