Lipid metabolism and storage in neuroglia: role in brain development and neurodegenerative diseases

Abstract

The importance of neuroglia in maintaining normal brain function under physiological and pathological conditions has been supported by growing evidence in recent years. The most important issues regarding glial metabolism and function include the cooperation between glial populations and neurons, morphological and functional changes in pathological states, and the role in the onset and progression of neurodegenerative diseases. Although lipid accumulation and further lipid droplet production in neurodegenerative disease brain models have been observed for a long time, the dynamic development of brain lipid droplet research in recent years suggests its role in the development and progression of neurodegenerative diseases was previously underestimated. First recognized as organelles of lipid storage, lipid droplets (LDs) have emerged as an important organelle in metabolic diseases, inflammation, and host defense. Dynamic changes in lipid metabolism within neurons and glial cells resulting in lipid accumulation and lipid droplet formation are present in brain models of various neurodegenerative diseases, yet their role in the brain remains largely unexplored. This paper first reviews the metabolism and accumulation of several major lipids in the brain and discusses the regulation of lipid accumulation in different types of brain cells. We explore the potential role of intracellular lipid accumulation in the pathogenesis of neurodegeneration, starting from lipid metabolism and LDs biogenesis in glial cells, and discuss several pathological factors that promote lipid droplet formation, mainly focusing on oxidative stress, energy metabolism and glial cell-neuron coupling, which are closely related to the etiology and progression of neurodegenerative diseases. Finally, the directions and challenges of intracellular lipid metabolism in glial cells in neurodegeneration are discussed.

Multi-omics analysis revealed the role of CYP1A2 in the induction of mechanical allodynia in type 1 diabetes

“…Integrated analysis was performed to understand the network of relationships between altered lipidomics and transcriptomics. Dynamic changes in lipid metabolism within neurons and glial cells resulting in lipid accumulation and lipid droplet formation are present in brain models of various neurodegenerative diseases ( Yang et al, 2022 ), and myelin sheath is essential for the normal function of peripheral nerves. The results suggested that the downregulation of CYP1A2 expression may be responsible for PC accumulation, as shown in Figure 4 .…”

Resident Astrocytes can Limit Injury to Developing Hippocampal Neurons upon THC Exposure

“…These thoughts are consistent with our co-culture experiments in which low density astrocytes (10%), in comparison to physiological numbers of 1.5 astrocyte-to-neurons in the cerebral cortex [ 29 ], were enough to significantly protect neurons from THC-induced damage. We firstly attribute the protective effect on the physical presence of astrocytes, providing passive protection by forming a larger lipid bilayer pool for THC to interact with [ 56 ], in addition to its possible capture into de novo created astrocytic lipid droplets in response to stressors [ 57 , 58 ]. Second, even though astrocyte conditioned medium had no effect in preventing THC-induced damage, the close physical contact of neurons with astrocytes would allow for immediate local glutamate scavenging, as well as the release of high concentrations of ATP [ 59 ] and antioxidants [ 55 ], both independent of vesicular release [ 60 , 61 ], directly onto the neuron, otherwise diluted in cell culture medium.…”

Monitoring lipid alterations in Drosophila heads in an amyotrophic lateral sclerosis model with time-of-flight secondary ion mass spectrometry

“…31 The LD-rich glial cells are less sensitive to harmful reactive oxygen species (ROS) activity than neurons, so they are considered the main site of FA storage and lipid metabolism in the brain. 32 Neuronal FAs that are not been used during the electron transport chain (ETC)-mediated synthesis of adenosine triphosphate (ATP) are transported to glial cells by apolipoproteins. As the accumulation of FAs is toxic to neuronal cells, FAs must be stored as TAGs in LDs.…”