cAMP-Dependent Calcium Oscillations of Astrocytes: An Implication for Pathology

Ujita, Sakiko; Sasaki, Takuya; Asada, Akiko; Funayama, Kenta; Gao, Mengxuan; Mikoshiba, Katsuhiko; Matsuki, Norio; Ikegaya, Yuji

doi:10.1093/cercor/bhv310

Cited by 16 publications

(13 citation statements)

References 91 publications

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“…Ca 2+ dynamics, including amplitude, duration, and frequency, may encode information of astrocytes. For example, in situ imaging data indicate that Ca 2+ oscillations are associated with hypertrophy of astrocytes [49]. Therefore, exploring Ca 2+ signals in reactive astrocytes provides insight into functional changes.…”

Section: Ca2+ Signals In Reactive Astrocytesmentioning

confidence: 99%

Aberrant Calcium Signals in Reactive Astrocytes: A Key Process in Neurological Disorders

Shigetomi

Saito

Sano

et al. 2019

IJMS

135

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Astrocytes are abundant cells in the brain that regulate multiple aspects of neural tissue homeostasis by providing structural and metabolic support to neurons, maintaining synaptic environments and regulating blood flow. Recent evidence indicates that astrocytes also actively participate in brain functions and play a key role in brain disease by responding to neuronal activities and brain insults. Astrocytes become reactive in response to injury and inflammation, which is typically described as hypertrophy with increased expression of glial fibrillary acidic protein (GFAP). Reactive astrocytes are frequently found in many neurological disorders and are a hallmark of brain disease. Furthermore, reactive astrocytes may drive the initiation and progression of disease processes. Recent improvements in the methods to visualize the activity of reactive astrocytes in situ and in vivo have helped elucidate their functions. Ca2+ signals in reactive astrocytes are closely related to multiple aspects of disease and can be a good indicator of disease severity/state. In this review, we summarize recent findings concerning reactive astrocyte Ca2+ signals. We discuss the molecular mechanisms underlying aberrant Ca2+ signals in reactive astrocytes and the functional significance of aberrant Ca2+ signals in neurological disorders.

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Section: Ca2+ Signals In Reactive Astrocytesmentioning

confidence: 99%

Aberrant Calcium Signals in Reactive Astrocytes: A Key Process in Neurological Disorders

Shigetomi

Saito

Sano

et al. 2019

IJMS

135

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“…Astrocyte-induced glutamate-mediated SICs of thalamo-cortical neurons seem to be dependent on extracellular glutamate levels, since exogenous exposure to the glutamate-mimetic D-aspartate increased the frequency of SICs ( 243 ). Although it is still unclear if abnormal or hypersynchronous astroglial Ca 2+ signals could promote epileptiform network activity by itself, this evidence further supports an astroglial contribution to the propagation and self-sustain of seizure-like activity ( 244 , 245 ).…”

Section: Astrocytes Contribute To Network Priming and Synchronization As Well As Swd Induction Propagation And Terminationmentioning

confidence: 53%

From Physiology to Pathology of Cortico-Thalamo-Cortical Oscillations: Astroglia as a Target for Further Research

2021

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The electrographic hallmark of childhood absence epilepsy (CAE) and other idiopathic forms of epilepsy are 2.5–4 Hz spike and wave discharges (SWDs) originating from abnormal electrical oscillations of the cortico-thalamo-cortical network. SWDs are generally associated with sudden and brief non-convulsive epileptic events mostly generating impairment of consciousness and correlating with attention and learning as well as cognitive deficits. To date, SWDs are known to arise from locally restricted imbalances of excitation and inhibition in the deep layers of the primary somatosensory cortex. SWDs propagate to the mostly GABAergic nucleus reticularis thalami (NRT) and the somatosensory thalamic nuclei that project back to the cortex, leading to the typical generalized spike and wave oscillations. Given their shared anatomical basis, SWDs have been originally considered the pathological transition of 11–16 Hz bursts of neural oscillatory activity (the so-called sleep spindles) occurring during Non-Rapid Eye Movement (NREM) sleep, but more recent research revealed fundamental functional differences between sleep spindles and SWDs, suggesting the latter could be more closely related to the slow (<1 Hz) oscillations alternating active (Up) and silent (Down) cortical activity and concomitantly occurring during NREM. Indeed, several lines of evidence support the fact that SWDs impair sleep architecture as well as sleep/wake cycles and sleep pressure, which, in turn, affect seizure circadian frequency and distribution. Given the accumulating evidence on the role of astroglia in the field of epilepsy in the modulation of excitation and inhibition in the brain as well as on the development of aberrant synchronous network activity, we aim at pointing at putative contributions of astrocytes to the physiology of slow-wave sleep and to the pathology of SWDs. Particularly, we will address the astroglial functions known to be involved in the control of network excitability and synchronicity and so far mainly addressed in the context of convulsive seizures, namely (i) interstitial fluid homeostasis, (ii) K+ clearance and neurotransmitter uptake from the extracellular space and the synaptic cleft, (iii) gap junction mechanical and functional coupling as well as hemichannel function, (iv) gliotransmission, (v) astroglial Ca2+ signaling and downstream effectors, (vi) reactive astrogliosis and cytokine release.

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“…Oscillatory gating dynamics of plasma-membrane-embedded channels or cyclic calcium release from intracellular stores can generate calcium spikes ( 23 ). Changes in the amplitude and frequency of these oscillating signals along with the intracellular concentrations of these second messengers can trigger diverse cellular responses in neurons ( 23 , 52 , 53 , 54 ). Studies have shown that calcium oscillates spontaneously in spines ( 55 ) and that CaMKII activity is sensitive to calcium frequency ( 56 , 57 , 58 , 59 , 60 ).…”

Section: Introductionmentioning

confidence: 99%

Computational Modeling Reveals Frequency Modulation of Calcium-cAMP/PKA Pathway in Dendritic Spines

Ohadi

Schmitt

Calabrese

et al. 2019

Biophysical Journal

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Dendritic spines are the primary excitatory postsynaptic sites that act as subcompartments of signaling. Ca 2þ is often the first and most rapid signal in spines. Downstream of calcium, the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway plays a critical role in the regulation of spine formation, morphological modifications, and ultimately, learning and memory. Although the dynamics of calcium are reasonably well-studied, calcium-induced cAMP/PKA dynamics, particularly with respect to frequency modulation, are not fully explored. In this study, we present a well-mixed model for the dynamics of calcium-induced cAMP/PKA dynamics in dendritic spines. The model is constrained using experimental observations in the literature. Further, we measured the calcium oscillation frequency in dendritic spines of cultured hippocampal CA1 neurons and used these dynamics as model inputs. Our model predicts that the various steps in this pathway act as frequency modulators for calcium, and the high frequency of calcium input is filtered by adenylyl cyclase 1 and phosphodiesterases in this pathway such that cAMP/PKA only responds to lower frequencies. This prediction has important implications for noise filtering and long-timescale signal transduction in dendritic spines. A companion manuscript presents a three-dimensional spatial model for the same pathway.

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cAMP-Dependent Calcium Oscillations of Astrocytes: An Implication for Pathology

Cited by 16 publications

References 91 publications

Aberrant Calcium Signals in Reactive Astrocytes: A Key Process in Neurological Disorders

Aberrant Calcium Signals in Reactive Astrocytes: A Key Process in Neurological Disorders

From Physiology to Pathology of Cortico-Thalamo-Cortical Oscillations: Astroglia as a Target for Further Research

Computational Modeling Reveals Frequency Modulation of Calcium-cAMP/PKA Pathway in Dendritic Spines

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