Differential deregulation of astrocytic calcium signalling by amyloid-β, TNFα, IL-1β and LPS

Ronco, Virginia; Grolla, Ambra A.; Glasnov, Toma N.; Canonico, Pier Luigi; Verkhratsky, Alexei; Genazzani, Armando A.; Lim, Dmitry

doi:10.1016/j.ceca.2014.02.016

Cited by 72 publications

(80 citation statements)

References 33 publications

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“…Similar, high-frequency Ca 2+ waves were also monitored in astrocytes from APP Swe mice even before the formation of β-amyloid deposits [141]. In hippocampal astrocytes isolated and cultured from neonatal 3xTg-AD mice, the amplitude of ATP-induced [Ca 2+ ] i transients as well as the store-operated Ca 2+ entry were significantly increased [125,137]. In contrast, store-operated Ca 2+ entry in astrocytes from APP-over-expressing Tg5469 AD mice was not affected, although the deletion of APP inhibited SOCE, possibly due to down-regulation of Orai1 and TRPC1 channels [142].…”

Section: Ca 2+ Signalling In Ad Astrocytesmentioning

confidence: 79%

“…In human post-mortem tissues, however, an overall decrease in the expression of InsP 3 receptors is observed [133][134][135], which may, however, indicate the overall cell loss and, hence, a decrease in the total expression of receptors. Finally, a chronic treatment with β-amyloid was also reported to increase the store-operated Ca 2+ entry in astrocytes [136,137].…”

Section: Effects Of β-Amyloidmentioning

confidence: 99%

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Astroglial calcium signalling in Alzheimer's disease

Verkhratsky

Rodriguez-Arellano

Parpura

et al. 2017

Biochemical and Biophysical Research Communications

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Neuroglial contribution to Alzheimer's disease (AD) is pathologically relevant and highly heterogeneous. Reactive astrogliosis and activation of microglia contribute to neuroinflammation, whereas astroglial and oligodendroglial atrophy affect synaptic transmission and underlie the overall disruption of the central nervous system (CNS) connectome. Astroglial function is tightly integrated with the intracellular ionic signalling mediated by complex dynamics of cytosolic concentrations of free Ca 2+ and Na + . Astroglial ionic signalling is mediated by plasmalemmal ion channels, mainly associated with ionotropic receptors, pumps and solute carrier transporters, and by intracellular organelles comprised of the endoplasmic reticulum and mitochondria. The relative contribution of these molecular cascades/organelles can be plastically remodelled in development and under environmental stress. In AD astroglial Ca 2+ signalling undergoes substantial reorganisation due to an abnormal regulation of expression of Ca 2+ handling molecular cascades.

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Section: Ca 2+ Signalling In Ad Astrocytesmentioning

confidence: 79%

Section: Effects Of β-Amyloidmentioning

confidence: 99%

Astroglial calcium signalling in Alzheimer's disease

Verkhratsky

Rodriguez-Arellano

Parpura

et al. 2017

Biochemical and Biophysical Research Communications

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“…Ab 42 induces store-operated calcium entry, while the other agents inhibited store-operated calcium entry. Treatment with Ab 42 significantly increased mRNA levels of IP 3 R1/2 and mGluR5, whereas pro-inflammatory agents reduced expression of those mRNAs [117].…”

Section: Alzheimer's Diseasementioning

confidence: 92%

Inositol 1,4,5‐trisphosphate receptors and neurodegenerative disorders

Egorova

Bezprozvanny

2018

The FEBS Journal

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The inositol 1,4,5-trisphosphate receptor (IP 3 R) is an intracellular ion channel that mediates the release of calcium ions from the endoplasmic reticulum. It plays a role in basic biological functions, such as cell division, differentiation, fertilization and cell death, and is involved in developmental processes including learning, memory and behavior. Deregulation of neuronal calcium signaling results in disturbance of cell homeostasis, synaptic loss and dysfunction, eventually leading to cell death. Three IP 3 R subtypes have been identified in mammalian cells and the predominant isoform in neurons is IP 3 R type 1. Dysfunction of IP 3 R type 1 may play a role in the pathogenesis of certain neurodegenerative diseases as enhanced activity of the IP 3 R was observed in models of Huntington's disease, spinocerebellar ataxias and Alzheimer's disease. These results suggest that IP 3 R-mediated signaling is a potential target for treatment of these disorders. In this review we discuss the structure, functions and regulation of the IP 3 R in healthy neurons and in conditions of neurodegeneration. IntroductionInositol 1,4,5-trisphosphate receptors (IP 3 Rs) are a family of intracellular ion channels that mediate calcium (Ca 2+ ) release from the endoplasmic reticulum (ER) following stimulation by the second messenger inositol 1,4,5-trisphosphate (IP 3 ). Generation of IP 3 molecules is caused by the activation of phospholipase C in response to the activation of G proteincoupled receptors such as serotonergic receptors, adrenergic receptors, calcitonin receptors, histamine receptors, metabotropic glutamate receptors (mGluRs), Abbreviations AAV, adeno-associated virus; AD, Alzheimer's disease; ALG-2, apoptosis-linked gene 2; ARM, armadillo; Ab, beta amyloid; BH, Bcl-2 homology; CaBP1, calcium-binding protein 1; CTD, C-terminal domain; EM, electron microscopy; ER, endoplasmic reticulum; FAD, familial Alzheimer's disease; GRP78, 78-kDa glucose regulated protein; HAP1, huntingtin-associated protein 1; HD, Huntington's disease; HelD, helical domain; Htt, huntingtin; IBC, IP 3 -binding core; IICR, inositol 1,4,5-trisphosphate-induced calcium release; ILD, 'intervening lateral' domain; IP 3 , inositol 1,4,5-trisphosphate; IP 3 R1, IP 3 R type 1; IP 3 R, inositol 1,4,5-trisphosphate receptor; IRBIT, IP 3 R binding protein released with IP 3 ; KO, knock-out; LBD, ligand-binding domain; LNK, helical linker domain; MCI, mild cognitive impairment; mGluR, metabotropic glutamate receptor; mPTP, mitochondrial permeability transition pore; MSN, medium spiny neuron; NMDA, N-methyl-D-aspartate; NTR, Nterminal region; Opt, opisthotonos; PC, Purkinje cell; polyQ, polyglutamine; PS, presenilin; RyR, ryanodine receptor; SAD, sporadic Alzheimer's disease; SCA, spinocerebellar ataxia; SD, IP 3 -binding suppressor domain; SUMF1, sulfatase modifying factor 1; TG2, transglutaminase type 2; TMD, transmembrane domain; WT, wild-type; YAC, yeast artificial chromosome; b-TF, b-trefoil. 3547The (Fig. 1). Upon extracellular stimulation -by various ...

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“…mGluR-mediated calcium signaling as well as store-operated calcium entry were augmented in response to Aβ while opposite changes were observed when astrocytes were treated with pro-inflammatory agents TNFα, IL1β and LPS (Ronco et al, 2014). In line with our present study, it could be concluded that Aβ cannot be regarded as a traditional pro-inflammatory agent in monocytic cells; to the contrary, Aβ employs alternative pathways to affect the state and function of these cells.…”

Section: Discussionmentioning

confidence: 99%

Aβ and Inflammatory Stimulus Activate Diverse Signaling Pathways in Monocytic Cells: Implications in Retaining Phagocytosis in Aβ-Laden Environment

Savchenko

Malm

Konttinen

et al. 2016

Front. Cell. Neurosci.

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Background: Accumulation of amyloid β (Aβ) is one of the main hallmarks of Alzheimer’s disease (AD). The enhancement of Aβ clearance may provide therapeutic means to restrict AD pathology. The cellular responses to different forms of Aβ in monocytic cells are poorly known. We aimed to study whether different forms of Aβ induce inflammatory responses in monocytic phagocytes and how Aβ may affect monocytic cell survival and function to retain phagocytosis in Aβ-laden environment.Methods: Monocytic cells were differentiated from bone marrow hematopoietic stem cells (HSC) in the presence of macrophage-colony stimulating factor. Monocytic cells were stimulated with synthetic Aβ42 and intracellular calcium responses were recorded with calcium imaging. The formation of reactive oxygen species (ROS), secretion of cytokines and cell viability were also assessed. Finally, monocytic cells were introduced to native Aβ deposits ex vivo and the cellular responses in terms of cell viability, pro-inflammatory activation and phagocytosis were determined. The ability of monocytic cells to phagocytose Aβ plaques was determined after intrahippocampal transplantation in vivo.Results: Freshly solubilized Aβ induced calcium oscillations, which persisted after removal of the stimulus. After few hours of aggregation, Aβ was not able to induce oscillations in monocytic cells. Instead, lipopolysaccharide (LPS) induced calcium responses divergent from Aβ-induced response. Furthermore, while LPS induced massive production of pro-inflammatory cytokines, neither synthetic Aβ species nor native Aβ deposits were able to induce pro-inflammatory activation of monocytic cells, contrary to primary microglia. Finally, monocytic cells retained their viability in the presence of Aβ and exhibited phagocytic activity towards native fibrillar Aβ deposits and congophilic Aβ plaques.Conclusion: Monocytic cells carry diverse cellular responses to Aβ and inflammatory stimulus LPS. Even though Aβ species cause specific responses in calcium signaling, they completely lack the ability to induce pro-inflammatory phenotype of monocytic cells. Monocytes retain their viability and function in Aβ-laden brain.

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Differential deregulation of astrocytic calcium signalling by amyloid-β, TNFα, IL-1β and LPS

Cited by 72 publications

References 33 publications

Astroglial calcium signalling in Alzheimer's disease

Astroglial calcium signalling in Alzheimer's disease

Inositol 1,4,5‐trisphosphate receptors and neurodegenerative disorders

Aβ and Inflammatory Stimulus Activate Diverse Signaling Pathways in Monocytic Cells: Implications in Retaining Phagocytosis in Aβ-Laden Environment

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