---
_id: '3'
abstract:
- lang: eng
  text: SETD5 gene mutations have been identified as a frequent cause of idiopathic
    intellectual disability. Here we show that Setd5-haploinsufficient mice present
    developmental defects such as abnormal brain-to-body weight ratios and neural
    crest defect-associated phenotypes. Furthermore, Setd5-mutant mice show impairments
    in cognitive tasks, enhanced long-term potentiation, delayed ontogenetic profile
    of ultrasonic vocalization, and behavioral inflexibility. Behavioral issues are
    accompanied by abnormal expression of postsynaptic density proteins previously
    associated with cognition. Our data additionally indicate that Setd5 regulates
    RNA polymerase II dynamics and gene transcription via its interaction with the
    Hdac3 and Paf1 complexes, findings potentially explaining the gene expression
    defects observed in Setd5-haploinsufficient mice. Our results emphasize the decisive
    role of Setd5 in a biological pathway found to be disrupted in humans with intellectual
    disability and autism spectrum disorder.
acknowledged_ssus:
- _id: M-Shop
- _id: PreCl
acknowledgement: This work was supported by the Simons Foundation Autism Research
  Initiative (grant 401299) to G.N. and the DFG (SPP1738 grant NO 1249) to K.-M.N.
article_processing_charge: No
article_type: original
author:
- first_name: Elena
  full_name: Deliu, Elena
  id: 37A40D7E-F248-11E8-B48F-1D18A9856A87
  last_name: Deliu
  orcid: 0000-0002-7370-5293
- first_name: Niccoló
  full_name: Arecco, Niccoló
  last_name: Arecco
- first_name: Jasmin
  full_name: Morandell, Jasmin
  id: 4739D480-F248-11E8-B48F-1D18A9856A87
  last_name: Morandell
- first_name: Christoph
  full_name: Dotter, Christoph
  id: 4C66542E-F248-11E8-B48F-1D18A9856A87
  last_name: Dotter
  orcid: 0000-0002-9033-9096
- first_name: Ximena
  full_name: Contreras, Ximena
  id: 475990FE-F248-11E8-B48F-1D18A9856A87
  last_name: Contreras
- first_name: Charles
  full_name: Girardot, Charles
  last_name: Girardot
- first_name: Eva
  full_name: Käsper, Eva
  last_name: Käsper
- first_name: Alena
  full_name: Kozlova, Alena
  id: C50A9596-02D0-11E9-976E-E38CFE5CBC1D
  last_name: Kozlova
- first_name: Kasumi
  full_name: Kishi, Kasumi
  id: 3065DFC4-F248-11E8-B48F-1D18A9856A87
  last_name: Kishi
- first_name: Ilaria
  full_name: Chiaradia, Ilaria
  id: B6467F20-02D0-11E9-BDA5-E960C241894A
  last_name: Chiaradia
  orcid: 0000-0002-9529-4464
- first_name: Kyung
  full_name: Noh, Kyung
  last_name: Noh
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
citation:
  ama: Deliu E, Arecco N, Morandell J, et al. Haploinsufficiency of the intellectual
    disability gene SETD5 disturbs developmental gene expression and cognition. <i>Nature
    Neuroscience</i>. 2018;21(12):1717-1727. doi:<a href="https://doi.org/10.1038/s41593-018-0266-2">10.1038/s41593-018-0266-2</a>
  apa: Deliu, E., Arecco, N., Morandell, J., Dotter, C., Contreras, X., Girardot,
    C., … Novarino, G. (2018). Haploinsufficiency of the intellectual disability gene
    SETD5 disturbs developmental gene expression and cognition. <i>Nature Neuroscience</i>.
    Nature Publishing Group. <a href="https://doi.org/10.1038/s41593-018-0266-2">https://doi.org/10.1038/s41593-018-0266-2</a>
  chicago: Deliu, Elena, Niccoló Arecco, Jasmin Morandell, Christoph Dotter, Ximena
    Contreras, Charles Girardot, Eva Käsper, et al. “Haploinsufficiency of the Intellectual
    Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” <i>Nature
    Neuroscience</i>. Nature Publishing Group, 2018. <a href="https://doi.org/10.1038/s41593-018-0266-2">https://doi.org/10.1038/s41593-018-0266-2</a>.
  ieee: E. Deliu <i>et al.</i>, “Haploinsufficiency of the intellectual disability
    gene SETD5 disturbs developmental gene expression and cognition,” <i>Nature Neuroscience</i>,
    vol. 21, no. 12. Nature Publishing Group, pp. 1717–1727, 2018.
  ista: Deliu E, Arecco N, Morandell J, Dotter C, Contreras X, Girardot C, Käsper
    E, Kozlova A, Kishi K, Chiaradia I, Noh K, Novarino G. 2018. Haploinsufficiency
    of the intellectual disability gene SETD5 disturbs developmental gene expression
    and cognition. Nature Neuroscience. 21(12), 1717–1727.
  mla: Deliu, Elena, et al. “Haploinsufficiency of the Intellectual Disability Gene
    SETD5 Disturbs Developmental Gene Expression and Cognition.” <i>Nature Neuroscience</i>,
    vol. 21, no. 12, Nature Publishing Group, 2018, pp. 1717–27, doi:<a href="https://doi.org/10.1038/s41593-018-0266-2">10.1038/s41593-018-0266-2</a>.
  short: E. Deliu, N. Arecco, J. Morandell, C. Dotter, X. Contreras, C. Girardot,
    E. Käsper, A. Kozlova, K. Kishi, I. Chiaradia, K. Noh, G. Novarino, Nature Neuroscience
    21 (2018) 1717–1727.
date_created: 2018-12-11T11:44:05Z
date_published: 2018-11-19T00:00:00Z
date_updated: 2024-03-25T23:30:25Z
day: '19'
ddc:
- '570'
department:
- _id: GaNo
- _id: EdHa
doi: 10.1038/s41593-018-0266-2
external_id:
  isi:
  - '000451324700010'
file:
- access_level: open_access
  checksum: 60abd0f05b7cdc08a6b0ec460884084f
  content_type: application/pdf
  creator: dernst
  date_created: 2019-04-09T07:41:57Z
  date_updated: 2020-07-14T12:45:58Z
  file_id: '6255'
  file_name: 2017_NatureNeuroscience_Deliu.pdf
  file_size: 8167169
  relation: main_file
file_date_updated: 2020-07-14T12:45:58Z
has_accepted_license: '1'
intvolume: '        21'
isi: 1
issue: '12'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Submitted Version
page: 1717 - 1727
project:
- _id: 254BA948-B435-11E9-9278-68D0E5697425
  grant_number: '401299'
  name: Probing development and reversibility of autism spectrum disorders
publication: Nature Neuroscience
publication_status: published
publisher: Nature Publishing Group
publist_id: '8054'
pubrep_id: '1071'
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/mutation-that-causes-autism-and-intellectual-disability-makes-brain-less-flexible/
  record:
  - id: '6074'
    relation: popular_science
    status: public
  - id: '12364'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental
  gene expression and cognition
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 21
year: '2018'
...
---
_id: '714'
abstract:
- lang: eng
  text: Background HIV-1 infection and drug abuse are frequently co-morbid and their
    association greatly increases the severity of HIV-1-induced neuropathology. While
    nucleus accumbens (NAcc) function is severely perturbed by drugs of abuse, little
    is known about how HIV-1 infection affects NAcc. Methods We used calcium and voltage
    imaging to investigate the effect of HIV-1 trans-activator of transcription (Tat)
    on rat NAcc. Based on previous neuronal studies, we hypothesized that Tat modulates
    intracellular Ca2+ homeostasis of NAcc neurons. Results We provide evidence that
    Tat triggers a Ca2+ signaling cascade in NAcc medium spiny neurons (MSN) expressing
    D1-like dopamine receptors leading to neuronal depolarization. Firstly, Tat induced
    inositol 1,4,5-trisphsophate (IP3) receptor-mediated Ca2+ release from endoplasmic
    reticulum, followed by Ca2+ and Na+ influx via transient receptor potential canonical
    channels. The influx of cations depolarizes the membrane promoting additional
    Ca2+ entry through voltage-gated P/Q-type Ca2+ channels and opening of tetrodotoxin-sensitive
    Na+ channels. By activating this mechanism, Tat elicits a feed-forward depolarization
    increasing the excitability of D1-phosphatidylinositol-linked NAcc MSN. We previously
    found that cocaine targets NAcc neurons directly (independent of the inhibition
    of dopamine transporter) only when IP3-generating mechanisms are concomitantly
    initiated. When tested here, cocaine produced a dose-dependent potentiation of
    the effect of Tat on cytosolic Ca2+. Conclusion We describe for the first time
    a HIV-1 Tat-triggered Ca2+ signaling in MSN of NAcc involving TRPC and depolarization
    and a potentiation of the effect of Tat by cocaine, which may be relevant for
    the reward axis in cocaine-abusing HIV-1-positive patients.
acknowledgement: This work was supported by the National Institutes of Health grants
  DA035926 (to MEA), and P30DA013429 (to EMU).
article_processing_charge: No
article_type: original
author:
- first_name: Gabriela
  full_name: Brailoiu, Gabriela
  last_name: Brailoiu
- first_name: Elena
  full_name: Deliu, Elena
  id: 37A40D7E-F248-11E8-B48F-1D18A9856A87
  last_name: Deliu
  orcid: 0000-0002-7370-5293
- first_name: Jeffrey
  full_name: Barr, Jeffrey
  last_name: Barr
- first_name: Linda
  full_name: Console Bram, Linda
  last_name: Console Bram
- first_name: Alexandra
  full_name: Ciuciu, Alexandra
  last_name: Ciuciu
- first_name: Mary
  full_name: Abood, Mary
  last_name: Abood
- first_name: Ellen
  full_name: Unterwald, Ellen
  last_name: Unterwald
- first_name: Eugen
  full_name: Brǎiloiu, Eugen
  last_name: Brǎiloiu
citation:
  ama: Brailoiu G, Deliu E, Barr J, et al. HIV Tat excites D1 receptor-like expressing
    neurons from rat nucleus accumbens. <i>Drug and Alcohol Dependence</i>. 2017;178:7-14.
    doi:<a href="https://doi.org/10.1016/j.drugalcdep.2017.04.015">10.1016/j.drugalcdep.2017.04.015</a>
  apa: Brailoiu, G., Deliu, E., Barr, J., Console Bram, L., Ciuciu, A., Abood, M.,
    … Brǎiloiu, E. (2017). HIV Tat excites D1 receptor-like expressing neurons from
    rat nucleus accumbens. <i>Drug and Alcohol Dependence</i>. Elsevier. <a href="https://doi.org/10.1016/j.drugalcdep.2017.04.015">https://doi.org/10.1016/j.drugalcdep.2017.04.015</a>
  chicago: Brailoiu, Gabriela, Elena Deliu, Jeffrey Barr, Linda Console Bram, Alexandra
    Ciuciu, Mary Abood, Ellen Unterwald, and Eugen Brǎiloiu. “HIV Tat Excites D1 Receptor-like
    Expressing Neurons from Rat Nucleus Accumbens.” <i>Drug and Alcohol Dependence</i>.
    Elsevier, 2017. <a href="https://doi.org/10.1016/j.drugalcdep.2017.04.015">https://doi.org/10.1016/j.drugalcdep.2017.04.015</a>.
  ieee: G. Brailoiu <i>et al.</i>, “HIV Tat excites D1 receptor-like expressing neurons
    from rat nucleus accumbens,” <i>Drug and Alcohol Dependence</i>, vol. 178. Elsevier,
    pp. 7–14, 2017.
  ista: Brailoiu G, Deliu E, Barr J, Console Bram L, Ciuciu A, Abood M, Unterwald
    E, Brǎiloiu E. 2017. HIV Tat excites D1 receptor-like expressing neurons from
    rat nucleus accumbens. Drug and Alcohol Dependence. 178, 7–14.
  mla: Brailoiu, Gabriela, et al. “HIV Tat Excites D1 Receptor-like Expressing Neurons
    from Rat Nucleus Accumbens.” <i>Drug and Alcohol Dependence</i>, vol. 178, Elsevier,
    2017, pp. 7–14, doi:<a href="https://doi.org/10.1016/j.drugalcdep.2017.04.015">10.1016/j.drugalcdep.2017.04.015</a>.
  short: G. Brailoiu, E. Deliu, J. Barr, L. Console Bram, A. Ciuciu, M. Abood, E.
    Unterwald, E. Brǎiloiu, Drug and Alcohol Dependence 178 (2017) 7–14.
date_created: 2018-12-11T11:48:05Z
date_published: 2017-09-01T00:00:00Z
date_updated: 2021-01-12T08:12:00Z
day: '01'
department:
- _id: GaNo
doi: 10.1016/j.drugalcdep.2017.04.015
external_id:
  pmid:
  - '28623807'
intvolume: '       178'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797705
month: '09'
oa: 1
oa_version: Submitted Version
page: 7 - 14
pmid: 1
publication: Drug and Alcohol Dependence
publication_identifier:
  issn:
  - '03768716'
publication_status: published
publisher: Elsevier
publist_id: '6967'
quality_controlled: '1'
scopus_import: 1
status: public
title: HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 178
year: '2017'
...
---
_id: '747'
abstract:
- lang: eng
  text: Bradykinin (BK), a component of the kallikrein-kininogen-kinin system exerts
    multiple effects via B1 and B2 receptor activation. In the cardiovascular system,
    bradykinin has cardioprotective and vasodilator properties. We investigated the
    effect of BK on cardiac-projecting neurons of nucleus ambiguus, a key site for
    the parasympathetic cardiac regulation. BK produced a dose-dependent increase
    in cytosolic Ca2+ concentration. Pretreatment with HOE140, a B2 receptor antagonist,
    but not with R715, a B1 receptor antagonist, abolished the response to BK. A selective
    B2 receptor agonist, but not a B1 receptor agonist, elicited an increase in cytosolic
    Ca2+ similarly to BK. Inhibition of N-type voltage-gated Ca2+ channels with ω-conotoxin
    GVIA had no effect on the Ca2+ signal produced by BK, while pretreatment with
    ω-conotoxin MVIIC, a blocker of P/Q-type of Ca2+ channels, significantly diminished
    the effect of BK. Pretreatment with xestospongin C and 2-aminoethoxydiphenyl borate,
    antagonists of inositol 1,4,5-trisphosphate receptors, abolished the response
    to BK. Inhibition of ryanodine receptors reduced the BK-induced Ca2+ increase,
    while disruption of lysosomal Ca2+ stores with bafilomycin A1 did not affect the
    response. BK produced a dose-dependent depolarization of nucleus ambiguus neurons,
    which was prevented by the B2 receptor antagonist. In vivo studies indicate that
    microinjection of BK into nucleus ambiguus elicited bradycardia in conscious rats
    via B2 receptors. In summary, in cardiac vagal neurons of nucleus ambiguus, BK
    activates B2 receptors promoting Ca2+ influx and Ca2+ release from endoplasmic
    reticulum, and membrane depolarization; these effects are translated in vivo by
    bradycardia.
article_processing_charge: No
article_type: original
author:
- first_name: Eugen
  full_name: Brǎiloiu, Eugen
  last_name: Brǎiloiu
- first_name: Matthew
  full_name: Mcguire, Matthew
  last_name: Mcguire
- first_name: Shadaria
  full_name: Shuler, Shadaria
  last_name: Shuler
- first_name: Elena
  full_name: Deliu, Elena
  id: 37A40D7E-F248-11E8-B48F-1D18A9856A87
  last_name: Deliu
  orcid: 0000-0002-7370-5293
- first_name: Jeffrey
  full_name: Barr, Jeffrey
  last_name: Barr
- first_name: Mary
  full_name: Abood, Mary
  last_name: Abood
- first_name: Gabriela
  full_name: Brailoiu, Gabriela
  last_name: Brailoiu
citation:
  ama: Brǎiloiu E, Mcguire M, Shuler S, et al. Modulation of cardiac vagal tone by
    bradykinin acting on nucleus ambiguus. <i>Neuroscience</i>. 2017;365:23-32. doi:<a
    href="https://doi.org/10.1016/j.neuroscience.2017.09.034">10.1016/j.neuroscience.2017.09.034</a>
  apa: Brǎiloiu, E., Mcguire, M., Shuler, S., Deliu, E., Barr, J., Abood, M., &#38;
    Brailoiu, G. (2017). Modulation of cardiac vagal tone by bradykinin acting on
    nucleus ambiguus. <i>Neuroscience</i>. Elsevier. <a href="https://doi.org/10.1016/j.neuroscience.2017.09.034">https://doi.org/10.1016/j.neuroscience.2017.09.034</a>
  chicago: Brǎiloiu, Eugen, Matthew Mcguire, Shadaria Shuler, Elena Deliu, Jeffrey
    Barr, Mary Abood, and Gabriela Brailoiu. “Modulation of Cardiac Vagal Tone by
    Bradykinin Acting on Nucleus Ambiguus.” <i>Neuroscience</i>. Elsevier, 2017. <a
    href="https://doi.org/10.1016/j.neuroscience.2017.09.034">https://doi.org/10.1016/j.neuroscience.2017.09.034</a>.
  ieee: E. Brǎiloiu <i>et al.</i>, “Modulation of cardiac vagal tone by bradykinin
    acting on nucleus ambiguus,” <i>Neuroscience</i>, vol. 365. Elsevier, pp. 23–32,
    2017.
  ista: Brǎiloiu E, Mcguire M, Shuler S, Deliu E, Barr J, Abood M, Brailoiu G. 2017.
    Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus. Neuroscience.
    365, 23–32.
  mla: Brǎiloiu, Eugen, et al. “Modulation of Cardiac Vagal Tone by Bradykinin Acting
    on Nucleus Ambiguus.” <i>Neuroscience</i>, vol. 365, Elsevier, 2017, pp. 23–32,
    doi:<a href="https://doi.org/10.1016/j.neuroscience.2017.09.034">10.1016/j.neuroscience.2017.09.034</a>.
  short: E. Brǎiloiu, M. Mcguire, S. Shuler, E. Deliu, J. Barr, M. Abood, G. Brailoiu,
    Neuroscience 365 (2017) 23–32.
date_created: 2018-12-11T11:48:17Z
date_published: 2017-12-04T00:00:00Z
date_updated: 2023-09-27T12:26:59Z
day: '04'
department:
- _id: GaNo
doi: 10.1016/j.neuroscience.2017.09.034
external_id:
  isi:
  - '000415966200003'
  pmid:
  - '28951324'
intvolume: '       365'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798458
month: '12'
oa: 1
oa_version: Submitted Version
page: 23 - 32
pmid: 1
publication: Neuroscience
publication_identifier:
  issn:
  - '03064522'
publication_status: published
publisher: Elsevier
publist_id: '6911'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 365
year: '2017'
...
---
_id: '529'
abstract:
- lang: eng
  text: The pituitary adenylyl cyclase-activating polypeptide (PACAP) and its G protein-coupled
    receptors, PAC1, VPAC1 and VPAC2 form a system involved in a variety of biological
    processes. Although some sympathetic stimulatory effects of this system have been
    reported, its central cardiovascular regulatory properties are poorly characterized.
    VPAC1 receptors are expressed in the nucleus ambiguus (nAmb), a key center controlling
    cardiac parasympathetic tone. In this study, we report that selective VPAC1 activation
    in rhodamine-labeled cardiac vagal preganglionic neurons of the rat nAmb produces
    inositol 1,4,5-trisphosphate receptor-mediated Ca2+ mobilization, membrane depolarization
    and activation of P/Q-type Ca2+ channels. In vivo, this pathway converges onto
    transient reduction in heart rate of conscious rats. Therefore we demonstrate
    a VPAC1-dependent mechanism in the central parasympathetic regulation of the heart
    rate, adding to the complexity of PACAP-mediated cardiovascular modulation.
acknowledgement: This study was supported by startup funds from the Jefferson College
  of Pharmacy, and by the National Institutes of Health DA023204 (to M.E.A) and P30
  DA 013429 to Center for Substance Abuse Research, Temple University.
author:
- first_name: Florin
  full_name: Gherghina, Florin L
  last_name: Gherghina
- first_name: Andrei
  full_name: Tica, Andrei A
  last_name: Tica
- first_name: Elena
  full_name: Elena Deliu
  id: 37A40D7E-F248-11E8-B48F-1D18A9856A87
  last_name: Deliu
  orcid: 0000-0002-7370-5293
- first_name: Mary
  full_name: Abood, Mary E
  last_name: Abood
- first_name: G.
  full_name: Brailoiu, G. Christina
  last_name: Brailoiu
- first_name: Eugen
  full_name: Brǎiloiu, Eugen
  last_name: Brǎiloiu
citation:
  ama: Gherghina F, Tica A, Deliu E, Abood M, Brailoiu G, Brǎiloiu E. Effects of VPAC1
    activation in nucleus ambiguus neurons. <i>Brain Research</i>. 2017;1657:297-303.
    doi:<a href="https://doi.org/10.1016/j.brainres.2016.12.026">10.1016/j.brainres.2016.12.026</a>
  apa: Gherghina, F., Tica, A., Deliu, E., Abood, M., Brailoiu, G., &#38; Brǎiloiu,
    E. (2017). Effects of VPAC1 activation in nucleus ambiguus neurons. <i>Brain Research</i>.
    Elsevier. <a href="https://doi.org/10.1016/j.brainres.2016.12.026">https://doi.org/10.1016/j.brainres.2016.12.026</a>
  chicago: Gherghina, Florin, Andrei Tica, Elena Deliu, Mary Abood, G. Brailoiu, and
    Eugen Brǎiloiu. “Effects of VPAC1 Activation in Nucleus Ambiguus Neurons.” <i>Brain
    Research</i>. Elsevier, 2017. <a href="https://doi.org/10.1016/j.brainres.2016.12.026">https://doi.org/10.1016/j.brainres.2016.12.026</a>.
  ieee: F. Gherghina, A. Tica, E. Deliu, M. Abood, G. Brailoiu, and E. Brǎiloiu, “Effects
    of VPAC1 activation in nucleus ambiguus neurons,” <i>Brain Research</i>, vol.
    1657. Elsevier, pp. 297–303, 2017.
  ista: Gherghina F, Tica A, Deliu E, Abood M, Brailoiu G, Brǎiloiu E. 2017. Effects
    of VPAC1 activation in nucleus ambiguus neurons. Brain Research. 1657, 297–303.
  mla: Gherghina, Florin, et al. “Effects of VPAC1 Activation in Nucleus Ambiguus
    Neurons.” <i>Brain Research</i>, vol. 1657, Elsevier, 2017, pp. 297–303, doi:<a
    href="https://doi.org/10.1016/j.brainres.2016.12.026">10.1016/j.brainres.2016.12.026</a>.
  short: F. Gherghina, A. Tica, E. Deliu, M. Abood, G. Brailoiu, E. Brǎiloiu, Brain
    Research 1657 (2017) 297–303.
date_created: 2018-12-11T11:46:59Z
date_published: 2017-02-15T00:00:00Z
date_updated: 2021-01-12T08:01:26Z
day: '15'
doi: 10.1016/j.brainres.2016.12.026
extern: 1
intvolume: '      1657'
month: '02'
page: 297 - 303
publication: Brain Research
publication_status: published
publisher: Elsevier
publist_id: '7290'
quality_controlled: 0
status: public
title: Effects of VPAC1 activation in nucleus ambiguus neurons
type: journal_article
volume: 1657
year: '2017'
...
---
_id: '634'
abstract:
- lang: eng
  text: As autism spectrum disorder (ASD) is largely regarded as a neurodevelopmental
    condition, long-time consensus was that its hallmark features are irreversible.
    However, several studies from recent years using defined mouse models of ASD have
    provided clear evidence that in mice neurobiological and behavioural alterations
    can be ameliorated or even reversed by genetic restoration or pharmacological
    treatment either before or after symptom onset. Here, we review findings on genetic
    and pharmacological reversibility of phenotypes in mouse models of ASD. Our review
    should give a comprehensive overview on both aspects and encourage future studies
    to better understand the underlying molecular mechanisms that might be translatable
    from animals to humans.
alternative_title:
- ADVSANAT
author:
- first_name: Jan
  full_name: Schroeder, Jan
  last_name: Schroeder
- first_name: Elena
  full_name: Deliu, Elena
  id: 37A40D7E-F248-11E8-B48F-1D18A9856A87
  last_name: Deliu
  orcid: 0000-0002-7370-5293
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Michael
  full_name: Schmeisser, Michael
  last_name: Schmeisser
citation:
  ama: 'Schroeder J, Deliu E, Novarino G, Schmeisser M. Genetic and pharmacological
    reversibility of phenotypes in mouse models of autism spectrum disorder. In: Schmeisser
    M, Boekers T, eds. <i>Translational Anatomy and Cell Biology of Autism Spectrum
    Disorder</i>. Vol 224. Advances in Anatomy Embryology and Cell Biology. Springer;
    2017:189-211. doi:<a href="https://doi.org/10.1007/978-3-319-52498-6_10">10.1007/978-3-319-52498-6_10</a>'
  apa: Schroeder, J., Deliu, E., Novarino, G., &#38; Schmeisser, M. (2017). Genetic
    and pharmacological reversibility of phenotypes in mouse models of autism spectrum
    disorder. In M. Schmeisser &#38; T. Boekers (Eds.), <i>Translational Anatomy and
    Cell Biology of Autism Spectrum Disorder</i> (Vol. 224, pp. 189–211). Springer.
    <a href="https://doi.org/10.1007/978-3-319-52498-6_10">https://doi.org/10.1007/978-3-319-52498-6_10</a>
  chicago: Schroeder, Jan, Elena Deliu, Gaia Novarino, and Michael Schmeisser. “Genetic
    and Pharmacological Reversibility of Phenotypes in Mouse Models of Autism Spectrum
    Disorder.” In <i>Translational Anatomy and Cell Biology of Autism Spectrum Disorder</i>,
    edited by Michael Schmeisser and Tobias Boekers, 224:189–211. Advances in Anatomy
    Embryology and Cell Biology. Springer, 2017. <a href="https://doi.org/10.1007/978-3-319-52498-6_10">https://doi.org/10.1007/978-3-319-52498-6_10</a>.
  ieee: J. Schroeder, E. Deliu, G. Novarino, and M. Schmeisser, “Genetic and pharmacological
    reversibility of phenotypes in mouse models of autism spectrum disorder,” in <i>Translational
    Anatomy and Cell Biology of Autism Spectrum Disorder</i>, vol. 224, M. Schmeisser
    and T. Boekers, Eds. Springer, 2017, pp. 189–211.
  ista: 'Schroeder J, Deliu E, Novarino G, Schmeisser M. 2017.Genetic and pharmacological
    reversibility of phenotypes in mouse models of autism spectrum disorder. In: Translational
    Anatomy and Cell Biology of Autism Spectrum Disorder. ADVSANAT, vol. 224, 189–211.'
  mla: Schroeder, Jan, et al. “Genetic and Pharmacological Reversibility of Phenotypes
    in Mouse Models of Autism Spectrum Disorder.” <i>Translational Anatomy and Cell
    Biology of Autism Spectrum Disorder</i>, edited by Michael Schmeisser and Tobias
    Boekers, vol. 224, Springer, 2017, pp. 189–211, doi:<a href="https://doi.org/10.1007/978-3-319-52498-6_10">10.1007/978-3-319-52498-6_10</a>.
  short: J. Schroeder, E. Deliu, G. Novarino, M. Schmeisser, in:, M. Schmeisser, T.
    Boekers (Eds.), Translational Anatomy and Cell Biology of Autism Spectrum Disorder,
    Springer, 2017, pp. 189–211.
date_created: 2018-12-11T11:47:37Z
date_published: 2017-05-28T00:00:00Z
date_updated: 2021-01-12T08:07:08Z
day: '28'
department:
- _id: GaNo
doi: 10.1007/978-3-319-52498-6_10
editor:
- first_name: Michael
  full_name: Schmeisser, Michael
  last_name: Schmeisser
- first_name: Tobias
  full_name: Boekers, Tobias
  last_name: Boekers
intvolume: '       224'
language:
- iso: eng
month: '05'
oa_version: None
page: 189 - 211
project:
- _id: 25473368-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: F03523
  name: Transmembrane Transporters in Health and Disease
publication: Translational Anatomy and Cell Biology of Autism Spectrum Disorder
publication_identifier:
  eisbn:
  - 978-3-319-52498-6
publication_status: published
publisher: Springer
publist_id: '7156'
quality_controlled: '1'
scopus_import: 1
series_title: Advances in Anatomy Embryology and Cell Biology
status: public
title: Genetic and pharmacological reversibility of phenotypes in mouse models of
  autism spectrum disorder
type: book_chapter
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 224
year: '2017'
...
---
_id: '1183'
abstract:
- lang: eng
  text: Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping
    with other neurological conditions. We previously described abnormalities in the
    branched-chain amino acid (BCAA) catabolic pathway as a cause of ASD. Here, we
    show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid
    transporter localized at the blood brain barrier (BBB), has an essential role
    in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from
    the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal
    mRNA translation, and severe neurological abnormalities. Furthermore, we identified
    several patients with autistic traits and motor delay carrying deleterious homozygous
    mutations in the SLC7A5 gene. Finally, we demonstrate that BCAA intracerebroventricular
    administration ameliorates abnormal behaviors in adult mutant mice. Our data elucidate
    a neurological syndrome defined by SLC7A5 mutations and support an essential role
    for the BCAA in human brain function.
acknowledgement: "This work was supported by NICHD (P01HD070494) and SFARI (grant
  275275) to J.G.G., and FWF (SFB35_3523) to G.N.\r\nWe thank A.C. Manzano, Mike Liu,
  and F. Marr for technical assistance, and R. Shigemoto and the IST Austria Electron
  Microscopy (EM) Facility for assistance. We acknowledge support from CIDR for genome-wide
  SNP analysis (X01HG008823) and Broad Institute Center for Mendelian Disorders (UM1HG008900
  to D. MacArthur), the Yale Center for Mendelian Disorders (U54HG006504 to M.G.),
  the Gregory M. Kiez and Mehmet Kutman Foundation (M.G.), Italian Ministry of Instruction
  University and Research (PON01_00937 to C.I.), and NIH (R01-GM108911 to A.S.). This
  work was supported by NICHD (P01HD070494) and SFARI (grant 275275) to J.G.G., and
  FWF (SFB35_3523) to G.N.\r\n\r\n#EMFacility"
article_processing_charge: No
article_type: original
author:
- first_name: Dora-Clara
  full_name: Tarlungeanu, Dora-Clara
  id: 2ABCE612-F248-11E8-B48F-1D18A9856A87
  last_name: Tarlungeanu
- first_name: Elena
  full_name: Deliu, Elena
  id: 37A40D7E-F248-11E8-B48F-1D18A9856A87
  last_name: Deliu
  orcid: 0000-0002-7370-5293
- first_name: Christoph
  full_name: Dotter, Christoph
  id: 4C66542E-F248-11E8-B48F-1D18A9856A87
  last_name: Dotter
  orcid: 0000-0002-9033-9096
- first_name: Majdi
  full_name: Kara, Majdi
  last_name: Kara
- first_name: Philipp
  full_name: Janiesch, Philipp
  last_name: Janiesch
- first_name: Mariafrancesca
  full_name: Scalise, Mariafrancesca
  last_name: Scalise
- first_name: Michele
  full_name: Galluccio, Michele
  last_name: Galluccio
- first_name: Mateja
  full_name: Tesulov, Mateja
  last_name: Tesulov
- first_name: Emanuela
  full_name: Morelli, Emanuela
  id: 3F4D1282-F248-11E8-B48F-1D18A9856A87
  last_name: Morelli
- first_name: Fatma
  full_name: Sönmez, Fatma
  last_name: Sönmez
- first_name: Kaya
  full_name: Bilgüvar, Kaya
  last_name: Bilgüvar
- first_name: Ryuichi
  full_name: Ohgaki, Ryuichi
  last_name: Ohgaki
- first_name: Yoshikatsu
  full_name: Kanai, Yoshikatsu
  last_name: Kanai
- first_name: Anide
  full_name: Johansen, Anide
  last_name: Johansen
- first_name: Seham
  full_name: Esharif, Seham
  last_name: Esharif
- first_name: Tawfeg
  full_name: Ben Omran, Tawfeg
  last_name: Ben Omran
- first_name: Meral
  full_name: Topcu, Meral
  last_name: Topcu
- first_name: Avner
  full_name: Schlessinger, Avner
  last_name: Schlessinger
- first_name: Cesare
  full_name: Indiveri, Cesare
  last_name: Indiveri
- first_name: Kent
  full_name: Duncan, Kent
  last_name: Duncan
- first_name: Ahmet
  full_name: Caglayan, Ahmet
  last_name: Caglayan
- first_name: Murat
  full_name: Günel, Murat
  last_name: Günel
- first_name: Joseph
  full_name: Gleeson, Joseph
  last_name: Gleeson
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
citation:
  ama: Tarlungeanu D-C, Deliu E, Dotter C, et al. Impaired amino acid transport at
    the blood brain barrier is a cause of autism spectrum disorder. <i>Cell</i>. 2016;167(6):1481-1494.
    doi:<a href="https://doi.org/10.1016/j.cell.2016.11.013">10.1016/j.cell.2016.11.013</a>
  apa: Tarlungeanu, D.-C., Deliu, E., Dotter, C., Kara, M., Janiesch, P., Scalise,
    M., … Novarino, G. (2016). Impaired amino acid transport at the blood brain barrier
    is a cause of autism spectrum disorder. <i>Cell</i>. Cell Press. <a href="https://doi.org/10.1016/j.cell.2016.11.013">https://doi.org/10.1016/j.cell.2016.11.013</a>
  chicago: Tarlungeanu, Dora-Clara, Elena Deliu, Christoph Dotter, Majdi Kara, Philipp
    Janiesch, Mariafrancesca Scalise, Michele Galluccio, et al. “Impaired Amino Acid
    Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.”
    <i>Cell</i>. Cell Press, 2016. <a href="https://doi.org/10.1016/j.cell.2016.11.013">https://doi.org/10.1016/j.cell.2016.11.013</a>.
  ieee: D.-C. Tarlungeanu <i>et al.</i>, “Impaired amino acid transport at the blood
    brain barrier is a cause of autism spectrum disorder,” <i>Cell</i>, vol. 167,
    no. 6. Cell Press, pp. 1481–1494, 2016.
  ista: Tarlungeanu D-C, Deliu E, Dotter C, Kara M, Janiesch P, Scalise M, Galluccio
    M, Tesulov M, Morelli E, Sönmez F, Bilgüvar K, Ohgaki R, Kanai Y, Johansen A,
    Esharif S, Ben Omran T, Topcu M, Schlessinger A, Indiveri C, Duncan K, Caglayan
    A, Günel M, Gleeson J, Novarino G. 2016. Impaired amino acid transport at the
    blood brain barrier is a cause of autism spectrum disorder. Cell. 167(6), 1481–1494.
  mla: Tarlungeanu, Dora-Clara, et al. “Impaired Amino Acid Transport at the Blood
    Brain Barrier Is a Cause of Autism Spectrum Disorder.” <i>Cell</i>, vol. 167,
    no. 6, Cell Press, 2016, pp. 1481–94, doi:<a href="https://doi.org/10.1016/j.cell.2016.11.013">10.1016/j.cell.2016.11.013</a>.
  short: D.-C. Tarlungeanu, E. Deliu, C. Dotter, M. Kara, P. Janiesch, M. Scalise,
    M. Galluccio, M. Tesulov, E. Morelli, F. Sönmez, K. Bilgüvar, R. Ohgaki, Y. Kanai,
    A. Johansen, S. Esharif, T. Ben Omran, M. Topcu, A. Schlessinger, C. Indiveri,
    K. Duncan, A. Caglayan, M. Günel, J. Gleeson, G. Novarino, Cell 167 (2016) 1481–1494.
date_created: 2018-12-11T11:50:35Z
date_published: 2016-12-01T00:00:00Z
date_updated: 2024-03-25T23:30:07Z
day: '01'
ddc:
- '576'
- '616'
department:
- _id: GaNo
doi: 10.1016/j.cell.2016.11.013
file:
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  file_name: IST-2017-771-v1+1_Tarlungeanu_et_al._Final_edited.pdf
  file_size: 73907957
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file_date_updated: 2020-07-14T12:44:37Z
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intvolume: '       167'
issue: '6'
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oa: 1
oa_version: Submitted Version
page: 1481 - 1494
project:
- _id: 25473368-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: F03523
  name: Transmembrane Transporters in Health and Disease
publication: Cell
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publisher: Cell Press
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quality_controlled: '1'
related_material:
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    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Impaired amino acid transport at the blood brain barrier is a cause of autism
  spectrum disorder
type: journal_article
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
volume: 167
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...