schliessen

Filtern

 

Bibliotheken

The within-subject application of diffusion tensor MRI and CLARITY reveals brain structural changes in Nrxn2 deletion mice

Background: Of the many genetic mutations known to increase the risk of autism spectrum disorder, a large proportion cluster upon synaptic proteins. One such family of presynaptic proteins are the neurexins (NRXN), and recent genetic and mouse evidence has suggested a causative role for NRXN2 in gen... Full description

Journal Title: BioRxiv Feb 19, 2019
Main Author: Pervolaraki, Eleftheria
Other Authors: Tyson, Adam , Pibiri, Francesca , Poulter, Steven , Reichelt, Amy , Rodgers, Robert , Clapcote, Steven , Lever, Colin , Andreae, Laura , Dachtler, James
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: © ProQuest LLC All rights reserved
ID: DOI: 10.1101/300806
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: proquest2071226560
title: The within-subject application of diffusion tensor MRI and CLARITY reveals brain structural changes in Nrxn2 deletion mice
format: Article
creator:
  • Pervolaraki, Eleftheria
  • Tyson, Adam
  • Pibiri, Francesca
  • Poulter, Steven
  • Reichelt, Amy
  • Rodgers, Robert
  • Clapcote, Steven
  • Lever, Colin
  • Andreae, Laura
  • Dachtler, James
subjects:
  • Diffusion Coefficient
  • Cell Density
  • Amygdala
  • Magnetic Resonance Imaging
  • Anisotropy
  • Autism
  • Gene Deletion
  • Mutation
  • Clonal Deletion
  • Autism
  • Axons
  • Connectivity
  • Statistical Analysis
  • Neuroimaging
  • Mutation
  • Cortex (Cingulate)
  • Neural Networks
ispartof: BioRxiv, Feb 19, 2019
description: Background: Of the many genetic mutations known to increase the risk of autism spectrum disorder, a large proportion cluster upon synaptic proteins. One such family of presynaptic proteins are the neurexins (NRXN), and recent genetic and mouse evidence has suggested a causative role for NRXN2 in generating altered social behaviours. Autism has been conceptualised as a disorder of atypical connectivity, yet how single-gene mutations affect such connectivity remains under-explored. To attempt to address this, we have developed a quantitative analysis of microstructure and structural connectivity leveraging diffusion tensor MRI (DTI) with high-resolution 3D imaging in optically cleared (CLARITY) brain tissue in the same mouse, applied here to the Nrxn2α knockout (KO) model. Methods: Fixed brains of Nrxn2α KO mice underwent DTI using 9.4T MRI, and diffusion properties of socially-relevant brain regions were quantified. The same tissue was then subjected to CLARITY to immunolabel axons and cell bodies, which were also quantified. Results: DTI revealed increases in fractional anisotropy in the amygdala (including the basolateral nuclei), the anterior cingulate cortex, the orbitofrontal cortex and the hippocampus. Axial diffusivity of the anterior cingulate cortex and orbitofrontal cortex was significantly increased in Nrxn2α KO mice, as were tracts between the amygdala and the orbitofrontal cortex. Using CLARITY, we find significantly altered axonal orientation in the amygdala, orbitofrontal cortex and the anterior cingulate cortex, which was unrelated to cell density. Conclusions: Our findings demonstrate that deleting a single neurexin gene (Nrxn2α) induces atypical structural connectivity within socially-relevant brain regions. More generally, our combined within-subject DTI and CLARITY approach presents a new, more sensitive method of revealing hitherto undetectable differences in the autistic brain. Footnotes * We have added new text in Supp. Materials to more fully explain the methodology of CLARITY. We have also added more depth to our introduction, results and discussion. We have also improved the narrative of the manuscript and have included observed power of statistically significant results.
language: eng
source: © ProQuest LLC All rights reserved
identifier: DOI: 10.1101/300806
fulltext: fulltext_linktorsrc
url: Link


@attributes
ID1538623233
RANK0.07
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
LOCALfalse
PrimoNMBib
record
control
sourcerecordid2071226560
sourceidproquest
recordidTN_proquest2071226560
sourcesystemOther
pqid2071226560
display
typearticle
titleThe within-subject application of diffusion tensor MRI and CLARITY reveals brain structural changes in Nrxn2 deletion mice
creatorPervolaraki, Eleftheria ; Tyson, Adam ; Pibiri, Francesca ; Poulter, Steven ; Reichelt, Amy ; Rodgers, Robert ; Clapcote, Steven ; Lever, Colin ; Andreae, Laura ; Dachtler, James
contributorDachtler, James (pacrepositoryorg)
ispartofBioRxiv, Feb 19, 2019
identifierDOI: 10.1101/300806
subjectDiffusion Coefficient ; Cell Density ; Amygdala ; Magnetic Resonance Imaging ; Anisotropy ; Autism ; Gene Deletion ; Mutation ; Clonal Deletion ; Autism ; Axons ; Connectivity ; Statistical Analysis ; Neuroimaging ; Mutation ; Cortex (Cingulate) ; Neural Networks
descriptionBackground: Of the many genetic mutations known to increase the risk of autism spectrum disorder, a large proportion cluster upon synaptic proteins. One such family of presynaptic proteins are the neurexins (NRXN), and recent genetic and mouse evidence has suggested a causative role for NRXN2 in generating altered social behaviours. Autism has been conceptualised as a disorder of atypical connectivity, yet how single-gene mutations affect such connectivity remains under-explored. To attempt to address this, we have developed a quantitative analysis of microstructure and structural connectivity leveraging diffusion tensor MRI (DTI) with high-resolution 3D imaging in optically cleared (CLARITY) brain tissue in the same mouse, applied here to the Nrxn2α knockout (KO) model. Methods: Fixed brains of Nrxn2α KO mice underwent DTI using 9.4T MRI, and diffusion properties of socially-relevant brain regions were quantified. The same tissue was then subjected to CLARITY to immunolabel axons and cell bodies, which were also quantified. Results: DTI revealed increases in fractional anisotropy in the amygdala (including the basolateral nuclei), the anterior cingulate cortex, the orbitofrontal cortex and the hippocampus. Axial diffusivity of the anterior cingulate cortex and orbitofrontal cortex was significantly increased in Nrxn2α KO mice, as were tracts between the amygdala and the orbitofrontal cortex. Using CLARITY, we find significantly altered axonal orientation in the amygdala, orbitofrontal cortex and the anterior cingulate cortex, which was unrelated to cell density. Conclusions: Our findings demonstrate that deleting a single neurexin gene (Nrxn2α) induces atypical structural connectivity within socially-relevant brain regions. More generally, our combined within-subject DTI and CLARITY approach presents a new, more sensitive method of revealing hitherto undetectable differences in the autistic brain. Footnotes * We have added new text in Supp. Materials to more fully explain the methodology of CLARITY. We have also added more depth to our introduction, results and discussion. We have also improved the narrative of the manuscript and have included observed power of statistically significant results.
languageeng
source
0© ProQuest LLC All rights reserved
1Biological Science Database
2Publicly Available Content Database
3ProQuest Biological Science Collection
4ProQuest Natural Science Collection
5ProQuest SciTech Collection
6Natural Science Collection
7ProQuest Central (new)
8ProQuest Central K-12
9ProQuest Central Korea
10SciTech Premium Collection
11ProQuest Central Essentials
oafree_for_read
links
openurl$$Topenurl_article
openurlfulltext$$Topenurlfull_article
linktorsrc$$Uhttp://search.proquest.com/docview/2071226560/?pq-origsite=primo$$EView_record_in_ProQuest_(subscribers_only)
search
creatorcontrib
0Pervolaraki, Eleftheria
1Tyson, Adam
2Pibiri, Francesca
3Poulter, Steven
4Reichelt, Amy
5Rodgers, Robert
6Clapcote, Steven
7Lever, Colin
8Andreae, Laura
9Dachtler, James
titleThe within-subject application of diffusion tensor MRI and CLARITY reveals brain structural changes in Nrxn2 deletion mice
descriptionBackground: Of the many genetic mutations known to increase the risk of autism spectrum disorder, a large proportion cluster upon synaptic proteins. One such family of presynaptic proteins are the neurexins (NRXN), and recent genetic and mouse evidence has suggested a causative role for NRXN2 in generating altered social behaviours. Autism has been conceptualised as a disorder of atypical connectivity, yet how single-gene mutations affect such connectivity remains under-explored. To attempt to address this, we have developed a quantitative analysis of microstructure and structural connectivity leveraging diffusion tensor MRI (DTI) with high-resolution 3D imaging in optically cleared (CLARITY) brain tissue in the same mouse, applied here to the Nrxn2α knockout (KO) model. Methods: Fixed brains of Nrxn2α KO mice underwent DTI using 9.4T MRI, and diffusion properties of socially-relevant brain regions were quantified. The same tissue was then subjected to CLARITY to immunolabel axons and cell bodies, which were also quantified. Results: DTI revealed increases in fractional anisotropy in the amygdala (including the basolateral nuclei), the anterior cingulate cortex, the orbitofrontal cortex and the hippocampus. Axial diffusivity of the anterior cingulate cortex and orbitofrontal cortex was significantly increased in Nrxn2α KO mice, as were tracts between the amygdala and the orbitofrontal cortex. Using CLARITY, we find significantly altered axonal orientation in the amygdala, orbitofrontal cortex and the anterior cingulate cortex, which was unrelated to cell density. Conclusions: Our findings demonstrate that deleting a single neurexin gene (Nrxn2α) induces atypical structural connectivity within socially-relevant brain regions. More generally, our combined within-subject DTI and CLARITY approach presents a new, more sensitive method of revealing hitherto undetectable differences in the autistic brain. Footnotes * We have added new text in Supp. Materials to more fully explain the methodology of CLARITY. We have also added more depth to our introduction, results and discussion. We have also improved the narrative of the manuscript and have included observed power of statistically significant results.
subject
0Diffusion Coefficient
1Cell Density
2Amygdala
3Magnetic Resonance Imaging
4Anisotropy
5Autism
6Gene Deletion
7Mutation
8Clonal Deletion
9Axons
10Connectivity
11Statistical Analysis
12Neuroimaging
13Cortex (Cingulate)
14Neural Networks
general
0English
1Cold Spring Harbor Laboratory Press
210.1101/300806
3Biological Science Database
4Publicly Available Content Database
5ProQuest Biological Science Collection
6ProQuest Natural Science Collection
7ProQuest SciTech Collection
8Natural Science Collection
9ProQuest Central (new)
10ProQuest Central K-12
11ProQuest Central Korea
12SciTech Premium Collection
13ProQuest Central Essentials
sourceidproquest
recordidproquest2071226560
rsrctypearticle
creationdate2019
addtitleBioRxiv
searchscope
01007856
11008875
21008886
31009127
41009240
510000038
610000050
710000120
810000238
910000253
1010000255
1110000256
1210000257
1310000258
1410000260
1510000268
1610000281
1710000348
1810000360
19proquest
scope
01007856
11008875
21008886
31009127
41009240
510000038
610000050
710000120
810000238
910000253
1010000255
1110000256
1210000257
1310000258
1410000260
1510000268
1610000281
1710000348
1810000360
19proquest
lsr43
01007856true
11008875true
21008886true
31009127true
41009240true
510000038true
610000050true
710000120true
810000238true
910000253true
1010000255true
1110000256true
1210000257true
1310000258true
1410000260true
1510000268true
1610000281true
1710000348true
1810000360true
startdate20190219
enddate20190219
sort
titleThe within-subject application of diffusion tensor MRI and CLARITY reveals brain structural changes in Nrxn2 deletion mice
authorPervolaraki, Eleftheria ; Tyson, Adam ; Pibiri, Francesca ; Poulter, Steven ; Reichelt, Amy ; Rodgers, Robert ; Clapcote, Steven ; Lever, Colin ; Andreae, Laura ; Dachtler, James
creationdate20190219
lso0120190219
facets
frbrgroupid5457601498112554669
frbrtype6
newrecords20180917
languageeng
creationdate2019
topic
0Diffusion Coefficient
1Cell Density
2Amygdala
3Magnetic Resonance Imaging
4Anisotropy
5Autism
6Gene Deletion
7Mutation
8Clonal Deletion
9Axons
10Connectivity
11Statistical Analysis
12Neuroimaging
13Cortex (Cingulate)
14Neural Networks
collection
0Biological Science Database
1Publicly Available Content Database
2ProQuest Biological Science Collection
3ProQuest Natural Science Collection
4ProQuest SciTech Collection
5Natural Science Collection
6ProQuest Central (new)
7ProQuest Central K-12
8ProQuest Central Korea
9SciTech Premium Collection
10ProQuest Central Essentials
prefilterarticles
rsrctypearticles
creatorcontrib
0Pervolaraki, Eleftheria
1Tyson, Adam
2Pibiri, Francesca
3Poulter, Steven
4Reichelt, Amy
5Rodgers, Robert
6Clapcote, Steven
7Lever, Colin
8Andreae, Laura
9Dachtler, James
jtitleBioRxiv
delivery
delcategoryRemote Search Resource
fulltextfulltext_linktorsrc
addata
aulast
0Pervolaraki
1Tyson
2Pibiri
3Poulter
4Reichelt
5Rodgers
6Clapcote
7Lever
8Andreae
9Dachtler
aufirst
0Eleftheria
1Adam
2Francesca
3Steven
4Amy
5Robert
6Colin
7Laura
8James
au
0Pervolaraki, Eleftheria
1Tyson, Adam
2Pibiri, Francesca
3Poulter, Steven
4Reichelt, Amy
5Rodgers, Robert
6Clapcote, Steven
7Lever, Colin
8Andreae, Laura
9Dachtler, James
atitleThe within-subject application of diffusion tensor MRI and CLARITY reveals brain structural changes in Nrxn2 deletion mice
jtitleBioRxiv
risdate20190219
formatjournal
genrearticle
ristypeJOUR
abstractBackground: Of the many genetic mutations known to increase the risk of autism spectrum disorder, a large proportion cluster upon synaptic proteins. One such family of presynaptic proteins are the neurexins (NRXN), and recent genetic and mouse evidence has suggested a causative role for NRXN2 in generating altered social behaviours. Autism has been conceptualised as a disorder of atypical connectivity, yet how single-gene mutations affect such connectivity remains under-explored. To attempt to address this, we have developed a quantitative analysis of microstructure and structural connectivity leveraging diffusion tensor MRI (DTI) with high-resolution 3D imaging in optically cleared (CLARITY) brain tissue in the same mouse, applied here to the Nrxn2α knockout (KO) model. Methods: Fixed brains of Nrxn2α KO mice underwent DTI using 9.4T MRI, and diffusion properties of socially-relevant brain regions were quantified. The same tissue was then subjected to CLARITY to immunolabel axons and cell bodies, which were also quantified. Results: DTI revealed increases in fractional anisotropy in the amygdala (including the basolateral nuclei), the anterior cingulate cortex, the orbitofrontal cortex and the hippocampus. Axial diffusivity of the anterior cingulate cortex and orbitofrontal cortex was significantly increased in Nrxn2α KO mice, as were tracts between the amygdala and the orbitofrontal cortex. Using CLARITY, we find significantly altered axonal orientation in the amygdala, orbitofrontal cortex and the anterior cingulate cortex, which was unrelated to cell density. Conclusions: Our findings demonstrate that deleting a single neurexin gene (Nrxn2α) induces atypical structural connectivity within socially-relevant brain regions. More generally, our combined within-subject DTI and CLARITY approach presents a new, more sensitive method of revealing hitherto undetectable differences in the autistic brain. Footnotes * We have added new text in Supp. Materials to more fully explain the methodology of CLARITY. We have also added more depth to our introduction, results and discussion. We have also improved the narrative of the manuscript and have included observed power of statistically significant results.
copCold Spring Harbor
pubCold Spring Harbor Laboratory Press
doi10.1101/300806
urlhttp://search.proquest.com/docview/2071226560/
oafree_for_read
date2019-02-19