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HepaCAM knockdown impairs learning and memory in mice by regulating cholesterol synthesis pathway

GSE280264 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/07/01 Platform GPL24247
Summary
Astrocytes engage in metabolic interactions with nearby neurons by supplying various substances. However, how they regulate learning and memory through changes in the metabolic state of neurons is still unclear. In this study, we show that knocking down astrocytic hepaCAM silences genes related to cholesterol biosynthesis in astrocytes, leading to a decrease in cholesterol levels. Additionally, astrocytes play a crucial role in synapse development and function by releasing signals that guide neurons. Consequently, without enough cholesterol, the level of neuronal synaptic proteins and the density of dendritic spines decrease. Then we demonstrate that knocking down hepaCAM leads to impaired learning and memory in mice. Collectively, hepaCAM, a cell adhesion molecules specifically expressed in astrocytes, regulates learning and memory by regulating the cholesterol synthesis pathway.
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Also filed as BioProject PRJNA1177475 and SRA study SRP540696. Searching any of these in the dataset finder brings you back here.

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