Chronic mild hypoxia increases expression of laminins 111 and 411 and the laminin receptor α6β1 integrin at the blood-brain barrier

Halder, Sebok Kumar; Kant, Ravi; Milner, Richard

doi:10.1016/j.brainres.2018.07.012

Cited by 17 publications

(15 citation statements)

References 39 publications

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“…Remodelling of the ECM is a common feature in ageing and neuropathological conditions [22,23]. Experimental work in rodents demonstrates that ischaemia in the white matter is characterised by an upregulation of the extracellular matrix proteins laminin and fibronectin [24][25][26] but it is not known if similar changes occur in human white matter. As BMs are key to IPAD, remodelling of the ECM associated with ischaemia will likely have an impact on the IPAD pathways.…”

Section: Introductionmentioning

confidence: 99%

Demonstrating a reduced capacity for removal of fluid from cerebral white matter and hypoxia in areas of white matter hyperintensity associated with age and dementia

Sharp

Saitô

Keable

et al. 2020

acta neuropathol commun

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White matter hyperintensities (WMH) occur in association with dementia but the aetiology is unclear. Here we test the hypothesis that there is a combination of impaired elimination of interstitial fluid from the white matter together with a degree of hypoxia in WMH. One of the mechanisms for the elimination of amyloid-β (Aβ) from the brain is along the basement membranes in the walls of capillaries and arteries (Intramural Peri-Arterial Drainage-IPAD). We compared the dynamics of IPAD in the grey matter of the hippocampus and in the white matter of the corpus callosum in 10 week old C57/B16 mice by injecting soluble Aβ as a tracer. The dynamics of IPAD in the white matter were significantly slower compared with the grey matter and this was associated with a lower density of capillaries in the white matter. Exposing cultures of smooth muscle cells to hypercapnia as a model of cerebral hypoperfusion resulted in a reduction in fibronectin and an increase in laminin in the extracellular matrix. Similar changes were detected in the white matter in human WMH suggesting that hypercapnia/hypoxia may play a role in WMH. Employing therapies to enhance both IPAD and blood flow in the white matter may reduce WMH in patients with dementia.

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Section: Introductionmentioning

confidence: 99%

Demonstrating a reduced capacity for removal of fluid from cerebral white matter and hypoxia in areas of white matter hyperintensity associated with age and dementia

Sharp

Saitô

Keable

et al. 2020

acta neuropathol commun

View full text Add to dashboard Cite

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“…The proteincoding content could be activated in a rigorously predicted "enhanced" manner only when mRNA amplification process is induced. Such an experiment can be carried out in a murine astrocyte cell line known to elevate the expression of laminin under hypoxic conditions [69]. There are good reasons to believe that severe chronic hypoxia would induce the mRNA amplification process in these cells and enable the testing of the above experimental design.…”

Section: A Definitive Proof Of the Occurrence Of Mammalian Mrna Amplimentioning

confidence: 99%

Protein-Encoding RNA-to-RNA Information Transfer in Mammalian Cells: Principles of RNA-Dependent mRNA Amplification

Volloch

2019

AIMM

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RNA-dependent RNA synthesis and the corresponding enzymatic activity, RNA-dependent RNA polymerase (RdRp), were discovered in studies of mengovirus and polio virus [1-6]. Eventually, with the discovery of the RNA-dependent DNA synthesis and the enzyme associated with this process [7,8], it became clear that among RNA viruses, retroviruses utilize reverse transcriptase for their genomic information transfer whereas almost all other RNA viruses encode and utilize RdRp for this purpose [9,10]. The exceptions are viruses that do not encode their own RNA-dependent RNA polymerase but rely on RdRp activity of either their partners (helper viruses within the same cells) or their hosts. The latter category includes plant viroids and hepatitis delta virus, HDV [11]. These viruses do not encode an RdRp yet they undergo a robust RNA replication once inside the host cells [9-11]. These findings imply that both groups utilize cellular RNA-dependent RNA polymerase activities: viroids in plant cells and

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“…The proteincoding content could be activated in a rigorously predicted "enhanced" manner only when mRNA amplification process is induced. Such an experiment can be carried out in a murine astrocyte cell line known to elevate the expression of laminin under hypoxic conditions [34]. There are good reasons to believe that severe chronic hypoxia would induce the mRNA amplification process in these cells and enable the testing of the above experimental design [6].…”

Section: Novel Experimental Strategiesmentioning

confidence: 99%

RNA-dependent Amplification of Mammalian mRNA Encoding Extracellullar Matrix Proteins: Identification of Chimeric RNA Intermediates for α1, β1, and γ1 Chains of Laminin

Volloch

Rits

Olsen

2019

AIMM

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De novo production of RNA on RNA template, a process known as RNA-dependent RNA synthesis, RdRs, and the enzymatic activity conducting it, RNA-dependent RNA polymerase, RdRp, were initially considered to be exclusively virus-specific. Eventually, however, the occurrence of RdRs and the ubiquitous presence of conventional RdRp were demonstrated in numerous eukaryotic organisms. The evidence that the enzymatic machinery capable of RdRs is present in mammalian cells was derived from studies of viruses, such as hepatitis delta virus, HDV, that do not encode RdRp yet undergo a robust RNA replication once inside the mammalian host; thus firmly establishing its occurrence and functionality. Moreover, it became clear that RdRp activity, apparently in a non-conventional form, is constitutively present in most, if not in all, mammalian cells. Because such activity was shown to produce short transcripts, given its apparent involvement in RNA interference phenomena, and because double-stranded RNA is known to trigger cellular responses leading to its degradation, it was generally assumed that its role in mammalian cells is restricted to a regulatory function. However, at the same time, an enzymatic activity capable of generating complete antisense RNA complements of mRNAs was discovered in mammalian cells undergoing terminal differentiation. Moreover, observations of widespread synthesis of antisense RNA initiating at the 3'poly(A) of mRNAs in human cells suggested an extensive cellular utilization of mammalian RdRp. These results led to the development of a model of RdRp-facilitated and antisense RNA-mediated amplification of mammalian mRNA. Recent detection of the major model-predicted identifiers, chimeric RNA intermediates containing both sense and antisense RNA strands covalently joined in a rigorously predicted and uniquely defined manner, as well as the identification of a putative chimeric RNA end product of this process, validated the proposed model. The results corroborating mammalian RNA-dependent mRNA amplification were obtained in vivo with cells undergoing terminal erythroid differentiation and programmed for only a short survival span. This raises a question of whether mammalian RNA-dependent mRNA amplification is a specialized occurrence limited to extreme circumstances of terminal differentiation or a general physiological phenomenon. The present study addresses this question by testing for the occurrence of RNA-dependent amplification of mRNA encoding extracellular matrix proteins abundantly produced throughout the tissue and organ development and homeostasis, an exceptionally revealing indicator of the range and scope of this phenomenon. We report here the detection of major identifiers of RNA-dependent amplification of mRNA encoding α1, β1, and γ1 chains of laminin in mouse tissues producing large quantities of extracellular matrix proteins. The results obtained warrant reinterpretation of the mechanisms involved in ubiquitous and abundant production and deposition of extracellular matrix proteins, confir...

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Chronic mild hypoxia increases expression of laminins 111 and 411 and the laminin receptor α6β1 integrin at the blood-brain barrier

Cited by 17 publications

References 39 publications

Demonstrating a reduced capacity for removal of fluid from cerebral white matter and hypoxia in areas of white matter hyperintensity associated with age and dementia

Demonstrating a reduced capacity for removal of fluid from cerebral white matter and hypoxia in areas of white matter hyperintensity associated with age and dementia

Protein-Encoding RNA-to-RNA Information Transfer in Mammalian Cells: Principles of RNA-Dependent mRNA Amplification

RNA-dependent Amplification of Mammalian mRNA Encoding Extracellullar Matrix Proteins: Identification of Chimeric RNA Intermediates for α1, β1, and γ1 Chains of Laminin

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