Reciprocal Regulation of Very Low Density Lipoprotein Receptors (VLDLRs) in Neurons by Brain-derived Neurotrophic Factor (BDNF) and Reelin

Do, Hai Thi; Bruelle, Céline; Tselykh, Timofey V.; Jalonen, Pilvi; Korhonen, Laura; Lindholm, Dan

doi:10.1074/jbc.m113.500967

Cited by 20 publications

(24 citation statements)

References 48 publications

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“…This mechanism has been shown to be regulated in a tissue- and species-dependent manner [28]. In cultured cells, it was determined that LXR activation increased IDOL transcript and protein and reduced VLDLR protein levels, implying a potential role for IDOL in development by regulating the ability of neuronal guidance cue Reelin to signal through its receptor VLDLR [27,29]. …”

Section: Lipoprotein Receptor Regulationmentioning

confidence: 99%

LXR Regulation of Brain Cholesterol: From Development to Disease

Courtney

Landreth

2016

Trends in Endocrinology & Metabolism

135

105

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Liver X Receptors (LXRs) are master regulators of cholesterol homeostasis and inflammation in the central nervous system (CNS). The brain, which contains a disproportionately large amount of the body's total cholesterol (~25%), requires a complex and delicately balanced cholesterol metabolism to maintain neuronal function. Dysregulation of cholesterol metabolism has been implicated in a number of neurodegenerative diseases including Alzheimer's (AD), Parkinson's (PD), and Huntington's (HD) diseases, among others. Due to their cholesterol sensing and anti-inflammatory activities, LXRs are positioned centrally in the everyday maintenance of central nervous system function. This review will focus on recent research into the role of LXRs in the CNS during normal development and homeostasis and in disease states.

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Section: Lipoprotein Receptor Regulationmentioning

confidence: 99%

LXR Regulation of Brain Cholesterol: From Development to Disease

Courtney

Landreth

2016

Trends in Endocrinology & Metabolism

135

105

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“…As a control for transfection efficiency, we used the Renilla luciferase pRL-TK vector (Promega). Cells were stimulated with 50 ng/ml NGF, 5 ng/ml pro-NGF, or 1 M simvastatin for 24 h followed by measurement of firefly and Renilla luciferase activities using a luminometer (Promega, Biofellows, Helsinki, Finland) as described (29,30). Results are shown as fold increase in firefly luciferase activity normalized to that of Renilla luciferase.…”

Section: Methodsmentioning

confidence: 99%

“…Immunoblotting-Tissue and cells were lysed in a buffer containing 150 mM NaCl, 1 mM EDTA, and 50 mM Tris-HCl, pH 7.4, supplemented with 1% Nonidet P-40, 0.25% sodium deoxycholate, 1% SDS, and protease inhibitors (24,29). Protein concentrations were determined using the Bradford assay, and an equal amount of protein per sample was subjected to SDS-PAGE and then blotted onto nitrocellulose filters (Amersham Biosciences, Helsinki, Finland).…”

Section: Methodsmentioning

confidence: 99%

p75 Neurotrophin Receptor Signaling Activates Sterol Regulatory Element-binding Protein-2 in Hepatocyte Cells via p38 Mitogen-activated Protein Kinase and Caspase-3

Pham

Bruelle

et al. 2016

Journal of Biological Chemistry

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Nerve growth factor (NGF) influences the survival and differentiation of a specific population of neurons during development, but its role in non-neuronal cells has been less studied. We observed here that NGF and its pro-form, pro-NGF, are elevated in fatty livers from leptin-deficient mice compared with controls, concomitant with an increase in low density lipoprotein receptors (LDLRs). Stimulation of mouse primary hepatocytes with NGF or pro-NGF increased LDLR expression through the p75 neurotrophin receptor (p75NTR). Studies using Huh7 human hepatocyte cells showed that the neurotrophins activate the sterol regulatory element-binding protein-2 (SREBP2) that regulates genes involved in lipid metabolism. The mechanisms for this were related to stimulation of p38 mitogen-activated protein kinase (p38 MAPK) and activation of caspase-3 and SREBP2 cleavage following NGF and pro-NGF stimulations. Cell fractionation experiments showed that caspase-3 activity was increased particularly in the membrane fraction that harbors SREBP2 and caspase-2. Experiments showed further that caspase-2 interacts with pro-caspase-3 and that p38 MAPK reduced this interaction and caused caspase-3 activation. Because of the increased caspase-3 activity, the cells did not undergo cell death following p75NTR stimulation, possibly due to concomitant activation of nuclear factor-B (NF-B) pathway by the neurotrophins. These results identify a novel signaling pathway triggered by ligand-activated p75NTR that via p38 MAPK and caspase-3 mediate the activation of SREBP2. This pathway may regulate LDLRs and lipid uptake particularly after injury or during tissue inflammation accompanied by an increased production of growth factors, including NGF and pro-NGF.

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“…VLDLR downregulation may be related to the decreased number of reelin + interneurons in the dentate hilus. It is reported that BDNF increases the expression levels of VLDLR in cultured rat hippocampal neurons (Do et al ., ), suggesting that expression of Vldlr may be linked to Bdnf mRNA levels. While the reason for the decrease in reelin + interneurons by IDPN exposure is not clear, epigenetic gene silencing by hypermethylation of the promoter sequence is reported in the hippocampus of offspring after maternal deprivation in rats (Qin et al ., ).…”

Section: Discussionmentioning

confidence: 98%

Maternal exposure to 3,3’‐iminodipropionitrile targets late‐stage differentiation of hippocampal granule cell lineages to affect brain‐derived neurotrophic factor signaling and interneuron subpopulations in rat offspring

Itahashi

Abe

Tanaka

et al. 2014

J of Applied Toxicology

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3,3'-Iminodipropionitrile (IDPN) causes neurofilament (NF)-filled swellings in the proximal segments of many large-caliber myelinated axons. This study investigated the effect of maternal exposure to IDPN on hippocampal neurogenesis in rat offspring using pregnant rats supplemented with 0 (controls), 67 or 200 ppm IDPN in drinking water from gestational day 6 to day 21 after delivery. On postnatal day (PND) 21, female offspring subjected to analysis had decreased parvalbumin(+), reelin(+) and phospho-TrkB(+) interneurons in the dentate hilus at 200 ppm and increased granule cell populations expressing immediate-early gene products, Arc or c-Fos, at ≥ 67 ppm. mRNA expression in the dentate gyrus examined at 200 ppm decreased with brain-derived neurotrophic factor (Bdnf) and very low density lipoprotein receptor. Immunoreactivity for phosphorylated NF heavy polypeptide decreased in the molecular layer of the dentate gyrus and the stratum radiatum of the cornu ammonis (CA) 3, portions showing axonal projections from mossy cells and pyramidal neurons, at 200 ppm on PND 21, whereas immunoreactivity for synaptophysin was unchanged in the dentate gyrus. Observed changes all disappeared on PND 77. There were no fluctuations in the numbers of apoptotic cells, proliferating cells and subpopulations of granule cell lineage in the subgranular zone on PND 21 and PND 77. Thus, maternal IDPN exposure may reversibly affect late-stage differentiation of granule cell lineages involving neuronal plasticity as evident by immediate-early gene responses to cause BDNF downregulation resulting in a reduction in parvalbumin(+) or reelin(+) interneurons and suppression of axonal plasticity in the mossy cells and CA3 pyramidal neurons.

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Reciprocal Regulation of Very Low Density Lipoprotein Receptors (VLDLRs) in Neurons by Brain-derived Neurotrophic Factor (BDNF) and Reelin

Cited by 20 publications

References 48 publications

LXR Regulation of Brain Cholesterol: From Development to Disease

LXR Regulation of Brain Cholesterol: From Development to Disease

p75 Neurotrophin Receptor Signaling Activates Sterol Regulatory Element-binding Protein-2 in Hepatocyte Cells via p38 Mitogen-activated Protein Kinase and Caspase-3

Maternal exposure to 3,3’‐iminodipropionitrile targets late‐stage differentiation of hippocampal granule cell lineages to affect brain‐derived neurotrophic factor signaling and interneuron subpopulations in rat offspring

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