Heparan sulfate: Resilience factor and therapeutic target for cocaine abuse

Abstract Substance abuse is a pressing problem with few therapeutic options. The identification of addiction resilience factors is a potential strategy to identify new mechanisms that can be targeted therapeutically. Heparan sulfate (HS) is a linear sulfated polysaccharide that is a component of the...

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Autores principales:	Jihuan Chen, Tomoya Kawamura, Manveen K. Sethi, Joseph Zaia, Vez Repunte-Canonigo, Pietro Paolo Sanna
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/00157ec978ec40258256ee7bb42d115d
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spelling	oai:doaj.org-article:00157ec978ec40258256ee7bb42d115d2021-12-02T15:05:25ZHeparan sulfate: Resilience factor and therapeutic target for cocaine abuse10.1038/s41598-017-13960-62045-2322https://doaj.org/article/00157ec978ec40258256ee7bb42d115d2017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-13960-6https://doaj.org/toc/2045-2322Abstract Substance abuse is a pressing problem with few therapeutic options. The identification of addiction resilience factors is a potential strategy to identify new mechanisms that can be targeted therapeutically. Heparan sulfate (HS) is a linear sulfated polysaccharide that is a component of the cell surface and extracellular matrix. Heparan sulfate modulates the activity and distribution of a set of negatively charged signaling peptides and proteins — known as the HS interactome — by acting as a co-receptor or alternative receptor for growth factors and other signaling peptides and sequestering and localizing them, among other actions. Here, we show that stimulants like cocaine and methamphetamine greatly increase HS content and sulfation levels in the lateral hypothalamus and that HS contributes to the regulation of cocaine seeking and taking. The ability of the HS-binding neuropeptide glial-cell-line-derived neurotrophic factor (GDNF) to increase cocaine intake was potentiated by a deletion that abolished its HS binding. The delivery of heparanase, the endo-β-D-glucuronidase that degrades HS, accelerated the acquisition of cocaine self-administration and promoted persistent responding during extinction. Altogether, these results indicate that HS is a resilience factor for cocaine abuse and a novel therapeutic target for the treatment of cocaine addiction.Jihuan ChenTomoya KawamuraManveen K. SethiJoseph ZaiaVez Repunte-CanonigoPietro Paolo SannaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-7 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jihuan Chen Tomoya Kawamura Manveen K. Sethi Joseph Zaia Vez Repunte-Canonigo Pietro Paolo Sanna Heparan sulfate: Resilience factor and therapeutic target for cocaine abuse
description	Abstract Substance abuse is a pressing problem with few therapeutic options. The identification of addiction resilience factors is a potential strategy to identify new mechanisms that can be targeted therapeutically. Heparan sulfate (HS) is a linear sulfated polysaccharide that is a component of the cell surface and extracellular matrix. Heparan sulfate modulates the activity and distribution of a set of negatively charged signaling peptides and proteins — known as the HS interactome — by acting as a co-receptor or alternative receptor for growth factors and other signaling peptides and sequestering and localizing them, among other actions. Here, we show that stimulants like cocaine and methamphetamine greatly increase HS content and sulfation levels in the lateral hypothalamus and that HS contributes to the regulation of cocaine seeking and taking. The ability of the HS-binding neuropeptide glial-cell-line-derived neurotrophic factor (GDNF) to increase cocaine intake was potentiated by a deletion that abolished its HS binding. The delivery of heparanase, the endo-β-D-glucuronidase that degrades HS, accelerated the acquisition of cocaine self-administration and promoted persistent responding during extinction. Altogether, these results indicate that HS is a resilience factor for cocaine abuse and a novel therapeutic target for the treatment of cocaine addiction.
format	article
author	Jihuan Chen Tomoya Kawamura Manveen K. Sethi Joseph Zaia Vez Repunte-Canonigo Pietro Paolo Sanna
author_facet	Jihuan Chen Tomoya Kawamura Manveen K. Sethi Joseph Zaia Vez Repunte-Canonigo Pietro Paolo Sanna
author_sort	Jihuan Chen
title	Heparan sulfate: Resilience factor and therapeutic target for cocaine abuse
title_short	Heparan sulfate: Resilience factor and therapeutic target for cocaine abuse
title_full	Heparan sulfate: Resilience factor and therapeutic target for cocaine abuse
title_fullStr	Heparan sulfate: Resilience factor and therapeutic target for cocaine abuse
title_full_unstemmed	Heparan sulfate: Resilience factor and therapeutic target for cocaine abuse
title_sort	heparan sulfate: resilience factor and therapeutic target for cocaine abuse
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/00157ec978ec40258256ee7bb42d115d
work_keys_str_mv	AT jihuanchen heparansulfateresiliencefactorandtherapeutictargetforcocaineabuse AT tomoyakawamura heparansulfateresiliencefactorandtherapeutictargetforcocaineabuse AT manveenksethi heparansulfateresiliencefactorandtherapeutictargetforcocaineabuse AT josephzaia heparansulfateresiliencefactorandtherapeutictargetforcocaineabuse AT vezrepuntecanonigo heparansulfateresiliencefactorandtherapeutictargetforcocaineabuse AT pietropaolosanna heparansulfateresiliencefactorandtherapeutictargetforcocaineabuse
_version_	1718388808264712192

Heparan sulfate: Resilience factor and therapeutic target for cocaine abuse

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