相关实验视频

Updated: Jul 13, 2025

Modified Yeast-Two-Hybrid System to Identify Proteins Interacting with the Growth Factor Progranulin

Modified Yeast-Two-Hybrid System to Identify Proteins Interacting with the Growth Factor Progranulin

Published on: January 17, 2012

在中部前额叶皮层中调节细胞外原蛋白的调节

Azariah K Kaplelach¹, Stephanie N Fox¹, Anna K Cook¹

¹Center for Neurodegeneration and Experimental Therapeutics, Alzheimer's Disease Center, Evelyn F. McKnight Brain Institute, Departments of Neurology and Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA.

Neurobiology of disease

|October 14, 2023

概括

进子素 (GRN) 对大脑健康和 lysosomal 功能至关重要. 这项研究确定了微质细胞和神经元是大脑进激素的关键来源,为前性痴呆症提供了新的治疗策略.

科学领域:

神经科学是一个神经科学.
细胞生物学细胞生物学
神经退行性疾病神经退行性疾病

背景情况:

进子素 (GRN) 是一种具有神经和抗炎作用的分泌蛋白质,对溶酶体功能至关重要.
GRN中的突变会导致前性痴呆症,通常是通过progranulin哈普洛缺陷,使得progranulin增强疗法成为一个有希望的策略.
了解大脑中的细胞外progranulin调节对于开发有效疗法至关重要,但细胞特异性分泌和吸收机制仍然不太清楚.

研究的目的:

在小鼠中介前额叶皮质 (mPFC) 中识别主要细胞类型,负责孕蛋白分泌.
研究大脑中细胞外原蛋白水平的调节,特别是对炎症和神经元活动刺激的反应.
提供对progranulin的作用机制的见解,并为前性痴呆症的progranulin增强疗法的设计提供信息.

主要方法:

微透析被用来测量小鼠mPFC的间歇液体 (ISF) 中的progranulin水平.
使用GRN+/-小鼠和条件淘汰赛小鼠 (微结质特异性和神经元特异性) 来评估细胞类型特异性贡献.
免疫光和现场杂交被用来识别表达前列腺素的细胞类型.
在LPS注射 (诱导炎症) 和KCl或皮克托克辛注射 (调节神经元活动) 后,测量了progranulin水平.

主要成果:

与野生类型的小鼠相比,GRN+/-小鼠的ISF原蛋白水平大约降低了50%.
微质细胞和神经元被证实是mPFC中主要的progranulin表达细胞类型.
在微质或神经元中失去益格拉努林导致ISF益格拉努林减少了50%左右.
LPS注射急性增加了ISF前列腺素,这表明在炎症中发挥了作用,可能是由微质细胞或外周免疫细胞驱动的.
KCl诱导的脱极化增加了ISF的progranulin,但这种效应独立于神经元的progranulin分泌,涉及非神经元来源.
用皮克罗毒素调节神经元活动并没有改变ISF进激素水平,这表明神经元分泌是构成性的,而不是活动依赖的.

结论:

微质和神经元是小鼠mPFC中细胞外原蛋白的主要来源,微质可能在每个细胞中贡献更多.
细胞外原蛋白在炎症反应中起作用,如LPS挑战后ISF水平增加所证明.
神经元的progranulin分泌是构成性的,并不是由神经元活动急性调节的,而非神经元细胞有助于活动依赖的分泌.

关键词:

微透析是一种微透析.微质细胞中的微质细胞益格拉努林是一种Progranulin.密封的分泌密封的分泌

更多相关视频

Establishment of a Surgically-induced Model in Mice to Investigate the Protective Role of Progranulin in Osteoarthritis

Establishment of a Surgically-induced Model in Mice to Investigate the Protective Role of Progranulin in Osteoarthritis

Published on: February 25, 2014

Assessing Social Dominance in Mouse Models Using the Tube Test

Assessing Social Dominance in Mouse Models Using the Tube Test

Published on: June 6, 2025

相关概念视频

Neural Regulation

Neural Regulation

Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.

Regulation of Food Intake

Regulation of Food Intake

Short-term regulation of food intake primarily involves neural signals from the gastrointestinal (GI) tract, blood nutrient levels, and GI tract hormones. Communication between the gut and brain via vagal nerve fibers plays a significant role in evaluating the contents of the gut. Clinical studies have shown that protein ingestion produces a more prolonged response in these nerve fibers compared to an equivalent amount of glucose. Additionally, the activation of stretch receptors caused by GI...

Receptor Downregulation in MVBs

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...