Calcium Dynamics in Astrocytes During Cell Injury.
Ontology highlight
ABSTRACT:
SUBMITTER: Wakida NM
PROVIDER: S-EPMC7481337 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Calcium Dynamics in Astrocytes During Cell Injury.
Wakida Nicole M NM Gomez-Godinez Veronica V Li Huayan H Nguyen Jessica J Kim Edward K EK Dynes Joseph L JL Othy Shivashankar S Lau Alice L AL Ding Peng P Shi Linda L Carmona Christopher C Thompson Leslie M LM Cahalan Michael D MD Berns Michael W MW
Frontiers in bioengineering and biotechnology 20200827
The changes in intracellular calcium concentration ([Ca<sup>2+</sup>]) following laser-induced cell injury in nearby cells were studied in primary mouse astrocytes selectively expressing the Ca<sup>2+</sup> sensitive GFAP-Cre Salsa6f fluorescent tandem protein, in an Ast1 astrocyte cell line, and in primary mouse astrocytes loaded with Fluo4. Astrocytes in these three systems exhibit distinct changes in [Ca<sup>2+</sup>] following induced death of nearby cells. Changes in [Ca<sup>2+</sup>] appea ...[more]
Similar Datasets
Project description:Recent years have witnessed an increasing interest in neuron-glia communication. This interest stems from the realization that glia participate in cognitive functions and information processing and are involved in many brain disorders and neurodegenerative diseases. An important process in neuron-glia communications is astrocyte encoding of synaptic information transfer-the modulation of intracellular calcium (Ca(2+)) dynamics in astrocytes in response to synaptic activity. Here, we derive and investigate a concise mathematical model for glutamate-induced astrocytic intracellular Ca(2+) dynamics that captures the essential biochemical features of the regulatory pathway of inositol 1,4,5-trisphosphate (IP(3)). Starting from the well-known two-variable (intracellular Ca(2+) and inactive IP(3) receptors) Li-Rinzel model for calcium-induced calcium release, we incorporate the regulation of IP(3) production and phosphorylation. Doing so, we extend it to a three-variable model (which we refer to as the ChI model) that could account for Ca(2+) oscillations with endogenous IP(3) metabolism. This ChI model is then further extended into the G-ChI model to include regulation of IP(3) production by external glutamate signals. Compared with previous similar models, our three-variable models include a more realistic description of IP(3) production and degradation pathways, lumping together their essential nonlinearities within a concise formulation. Using bifurcation analysis and time simulations, we demonstrate the existence of new putative dynamical features. The cross-couplings between IP(3) and Ca(2+) pathways endow the system with self-consistent oscillatory properties and favor mixed frequency-amplitude encoding modes over pure amplitude-modulation ones. These and additional results of our model are in general agreement with available experimental data and may have important implications for the role of astrocytes in the synaptic transfer of information.
| S-EPMC2750743 | biostudies-literature
Project description:Cumulative evidence supports bidirectional interactions between astrocytes and neurons, suggesting glial involvement of neuronal information processing in the brain. Cytosolic calcium (Ca(2+)) concentration is important for astrocytes as Ca(2+) surges co-occur with gliotransmission and neurotransmitter reception. Cerebral cortex is organized in layers which are characterized by distinct cytoarchitecture. We asked if astrocyte-dominant layer 1 (L1) of the somatosensory cortex was different from layer 2/3 (L2/3) in spontaneous astrocytic Ca(2+) activity and if it was influenced by background neural activity. Using a two-photon laser scanning microscope, we compared spontaneous Ca(2+) activity of astrocytic somata and processes in L1 and L2/3 of anesthetized mature rat somatosensory cortex. We also assessed the contribution of background neural activity to the spontaneous astrocytic Ca(2+) dynamics by investigating two distinct EEG states ("synchronized" vs. "de-synchronized" states). We found that astrocytes in L1 had nearly twice higher Ca(2+) activity than L2/3. Furthermore, Ca(2+) fluctuations of processes within an astrocyte were independent in L1 while those in L2/3 were synchronous. Pharmacological blockades of metabotropic receptors for glutamate, ATP, and acetylcholine, as well as suppression of action potentials did not have a significant effect on the spontaneous somatic Ca(2+) activity. These results suggest that spontaneous astrocytic Ca(2+) surges occurred in large part intrinsically, rather than neural activity-driven. Our findings propose a new functional segregation of layer 1 and 2/3 that is defined by autonomous astrocytic activity.
| S-EPMC2424136 | biostudies-literature
Project description:Astrocytes are nonneuronal cells in the brain (glia) that do not generate electrical impulses but communicate by chemical signaling. This communication can be observed under a microscope with fluorescent calcium indicators that glow more brightly when the concentration of calcium increases inside the cell. Astrocytes release adenosine 5'-triphosphate and other cell signaling molecules that excite membrane receptors on other astrocytes to cause an increase in intracellular calcium in the recipient cell. Many of the substances released by astrocytes also excite neurons, and astrocytes have on their own cell membrane many of the same neurotransmitter receptors used by neurons to communicate across synapses. This allows astrocytes to respond to neural impulse activity, communicate among other astrocytes, and influence neuronal communication by taking up or releasing neurotransmitters from synapses.
| S-EPMC5017150 | biostudies-literature
Project description:Examining calcium dynamics within the neural crest (NC) has the potential to shed light on mechanisms that regulate complex cell migration and patterning events during embryogenesis. Unfortunately, typical calcium indicators are added to culture media or have low signal to noise after microinjection into tissue that severely limit analyses to cultured cells or superficial events. Here, we studied in vivo calcium dynamics during NC cell migration and patterning, using a genetically encoded calcium sensor, GCaMP3. We discovered that trunk NC cells displayed significantly more spontaneous calcium transients than cranial NC cells, and during cell aggregation versus cell migration events. Spontaneous calcium transients were more prevalent during NC cell aggregation into discrete sympathetic ganglia (SG). Blocking of N-cadherin activity in trunk NC cells near the presumptive SG led to a dramatic decrease in the frequency of spontaneous calcium transients. Detailed analysis and mathematical modeling of cell behaviors during SG formation showed NC cells aggregated into clusters after displaying a spontaneous calcium transient. This approach highlights the novel application of a genetically encoded calcium indicator to study subsets of cells during ventral events in embryogenesis.
| S-EPMC3395469 | biostudies-literature
Project description:BackgroundOf the animals typically used to study fertilization-induced calcium dynamics, none is as accessible to genetics and molecular biology as the model organism Caenorhabditis elegans. Motivated by the experimental possibilities inherent in using such a well-established model organism, we have characterized fertilization-induced calcium dynamics in C. elegans.ResultsOwing to the transparency of the nematode, we have been able to study the calcium signal in C. elegans fertilization in vivo by monitoring the fluorescence of calcium indicator dyes that we introduce into the cytosol of oocytes. In C. elegans, fertilization induces a single calcium transient that is initiated soon after oocyte entry into the spermatheca, the compartment that contains sperm. Therefore, it is likely that the calcium transient is initiated by contact with sperm. This calcium elevation spreads throughout the oocyte, and decays monotonically after which the cytosolic calcium concentration returns to that preceding fertilization. Only this single calcium transient is observed.ConclusionDevelopment of a technique to study fertilization induced calcium transients opens several experimental possibilities, e.g., identification of the signaling events intervening sperm binding and calcium elevation, identifying the possible roles of the calcium elevation such as the completion of meiosis, the formation of the eggshell, and the establishing of the embryo's axis of symmetry.
| S-EPMC31342 | biostudies-literature
Project description:Astrocytes serve many functions in the brain related to maintaining nerve tissue homeostasis and regulating neuronal function, including synaptic transmission. It is assumed that astrocytes are crucial players in determining the physiological or pathological outcome of the brain aging process and the development of neurodegenerative diseases. Therefore, studies on the peculiarities of astrocyte physiology and interastrocytic signaling during aging are of utmost importance. Calcium waves are one of the main mechanisms of signal transmission between astrocytes, and in the present study we investigated the features of calcium dynamics in primary cultures of murine cortical astrocytes in physiological aging and hypoxia modeling in vitro. Specifically, we focused on the assessment of calcium network dynamics and the restructuring of the functional network architecture in primary astrocytic cultures. Calcium imaging was performed on days 21 ("young" astrocyte group) and 150 ("old" astrocyte group) of cultures' development in vitro. While the number of active cells and frequency of calcium events were decreased, we observed a reduced degree of correlation in calcium dynamics between neighboring cells, which was accompanied by a reduced number of functionally connected cells with fewer and slower signaling events. At the same time, an increase in the mRNA expression of anti-apoptotic factor Bcl-2 and connexin 43 was observed in "old" astrocytic cultures, which can be considered as a compensatory response of cells with a decreased level of intercellular communication. A hypoxic episode aggravates the depression of the connectivity of calcium dynamics of "young" astrocytes rather than that of "old" ones.
| S-EPMC10419080 | biostudies-literature
Project description:The accumulation of amyloid β peptide (Aβ) in the brain is hypothesized to be the major factor driving Alzheimer's disease (AD) pathogenesis. Mounting evidence suggests that astrocytes are the primary target of Aβ neurotoxicity. Aβ is known to interfere with multiple calcium fluxes, thus disrupting the calcium homeostasis regulation of astrocytes, which are likely to produce calcium oscillations. Ca2+ dyshomeostasis has been observed to precede the appearance of clinical symptoms of AD; however, it is experimentally very difficult to investigate the interactions of many mechanisms. Given that Ca2+ disruption is ubiquitously involved in AD progression, it is likely that focusing on Ca2+ dysregulation may serve as a potential therapeutic approach to preventing or treating AD, while current hypotheses concerning AD have so far failed to yield curable therapies. For this purpose, we derive and investigate a concise mathematical model for Aβ-mediated multi-pathway astrocytic intracellular Ca2+ dynamics. This model accounts for how Aβ affects various fluxes contributions through voltage-gated calcium channels, Aβ-formed channels and ryanodine receptors. Bifurcation analysis of Aβ level, which reflected the corresponding progression of the disease, revealed that Aβ significantly induced the increasing [Ca2+] i and frequency of calcium oscillations. The influence of inositol 1,4,5-trisphosphate production (IP3) is also investigated in the presence of Aβ as well as the impact of changes in resting membrane potential. In turn, the Ca2+ flux can be considerably changed by exerting specific interventions, such as ion channel blockers or receptor antagonists. By doing so, a "combination therapy" targeting multiple pathways simultaneously has finally been demonstrated to be more effective. This study helps to better understand the effect of Aβ, and our findings provide new insight into the treatment of AD.
| S-EPMC8581622 | biostudies-literature
Project description:Intracellular calcium release is essential for regulating almost all cellular functions. Specific spatio-temporal patterns of cytosolic calcium elevations are critical determinants of cell fate in response to pro-apoptotic cellular stressors. As the apoptotic program can take hours or days, measurement of long-term calcium dynamics are essential for understanding the mechanistic role of calcium in apoptotic cell death. Due to the technical limitations of using calcium-sensitive dyes to measure cytosolic calcium little is known about long-term calcium dynamics in living cells after treatment with apoptosis-inducing drugs. Genetically encoded calcium indicators could potentially overcome some of the limitations of calcium-sensitive dyes. Here, we compared the performance of the genetically encoded calcium indicators GCaMP6s and GCaMP6f with the ratiometric dye Fura-2. GCaMP6s performed as well or better than Fura-2 in detecting agonist-induced calcium transients. We then examined the utility of GCaMP6s for continuously measuring apoptotic calcium release over the course of ten hours after treatment with staurosporine. We found that GCaMP6s was suitable for measuring apoptotic calcium release over long time courses and revealed significant heterogeneity in calcium release dynamics in individual cells challenged with staurosporine. Our results suggest GCaMP6s is an excellent indicator for monitoring long-term changes cytosolic calcium during apoptosis.
| S-EPMC5512452 | biostudies-literature
Project description:Enhanced neuronal activity in the brain triggers a local increase in blood flow, termed functional hyperemia, via several mechanisms, including calcium (Ca(2+)) signaling in astrocytes. However, recent in vivo studies have questioned the role of astrocytes in functional hyperemia because of the slow and sparse dynamics of their somatic Ca(2+) signals and the absence of glutamate metabotropic receptor 5 in adults. Here, we reexamined their role in neurovascular coupling by selectively expressing a genetically encoded Ca(2+) sensor in astrocytes of the olfactory bulb. We show that in anesthetized mice, the physiological activation of olfactory sensory neuron (OSN) terminals reliably triggers Ca(2+) increases in astrocyte processes but not in somata. These Ca(2+) increases systematically precede the onset of functional hyperemia by 1-2 s, reestablishing astrocytes as potential regulators of neurovascular coupling.
| S-EPMC4651918 | biostudies-literature
Project description:Astrocytes perform control and regulatory functions in the central nervous system; heterogeneity among them is still a matter of debate due to limited knowledge of their gene expression profiles and functional diversity. To unravel astrocyte heterogeneity during postnatal development and after focal cerebral ischemia, we employed single-cell gene expression profiling in acutely isolated cortical GFAP/EGFP-positive cells. Using a microfluidic qPCR platform, we profiled 47 genes encoding glial markers and ion channels/transporters/receptors participating in maintaining K(+) and glutamate homeostasis per cell. Self-organizing maps and principal component analyses revealed three subpopulations within 10-50 days of postnatal development (P10-P50). The first subpopulation, mainly immature glia from P10, was characterized by high transcriptional activity of all studied genes, including polydendrocytic markers. The second subpopulation (mostly from P20) was characterized by low gene transcript levels, while the third subpopulation encompassed mature astrocytes (mainly from P30, P50). Within 14 days after ischemia (D3, D7, D14), additional astrocytic subpopulations were identified: resting glia (mostly from P50 and D3), transcriptionally active early reactive glia (mainly from D7) and permanent reactive glia (solely from D14). Following focal cerebral ischemia, reactive astrocytes underwent pronounced changes in the expression of aquaporins, nonspecific cationic and potassium channels, glutamate receptors and reactive astrocyte markers.
| S-EPMC3734191 | biostudies-literature