Optogenetic manipulation of astrocytes from synapses to neuronal networks: A potential therapeutic strategy for neurodegenerative diseases

Xie, Zhen; Yang, Qinghu; Song, Da; Quan, Zhenzhen; Qing, Hong

doi:10.1002/glia.23693

Cited by 20 publications

(16 citation statements)

References 137 publications

(198 reference statements)

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“…Next, the electrode array should be either highly transparent (Park et al, 2014 ) or provide an optical window to perform imaging (multiphoton, coherent anti-stokes Raman spectroscopic microscopy etc. ), potentially coupled to optogenetic approaches (Park et al, 2014 ; Xie et al, 2020 ). However, the biomaterial should be stable yet flexible for optimal tissue contact and withstand the impact of laser radiation during 2P-imaging without excessive heat generation.…”

Section: Introductionmentioning

confidence: 99%

Versatile Surface Electrodes for Combined Electrophysiology and Two-Photon Imaging of the Mouse Central Nervous System

Schweigmann

Caudal

Stopper

et al. 2021

Front. Cell. Neurosci.

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Understanding and modulating CNS function in physiological as well as pathophysiological contexts remains a significant ambition in research and clinical applications. The investigation of the multifaceted CNS cell types including their interactions and contributions to neural function requires a combination of the state-of-the-art in vivo electrophysiology and imaging techniques. We developed a novel type of liquid crystal polymer (LCP) surface micro-electrode manufactured in three customized designs with up to 16 channels for recording and stimulation of brain activity. All designs include spare central spaces for simultaneous 2P-imaging. Nanoporous platinum-plated contact sites ensure a low impedance and high current transfer. The epidural implantation of the LCP micro-electrodes could be combined with standard cranial window surgery. The epidurally positioned electrodes did not only display long-term biocompatibility, but we also observed an additional stabilization of the underlying CNS tissue. We demonstrate the electrode’s versatility in combination with in vivo 2P-imaging by monitoring anesthesia-awake cycles of transgenic mice with GCaMP3 expression in neurons or astrocytes. Cortical stimulation and simultaneous 2P Ca2+ imaging in neurons or astrocytes highlighted the astrocytes’ integrative character in neuronal activity processing. Furthermore, we confirmed that spontaneous astroglial Ca2+ signals are dampened under anesthesia, while evoked signals in neurons and astrocytes showed stronger dependency on stimulation intensity rather than on various levels of anesthesia. Finally, we show that the electrodes provide recordings of the electrocorticogram (ECoG) with a high signal-to noise ratio and spatial signal differences which help to decipher brain activity states during experimental procedures. Summarizing, the novel LCP surface micro-electrode is a versatile, convenient, and reliable tool to investigate brain function in vivo.

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Section: Introductionmentioning

confidence: 99%

Versatile Surface Electrodes for Combined Electrophysiology and Two-Photon Imaging of the Mouse Central Nervous System

Schweigmann

Caudal

Stopper

et al. 2021

Front. Cell. Neurosci.

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“…Astrocyte‐specific techniques are being developed to manipulate astrocyte function and to study neuron–glia interactions. Optogenetics and chemogenetics enable the manipulation of astrocytes (Agulhon et al, 2013; Mederos et al, 2018; Xie, Yang, Song, Quan, & Qing, 2019). Genetically encoded calcium indicators and sensors for transmitters allow for the functional measurement in astrocytes (Almad & Maragakis, 2018).…”

Section: Discussionmentioning

confidence: 99%

Reactive astrocytes as treatment targets in Alzheimer's disease—Systematic review of studies using the APPswePS1dE9 mouse model

Smit

Deshayes

Borchelt

et al. 2021

Glia

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Astrocytes regulate synaptic communication and are essential for proper brain functioning. In Alzheimer's disease (AD) astrocytes become reactive, which is characterized by an increased expression of intermediate filament proteins and cellular hypertrophy. Reactive astrocytes are found in close association with amyloid‐beta (Aβ) deposits. Synaptic communication and neuronal network function could be directly modulated by reactive astrocytes, potentially contributing to cognitive decline in AD. In this review, we focus on reactive astrocytes as treatment targets in AD in the APPswePS1dE9 AD mouse model, a widely used model to study amyloidosis and gliosis. We first give an overview of the model; that is, how it was generated, which cells express the transgenes, and the effect of its genetic background on Aβ pathology. Subsequently, to determine whether modifying reactive astrocytes in AD could influence pathogenesis and cognition, we review studies using this mouse model in which interventions were directly targeted at reactive astrocytes or had an indirect effect on reactive astrocytes. Overall, studies specifically targeting astrocytes to reduce astrogliosis showed beneficial effects on cognition, which indicates that targeting astrocytes should be included in developing novel therapies for AD.

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“…Light stimulation of astrocytes with optogenetics has now being applied to reveal the function of astrocytes in physiology and pathology. This novel approach modulates the bidirectional interactions between astrocytes and neurons in both synaptic and neuronal networks [ 356 , 357 ]. This strategy allows specific cell stimulation by external illumination which may remotely manipulate intracellular pathways in single cells, using channelrhodopsin-2 (ChR2) activation to allow cationic currents to depolarize genetically targeted cells [356, 357, and Refs herein].…”

Section: The Therapeutic Impact: a Glial Avenue For Nigrostriatal Resmentioning

confidence: 99%

“…Optogenetic activation of VM astrocytes was used by Yang et al [ 358 ], showing that it can enhance the DAergic differentiation of stem cells and promote brain repair in PD models in vivo and in vitro with basic fibroblast growth factor (bFGF) being identified as a prominent mediator. As recently reviewed by Xie et al [ 357 ], recent findings highlight the possibility to use optogenetics to control the release of gliotransmitters and regulate astrocytic membrane channels. Thus, the capability of modulating the bidirectional interactions between astrocytes and neurons in both synaptic and neuronal networks via optogenetics represents a novel way to manipulate astrocytes that might represent a feasible and be an effective way to investigate the potential therapeutic strategy for PD and other NDs [ 356 , 357 ].…”

Section: The Therapeutic Impact: a Glial Avenue For Nigrostriatal Resmentioning

confidence: 99%

“…As recently reviewed by Xie et al [ 357 ], recent findings highlight the possibility to use optogenetics to control the release of gliotransmitters and regulate astrocytic membrane channels. Thus, the capability of modulating the bidirectional interactions between astrocytes and neurons in both synaptic and neuronal networks via optogenetics represents a novel way to manipulate astrocytes that might represent a feasible and be an effective way to investigate the potential therapeutic strategy for PD and other NDs [ 356 , 357 ]. Mederos and co [ 356 ] used a new approach based on selective expression of melanopsin, a G-protein-coupled photopigment, in astrocytes to trigger Ca 2+ signaling.…”

Section: The Therapeutic Impact: a Glial Avenue For Nigrostriatal Resmentioning

confidence: 99%

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Nrf2/Wnt resilience orchestrates rejuvenation of glia-neuron dialogue in Parkinson's disease

Marchetti

2020

Redox Biology

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Oxidative stress and inflammation have long been recognized to contribute to Parkinson's disease (PD), a common movement disorder characterized by the selective loss of midbrain dopaminergic neurons (mDAn) of the substantia nigra pars compacta (SNpc). The causes and mechanisms still remain elusive, but a complex interplay between several genes and a number of interconnected environmental factors, are chiefly involved in mDAn demise, as they intersect the key cellular functions affected in PD, such as the inflammatory response, mitochondrial, lysosomal, proteosomal and autophagic functions. Nuclear factor erythroid 2 -like 2 ( NFE2L2/Nrf2 ), the master regulator of cellular defense against oxidative stress and inflammation, and Wingless ( Wnt ) /β-catenin signaling cascade, a vital pathway for mDAn neurogenesis and neuroprotection, emerge as critical intertwinned actors in mDAn physiopathology, as a decline of an Nrf2/Wnt/β-catenin prosurvival axis with age underlying PD mutations and a variety of noxious environmental exposures drive PD neurodegeneration. Unexpectedly, astrocytes, the so-called “ star-shaped ” cells, harbouring an arsenal of “beneficial” and “harmful” molecules represent the turning point in the physiopathological and therapeutical scenario of PD. Fascinatingly, “ astrocyte's fil rouge” brings back to Nrf2/Wnt resilience, as boosting the Nrf2/Wnt resilience program rejuvenates astrocytes, in turn (i) mitigating nigrostriatal degeneration of aged mice, (ii) reactivating neural stem progenitor cell proliferation and neuron differentiation in the brain and (iii) promoting a beneficial immunomodulation via bidirectional communication with mDAns. Then, through resilience of Nrf2/Wnt/β-catenin anti-ageing, prosurvival and proregenerative molecular programs, it seems possible to boost the inherent endogenous self-repair mechanisms. Here, the cellular and molecular aspects as well as the therapeutical options for rejuvenating glia-neuron dialogue will be discussed together with major glial-derived mechanisms and therapies that will be fundamental to the identification of novel diagnostic tools and treatments for neurodegenerative diseases (NDs), to fight ageing and nigrostriatal DAergic degeneration and promote functional recovery.

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Optogenetic manipulation of astrocytes from synapses to neuronal networks: A potential therapeutic strategy for neurodegenerative diseases

Cited by 20 publications

References 137 publications

Versatile Surface Electrodes for Combined Electrophysiology and Two-Photon Imaging of the Mouse Central Nervous System

Versatile Surface Electrodes for Combined Electrophysiology and Two-Photon Imaging of the Mouse Central Nervous System

Reactive astrocytes as treatment targets in Alzheimer's disease—Systematic review of studies using the APPswePS1dE9 mouse model

Nrf2/Wnt resilience orchestrates rejuvenation of glia-neuron dialogue in Parkinson's disease

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