Low Density Lipoprotein-Receptor Related Protein 1 Is Differentially Expressed by Neuronal and Glial Populations in the Developing and Mature Mouse Central Nervous System

Abstract

The low density lipoprotein-receptor related protein 1 (LRP1) is a large endocytic cell surface receptor that is known to interact with a variety of ligands, intracellular adaptor proteins and other cell surface receptors to regulate cellular behaviours ranging from proliferation to cell fate specification, migration, axon guidance, and lipid metabolism. A number of studies have demonstrated that LRP1 is expressed in the brain, yet it is unclear which central nervous system cell types express LRP1 during development and in adulthood. Herein we undertake a detailed study of LRP1 expression within the mouse brain and spinal cord, examining a number of developmental stages ranging from embryonic day 13.5 to postnatal day 60. We report that LRP1 expression in the brain peaks during postnatal development. On a cellular level, LRP1 is expressed by radial glia, neuroblasts, microglia, oligodendrocyte progenitor cells (OPCs), astrocytes and neurons, with the exception of parvalbumin+ interneurons in the cortex. Most cell populations exhibit stable expression of LRP1 throughout development; however, the proportion of OPCs that express LRP1 increases significantly from ~69% at E15.5 to ~99% in adulthood. We also report that LRP1 expression is rapidly lost as OPCs differentiate, and is absent from all oligodendrocytes, including newborn oligodendrocytes. While LRP1 function has been primarily examined in mature neurons, these expression data suggest it plays a more critical role in glial cell regulation–where expression levels are much higher.

LRP1 deficiency in microglia blocks neuro‐inflammation in the spinal dorsal horn and neuropathic pain processing

“…Spinal cords were harvested 3 days later and cross sections of SDH tissue centered at L4 were immunostained for the microglial marker, Iba1 (green), and for LRP1 (red). In sham‐operated LysM‐ Cre ‐negative‐ LRP1 fl/fl mice, LRP1 immunopositivity in the SDH was diffuse (Figure a, middle panels ), as anticipated because diverse cell types in the CNS, including neurons, astrocytes, and oligodendrocytes, express LRP1 (Auderset, Cullen, & Young, ; Bu, Maksymovitch, Nerbonne, & Schwartz A, ; Gaultier et al, ; Wolf, Lopes, VandenBerg, & Gonias, ). However, Iba1‐immunopositive microglia were mostly LRP1‐negative (see panel labeled “merged”).…”

“…To study LRP1 expression in SDH microglia in situ, LysM-Cre-negative- (Figure 3a, middle panels), as anticipated because diverse cell types in the CNS, including neurons, astrocytes, and oligodendrocytes, express LRP1 (Auderset, Cullen, & Young, 2016;Bu, Maksymovitch, Nerbonne, & Schwartz A, 1994;Gaultier et al, 2009;Wolf, Lopes, VandenBerg, & Gonias, 1992). However, Iba1-immunopositive microglia were mostly LRP1-negative (see panel labeled "merged").…”

Oleocanthal ameliorates amyloid-β oligomers’ toxicity on astrocytes and neuronal cells: In vitro studies

“…Besides, the high levels of Aβo observed the brains of AD patients is associated with pathological activation of astrocytes leading to GLT1 down-regulation (Scimemi et al, 2013), and cytokines and free radicals secretion (Li et al, 2011). Astrocytes are capable of clearing Aβ by multiple mechanisms including: Aβ monomers (Aβm) uptake by the function of several receptors and transporters such as LRP1 (Auderset et al, 2016), by direct degradion via endosomal-lysosomal pathways and secretion of degradation enzymes, such as insulin-degrading enzyme (IDE) into the brain parenchyma (Son et al, 2016), and/or by indirect activation of ATP-binding cassette transporter-A1 (ABCA1) function, which is responsible for the lipidation of apolipoprotein E (ApoE) (Wahrle et al, 2004). …”

PLGA-PEG-ANG-2 Nanoparticles for Blood–Brain Barrier Crossing: Proof-of-Concept Study

“…Then, their ability to cross the BBB was qualitatively assessed on an animal model. Proof-of-concept studies with fluorescent and confocal microscopy studies highlighted that the brain-targeted PLGA nanoparticles were able to cross the BBB and accumulated in neuronal cells, thus showing a promising brain drug delivery system.Pharmaceutics 2020, 12, 72 2 of 11 system (CNS) (by endothelial cells on the basolateral surface, neuroblasts, microglia, astrocytes, and neurons) [9][10][11][12]. This ligand has been highly sought after in its use to deliver nanomedicines to the brain because of its ability to activate transcytosis across the BBB, as well as its upregulation in human glioma cells [13][14][15].…”