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脂滴在海马神经元和小胶质细胞中的分布：糖尿病和运动的影响

Distribution of lipid droplets in hippocampal neurons and microglia: impact of diabetes and exercise.

作者信息

Seferi Gezime, Mjønes Harald S, Havik Mona, Reiersen Herman, Dalen Knut Tomas, Nordengen Kaja, Morland Cecilie

机构信息

Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.

Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.

出版信息

Life Sci Alliance. 2024 Aug 8;7(10). doi: 10.26508/lsa.202302239. Print 2024 Oct.

DOI:10.26508/lsa.202302239
PMID:39117458
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11310565/
Abstract

Neuroinflammation, aging, and neurodegenerative disorders are associated with excessive accumulation of neutral lipids in lipid droplets (LDs) in microglia. Type 2 diabetes mellitus (T2DM) may cause neuroinflammation and is a risk factor for neurodegenerative disorders. Here, we show that hippocampal pyramidal neurons contain smaller, more abundant LDs than their neighboring microglia. The density of LDs varied between pyramidal cells in adjacent subregions, with CA3 neurons containing more LDs than CA1 neurons. Within the CA3 region, a gradual increase in the LD content along the pyramidal layer from the hilus toward CA2 was observed. Interestingly, the high neuronal LD content correlated with less ramified microglial morphotypes. Using the model of T2DM, we demonstrated that diabetes increased the number of LDs per microglial cell without affecting the neuronal LD density. High-intensity interval exercise induced smaller changes in the number of LDs in microglia but was not sufficient to counteract the diabetes-induced changes in LD accumulation. The changes observed in response to T2DM may contribute to the cerebral effects of T2DM and provide a mechanistic link between T2DM and neurodegenerative disorders.

摘要

神经炎症、衰老和神经退行性疾病与小胶质细胞中脂滴（LDs）内中性脂质的过度积累有关。2型糖尿病（T2DM）可能会引发神经炎症，并且是神经退行性疾病的一个风险因素。在此，我们发现海马锥体神经元所含的脂滴比其相邻的小胶质细胞更小、数量更多。相邻亚区域的锥体细胞中脂滴的密度有所不同，CA3神经元含有的脂滴比CA1神经元更多。在CA3区域内，沿着锥体层从门区向CA2观察到脂滴含量逐渐增加。有趣的是，神经元中高含量的脂滴与分支较少的小胶质细胞形态相关。利用T2DM模型，我们证明糖尿病增加了每个小胶质细胞的脂滴数量，而不影响神经元的脂滴密度。高强度间歇运动引起小胶质细胞中脂滴数量的变化较小，但不足以抵消糖尿病诱导的脂滴积累变化。对T2DM产生的反应中观察到的这些变化可能导致T2DM的脑部效应，并为T2DM与神经退行性疾病之间提供一个机制联系。

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Effects of diabetes on microglial physiology: a systematic review of in vitro, preclinical and clinical studies.
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