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dc.contributor.author
Durand, Daniela Elizabeth
dc.contributor.author
Carniglia, Lila
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Beauquis, Juan
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Caruso, Carla Mariana
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Saravia, Flavia Eugenia
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Lasaga, Mercedes Isabel
dc.date.available
2016-07-19T19:12:08Z
dc.date.issued
2013-11
dc.identifier.citation
Durand, Daniela Elizabeth; Carniglia, Lila; Beauquis, Juan; Caruso, Carla Mariana; Saravia, Flavia Eugenia; et al.; Astroglial mGlu3 receptors promote alpha-secretase-mediated amyloid precursor protein cleavage; Elsevier; Neuropharmacology; 79; 11-2013; 180-189
dc.identifier.issn
0028-3908
dc.identifier.uri
http://hdl.handle.net/11336/6590
dc.description.abstract
Amyloid precursor protein (APP) shedding yields the Alzheimer´s disease (AD)-related peptide amyloid B (AB) through beta- and gamma-secretase cleavage. Alternatively, alpha-secretase cleavage generates a soluble and neuroprotective fragment (sAPPalpha) while precludes the production of AB. Although metabotropic glutamate (mGlu) receptors were associated with induction of sAPPalpha production in astrocytes, there was no further evidence regarding the specific subtype receptor or the mechanisms involved in this action. In the present study, we used the dual mGlu2/3 receptor agonist LY379268, which in pure astrocyte cultures selectively activates mGlu3 receptor subtype since mGlu2 receptor subtype is not expressed by these cells. We showed that LY379268 incremented sAPPalpha release from cultured astrocytes by inducing alpha-secretases expression, whereas it decreased beta-secretase levels. LY379268-induced increase of PPAR-gamma levels could be involved in the effect of the agonist on sAPPalpha release. Using the PDAPP-J20 murine model of AD we described a strong reduction in mGlu2/3 receptor expression in the hippocampus of 5- and 14-month-old transgenic mice compared to control littermates. Moreover, mGlu3 receptor expression is also decreased specifically in hippocampal astrocytes of these transgenic animals as a function of age. Therefore, diminished levels of hippocampal mGlu3 receptors might have implications in the development of the disease in these transgenic mice considering the anti-amyloidogenic action of mGlu3 receptors in astrocytes.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Astrocytes
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Metabotropic Glutamate Receptor 3
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Amyloid Precursor Protein
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Secretases
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Neurociencias
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Astroglial mGlu3 receptors promote alpha-secretase-mediated amyloid precursor protein cleavage
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-05-10T13:47:38Z
dc.journal.volume
79
dc.journal.pagination
180-189
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Durand, Daniela Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
dc.description.fil
Fil: Carniglia, Lila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
dc.description.fil
Fil: Beauquis, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
dc.description.fil
Fil: Caruso, Carla Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
dc.description.fil
Fil: Saravia, Flavia Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
dc.description.fil
Fil: Lasaga, Mercedes Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
dc.journal.title
Neuropharmacology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0028390813005613
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info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neuropharm.2013.11.015
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info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.neuropharm.2013.11.015