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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Amyloid beta peptide directly impairs pineal gland melatonin synthesis and melatonin receptor signaling through the ERK pathway

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Cecon, Erika [1, 2, 3, 4] ; Chen, Min [1, 2, 3] ; Marcola, Marina [4] ; Fernandes, Pedro A. C. [4] ; Jockers, Ralf [1, 2, 3] ; Markus, Regina P. [4]
Total Authors: 6
[1] INSERM, Inst Cochin, U1016, Paris - France
[2] CNRS, Unite Mixte Rech 8104, Paris - France
[3] Univ Paris 05, Sorbonne Paris Cite, Paris - France
[4] Univ Sao Paulo, Inst Biosci, Chronopharmacol Lab, Sao Paulo - Brazil
Total Affiliations: 4
Document type: Journal article
Source: FASEB JOURNAL; v. 29, n. 6, p. 2566-2582, JUN 2015.
Web of Science Citations: 25

Melatonin is the hormone produced by the pineal gland known to regulate physiologic rhythms and to display immunomodulatory and neuroprotective properties. It has been reported that Alzheimer disease patients show impaired melatonin production and altered expression of the 2 G protein-coupled melatonin receptors (MTRs), MT1 and MT2, but the underlying mechanisms are not known. Here we evaluated whether this dysfunction of the melatonergic system is directly caused by amyloid beta peptides (A beta(1-40) and A beta(1-42)). A beta treatment of rat pineal glands elicited an inflammatory response within the gland, evidenced by the up-regulation of 52 inflammatory genes, and decreased the production of melatonin up to 75% compared to vehicle-treated glands. Blocking NF-kappa B activity prevented this effect. Exposure of HEK293 cells stably expressing recombinant MT1 or MT2 receptors to A beta lead to a 40% reduction in {[}I-125] iodomelatonin binding to MT1. ERK1/2 activation triggered by MTRs, but not by the beta(2)-adrenergic receptor, was markedly impaired by A beta in HEK293 transfected cells, as well as in primary rat endothelial cells expressing endogenous MTRs. Our data reveal the melatonergic system as a new target of A beta, opening new perspectives to Alzheimer disease diagnosis and therapeutic intervention. (AU)

FAPESP's process: 09/17923-9 - Pineal gland as a target for B-amyloid peptide
Grantee:Erika Cecon
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 13/13691-1 - Immune-pineal axis: time-niology integrated to surveillance and defense
Grantee:Regina Pekelmann Markus
Support type: Research Projects - Thematic Grants
FAPESP's process: 07/07871-6 - Imune-pineal Axis: injury shifts melatonin production from endocrine to paracrine
Grantee:Regina Pekelmann Markus
Support type: Research Projects - Thematic Grants
FAPESP's process: 11/01304-8 - Effect of melatonin on the subpopulations of cultured endothilial cells
Grantee:Marina Marçola Pereira de Freitas
Support type: Scholarships in Brazil - Doctorate