Decreased kainate receptors in the hippocampus of apolipoprotein D knockout mice

Boer, Simone; Sánchez, Diego; Reinieren, Ivo; Boom, Tom van den; Udawela, Madhara; Scarr, Elizabeth; Ganfornina, Marı́a D.; Dean, Brian

doi:10.1016/j.pnpbp.2009.11.016

Cited by 7 publications

(6 citation statements)

References 58 publications

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“…In relation to neurotransmission as well, the synaptic machinery appears to react with an increased transcription of ionotropic glutamate receptor GluR4 [a-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors] and the neurotransmitter vesicle-related genes (Kf1b and Vapb) to increase a possibly reduced synaptic efficacy in ApoD-KO brain. In relation to this, we have reported a significant decrease of functional glutamate receptors in the brain of ApoD-KO mice (Boer et al 2009) that could cause a compensatory transcriptional up-regulation of some glutamate receptors.…”

Section: Differential Gene Expression Upon Constitutive Loss-offunctimentioning

confidence: 84%

Apolipoprotein D alters the early transcriptional response to oxidative stress in the adult cerebellum

Bajo‐Grañeras

Sánchez

Gutiérrez

et al. 2011

Journal of Neurochemistry

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1These authors contributed equally to this study.Abbreviations used: ApoD, Apolipoprotein D; FC, fold change; FDR, false discovery rate; GC, GeneChip; GO, gene ontology; hApoD, human ApoD; KO, knock-out; NS, nervous system; OS, oxidative stress; Pkcd, Protein kinase Cd; PQ, paraquat; RMA, robust multiarray average algorithm; RS, reactive species; Tg, transgenic; WT, wild-type. AbstractThe lipocalin Apolipoprotein D (ApoD), known to protect the nervous system against oxidative stress (OS) in model organisms, is up-regulated early in the mouse brain in response to the ROS generator paraquat. However, the processes triggered by this up-regulation have not been explored. We present here a study of the effect of ApoD on the early transcriptional changes upon OS in the mouse cerebellum using microarray profiling. ApoD-KO and transgenic mice over-expressing ApoD in neurons are compared to wild-type controls. In control conditions, ApoD affects the transcriptional profile of neuron and oligodendrocyte-specific genes involved in neuronal excitability, synaptic function, and myelin homeostasis. When challenged with paraquat, the absence of ApoD modifies the response of genes mainly related to OS management and myelination. Interestingly, the over-expression of ApoD in neurons almost completely abolishes the early transcriptional response to OS. We independently evaluate the expression of protein kinase Cd, a gene up-regulated by OS only in the ApoD-KO cerebellum, and find it overexpressed in cultured ApoD-KO primary astrocytes, which points to a role for ApoD in astrocyte-microglia signaling. Our results support the hypothesis that ApoD is necessary for a proper response of the nervous system against physiological and pathological OS.

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Section: Differential Gene Expression Upon Constitutive Loss-offunctimentioning

confidence: 84%

Apolipoprotein D alters the early transcriptional response to oxidative stress in the adult cerebellum

Bajo‐Grañeras

Sánchez

Gutiérrez

et al. 2011

Journal of Neurochemistry

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“…Reference Collection 38 (Martineau et al, 2016;Yu et al, 2020). Reference Collection 39 (Hildebrand et al, 2005;Thomas and Yao, 2007;Do Carmo et al, 2008;Ganfornina et al, 2008Ganfornina et al, , 2010He et al, 2009;Kosacka et al, 2009;Rajput et al, 2009;Boer et al, 2010;Bajo-Grañeras et al, 2011a,b;Kumar, 2012;Martínez et al, 2012;Ruiz et al, 2013;García-Mateo et al, 2014, 2018Li et al, 2015;Sanchez et al, 2015;Najyb et al, 2017;Bhatia et al, 2019;El-Darzi et al, 2020;Pascua-Maestro et al, 2020).…”

Section: Apod Systematic Review Reference Collectionsmentioning

confidence: 99%

The Lipocalin Apolipoprotein D Functional Portrait: A Systematic Review

Sánchez

Ganfornina

2021

Front. Physiol.

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Apolipoprotein D is a chordate gene early originated in the Lipocalin protein family. Among other features, regulation of its expression in a wide variety of disease conditions in humans, as apparently unrelated as neurodegeneration or breast cancer, have called for attention on this gene. Also, its presence in different tissues, from blood to brain, and different subcellular locations, from HDL lipoparticles to the interior of lysosomes or the surface of extracellular vesicles, poses an interesting challenge in deciphering its physiological function: Is ApoD a moonlighting protein, serving different roles in different cellular compartments, tissues, or organisms? Or does it have a unique biochemical mechanism of action that accounts for such apparently diverse roles in different physiological situations? To answer these questions, we have performed a systematic review of all primary publications where ApoD properties have been investigated in chordates. We conclude that ApoD ligand binding in the Lipocalin pocket, combined with an antioxidant activity performed at the rim of the pocket are properties sufficient to explain ApoD association with different lipid-based structures, where its physiological function is better described as lipid-management than by long-range lipid-transport. Controlling the redox state of these lipid structures in particular subcellular locations or extracellular structures, ApoD is able to modulate an enormous array of apparently diverse processes in the organism, both in health and disease. The new picture emerging from these data should help to put the physiological role of ApoD in new contexts and to inspire well-focused future research.

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“…Because of the abundance of kainate receptors, the hippocampus is more sensitive to KAinduced neurotoxicity [30]. Also, glutamatergic pathways seem to be particularly affected in apoD knockout mice with a 20 % decrease of kainate receptors in the CA 2-3 subfields of the hippocampus, a global decrease in AMPA receptors and a global increase in muscarinic M2/M4 receptors [31]. These changes may potentially contribute to the impairments in learning and memory and in motor-and orientation-based tasks observed in these animals [17], all of which involve glutamatergic neurotransmission.…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein D Overexpression Protects Against Kainate-Induced Neurotoxicity in Mice

et al. 2016

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Excitotoxicity due to the excessive activation of glutamatergic receptors leads to neuronal dysfunction and death. Excitotoxicity has been implicated in the pathogenesis of a myriad of neurodegenerative diseases with distinct etiologies such as Alzheimer's and Parkinson's. Numerous studies link apolipoprotein D (apoD), a secreted glycoprotein highly expressed in the central nervous system (CNS), to maintain and protect neurons in various mouse models of acute stress and neurodegeneration. Here, we used a mouse model overexpressing human apoD in neurons (H-apoD Tg) to test the neuroprotective effects of apoD in the kainic acid (KA)-lesioned hippocampus. Our results show that apoD overexpression in H-apoD Tg mice induces an increased resistance to KA-induced seizures, significantly attenuates inflammatory responses and confers protection against KA-induced cell apoptosis in the hippocampus. The apoD-mediated protection against KA-induced toxicity is imputable in part to increased plasma membrane Ca2+ ATPase type 2 expression (1.7-fold), decreased N-methyl-D-aspartate receptor (NMDAR) subunit NR2B levels (30 %) and lipid metabolism alterations. Indeed, we demonstrate that apoD can attenuate intracellular cholesterol content in primary hippocampal neurons and in brain of H-apoD Tg mice. In addition, apoD can be internalised by neurons and this internalisation is accentuated in ageing and injury conditions. Our results provide additional mechanistic information on the apoD-mediated neuroprotection in neurodegenerative conditions.

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Decreased kainate receptors in the hippocampus of apolipoprotein D knockout mice

Cited by 7 publications

References 58 publications

Apolipoprotein D alters the early transcriptional response to oxidative stress in the adult cerebellum

Apolipoprotein D alters the early transcriptional response to oxidative stress in the adult cerebellum

The Lipocalin Apolipoprotein D Functional Portrait: A Systematic Review

Apolipoprotein D Overexpression Protects Against Kainate-Induced Neurotoxicity in Mice

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