Long-term depression: a cell biological view

Sheng, Morgan; Ertürk, Ali

doi:10.1098/rstb.2013.0138

Cited by 31 publications

(32 citation statements)

References 104 publications

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“…Interestingly, presynaptic mitochondrial morphology has been shown to correlate with impaired working memory in monkey brain 53 . Moreover, the mitochondrial apoptotic pathway can be moderately and locally activated to induce LTD, resulting in shrinkage and loss of dendritic spines in the absence of cell death 54,55 . This system as well as mitochondria morphological changes are sensitive to sublethal mitochondrial stress 55,56 , which can be induced by excess of Ca 2+ through disinhibition of glutamate release as a result of GABAergic dysfunction or by loss of Ca 2+ buffering capacity through loss of parvalbumin 57 , both observed in Brd1 +/mice 9 .…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Brain proteome changes in female Brd1 mice unmask dendritic spine pathology and show enrichment for schizophrenia risk

Paternoster

Svanborg

Edhager

et al. 2019

Neurobiology of Disease

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2018). Brain proteome changes in female Brd1 +/ mice unmask dendritic spine pathology and show enrichment for schizophrenia risk. Neurobiology of Disease. https://doi.Brain proteome changes in female Brd1+/− mice unmask dendritic spine pathology and show enrichment for schizophrenia risk. Ynbdi (2018), https://doi. AbstractGenetic and molecular studies have implicated the Bromodomain containing 1 (BRD1) gene in the pathogenesis of schizophrenia and bipolar disorder. Accordingly, mice heterozygous for a targeted deletion of Brd1 (Brd1 +/mice) show behavioral phenotypes with broad translational relevance to psychiatric disorders. BRD1 encodes a scaffold protein that affects the expression of many genes through modulation of histone acetylation. BRD1 target genes have been identified in cell lines; however the impact of reduced Brd1 levels on the brain proteome is largely unknown. In this study, we applied labelbased quantitative mass spectrometry to profile the frontal cortex, hippocampus and striatum proteome and synaptosomal proteome of female Brd1 +/mice. We successfully quantified between 1537 and 2196 proteins and show widespread changes in protein abundancies and compartmentalization. By integrative analysis of human genetic data, we find that the differentially abundant proteins in frontal cortex and hippocampus are enriched for schizophrenia risk further linking the actions of BRD1 to psychiatric disorders. Affected proteins were further enriched for proteins involved in processes known to influence neuronal and dendritic spine morphology e.g. regulation of cytoskeleton dynamics and mitochondrial function. Directly prompted in these findings, we investigated dendritic spine morphology of pyramidal neurons in anterior cingulate cortex and found them significantly altered, including reduced size of small dendritic spines and decreased number of the mature mushroom type. Collectively, our study describes known as well as new mechanisms related to BRD1 dysfunction and its role in psychiatric disorders, and provides evidence for the molecular and cellular dysfunctions underlying altered neurosignalling and cognition in Brd1 +/mice.

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Section: Accepted Manuscriptmentioning

confidence: 99%

Brain proteome changes in female Brd1 mice unmask dendritic spine pathology and show enrichment for schizophrenia risk

Paternoster

Svanborg

Edhager

et al. 2019

Neurobiology of Disease

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“…Spines are not static structures, but exhibit morphological plasticity in response to synaptic activity (5). Long-term potentiation inducing stimuli promote enlargement of spine heads, whereas stimuli that correlate with long-term depression induce spine shrinkage (6,7). The ability of pyramidal neurons to generate appropriate spine and synaptic architecture and modulate it in response to synaptic activity is critical for the integrity of the cellular machinery that underlies information storage (8 -10).…”

mentioning

confidence: 99%

δ-Catenin Regulates Spine Architecture via Cadherin and PDZ-dependent Interactions

Seong

Beuscher

et al. 2015

Journal of Biological Chemistry

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Background:The architecture of spines in pyramidal neurons is critical for function. Results: We identified ␦-catenin as a critical regulator of spine architecture in hippocampal neurons. Conclusion: ␦-Catenin regulates spine architecture via its ability to interact with cadherin and PDZ domain-containing proteins. Significance: The identification of molecular mechanisms underlying spine architecture is crucial for understanding the molecular and cellular basis of higher order brain functions.

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“…Indeed, mice whose genomic CamKIIα was altered so that its mRNA no longer localized to the PSD showed deficits in learning and establishing LTP at the cellular level . Importantly, nearby inactive synaptic connections, which do not receive any newly synthesized proteins, undergo long‐term depression and are eventually eliminated by synaptic pruning . In line with this model, the overexpression of the Fragile X mental retardation protein, which inhibits the translation of dendritically‐targeted mRNAs, results in an overall reduction in PSDs, while deletion of this gene has the opposite effect …”

Section: The Regulation Of Mrna Translation At Post‐synaptic Densitiesmentioning

confidence: 94%

mRNA localization as a rheostat to regulate subcellular gene expression

Kejiou

Palazzo

2017

WIREs RNA

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It is currently believed that certain messenger RNAs (mRNAs) are localized to distinct subcellular regions to efficiently target their encoded proteins. However, this simplistic model does not explain why in certain scenarios mRNA localization is dispensable for proper protein distribution. In other cases, mRNA localization is accompanied by translational silencing and degradation by the localization machinery. Here we propose that in certain scenarios mRNAs are localized so that they can either be stabilized and translated, or silenced and degraded, in response to the needs of the subcellular locale. In these cases, the localized mRNA, and its cadre of associated factors, act as a rheostat that regulates protein production and/or mRNA stability in response to the needs of its immediate subcellular environment. WIREs RNA 2017, 8:e1416. doi: 10.1002/wrna.1416 For further resources related to this article, please visit the WIREs website.

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Long-term depression: a cell biological view

Cited by 31 publications

References 104 publications

Brain proteome changes in female Brd1 mice unmask dendritic spine pathology and show enrichment for schizophrenia risk

Brain proteome changes in female Brd1 mice unmask dendritic spine pathology and show enrichment for schizophrenia risk

δ-Catenin Regulates Spine Architecture via Cadherin and PDZ-dependent Interactions

mRNA localization as a rheostat to regulate subcellular gene expression

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