Role of Apolipoprotein E Receptors in Regulating the Differential in vivo Neurotrophic Effects of Apolipoprotein E
| Autor: | Margaret Mallory, Christine McGiffert, M. Alford, Isaac Veinbergs, Richard DeTeresa, Emily Van Uden, Robert A. Orlando, Eliezer Masliah |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Apolipoprotein E
medicine.medical_specialty Interneuron Apolipoprotein E3 Heymann Nephritis Antigenic Complex Neocortex Context (language use) Hippocampus Mice Apolipoproteins E Developmental Neuroscience Interneurons In vivo Internal medicine medicine Animals Nerve Growth Factors Receptor Injections Intraventricular Receptors Lipoprotein Mice Knockout Neurons Membrane Glycoproteins biology Pyramidal Cells Recombinant Proteins Mice Inbred C57BL Endocrinology medicine.anatomical_structure Neurology LDL receptor biology.protein lipids (amino acids peptides and proteins) Somatostatin Microtubule-Associated Proteins Low Density Lipoprotein Receptor-Related Protein-1 Neurotrophin Lipoprotein |
| Zdroj: | Experimental Neurology. 170:15-26 |
| ISSN: | 0014-4886 |
| DOI: | 10.1006/exnr.2001.7684 |
| Popis: | Apolipoprotein E (apoE) is known to bind to at least five receptors, including the low-density lipoprotein (LDL) receptor-related protein (LRP), very low density LDL receptor (VLDL-R), LDL-R, apoE receptor 2 (apoER2), and megalin/gp330. In this context, the main objective of the present study was to better understand the contributions of LRP and LDL-R to the in vivo neurotrophic effects of apoE. For this purpose, apoE-deficient and receptor-associated protein (RAP)-deficient mice were infused with recombinant apoE3, RAP, or saline. Infusion of apoE3 into apoE-deficient mice resulted in amelioration of degenerative alterations of pyramidal neurons, but had no effect on somatostatin-producing interneurons. In contrast, infusion of apoE3 into RAP-deficient mice resulted in amelioration of degenerative alterations of somatostatin-producing interneurons. LRP and LDL-R levels were significantly reduced in RAP-deficient mice, but significantly increased in the apoE-deficient mice. In contrast, levels of apoE were reduced in the RAP-deficient mice compared to wildtype controls, suggesting that neurotrophic effects of apoE3 in the RAP-deficient mice were related to a combined deficit in endogenous apoE and selected apoE receptors. Furthermore, in apoE-deficient mice, infusion of apoE3 had a neurotrophic effect on somatostatin-producing interneurons only when combined with RAP, suggesting that increased expression of apoE receptors in apoE-deficient mice prevented apoE from rescuing somatostatin-producing neurons. This study supports the contention that some of the in vivo neurotrophic effects of apoE are mediated by LRP and LDL-R and that a critical balance between levels of apoE and its receptors is necessary for the differential neurotrophic effects to appear. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect