---
_id: '11542'
article_processing_charge: No
author:
- first_name: Rouven
  full_name: Schulz, Rouven
  id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87
  last_name: Schulz
  orcid: 0000-0001-5297-733X
citation:
  ama: Schulz R. Source Data (Chimeric GPCRs mimic distinct signaling pathways and
    modulate microglia responses). 2022. doi:<a href="https://doi.org/10.15479/AT:ISTA:11542">10.15479/AT:ISTA:11542</a>
  apa: Schulz, R. (2022). Source Data (Chimeric GPCRs mimic distinct signaling pathways
    and modulate microglia responses). Institute of Science and Technology Austria.
    <a href="https://doi.org/10.15479/AT:ISTA:11542">https://doi.org/10.15479/AT:ISTA:11542</a>
  chicago: Schulz, Rouven. “Source Data (Chimeric GPCRs Mimic Distinct Signaling Pathways
    and Modulate Microglia Responses).” Institute of Science and Technology Austria,
    2022. <a href="https://doi.org/10.15479/AT:ISTA:11542">https://doi.org/10.15479/AT:ISTA:11542</a>.
  ieee: R. Schulz, “Source Data (Chimeric GPCRs mimic distinct signaling pathways
    and modulate microglia responses).” Institute of Science and Technology Austria,
    2022.
  ista: Schulz R. 2022. Source Data (Chimeric GPCRs mimic distinct signaling pathways
    and modulate microglia responses), Institute of Science and Technology Austria,
    <a href="https://doi.org/10.15479/AT:ISTA:11542">10.15479/AT:ISTA:11542</a>.
  mla: Schulz, Rouven. <i>Source Data (Chimeric GPCRs Mimic Distinct Signaling Pathways
    and Modulate Microglia Responses)</i>. Institute of Science and Technology Austria,
    2022, doi:<a href="https://doi.org/10.15479/AT:ISTA:11542">10.15479/AT:ISTA:11542</a>.
  short: R. Schulz, (2022).
contributor:
- contributor_type: contact_person
  first_name: Sandra
  id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
  last_name: Siegert
  orcid: 0000-0001-8635-0877
date_created: 2022-07-08T11:03:02Z
date_published: 2022-01-01T00:00:00Z
date_updated: 2024-02-21T12:34:51Z
department:
- _id: GradSch
- _id: SaSi
doi: 10.15479/AT:ISTA:11542
file:
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oa: 1
oa_version: None
publisher: Institute of Science and Technology Austria
related_material:
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status: public
title: Source Data (Chimeric GPCRs mimic distinct signaling pathways and modulate
  microglia responses)
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
_id: '11945'
abstract:
- lang: eng
  text: "G protein-coupled receptors (GPCRs) respond to specific ligands and regulate
    multiple processes ranging from cell growth and immune responses to neuronal signal
    transmission. However, ligands for many GPCRs remain unknown, suffer from off-target
    effects or have poor bioavailability. Additional challenges exist to dissect cell-type
    specific responses when the same GPCR is expressed on several cell types within
    the body. Here, we overcome these limitations by engineering DREADD-based GPCR
    chimeras that selectively bind their agonist clozapine-N-oxide (CNO) and mimic
    a GPCR-of-interest in a desired cell type.\r\nWe validated our approach with β2-adrenergic
    receptor (β2AR/ADRB2) and show that our chimeric DREADD-β2AR triggers comparable
    responses on second messenger and kinase activity, post-translational modifications,
    and protein-protein interactions. Since β2AR is also enriched in microglia, which
    can drive inflammation in the central nervous system, we expressed chimeric DREADD-β2AR
    in primary microglia and successfully recapitulate β2AR-mediated filopodia formation
    through CNO stimulation. To dissect the role of selected GPCRs during microglial
    inflammation, we additionally generated DREADD-based chimeras for microglia-enriched
    GPR65 and GPR109A/HCAR2. In a microglia cell line, DREADD-β2AR and DREADD-GPR65
    both modulated the inflammatory response with a similar profile as endogenously
    expressed β2AR, while DREADD-GPR109A showed no impact.\r\nOur DREADD-based approach
    provides the means to obtain mechanistic and functional insights into GPCR signaling
    on a cell-type specific level."
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Rouven
  full_name: Schulz, Rouven
  id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87
  last_name: Schulz
  orcid: 0000-0001-5297-733X
citation:
  ama: Schulz R. Chimeric G protein-coupled receptors mimic distinct signaling pathways
    and modulate microglia function. 2022. doi:<a href="https://doi.org/10.15479/at:ista:11945">10.15479/at:ista:11945</a>
  apa: Schulz, R. (2022). <i>Chimeric G protein-coupled receptors mimic distinct signaling
    pathways and modulate microglia function</i>. Institute of Science and Technology
    Austria. <a href="https://doi.org/10.15479/at:ista:11945">https://doi.org/10.15479/at:ista:11945</a>
  chicago: Schulz, Rouven. “Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling
    Pathways and Modulate Microglia Function.” Institute of Science and Technology
    Austria, 2022. <a href="https://doi.org/10.15479/at:ista:11945">https://doi.org/10.15479/at:ista:11945</a>.
  ieee: R. Schulz, “Chimeric G protein-coupled receptors mimic distinct signaling
    pathways and modulate microglia function,” Institute of Science and Technology
    Austria, 2022.
  ista: Schulz R. 2022. Chimeric G protein-coupled receptors mimic distinct signaling
    pathways and modulate microglia function. Institute of Science and Technology
    Austria.
  mla: Schulz, Rouven. <i>Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling
    Pathways and Modulate Microglia Function</i>. Institute of Science and Technology
    Austria, 2022, doi:<a href="https://doi.org/10.15479/at:ista:11945">10.15479/at:ista:11945</a>.
  short: R. Schulz, Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling
    Pathways and Modulate Microglia Function, Institute of Science and Technology
    Austria, 2022.
date_created: 2022-08-23T11:33:11Z
date_published: 2022-08-23T00:00:00Z
date_updated: 2023-08-03T13:02:26Z
day: '23'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: SaSi
doi: 10.15479/at:ista:11945
file:
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  creator: rschulz
  date_created: 2022-08-25T09:00:11Z
  date_updated: 2022-08-25T09:33:31Z
  file_id: '11971'
  file_name: Thesis_Rouven_Schulz_2022_final.docx
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file_date_updated: 2022-08-25T09:33:31Z
has_accepted_license: '1'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: '133'
project:
- _id: 267F75D8-B435-11E9-9278-68D0E5697425
  name: Modulating microglia through G protein-coupled receptor (GPCR) signaling
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '11995'
    relation: dissertation_contains
    status: public
status: public
supervisor:
- first_name: Sandra
  full_name: Siegert, Sandra
  id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
  last_name: Siegert
  orcid: 0000-0001-8635-0877
title: Chimeric G protein-coupled receptors mimic distinct signaling pathways and
  modulate microglia function
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2022'
...
---
_id: '11995'
abstract:
- lang: eng
  text: G protein-coupled receptors (GPCRs) regulate processes ranging from immune
    responses to neuronal signaling. However, ligands for many GPCRs remain unknown,
    suffer from off-target effects or have poor bioavailability. Additionally, dissecting
    cell type-specific responses is challenging when the same GPCR is expressed on
    different cells within a tissue. Here, we overcome these limitations by engineering
    DREADD-based GPCR chimeras that bind clozapine-N-oxide and mimic a GPCR-of-interest.
    We show that chimeric DREADD-β2AR triggers responses comparable to β2AR on second
    messenger and kinase activity, post-translational modifications, and protein-protein
    interactions. Moreover, we successfully recapitulate β2AR-mediated filopodia formation
    in microglia, an immune cell capable of driving central nervous system inflammation.
    When dissecting microglial inflammation, we included two additional DREADD-based
    chimeras mimicking microglia-enriched GPR65 and GPR109A. DREADD-β2AR and DREADD-GPR65
    modulate the inflammatory response with high similarity to endogenous β2AR, while
    DREADD-GPR109A shows no impact. Our DREADD-based approach allows investigation
    of cell type-dependent pathways without known endogenous ligands.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: LifeSc
acknowledgement: The authors thank the Scientific Service Units at ISTA, in particular
  the Molecular Biology Service of the Lab Support Facility, Imaging & Optics Facility,
  and the Preclinical Facility, and the Novarino group, Harald Janoviak, and Marco
  Benevento for sharing reagents and expertise. This research was supported by a DOC
  Fellowship (24979) awarded to R.S. by the Austrian Academy of Sciences.
article_number: '4728'
article_processing_charge: No
article_type: original
author:
- first_name: Rouven
  full_name: Schulz, Rouven
  id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87
  last_name: Schulz
  orcid: 0000-0001-5297-733X
- first_name: Medina
  full_name: Korkut, Medina
  id: 4B51CE74-F248-11E8-B48F-1D18A9856A87
  last_name: Korkut
  orcid: 0000-0003-4309-2251
- first_name: Alessandro
  full_name: Venturino, Alessandro
  id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
  last_name: Venturino
  orcid: 0000-0003-2356-9403
- first_name: Gloria
  full_name: Colombo, Gloria
  id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
  last_name: Colombo
  orcid: 0000-0001-9434-8902
- first_name: Sandra
  full_name: Siegert, Sandra
  id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
  last_name: Siegert
  orcid: 0000-0001-8635-0877
citation:
  ama: Schulz R, Korkut M, Venturino A, Colombo G, Siegert S. Chimeric GPCRs mimic
    distinct signaling pathways and modulate microglia responses. <i>Nature Communications</i>.
    2022;13. doi:<a href="https://doi.org/10.1038/s41467-022-32390-1">10.1038/s41467-022-32390-1</a>
  apa: Schulz, R., Korkut, M., Venturino, A., Colombo, G., &#38; Siegert, S. (2022).
    Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses.
    <i>Nature Communications</i>. Springer Nature. <a href="https://doi.org/10.1038/s41467-022-32390-1">https://doi.org/10.1038/s41467-022-32390-1</a>
  chicago: Schulz, Rouven, Medina Korkut, Alessandro Venturino, Gloria Colombo, and
    Sandra Siegert. “Chimeric GPCRs Mimic Distinct Signaling Pathways and Modulate
    Microglia Responses.” <i>Nature Communications</i>. Springer Nature, 2022. <a
    href="https://doi.org/10.1038/s41467-022-32390-1">https://doi.org/10.1038/s41467-022-32390-1</a>.
  ieee: R. Schulz, M. Korkut, A. Venturino, G. Colombo, and S. Siegert, “Chimeric
    GPCRs mimic distinct signaling pathways and modulate microglia responses,” <i>Nature
    Communications</i>, vol. 13. Springer Nature, 2022.
  ista: Schulz R, Korkut M, Venturino A, Colombo G, Siegert S. 2022. Chimeric GPCRs
    mimic distinct signaling pathways and modulate microglia responses. Nature Communications.
    13, 4728.
  mla: Schulz, Rouven, et al. “Chimeric GPCRs Mimic Distinct Signaling Pathways and
    Modulate Microglia Responses.” <i>Nature Communications</i>, vol. 13, 4728, Springer
    Nature, 2022, doi:<a href="https://doi.org/10.1038/s41467-022-32390-1">10.1038/s41467-022-32390-1</a>.
  short: R. Schulz, M. Korkut, A. Venturino, G. Colombo, S. Siegert, Nature Communications
    13 (2022).
date_created: 2022-08-28T22:01:59Z
date_published: 2022-08-15T00:00:00Z
date_updated: 2024-02-21T12:34:51Z
day: '15'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1038/s41467-022-32390-1
external_id:
  isi:
  - '000840984400032'
  pmid:
  - '35970889'
file:
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  checksum: 191d9db0266e14a28d3a56dc7f65da84
  content_type: application/pdf
  creator: cchlebak
  date_created: 2022-08-29T06:44:30Z
  date_updated: 2022-08-29T06:44:30Z
  file_id: '12002'
  file_name: 2022_NatComm_Schulz.pdf
  file_size: 7317396
  relation: main_file
  success: 1
file_date_updated: 2022-08-29T06:44:30Z
has_accepted_license: '1'
intvolume: '        13'
isi: 1
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 267F75D8-B435-11E9-9278-68D0E5697425
  name: Modulating microglia through G protein-coupled receptor (GPCR) signaling
publication: Nature Communications
publication_identifier:
  eissn:
  - 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - description: News on ISTA website
    relation: press_release
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scopus_import: '1'
status: public
title: Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 13
year: '2022'
...
---
_id: '12244'
abstract:
- lang: eng
  text: Environmental cues influence the highly dynamic morphology of microglia. Strategies
    to characterize these changes usually involve user-selected morphometric features,
    which preclude the identification of a spectrum of context-dependent morphological
    phenotypes. Here we develop MorphOMICs, a topological data analysis approach,
    which enables semiautomatic mapping of microglial morphology into an atlas of
    cue-dependent phenotypes and overcomes feature-selection biases and biological
    variability. We extract spatially heterogeneous and sexually dimorphic morphological
    phenotypes for seven adult mouse brain regions. This sex-specific phenotype declines
    with maturation but increases over the disease trajectories in two neurodegeneration
    mouse models, with females showing a faster morphological shift in affected brain
    regions. Remarkably, microglia morphologies reflect an adaptation upon repeated
    exposure to ketamine anesthesia and do not recover to control morphologies. Finally,
    we demonstrate that both long primary processes and short terminal processes provide
    distinct insights to morphological phenotypes. MorphOMICs opens a new perspective
    to characterize microglial morphology.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: ScienComp
acknowledgement: We thank the scientific service units at ISTA, in particular M. Schunn’s
  team at the preclinical facility, and especially our colony manager S. Haslinger,
  for excellent support. We are also grateful to the ISTA Imaging & Optics Facility,
  and in particular C. Sommer for helping with the data file conversions. We thank
  R. Erhart from the ISTA Scientific Computing Unit for improving the script performance.
  We thank M. Maes, B. Nagy, S. Oakeley and M. Benevento and all members of the Siegert
  group for constant feedback on the project and on the manuscript. This research
  was supported by the European Union Horizon 2020 research and innovation program
  under the Marie Skłodowska-Curie Actions program (754411 to R.J.A.C.), and by the
  European Research Council (grant no. 715571 to S.S.). L.K. was supported by funding
  to the Blue Brain Project, a research center of the École polytechnique fédérale
  de Lausanne, from the Swiss government’s ETH Board of the Swiss Federal Institutes
  of Technology. L.-H.T. was supported by NIH (grant no. R37NS051874) and by the JPB
  Foundation. The funders had no role in study design, data collection and analysis,
  decision to publish or preparation of the manuscript.
article_processing_charge: No
article_type: original
author:
- first_name: Gloria
  full_name: Colombo, Gloria
  id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
  last_name: Colombo
  orcid: 0000-0001-9434-8902
- first_name: Ryan J
  full_name: Cubero, Ryan J
  id: 850B2E12-9CD4-11E9-837F-E719E6697425
  last_name: Cubero
  orcid: 0000-0003-0002-1867
- first_name: Lida
  full_name: Kanari, Lida
  last_name: Kanari
- first_name: Alessandro
  full_name: Venturino, Alessandro
  id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
  last_name: Venturino
  orcid: 0000-0003-2356-9403
- first_name: Rouven
  full_name: Schulz, Rouven
  id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87
  last_name: Schulz
  orcid: 0000-0001-5297-733X
- first_name: Martina
  full_name: Scolamiero, Martina
  last_name: Scolamiero
- first_name: Jens
  full_name: Agerberg, Jens
  last_name: Agerberg
- first_name: Hansruedi
  full_name: Mathys, Hansruedi
  last_name: Mathys
- first_name: Li-Huei
  full_name: Tsai, Li-Huei
  last_name: Tsai
- first_name: Wojciech
  full_name: Chachólski, Wojciech
  last_name: Chachólski
- first_name: Kathryn
  full_name: Hess, Kathryn
  last_name: Hess
- first_name: Sandra
  full_name: Siegert, Sandra
  id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
  last_name: Siegert
  orcid: 0000-0001-8635-0877
citation:
  ama: Colombo G, Cubero RJ, Kanari L, et al. A tool for mapping microglial morphology,
    morphOMICs, reveals brain-region and sex-dependent phenotypes. <i>Nature Neuroscience</i>.
    2022;25(10):1379-1393. doi:<a href="https://doi.org/10.1038/s41593-022-01167-6">10.1038/s41593-022-01167-6</a>
  apa: Colombo, G., Cubero, R. J., Kanari, L., Venturino, A., Schulz, R., Scolamiero,
    M., … Siegert, S. (2022). A tool for mapping microglial morphology, morphOMICs,
    reveals brain-region and sex-dependent phenotypes. <i>Nature Neuroscience</i>.
    Springer Nature. <a href="https://doi.org/10.1038/s41593-022-01167-6">https://doi.org/10.1038/s41593-022-01167-6</a>
  chicago: Colombo, Gloria, Ryan J Cubero, Lida Kanari, Alessandro Venturino, Rouven
    Schulz, Martina Scolamiero, Jens Agerberg, et al. “A Tool for Mapping Microglial
    Morphology, MorphOMICs, Reveals Brain-Region and Sex-Dependent Phenotypes.” <i>Nature
    Neuroscience</i>. Springer Nature, 2022. <a href="https://doi.org/10.1038/s41593-022-01167-6">https://doi.org/10.1038/s41593-022-01167-6</a>.
  ieee: G. Colombo <i>et al.</i>, “A tool for mapping microglial morphology, morphOMICs,
    reveals brain-region and sex-dependent phenotypes,” <i>Nature Neuroscience</i>,
    vol. 25, no. 10. Springer Nature, pp. 1379–1393, 2022.
  ista: Colombo G, Cubero RJ, Kanari L, Venturino A, Schulz R, Scolamiero M, Agerberg
    J, Mathys H, Tsai L-H, Chachólski W, Hess K, Siegert S. 2022. A tool for mapping
    microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes.
    Nature Neuroscience. 25(10), 1379–1393.
  mla: Colombo, Gloria, et al. “A Tool for Mapping Microglial Morphology, MorphOMICs,
    Reveals Brain-Region and Sex-Dependent Phenotypes.” <i>Nature Neuroscience</i>,
    vol. 25, no. 10, Springer Nature, 2022, pp. 1379–93, doi:<a href="https://doi.org/10.1038/s41593-022-01167-6">10.1038/s41593-022-01167-6</a>.
  short: G. Colombo, R.J. Cubero, L. Kanari, A. Venturino, R. Schulz, M. Scolamiero,
    J. Agerberg, H. Mathys, L.-H. Tsai, W. Chachólski, K. Hess, S. Siegert, Nature
    Neuroscience 25 (2022) 1379–1393.
date_created: 2023-01-16T09:53:07Z
date_published: 2022-10-01T00:00:00Z
date_updated: 2024-03-25T23:30:10Z
day: '01'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1038/s41593-022-01167-6
ec_funded: 1
external_id:
  isi:
  - '000862214700001'
  pmid:
  - '36180790'
file:
- access_level: open_access
  checksum: 28431146873096f52e0107b534f178c9
  content_type: application/pdf
  creator: dernst
  date_created: 2023-01-30T08:06:56Z
  date_updated: 2023-01-30T08:06:56Z
  file_id: '12437'
  file_name: 2022_NatureNeuroscience_Colombo.pdf
  file_size: 23789835
  relation: main_file
  success: 1
file_date_updated: 2023-01-30T08:06:56Z
has_accepted_license: '1'
intvolume: '        25'
isi: 1
issue: '10'
keyword:
- General Neuroscience
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: 1379-1393
pmid: 1
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715571'
  name: Microglia action towards neuronal circuit formation and function in health
    and disease
publication: Nature Neuroscience
publication_identifier:
  eissn:
  - 1546-1726
  issn:
  - 1097-6256
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - description: News on ISTA website
    relation: press_release
    url: https://ista.ac.at/en/news/morphomics-revealing-the-hidden-meaning-of-microglia-shape/
  record:
  - id: '12378'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: A tool for mapping microglial morphology, morphOMICs, reveals brain-region
  and sex-dependent phenotypes
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 25
year: '2022'
...
---
_id: '9642'
abstract:
- lang: eng
  text: Perineuronal nets (PNNs), components of the extracellular matrix, preferentially
    coat parvalbumin-positive interneurons and constrain critical-period plasticity
    in the adult cerebral cortex. Current strategies to remove PNN are long-lasting,
    invasive, and trigger neuropsychiatric symptoms. Here, we apply repeated anesthetic
    ketamine as a method with minimal behavioral effect. We find that this paradigm
    strongly reduces PNN coating in the healthy adult brain and promotes juvenile-like
    plasticity. Microglia are critically involved in PNN loss because they engage
    with parvalbumin-positive neurons in their defined cortical layer. We identify
    external 60-Hz light-flickering entrainment to recapitulate microglia-mediated
    PNN removal. Importantly, 40-Hz frequency, which is known to remove amyloid plaques,
    does not induce PNN loss, suggesting microglia might functionally tune to distinct
    brain frequencies. Thus, our 60-Hz light-entrainment strategy provides an alternative
    form of PNN intervention in the healthy adult brain.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: We thank the scientific service units at IST Austria, especially
  the IST bioimaging facility, the preclinical facility, and, specifically, Michael
  Schunn and Sonja Haslinger for excellent support; Plexxikon for the PLX food; the
  Csicsvari group for advice and equipment for in vivo recording; Jürgen Siegert for
  the light-entrainment design; Marco Benevento, Soledad Gonzalo Cogno, Pat King,
  and all Siegert group members for constant feedback on the project and manuscript;
  Lorena Pantano (PILM Bioinformatics Core) for assisting with sample-size determination
  for OD plasticity experiments; and Ana Morello from MIT for technical assistance
  with VEPs recordings. This research was supported by a DOC Fellowship from the Austrian
  Academy of Sciences at the Institute of Science and Technology Austria to R.S.,
  from the European Union Horizon 2020 research and innovation program under the Marie
  Skłodowska-Curie Actions program (grants 665385 to G.C.; 754411 to R.J.A.C.), the
  European Research Council (grant 715571 to S.S.), and the National Eye Institute
  of the National Institutes of Health under award numbers R01EY029245 (to M.F.B.)
  and R01EY023037 (diversity supplement to H.D.J-C.).
article_number: '109313'
article_processing_charge: No
article_type: original
author:
- first_name: Alessandro
  full_name: Venturino, Alessandro
  id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
  last_name: Venturino
  orcid: 0000-0003-2356-9403
- first_name: Rouven
  full_name: Schulz, Rouven
  id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87
  last_name: Schulz
  orcid: 0000-0001-5297-733X
- first_name: Héctor
  full_name: De Jesús-Cortés, Héctor
  last_name: De Jesús-Cortés
- first_name: Margaret E
  full_name: Maes, Margaret E
  id: 3838F452-F248-11E8-B48F-1D18A9856A87
  last_name: Maes
  orcid: 0000-0001-9642-1085
- first_name: Balint
  full_name: Nagy, Balint
  id: 93C65ECC-A6F2-11E9-8DF9-9712E6697425
  last_name: Nagy
- first_name: Francis
  full_name: Reilly-Andújar, Francis
  last_name: Reilly-Andújar
- first_name: Gloria
  full_name: Colombo, Gloria
  id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
  last_name: Colombo
  orcid: 0000-0001-9434-8902
- first_name: Ryan J
  full_name: Cubero, Ryan J
  id: 850B2E12-9CD4-11E9-837F-E719E6697425
  last_name: Cubero
  orcid: 0000-0003-0002-1867
- first_name: Florianne E
  full_name: Schoot Uiterkamp, Florianne E
  id: 3526230C-F248-11E8-B48F-1D18A9856A87
  last_name: Schoot Uiterkamp
- first_name: Mark F.
  full_name: Bear, Mark F.
  last_name: Bear
- first_name: Sandra
  full_name: Siegert, Sandra
  id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
  last_name: Siegert
  orcid: 0000-0001-8635-0877
citation:
  ama: Venturino A, Schulz R, De Jesús-Cortés H, et al. Microglia enable mature perineuronal
    nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment
    in the healthy brain. <i>Cell Reports</i>. 2021;36(1). doi:<a href="https://doi.org/10.1016/j.celrep.2021.109313">10.1016/j.celrep.2021.109313</a>
  apa: Venturino, A., Schulz, R., De Jesús-Cortés, H., Maes, M. E., Nagy, B., Reilly-Andújar,
    F., … Siegert, S. (2021). Microglia enable mature perineuronal nets disassembly
    upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain.
    <i>Cell Reports</i>. Elsevier. <a href="https://doi.org/10.1016/j.celrep.2021.109313">https://doi.org/10.1016/j.celrep.2021.109313</a>
  chicago: Venturino, Alessandro, Rouven Schulz, Héctor De Jesús-Cortés, Margaret
    E Maes, Balint Nagy, Francis Reilly-Andújar, Gloria Colombo, et al. “Microglia
    Enable Mature Perineuronal Nets Disassembly upon Anesthetic Ketamine Exposure
    or 60-Hz Light Entrainment in the Healthy Brain.” <i>Cell Reports</i>. Elsevier,
    2021. <a href="https://doi.org/10.1016/j.celrep.2021.109313">https://doi.org/10.1016/j.celrep.2021.109313</a>.
  ieee: A. Venturino <i>et al.</i>, “Microglia enable mature perineuronal nets disassembly
    upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain,”
    <i>Cell Reports</i>, vol. 36, no. 1. Elsevier, 2021.
  ista: Venturino A, Schulz R, De Jesús-Cortés H, Maes ME, Nagy B, Reilly-Andújar
    F, Colombo G, Cubero RJ, Schoot Uiterkamp FE, Bear MF, Siegert S. 2021. Microglia
    enable mature perineuronal nets disassembly upon anesthetic ketamine exposure
    or 60-Hz light entrainment in the healthy brain. Cell Reports. 36(1), 109313.
  mla: Venturino, Alessandro, et al. “Microglia Enable Mature Perineuronal Nets Disassembly
    upon Anesthetic Ketamine Exposure or 60-Hz Light Entrainment in the Healthy Brain.”
    <i>Cell Reports</i>, vol. 36, no. 1, 109313, Elsevier, 2021, doi:<a href="https://doi.org/10.1016/j.celrep.2021.109313">10.1016/j.celrep.2021.109313</a>.
  short: A. Venturino, R. Schulz, H. De Jesús-Cortés, M.E. Maes, B. Nagy, F. Reilly-Andújar,
    G. Colombo, R.J. Cubero, F.E. Schoot Uiterkamp, M.F. Bear, S. Siegert, Cell Reports
    36 (2021).
date_created: 2021-07-11T22:01:16Z
date_published: 2021-07-06T00:00:00Z
date_updated: 2023-08-10T14:09:39Z
day: '06'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1016/j.celrep.2021.109313
ec_funded: 1
external_id:
  isi:
  - '000670188500004'
  pmid:
  - '34233180'
file:
- access_level: open_access
  checksum: f056255f6d01fd9a86b5387635928173
  content_type: application/pdf
  creator: cziletti
  date_created: 2021-07-19T13:32:17Z
  date_updated: 2021-07-19T13:32:17Z
  file_id: '9693'
  file_name: 2021_CellReports_Venturino.pdf
  file_size: 56388540
  relation: main_file
  success: 1
file_date_updated: 2021-07-19T13:32:17Z
has_accepted_license: '1'
intvolume: '        36'
isi: 1
issue: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715571'
  name: Microglia action towards neuronal circuit formation and function in health
    and disease
publication: Cell Reports
publication_identifier:
  eissn:
  - '22111247'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/the-twinkle-and-the-brain/
scopus_import: '1'
status: public
title: Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine
  exposure or 60-Hz light entrainment in the healthy brain
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 36
year: '2021'
...
---
_id: '6521'
abstract:
- lang: eng
  text: Microglia have emerged as a critical component of neurodegenerative diseases.
    Genetic manipulation of microglia can elucidate their functional impact in disease.
    In neuroscience, recombinant viruses such as lentiviruses and adeno-associated
    viruses (AAVs) have been successfully used to target various cell types in the
    brain, although effective transduction of microglia is rare. In this review, we
    provide a short background of lentiviruses and AAVs, and strategies for designing
    recombinant viral vectors. Then, we will summarize recent literature on successful
    microglial transductions in vitro and in vivo, and discuss the current challenges.
    Finally, we provide guidelines for reporting the efficiency and specificity of
    viral targeting in microglia, which will enable the microglial research community
    to assess and improve methodologies for future studies.
article_number: '134310'
article_processing_charge: No
article_type: original
author:
- first_name: Margaret E
  full_name: Maes, Margaret E
  id: 3838F452-F248-11E8-B48F-1D18A9856A87
  last_name: Maes
  orcid: 0000-0001-9642-1085
- first_name: Gloria
  full_name: Colombo, Gloria
  id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
  last_name: Colombo
  orcid: 0000-0001-9434-8902
- first_name: Rouven
  full_name: Schulz, Rouven
  id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87
  last_name: Schulz
  orcid: 0000-0001-5297-733X
- first_name: Sandra
  full_name: Siegert, Sandra
  id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
  last_name: Siegert
  orcid: 0000-0001-8635-0877
citation:
  ama: 'Maes ME, Colombo G, Schulz R, Siegert S. Targeting microglia with lentivirus
    and AAV: Recent advances and remaining challenges. <i>Neuroscience Letters</i>.
    2019;707. doi:<a href="https://doi.org/10.1016/j.neulet.2019.134310">10.1016/j.neulet.2019.134310</a>'
  apa: 'Maes, M. E., Colombo, G., Schulz, R., &#38; Siegert, S. (2019). Targeting
    microglia with lentivirus and AAV: Recent advances and remaining challenges. <i>Neuroscience
    Letters</i>. Elsevier. <a href="https://doi.org/10.1016/j.neulet.2019.134310">https://doi.org/10.1016/j.neulet.2019.134310</a>'
  chicago: 'Maes, Margaret E, Gloria Colombo, Rouven Schulz, and Sandra Siegert. “Targeting
    Microglia with Lentivirus and AAV: Recent Advances and Remaining Challenges.”
    <i>Neuroscience Letters</i>. Elsevier, 2019. <a href="https://doi.org/10.1016/j.neulet.2019.134310">https://doi.org/10.1016/j.neulet.2019.134310</a>.'
  ieee: 'M. E. Maes, G. Colombo, R. Schulz, and S. Siegert, “Targeting microglia with
    lentivirus and AAV: Recent advances and remaining challenges,” <i>Neuroscience
    Letters</i>, vol. 707. Elsevier, 2019.'
  ista: 'Maes ME, Colombo G, Schulz R, Siegert S. 2019. Targeting microglia with lentivirus
    and AAV: Recent advances and remaining challenges. Neuroscience Letters. 707,
    134310.'
  mla: 'Maes, Margaret E., et al. “Targeting Microglia with Lentivirus and AAV: Recent
    Advances and Remaining Challenges.” <i>Neuroscience Letters</i>, vol. 707, 134310,
    Elsevier, 2019, doi:<a href="https://doi.org/10.1016/j.neulet.2019.134310">10.1016/j.neulet.2019.134310</a>.'
  short: M.E. Maes, G. Colombo, R. Schulz, S. Siegert, Neuroscience Letters 707 (2019).
date_created: 2019-06-05T13:16:24Z
date_published: 2019-08-10T00:00:00Z
date_updated: 2023-08-28T09:30:57Z
day: '10'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1016/j.neulet.2019.134310
ec_funded: 1
external_id:
  isi:
  - '000486094600037'
  pmid:
  - '31158432'
file:
- access_level: open_access
  checksum: 553c9dbd39727fbed55ee991c51ca4d1
  content_type: application/pdf
  creator: dernst
  date_created: 2019-06-08T11:44:20Z
  date_updated: 2020-07-14T12:47:33Z
  file_id: '6551'
  file_name: 2019_Neuroscience_Maes.pdf
  file_size: 1779287
  relation: main_file
file_date_updated: 2020-07-14T12:47:33Z
has_accepted_license: '1'
intvolume: '       707'
isi: 1
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715571'
  name: Microglia action towards neuronal circuit formation and function in health
    and disease
- _id: 267F75D8-B435-11E9-9278-68D0E5697425
  name: Modulating microglia through G protein-coupled receptor (GPCR) signaling
publication: Neuroscience Letters
publication_identifier:
  issn:
  - 0304-3940
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Targeting microglia with lentivirus and AAV: Recent advances and remaining
  challenges'
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 707
year: '2019'
...
