Anxio-d epressive phenotype and impaired memory in mice with a conditional knockout of brain-derived neurotrophic factor in endothelial cells.

IF 5 2区 生物学 Q2 CELL BIOLOGY
Aurore Quirié, Damien Mor, Alexandre Méloux, Adeline Etievant, Philippe Garnier, Perle Totoson, Julien Wirtz, Anne Prigent-Tessier, Christine Marie, Céline Demougeot
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引用次数: 0

Abstract

The present study investigated the role of endothelial BDNF in cognition. Male adult mice with a selective knockout of BDNF in endothelial cells (BDNFECKO) and their wild-type littermates (WT) were subjected to tests for detection of anxiety- and depression-like behaviors and impaired recognition memory. Neuronal activity and synaptogenesis were assessed from hippocampal levels of c-fos and synaptophysin, respectively, and cerebral capillary density from forebrain levels of CD31. BDNF/TrkB (tropomyosin-related kinase type B) receptor signaling was investigated through hippocampal levels of BDNF and activated TrkB receptors coupled with their immunolabelling by neurons and endothelial cells from both cerebrovascular fractions enriched in capillaries and hippocampal arterioles. Endothelial nitric oxide (NO) production was assessed from expression of endothelial NO synthase phosphorylated at serine 1177. BDNFECKO mice exhibited anxio-depressive phenotype, impaired memory and reduced synaptogenesis. Neither neuronal activity, neuronal BDNF/TrkB signaling nor capillary density differed between BDNFECKO and WT mice. However, endothelial-activated TrkB receptors as well as endothelial NO production and hippocampal BDNF levels were lower in BDNFECKO than WT mice. We conclude that endothelial BDNF is involved in cognition through mechanisms independent of neuronal BDNF/TrkB signaling and that endothelial NO might be a driver of the pro-cognitive effect of endothelial BDNF.

内皮细胞中脑源性神经营养因子条件性基因敲除小鼠的镇静表型和记忆受损。
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来源期刊
CiteScore
9.10
自引率
1.80%
发文量
252
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Cell Physiology is dedicated to innovative approaches to the study of cell and molecular physiology. Contributions that use cellular and molecular approaches to shed light on mechanisms of physiological control at higher levels of organization also appear regularly. Manuscripts dealing with the structure and function of cell membranes, contractile systems, cellular organelles, and membrane channels, transporters, and pumps are encouraged. Studies dealing with integrated regulation of cellular function, including mechanisms of signal transduction, development, gene expression, cell-to-cell interactions, and the cell physiology of pathophysiological states, are also eagerly sought. Interdisciplinary studies that apply the approaches of biochemistry, biophysics, molecular biology, morphology, and immunology to the determination of new principles in cell physiology are especially welcome.
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