A New Technical Approach for Cross-species Examination of Neuronal Wiring and Adult Neuron-glia Functions

Edwards-Faret, Gabriela; Vin, Filip De; Ślęzak, Michał; Gollenbeck, Lennart; Karaman, Ruçhan; Shinmyo, Yohei; Batiuk, Mykhailo Y.; Pando, Carmen Menacho; Urschitz, Johann; Rincón, Melvin Y.; Moisyadi, Stefan; Schnütgen, Frank; Kawasaki, Hiroshi; Schmucker, Dietmar; Holt, Matthew G.

doi:10.1016/j.neuroscience.2022.11.029

Cited by 3 publications

(3 citation statements)

References 65 publications

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“…However, LVs have been associated with the risk of mutagenesis since they integrate into the genome. IUE provides yet another alternative to express genes of interest in brain cells and has been successfully implemented in several animal models such as mice, rats, ferrets and cats ( Yamashiro et al, 2022 ; Edwards-Faret et al, 2023 ). As astrocytes start developing in the CNS shortly after birth, PALE, an adaptation of IUE, can be used to specifically target astrocytes ( García-Marqués and López-Mascaraque, 2013 ; Gee et al, 2015 ; Stogsdill et al, 2017 ; Kittock and Pilaz, 2023 ).…”

Section: Chemogenetic Manipulation Of Astrocyte Activitymentioning

confidence: 99%

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Chemogenetic manipulation of astrocyte activity at the synapse— a gateway to manage brain disease

Pereira

Ayana

Holt

et al. 2023

Front. Cell Dev. Biol.

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Astrocytes are the major glial cell type in the central nervous system (CNS). Initially regarded as supportive cells, it is now recognized that this highly heterogeneous cell population is an indispensable modulator of brain development and function. Astrocytes secrete neuroactive molecules that regulate synapse formation and maturation. They also express hundreds of G protein-coupled receptors (GPCRs) that, once activated by neurotransmitters, trigger intracellular signalling pathways that can trigger the release of gliotransmitters which, in turn, modulate synaptic transmission and neuroplasticity. Considering this, it is not surprising that astrocytic dysfunction, leading to synaptic impairment, is consistently described as a factor in brain diseases, whether they emerge early or late in life due to genetic or environmental factors. Here, we provide an overview of the literature showing that activation of genetically engineered GPCRs, known as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), to specifically modulate astrocyte activity partially mimics endogenous signalling pathways in astrocytes and improves neuronal function and behavior in normal animals and disease models. Therefore, we propose that expressing these genetically engineered GPCRs in astrocytes could be a promising strategy to explore (new) signalling pathways which can be used to manage brain disorders. The precise molecular, functional and behavioral effects of this type of manipulation, however, differ depending on the DREADD receptor used, targeted brain region and timing of the intervention, between healthy and disease conditions. This is likely a reflection of regional and disease/disease progression-associated astrocyte heterogeneity. Therefore, a thorough investigation of the effects of such astrocyte manipulation(s) must be conducted considering the specific cellular and molecular environment characteristic of each disease and disease stage before this has therapeutic applicability.

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Section: Chemogenetic Manipulation Of Astrocyte Activitymentioning

confidence: 99%

“…Region-specific I U E : †Ubi-hM3Dq-GFP (Hurni et al, 2017), mGFAP kmyrTdTomato; misPiggy plasmid system (Edwards-Faret et al, 2023) Less damaging since the young brain is more plastic and recovers better from insults than the adult brain;…”

Section: In Utero (Iue) and Postnatal (Pale) Electroporationmentioning

confidence: 99%

Chemogenetic manipulation of astrocyte activity at the synapse— a gateway to manage brain disease

Pereira

Ayana

Holt

et al. 2023

Front. Cell Dev. Biol.

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“…To move from descriptive to functional studies in amphibians, we require a toolkit to manipulate gene expression rapidly with spatiotemporal control. Electroporation can be used for the acute delivery of genes into amphibian cells, but it suffers from low efficacy and transient expression, with cell-type specificity additionally limited by the availability of cis-regulatory elements 31,32 . Direct injection of RNAs or morpholinos into developing frogs briefly perturbs gene expression, but its effect is also transient and only effective at early developmental stages 14,33 .…”

Section: Introductionmentioning

confidence: 99%

Adeno-Associated Viral Tools to Trace Neural Development and Connectivity Across Amphibians

Jaeger,

Vijatovic,

Deryckere

et al. 2024

Preprint

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The development, evolution, and function of the vertebrate central nervous system (CNS) can be best studied using diverse model organisms. Amphibians, with their unique phylogenetic position at the transition between aquatic and terrestrial lifestyles, are valuable for understanding the origin and evolution of the tetrapod brain and spinal cord. Their metamorphic developmental transitions and unique regenerative abilities also facilitate the discovery of mechanisms for neural circuit remodeling and replacement. The genetic toolkit for amphibians, however, remains limited, with only a few species having sequenced genomes and a small number of transgenic lines available. In mammals, recombinant adeno-associated viral vectors (AAVs) have become a powerful alternative to genome modification for visualizing and perturbing the nervous system. AAVs are DNA viruses that enable neuronal transduction in both developing and adult animals with low toxicity and spatial, temporal, and cell-type specificity. However, AAVs have never been shown to transduce amphibian cells efficiently. To bridge this gap, we established a simple, scalable, and robust strategy to screen AAV serotypes in three distantly-related amphibian species: the frogsXenopus laevisandPelophylax bedriagae, and the salamanderPleurodeles waltl, in both developing larval tadpoles and post-metamorphic animals. For each species, we successfully identified at least two AAV serotypes capable of infecting the CNS; however, no pan-amphibian serotype was identified, indicating rapid evolution of AAV tropism. In addition, we developed an AAV-based strategy that targets isochronic cohorts of developing neurons - a critical tool for parsing neural circuit assembly. Finally, to enable visualization and manipulation of neural circuits, we identified AAV variants for retrograde tracing of neuronal projections in adult animals. Our findings expand the toolkit for amphibians to include AAVs, establish a generalizable workflow for AAV screening in non-canonical research organisms, generate testable hypotheses for the evolution of AAV tropism, and lay the foundation for modern cross-species comparisons of vertebrate CNS development, function, and evolution.

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Astrocyte diversity in the ferret cerebrum revealed with astrocyte‐specific genetic manipulation

Tai,

Shinmyo,

Kawasaki

2024

Glia

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Astrocytes in the cerebrum play important roles such as the regulation of synaptic functions, homeostasis, water transport, and the blood–brain barrier. It has been proposed that astrocytes in the cerebrum acquired diversity and developed functionally during evolution. Here, we show that like human astrocytes, ferret astrocytes in the cerebrum exhibit various morphological subtypes which mice do not have. We found that layer 1 of the ferret cerebrum contained not only protoplasmic astrocytes but also pial interlaminar astrocytes and subpial interlaminar astrocytes. Morphologically polarized astrocytes, which have a long unbranched process, were found in layer 6. Like human white matter, ferret white matter exhibited four subtypes of astrocytes. Furthermore, our quantification showed that ferret astrocytes had a larger territory size and a longer radius length than mouse astrocytes. Thus, our results indicate that, similar to the human cerebrum, the ferret cerebrum has a well‐developed diversity of astrocytes. Ferrets should be useful for investigating the molecular and cellular mechanisms leading to astrocyte diversity, the functions of each astrocyte subtype and the involvement of different astrocyte subtypes in various neurological diseases.

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A New Technical Approach for Cross-species Examination of Neuronal Wiring and Adult Neuron-glia Functions

Cited by 3 publications

References 65 publications

Chemogenetic manipulation of astrocyte activity at the synapse— a gateway to manage brain disease

Chemogenetic manipulation of astrocyte activity at the synapse— a gateway to manage brain disease

Adeno-Associated Viral Tools to Trace Neural Development and Connectivity Across Amphibians

Astrocyte diversity in the ferret cerebrum revealed with astrocyte‐specific genetic manipulation

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