Abstract
The subventricular zone is a key site of adult neurogenesis and is also implicated in neurodegenerative diseases and brain cancers. In the subventricular zone, cell proliferation, migration and differentiation of nascent stem cells and neuroblasts are regulated at least in part by lipids. The human subventricular zone is distinctly layered and each layer contains discrete cell types that support the processes of neuroblast migration and neurogenesis. We set out to determine the lipid signatures of each subventricular layer in the adult human brain (n = 4). We utilised matrix-assisted laser desorption/ionisation (MALDI) imaging mass spectrometry and liquid chromatography-mass spectrometry to characterise the lipidome of the subventricular zone, with histology and microscopy used for identifying anatomical landmarks. Our findings showed that the subventricular zone was rich in sphingomyelins and phosphatidylserines but deficient in phosphatidylethanolamines. The ependymal layer had an abundance of phosphatidylinositols, whereas the myelin layer was rich in sulfatides and triglycerides. The hypocellular layer showed enrichment of sphingomyelins. No discrete lipid signature was seen in the astrocytic ribbon. The biochemical functions of these lipid classes are consistent with the localisation we observed within the SVZ. Our study may, therefore, shed new light on the role of lipids in the regulation of adult neurogenesis.
Highlights
Lipids are highly abundant in the brain, where they show great diversity of structure and function
The human subventricular zone (SVZ) is comprised of four anatomically distinct layers – a superficial ependymal layer that interfaces with the ventricular cavity, a hypocellular layer that contains few cell bodies but houses a dense network of glial fibrillary acid protein (GFAP)-positive astrocytic processes, an astrocytic ribbon with resident neural stem cells (NSCs) and a heavily myelinated zone that transitions to the underlying parenchyma of the caudate nucleus (CN)[17,18]
imaging mass spectrometry (IMS) was conducted at the highest achievable resolution (i.e. 10 μm raster width with minimum laser diameter) within an imaging region encompassing a medial section of the SVZ and a ventral area of the CN parenchyma
Summary
Lipids are highly abundant in the brain, where they show great diversity of structure and function. Lipids perform a broad range of functions including membrane structure, metabolism, cell proliferation and survival, transcriptional regulation and intracellular signaling. Deranged fatty acid homoeostasis in the SVZ of Alzheimer’s disease brains has been observed, where early lipid accumulation impairs neural progenitor activity[9] Such studies suggest that coordination of lipid synthesis and metabolism is involved in regulating the transition of NSCs from a quiescent (non-proliferating) to an active (proliferating) state. Adult neurogenesis occurs in the SVZ of the lateral ventricles and in the dentate gyrus of the hippocampus This process requires the regulation of an ensemble of cellular programmes including the proliferation of NSCs, lineage commitment of neural progenitors, migration and differentiation into functional neurons and their survival and integration into existing brain circuits. We report a comprehensive analysis of the lipidome of the SVZ in the human brain and demonstrate that the most abundant lipid classes in each layer align closely with the specific function of that layer
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