Age-dependent changes of collagen alpha-2(IV) expression in the extracellular matrix of brain arteriovenous malformations

Neyazi, Belal; Stein, Klaus-Peter; Wilkens, Ludwig; Maslehaty, Homajoun; Dumitru, Claudia A.; Sandalcioglu, I. Erol

doi:10.1016/j.clineuro.2019.105589

Cited by 2 publications

(2 citation statements)

References 39 publications

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“…In capillary malformation-AVM with Ephrin type-B receptor 4 ( Ephb4 ) or Ras p21 protein activator 1 ( Rasa1 ) mutation, Col IV accumulates in the EC endoplasmic reticulum, leading to EC apoptotic death [ 52 , 53 ]. An age-dependent increase in COL4A2 was also reported in bAVMs, suggesting a potential role of COL4A2 in bAVM pathophysiology [ 54 ]. We will analyze COL IV and its relationships with COL I and III and inflammatory cells in the future.…”

Section: Discussionmentioning

confidence: 99%

Increased Collagen I/Collagen III Ratio Is Associated with Hemorrhage in Brain Arteriovenous Malformations in Human and Mouse

Shabani,

Schuerger,

Zhu

et al. 2024

Cells

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Background: The increase in the collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. Activated microglia enhance inflammation-induced fibrosis. Hypotheses: The COL I/COL III ratio in human and mouse brain arteriovenous malformations (bAVMs) is associated with bAVM hemorrhage, and the depletion of microglia decreases the COL I/COL III ratio and hemorrhage. Method: COL I, COL III, and hemorrhages were analyzed in 12 human bAVMs and 6 control brains, and mouse bAVMs induced in three mouse lines with activin receptor-like kinase 1 (n = 7) or endoglin (n = 7) deleted in the endothelial cells or brain focally (n = 5). The controls for the mouse study were no-gene-deleted litter mates. Mouse bAVMs were used to test the relationships between the Col I/Col III ratio and hemorrhage and whether the transient depletion of microglia reduces the Col I/Col III ratio and hemorrhage. Results: The COL I/COL III ratio was higher in the human and mouse bAVMs than in controls. The microhemorrhage in mouse bAVMs was positively correlated with the Col I/Col III ratio. Transient depletion of microglia reduced the Col I/Col III ratio and microhemorrhage. Conclusions: The COL I/COL III ratio in the bAVMs was associated with bAVM hemorrhage. The depletion of microglia reduced the bAVM Col I/Col III ratio and hemorrhage.

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Section: Discussionmentioning

confidence: 99%

Increased Collagen I/Collagen III Ratio Is Associated with Hemorrhage in Brain Arteriovenous Malformations in Human and Mouse

Shabani,

Schuerger,

Zhu

et al. 2024

Cells

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“…Brain collagens have been shown to interact with hyaluronan and HAPLNs in the developing brain to modulate tissue stiffness properties (Long et al, 2018), which may suggest that the greater abundance of collagen in the midbrain is directly associated to regional differences in hyaluronan abundance. Collagen alpha-2 isoforms, which are associated with the basement membrane of brain vasculature (Kuo et al, 2012;Neyazi et al, 2020), were found to be more abundant with age in both brain regions and may reflect neurovascular dysfunction that is known to arise during brain aging (Banks et al, 2021;Verheggen et al, 2020). Finally, laminin glycoproteins were initially found at lower levels in the striatum but were significantly increased during aging compared to the midbrain.…”

Section: Proteomic Analysis Reveals Key Regional Differences In Matri...mentioning

confidence: 99%

Microglia promote extracellular matrix deposition and restrict excitatory synapse numbers in the mesolimbic dopamine system during healthy aging

Gray,

Guitierrez,

Jami-Alahmadi

et al. 2024

Preprint

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Synapse dysfunction has been definitively linked to cognitive impairments in the aging brain, and microglial physiology has emerged as a robust regulator of synapse status and cognitive aging outcomes. Hippocampal microglia have recently been shown to regulate synapse function via targeted remodeling of the extracellular matrix (ECM), yet the degree to which microglia-ECM interactions impact synapse function in the healthy aged brain remains virtually unexplored. This study combines high-resolution imaging and ECM-optimized tissue proteomics to examine the impact that microglial physiology has on ECM and synapse status in the basal ganglia of healthy aging mice. Our results demonstrate that deposition of the ubiquitous ECM scaffold hyaluronan increases during aging in the ventral tegmental area (VTA), but not its downstream target, the nucleus accumbens, and that VTA microglial tissue coverage correlates with local hyaluronan deposition. Proteomic mapping of core matrisome proteins showed prominent regional differences in ECM composition across basal ganglia nuclei that were significantly associated with abundance of chemokine receptors and synapse proteins. Finally, manipulation of microglial fractalkine signaling through Cx3Cr1 receptor deletion reversed age-associated ECM accumulation within the VTA and resulted in abnormally elevated synapse numbers in this brain region by middle age. These findings indicate that microglia promote age-related increases in ECM deposition in some, but not all, brain regions that may restrict local excitatory synapse numbers. This microglial function could represent an adaptive response to brain aging that helps to maintain appropriate activity patterns within basal ganglia circuits.

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Age-dependent changes of collagen alpha-2(IV) expression in the extracellular matrix of brain arteriovenous malformations

Cited by 2 publications

References 39 publications

Increased Collagen I/Collagen III Ratio Is Associated with Hemorrhage in Brain Arteriovenous Malformations in Human and Mouse

Increased Collagen I/Collagen III Ratio Is Associated with Hemorrhage in Brain Arteriovenous Malformations in Human and Mouse

Microglia promote extracellular matrix deposition and restrict excitatory synapse numbers in the mesolimbic dopamine system during healthy aging

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