Rescue of astrocyte activity by the calcium sensor STIM1 restores long-term synaptic plasticity in female mice modelling Alzheimer’s disease

Lia, Annamaria; Sansevero, Gabriele; Chiavegato, Angela; Sbrissa, Miriana; Pendin, Diana; Mariotti, Letizia; Pozzan, Tullio; Berardi, Nicoletta; Carmignoto, Giorgio; Fasolato, Cristina; Zonta, Micaela

doi:10.1038/s41467-023-37240-2

Cited by 18 publications

(9 citation statements)

References 83 publications

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“…But other candidates presenting similar sensitivity to heat and ROS, such as TRP Ankyrin 1, are likely to be rapidly integrated in the arsenal of Ca 2+ -permeable channels that could be probed for their therapeutic potential. In conclusion, this Symposium, which also engendered may fruitful discussions and opened the way to new collaborations among the participants (including many foreigner guests), confirmed that Italian Physiology is at the forefront of research in Ca 2+ signalling, as also proven by many other oral and poster presentations of the meeting ( Martinotti et al, 2019 ; Nesher et al, 2019 ; Badone et al, 2021 ; Lazzarini et al, 2022 ; Michelucci et al, 2022 ; Sforna et al, 2022 ; Arici et al, 2023 ; Lia et al, 2023 ).…”

Section: Discussionsupporting

confidence: 69%

Intracellular Ca2+ signalling: unexpected new roles for the usual suspect

et al. 2023

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Cytosolic Ca2+ signals are organized in complex spatial and temporal patterns that underlie their unique ability to regulate multiple cellular functions. Changes in intracellular Ca2+ concentration ([Ca2+]i) are finely tuned by the concerted interaction of membrane receptors and ion channels that introduce Ca2+ into the cytosol, Ca2+-dependent sensors and effectors that translate the elevation in [Ca2+]i into a biological output, and Ca2+-clearing mechanisms that return the [Ca2+]i to pre-stimulation levels and prevent cytotoxic Ca2+ overload. The assortment of the Ca2+ handling machinery varies among different cell types to generate intracellular Ca2+ signals that are selectively tailored to subserve specific functions. The advent of novel high-speed, 2D and 3D time-lapse imaging techniques, single-wavelength and genetic Ca2+ indicators, as well as the development of novel genetic engineering tools to manipulate single cells and whole animals, has shed novel light on the regulation of cellular activity by the Ca2+ handling machinery. A symposium organized within the framework of the 72nd Annual Meeting of the Italian Society of Physiology, held in Bari on 14–16th September 2022, has recently addressed many of the unexpected mechanisms whereby intracellular Ca2+ signalling regulates cellular fate in healthy and disease states. Herein, we present a report of this symposium, in which the following emerging topics were discussed: 1) Regulation of water reabsorption in the kidney by lysosomal Ca2+ release through Transient Receptor Potential Mucolipin 1 (TRPML1); 2) Endoplasmic reticulum-to-mitochondria Ca2+ transfer in Alzheimer’s disease-related astroglial dysfunction; 3) The non-canonical role of TRP Melastatin 8 (TRPM8) as a Rap1A inhibitor in the definition of some cancer hallmarks; and 4) Non-genetic optical stimulation of Ca2+ signals in the cardiovascular system.

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Section: Discussionsupporting

confidence: 69%

Intracellular Ca2+ signalling: unexpected new roles for the usual suspect

et al. 2023

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“…It is worth mentioning that transcriptome analysis in astrocytes from AD patients revealed expression changes in 32 genes associated with Ca 2+ signaling (Simpson et al, 2011). Consistently, early astrocyte calcium dysfunction is found in different AD mouse models, with both hyperactivity and hyporesponsiveness reported (Kuchibhotla et al, 2009;Lines et al, 2022;Åbjørsbråten et al, 2022;Lia et al, 2023). Along this line, an attenuated astrocyte endfeet response to neuronal stimulation has been recently suggested to contribute to NVC impairment in APP mice, in which reactive oxygen species (ROS) were also involved (Li L. et al, 2021).…”

Section: Alzheimer's Diseasementioning

confidence: 83%

Two decades of astrocytes in neurovascular coupling

Lia

Spiezio

Speggiorin

et al. 2023

Front. Netw. Physiol.

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The brain is a highly energy demanding organ, which accounts in humans for the 20% of total energy consumption at resting state although comprising only 2% of the body mass. The necessary delivery of nutrients to brain parenchyma is ensured by the cerebral circulatory system, through the exchange of glucose and oxygen (O2) at the capillary level. Notably, a tight spatial and temporal correlation exists between local increases in neuronal activity and the subsequent changes in regional cerebral blood flow. The recognized concept of neurovascular coupling (NVC), also named functional hyperemia, expresses this close relationship and stands at the basis of the modern functional brain imaging techniques. Different cellular and molecular mechanisms have been proposed to mediate this tight coupling. In this context, astrocytes are ideally positioned to act as relay elements that sense neuronal activity through their perisynaptic processes and release vasodilator agents at their endfeet in contact with brain parenchymal vessels. Two decades after the astrocyte involvement in neurovascular coupling has been proposed, we here review the experimental evidence that contributed to unraveling the molecular and cellular mechanisms underlying cerebral blood flow regulation. While traveling through the different controversies that moved the research in this field, we keep a peculiar focus on those exploring the role of astrocytes in neurovascular coupling and conclude with two sections related to methodological aspects in neurovascular research and to some pathological conditions resulting in altered neurovascular coupling.

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“…Stimulation‐elicited LTP is decreased by decoupling of astrocytes in the mouse hippocampus (Hösli et al, 2022 ). Astrocyte‐regulated LTP of the mouse somatosensory cortex is affected in the mouse model of Alzheimer's disease and the consequential reduction of astrocytic Ca 2+ signaling (Lia et al, 2023 ). The cognitive decline in aged mice is prevented in IP3KO mice with altered astrocytic calcium signaling (Guerra‐Gomes et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Astrocyte‐ and NMDA receptor‐dependent slow inward currents differently contribute to synaptic plasticity in an age‐dependent manner in mouse and human neocortex

Csemer,

Kovács,

Maamrah

et al. 2023

Aging Cell

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Slow inward currents (SICs) are known as excitatory events of neurons elicited by astrocytic glutamate via activation of extrasynaptic NMDA receptors. By using slice electrophysiology, we tried to provide evidence that SICs can elicit synaptic plasticity. Age dependence of SICs and their impact on synaptic plasticity was also investigated in both on murine and human cortical slices. It was found that SICs can induce a moderate synaptic plasticity, with features similar to spike timing‐dependent plasticity. Overall SIC activity showed a clear decline with aging in humans and completely disappeared above a cutoff age. In conclusion, while SICs contribute to a form of astrocyte‐dependent synaptic plasticity both in mice and humans, this plasticity is differentially affected by aging. Thus, SICs are likely to play an important role in age‐dependent physiological and pathological alterations of synaptic plasticity.

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Rescue of astrocyte activity by the calcium sensor STIM1 restores long-term synaptic plasticity in female mice modelling Alzheimer’s disease

Cited by 18 publications

References 83 publications

Intracellular Ca2+ signalling: unexpected new roles for the usual suspect

Intracellular Ca2+ signalling: unexpected new roles for the usual suspect

Two decades of astrocytes in neurovascular coupling

Astrocyte‐ and NMDA receptor‐dependent slow inward currents differently contribute to synaptic plasticity in an age‐dependent manner in mouse and human neocortex

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