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Comparative Morphology of Neuronal Ceroid Lipofuscinosis

神经元蜡质脂褐质沉积症的比较形态学

基本信息

批准号：
6789345
负责人：
JONATHAN D COOPER
金额：
$ 12.83万
依托单位：
KING'S COLLEGE LONDON
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-08-01 至 2005-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6789345
关键词：
brain morphology cerebellum clinical research dendrites glia hippocampus human tissue immunocytochemistry inflammation interneurons laboratory mouse neuronal ceroid lipofuscinosis neuropathology pathologic process postmortem soma

项目摘要

DESCRIPTION (provided by applicant) The neuronal ceroid lipofuscinoses (NCLs) are progressive, fatal neurodegenerative lysosomal storage disorders that collectively represent the most common inherited neurodegenerative storage disorder of childhood with an incidence of up to 1 in 12,500 five births. There is currently little known regarding which neuronal populations are affected in the NCLs and how their normal structure is compromised. These data can be obtained by systematically analyzing the cellular components of the affected CNS and looking for common themes by comparing tissue from patients to newly developed mouse models of NCL. The main goals of this project are to define the extent and progression of pathological changes in juvenile NCL (JNCL), the most prevalent form of the disorder. This information is currently lacking, but is absolutely essential for understanding disease processes and effectively targeting and evaluating the efficacy of novel therapeutic approaches. We shall use unbiased stereological methodology to characterize at a regional, perikaryal, dendritic and synaptic level the extent of neuropathological changes in murine and human JNCL tissue. We will accomplish our goals with the following specific aims: 1) To quantify changes in the volume and gross cellular organization of the hippocampus, cerebellum and cortical sub-regions; 2) To examine neuronal soma in these regions in more detail to define the extent and timing of changes in the number and volume of i) the total neuronal population and ii) GABAergic interneurons, a neuronal sub population which our preliminary evidence indicates are significantly affected in this disorder, and. iii) extend this analysis to neuronal populations that share common phenotypic characteristics; 3) To define pathologic changes in the dendritic arbor and synaptic contacts made by these neurons; 4) To determine the extent of glial activation and kfiammatory responses in JNCL and their timing in relation to pathological changes in neurons. The information gained from these comparative studies will a) further validate the clinical relevance of these animal models to test potential therapies; b) permit more efficient targeting of treatment strategies to appropriate neuronal populations; c) potentially reveal novel populations of affected neurons; and d) establish a series of pathological landmarks essential for evaluating therapeutic efficacy.

描述（由申请人提供）

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Progressive thalamocortical neuron loss in Cln5 deficient mice: Distinct effects in Finnish variant late infantile NCL.

Cln5 缺陷小鼠进行性丘脑皮质神经元丢失：对芬兰变异型婴儿晚期 NCL 的独特影响。

DOI：
10.1016/j.nbd.2009.02.001
发表时间：
2009
期刊：
Neurobiology of disease
影响因子：
6.1
作者：
vonSchantz,Carina;Kielar,Catherine;Hansen,StineN;Pontikis,CharlieC;Alexander,NoreenA;Kopra,Outi;Jalanko,Anu;Cooper,JonathanD
通讯作者：
Cooper,JonathanD

Hippocampal pathology in the human neuronal ceroid-lipofuscinoses: distinct patterns of storage deposition, neurodegeneration and glial activation.

人类神经元蜡样脂褐质病中的海马病理学：存储沉积、神经变性和神经胶质激活的不同模式。

DOI：
10.1111/j.1750-3639.2004.tb00077.x
发表时间：
2004
期刊：
Brain pathology (Zurich, Switzerland)
影响因子：
0
作者：
Tyynelä,Jaana;Cooper,JonathanD;Khan,MNadeem;Shemilts,StephenJA;Haltia,Matti
通讯作者：
Haltia,Matti

Early glial activation, synaptic changes and axonal pathology in the thalamocortical system of Niemann-Pick type C1 mice.

DOI：
10.1016/j.nbd.2011.12.027
发表时间：
2012-03
期刊：
NEUROBIOLOGY OF DISEASE
影响因子：
6.1
作者：
Pressey, Sarah N. R.;Smith, David A.;Wong, Andrew M. S.;Platt, Frances M.;Cooper, Jonathan D.
通讯作者：
Cooper, Jonathan D.

Pathogenesis and therapies for infantile neuronal ceroid lipofuscinosis (infantile CLN1 disease).