Cortical brain injury causes retrograde degeneration of afferent basal forebrain cholinergic neurons via the p75NTR

Autores
Dasgupta, Srestha; Montroull, Laura Ester; Pandya, Mansi; Zanin, Juan P.; Wang, Wei; Wu, Zhuhao; Friedman, Wilma J
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Traumatic brain injury elicits neuronal loss at the site of injury and progressive neuronal loss in the penumbra. However, the consequences of TBI on afferent neurons projecting to the injured tissue from distal locations is unknown. Basal forebrain cholinergic neurons (BFCNs) extend long projections to multiple brain regions including the cortex, regulate many cognitive functions and are compromised in numerous neurodegenerative disorders. To determine the consequence of cortical injury on these afferent neurons, we used the Fluid Percussion Injury (FPI) model of traumatic brain injury and assessed the effects on BFCN survival and axon integrity in male and female mice. Survival or death of BF neurons can be regulated by neurotrophins or proneurotrophins, respectively. The injury elicited an induction of proNGF and proBDNF in the cortex, and a loss of BFCNs ipsilateral to the injury compared to sham uninjured mice. p75NTR knockout mice did not show loss of BFCN neurons, indicating a retrograde degenerative effect of the cortical injury on the afferent BFCNs mediated through p75NTR. In contrast, locus coeruleus (LC) neurons which also project throughout the cortex were unaffected by the injury, suggesting specificity in retrograde degeneration after cortical TBI. Proneurotrophins (proNTs) provided directly to basal forebrain axons in microfluidic cultures triggered retrograde axonal degeneration and cell death, which did not occur in the absence of p75NTR. This study shows that after traumatic brain injury, proNTs induced in the injured cortex promote BFCN axonal degeneration and retrograde neuron loss through p75NTR.
Fil: Dasgupta, Srestha. Department Of Biological Sciences; Estados Unidos. Rutgers University; Estados Unidos
Fil: Montroull, Laura Ester. Department Of Biological Sciences; Estados Unidos. Rutgers University; Estados Unidos. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Centro de Biología Celular y Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pandya, Mansi. Rutgers University; Estados Unidos. Department Of Biological Sciences; Estados Unidos
Fil: Zanin, Juan P.. Department Of Biological Sciences; Estados Unidos. Rutgers University; Estados Unidos
Fil: Wang, Wei. Weill Cornell Medical College; Estados Unidos
Fil: Wu, Zhuhao. Weill Cornell Medical College; Estados Unidos
Fil: Friedman, Wilma J. Rutgers University; Estados Unidos. Department Of Biological Sciences; Estados Unidos
Materia
AXON DEGENERATION
BASAL FOREBRAIN NEURONS
P75NTR
PRONEUROTROPHINS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/230578
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/230578
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Cortical brain injury causes retrograde degeneration of afferent basal forebrain cholinergic neurons via the p75NTRDasgupta, SresthaMontroull, Laura EsterPandya, MansiZanin, Juan P.Wang, WeiWu, ZhuhaoFriedman, Wilma JAXON DEGENERATIONBASAL FOREBRAIN NEURONSP75NTRPRONEUROTROPHINShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Traumatic brain injury elicits neuronal loss at the site of injury and progressive neuronal loss in the penumbra. However, the consequences of TBI on afferent neurons projecting to the injured tissue from distal locations is unknown. Basal forebrain cholinergic neurons (BFCNs) extend long projections to multiple brain regions including the cortex, regulate many cognitive functions and are compromised in numerous neurodegenerative disorders. To determine the consequence of cortical injury on these afferent neurons, we used the Fluid Percussion Injury (FPI) model of traumatic brain injury and assessed the effects on BFCN survival and axon integrity in male and female mice. Survival or death of BF neurons can be regulated by neurotrophins or proneurotrophins, respectively. The injury elicited an induction of proNGF and proBDNF in the cortex, and a loss of BFCNs ipsilateral to the injury compared to sham uninjured mice. p75NTR knockout mice did not show loss of BFCN neurons, indicating a retrograde degenerative effect of the cortical injury on the afferent BFCNs mediated through p75NTR. In contrast, locus coeruleus (LC) neurons which also project throughout the cortex were unaffected by the injury, suggesting specificity in retrograde degeneration after cortical TBI. Proneurotrophins (proNTs) provided directly to basal forebrain axons in microfluidic cultures triggered retrograde axonal degeneration and cell death, which did not occur in the absence of p75NTR. This study shows that after traumatic brain injury, proNTs induced in the injured cortex promote BFCN axonal degeneration and retrograde neuron loss through p75NTR.Fil: Dasgupta, Srestha. Department Of Biological Sciences; Estados Unidos. Rutgers University; Estados UnidosFil: Montroull, Laura Ester. Department Of Biological Sciences; Estados Unidos. Rutgers University; Estados Unidos. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Centro de Biología Celular y Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pandya, Mansi. Rutgers University; Estados Unidos. Department Of Biological Sciences; Estados UnidosFil: Zanin, Juan P.. Department Of Biological Sciences; Estados Unidos. Rutgers University; Estados UnidosFil: Wang, Wei. Weill Cornell Medical College; Estados UnidosFil: Wu, Zhuhao. Weill Cornell Medical College; Estados UnidosFil: Friedman, Wilma J. Rutgers University; Estados Unidos. Department Of Biological Sciences; Estados UnidosSociety for Neuroscience2023-08-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/230578Dasgupta, Srestha; Montroull, Laura Ester; Pandya, Mansi; Zanin, Juan P.; Wang, Wei; et al.; Cortical brain injury causes retrograde degeneration of afferent basal forebrain cholinergic neurons via the p75NTR; Society for Neuroscience; eNeuro; 10; 8; 9-8-2023; 1-382373-2822CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.eneuro.org/lookup/doi/10.1523/ENEURO.0067-23.2023info:eu-repo/semantics/altIdentifier/doi/10.1523/ENEURO.0067-23.2023info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:44:30Zoai:ri.conicet.gov.ar:11336/230578instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:44:30.992CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cortical brain injury causes retrograde degeneration of afferent basal forebrain cholinergic neurons via the p75NTR
title Cortical brain injury causes retrograde degeneration of afferent basal forebrain cholinergic neurons via the p75NTR
spellingShingle Cortical brain injury causes retrograde degeneration of afferent basal forebrain cholinergic neurons via the p75NTR
Dasgupta, Srestha
AXON DEGENERATION
BASAL FOREBRAIN NEURONS
P75NTR
PRONEUROTROPHINS
title_short Cortical brain injury causes retrograde degeneration of afferent basal forebrain cholinergic neurons via the p75NTR
title_full Cortical brain injury causes retrograde degeneration of afferent basal forebrain cholinergic neurons via the p75NTR
title_fullStr Cortical brain injury causes retrograde degeneration of afferent basal forebrain cholinergic neurons via the p75NTR
title_full_unstemmed Cortical brain injury causes retrograde degeneration of afferent basal forebrain cholinergic neurons via the p75NTR
title_sort Cortical brain injury causes retrograde degeneration of afferent basal forebrain cholinergic neurons via the p75NTR
dc.creator.none.fl_str_mv Dasgupta, Srestha
Montroull, Laura Ester
Pandya, Mansi
Zanin, Juan P.
Wang, Wei
Wu, Zhuhao
Friedman, Wilma J
author Dasgupta, Srestha
author_facet Dasgupta, Srestha
Montroull, Laura Ester
Pandya, Mansi
Zanin, Juan P.
Wang, Wei
Wu, Zhuhao
Friedman, Wilma J
author_role author
author2 Montroull, Laura Ester
Pandya, Mansi
Zanin, Juan P.
Wang, Wei
Wu, Zhuhao
Friedman, Wilma J
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv AXON DEGENERATION
BASAL FOREBRAIN NEURONS
P75NTR
PRONEUROTROPHINS
topic AXON DEGENERATION
BASAL FOREBRAIN NEURONS
P75NTR
PRONEUROTROPHINS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Traumatic brain injury elicits neuronal loss at the site of injury and progressive neuronal loss in the penumbra. However, the consequences of TBI on afferent neurons projecting to the injured tissue from distal locations is unknown. Basal forebrain cholinergic neurons (BFCNs) extend long projections to multiple brain regions including the cortex, regulate many cognitive functions and are compromised in numerous neurodegenerative disorders. To determine the consequence of cortical injury on these afferent neurons, we used the Fluid Percussion Injury (FPI) model of traumatic brain injury and assessed the effects on BFCN survival and axon integrity in male and female mice. Survival or death of BF neurons can be regulated by neurotrophins or proneurotrophins, respectively. The injury elicited an induction of proNGF and proBDNF in the cortex, and a loss of BFCNs ipsilateral to the injury compared to sham uninjured mice. p75NTR knockout mice did not show loss of BFCN neurons, indicating a retrograde degenerative effect of the cortical injury on the afferent BFCNs mediated through p75NTR. In contrast, locus coeruleus (LC) neurons which also project throughout the cortex were unaffected by the injury, suggesting specificity in retrograde degeneration after cortical TBI. Proneurotrophins (proNTs) provided directly to basal forebrain axons in microfluidic cultures triggered retrograde axonal degeneration and cell death, which did not occur in the absence of p75NTR. This study shows that after traumatic brain injury, proNTs induced in the injured cortex promote BFCN axonal degeneration and retrograde neuron loss through p75NTR.
Fil: Dasgupta, Srestha. Department Of Biological Sciences; Estados Unidos. Rutgers University; Estados Unidos
Fil: Montroull, Laura Ester. Department Of Biological Sciences; Estados Unidos. Rutgers University; Estados Unidos. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Centro de Biología Celular y Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pandya, Mansi. Rutgers University; Estados Unidos. Department Of Biological Sciences; Estados Unidos
Fil: Zanin, Juan P.. Department Of Biological Sciences; Estados Unidos. Rutgers University; Estados Unidos
Fil: Wang, Wei. Weill Cornell Medical College; Estados Unidos
Fil: Wu, Zhuhao. Weill Cornell Medical College; Estados Unidos
Fil: Friedman, Wilma J. Rutgers University; Estados Unidos. Department Of Biological Sciences; Estados Unidos
description Traumatic brain injury elicits neuronal loss at the site of injury and progressive neuronal loss in the penumbra. However, the consequences of TBI on afferent neurons projecting to the injured tissue from distal locations is unknown. Basal forebrain cholinergic neurons (BFCNs) extend long projections to multiple brain regions including the cortex, regulate many cognitive functions and are compromised in numerous neurodegenerative disorders. To determine the consequence of cortical injury on these afferent neurons, we used the Fluid Percussion Injury (FPI) model of traumatic brain injury and assessed the effects on BFCN survival and axon integrity in male and female mice. Survival or death of BF neurons can be regulated by neurotrophins or proneurotrophins, respectively. The injury elicited an induction of proNGF and proBDNF in the cortex, and a loss of BFCNs ipsilateral to the injury compared to sham uninjured mice. p75NTR knockout mice did not show loss of BFCN neurons, indicating a retrograde degenerative effect of the cortical injury on the afferent BFCNs mediated through p75NTR. In contrast, locus coeruleus (LC) neurons which also project throughout the cortex were unaffected by the injury, suggesting specificity in retrograde degeneration after cortical TBI. Proneurotrophins (proNTs) provided directly to basal forebrain axons in microfluidic cultures triggered retrograde axonal degeneration and cell death, which did not occur in the absence of p75NTR. This study shows that after traumatic brain injury, proNTs induced in the injured cortex promote BFCN axonal degeneration and retrograde neuron loss through p75NTR.
publishDate 2023
dc.date.none.fl_str_mv 2023-08-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/230578
Dasgupta, Srestha; Montroull, Laura Ester; Pandya, Mansi; Zanin, Juan P.; Wang, Wei; et al.; Cortical brain injury causes retrograde degeneration of afferent basal forebrain cholinergic neurons via the p75NTR; Society for Neuroscience; eNeuro; 10; 8; 9-8-2023; 1-38
2373-2822
CONICET Digital
CONICET
url http://hdl.handle.net/11336/230578
identifier_str_mv Dasgupta, Srestha; Montroull, Laura Ester; Pandya, Mansi; Zanin, Juan P.; Wang, Wei; et al.; Cortical brain injury causes retrograde degeneration of afferent basal forebrain cholinergic neurons via the p75NTR; Society for Neuroscience; eNeuro; 10; 8; 9-8-2023; 1-38
2373-2822
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.eneuro.org/lookup/doi/10.1523/ENEURO.0067-23.2023
info:eu-repo/semantics/altIdentifier/doi/10.1523/ENEURO.0067-23.2023
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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