In Vivo Neocortical [K]o Modulation by Targeted Stimulation of Astrocytes

EbrahimAmini, Azin; Mylvaganam, Shanthini; Bazzigaluppi, Paolo; Khazaei, Mohamad; Velumian, Alexander A.; Stefanović, Bojana; Carlen, Peter L.

doi:10.3390/ijms22168658

Cited by 3 publications

(5 citation statements)

References 29 publications

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“…2 ). Photostimulation on astrocytes decreases the resting potassium concentration, thereby increasing the likelihood of action potentials at synapses [ 142 ]. Additionally, inwardly rectifying Kir4.1 channels in astrocytes, linked to cerebral disorders, transmit surplus potassium to intercellular spaces [ 143 ].…”

Section: Astrocyte and Synaptic Dysfunctionmentioning

confidence: 99%

The Role of Glial Cells in Synaptic Dysfunction: Insights into Alzheimer's Disease Mechanisms

Yu,

Chen,

Mao

et al. 2024

Aging and disease

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Alzheimer's disease (AD) is a devastating neurodegenerative disorder that impacts a substantial number of individuals globally. Despite its widespread prevalence, there is currently no cure for AD. It is widely acknowledged that normal synaptic function holds a key role in memory, cognitive abilities, and the interneuronal transfer of information. As AD advances, symptoms including synaptic impairment, decreased synaptic density, and cognitive decline become increasingly noticeable. The importance of glial cells in the formation of synapses, the growth of neurons, brain maturation, and safeguarding the microenvironment of the central nervous system is well recognized. However, during AD progression, overactive glial cells can cause synaptic dysfunction, neuronal death, and abnormal neuroinflammation. Both neuroinflammation and synaptic dysfunction are present in the early stages of AD. Therefore, focusing on the changes in glia-synapse communication could provide insights into the mechanisms behind AD. In this review, we aim to provide a summary of the role of various glial cells, including microglia, astrocytes, oligodendrocytes, and oligodendrocyte precursor cells, in regulating synaptic dysfunction. This may offer a new perspective on investigating the underlying mechanisms of AD.

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Section: Astrocyte and Synaptic Dysfunctionmentioning

confidence: 99%

The Role of Glial Cells in Synaptic Dysfunction: Insights into Alzheimer's Disease Mechanisms

Yu,

Chen,

Mao

et al. 2024

Aging and disease

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“…To better overcome disorders involving abnormally high levels of neocortical [K]o, it is critical to unravel mechanisms involved in [K]o regulation. Knowing that astrocytic gap junctional coupling and astrocytic membrane potential play only partial roles in [K]o regulation [ 21 , 22 ], we examined the role of another candidate—[ATP]i depletion—in this complicated yet fascinating topic. [ATP]i depletion was attained via collapsing the proton motive force by using DNP, vasoconstriction by using ET-1, or inhibiting glycolysis by using 2-DG.…”

Section: Discussionmentioning

confidence: 99%

“…A K-sensitive electrode was coupled with a double-barreled LFP recording electrode, creating a K-LFP recording electrode. The double-barreled electrode was filled with saline and cemented to the K-sensitive electrode such that the distance between the tips of the electrodes was approximately 50 μm apart [ 22 ]. First, the K-sensitive electrode was mounted to a head stage of an Axopatch 200B amplifier.…”

Section: Methodsmentioning

confidence: 99%

Effects of In Vivo Intracellular ATP Modulation on Neocortical Extracellular Potassium Concentration

2022

Self Cite

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Neuronal and glial activity are dependent on the efflux of potassium ions into the extracellular space. Efflux of K is partly energy-dependent as the activity of pumps and channels which are involved in K transportation is ATP-dependent. In this study, we investigated the effect of decreased intracellular ATP concentration ([ATP]i) on the extracellular potassium ion concentration ([K]o). Using in vivo electrophysiological techniques, we measured neocortical [K]o and the local field potential (LFP) while [ATP]i was reduced through various pharmacological interventions. We observed that reducing [ATP]i led to raised [K]o and DC-shifts resembling spreading depolarization-like events. We proposed that most likely, the increased [K]o is mainly due to the impairment of the Na/K ATPase pump and the ATP-sensitive potassium channel in the absence of sufficient ATP, because Na/K ATPase inhibition led to increased [K]o and ATP-sensitive potassium channel impairment resulted in decreased [K]o. Therefore, an important consequence of decreased [ATP]i is an increased [K]o. The results of this study acknowledge one of the mechanisms involved in [K]o dynamics.

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“…Optogenetic modulation is based on opsins, light‐sensitive proteins. These proteins can be ion channels, ion pumps or GPCRs, and intracellular signaling will be initiated by light of a specific wavelength rather than selective ligands (Airan et al, 2009; EbrahimAmini et al, 2021; Octeau et al, 2019). Practically, the opsins will be activated by light delivered through an optic fiber implanted at the region of interest.…”

Section: Strengths and Shortcomings Of Chemogenetic Approaches In Gli...mentioning

confidence: 99%

“…injection in mice (Nagai et al, 2020). As is the case for all cell types, the choice of the DREADD agonist has to be carefully evaluated when considering therapeutic use (which has been extensively covered by EbrahimAmini et al, 2021; Geng et al, 2023; Pestana et al, 2020; Zotova et al, 2013).…”

Section: Translational Aspects Of the Dreadd‐based Manipulation Of Gliamentioning

confidence: 99%

Chemogenetic modulation of astrocytes and microglia: State‐of‐the‐art and implications in neuroscience

Bossuyt

Herrewegen

Nestor

et al. 2023

Glia

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Insights into the role astrocytes and microglia play in normal and diseased brain functioning has expanded drastically over the last decade. Recently, chemogenetic tools have emerged as cutting-edge techniques, allowing targeted and spatiotemporal precise manipulation of a specific glial cell type. As a result, significant advances in astrocyte and microglial cell function have been made, showing how glial cells can intervene in central nervous system (CNS) functions such as cognition, reward and feeding behavior in addition to their established contribution in brain diseases, pain, and CNS inflammation. Here, we discuss the latest insights in glial functions in health and disease that have been made through the application of chemogenetics. We will focus on the manipulation of intracellular signaling pathways induced by activation of the designer receptors exclusively activated by designer drugs (DREADDs) in astrocytes and microglia. We will also elaborate on some of the potential pitfalls and the translational potential of the DREADD technology.

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In Vivo Neocortical [K]o Modulation by Targeted Stimulation of Astrocytes

Cited by 3 publications

References 29 publications

The Role of Glial Cells in Synaptic Dysfunction: Insights into Alzheimer's Disease Mechanisms

The Role of Glial Cells in Synaptic Dysfunction: Insights into Alzheimer's Disease Mechanisms

Effects of In Vivo Intracellular ATP Modulation on Neocortical Extracellular Potassium Concentration

Chemogenetic modulation of astrocytes and microglia: State‐of‐the‐art and implications in neuroscience

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