Please use this identifier to cite or link to this item:
http://hdl.handle.net/1942/30332
Title: | Sex-regulated gene dosage effect of PPARα on synaptic plasticity | Authors: | Pierrot, Nathalie Ris, Laurence STANCU, Ilie Cosmin Doshina, Anna Ribeiro, Floriane Tyteca, Donatienne Baugé, Eric Lalloyer, Fanny Malong, Liza Schakman, Olivier Leroy, Karelle Kienlen-Campard, Pascal Gailly, Philippe Brion, Jean-Pierre DEWACHTER, Ilse Staels, Bart Octave, Jean-Noël |
Issue Date: | 2019 | Publisher: | LIFE SCIENCE ALLIANCE LLC | Source: | Life science alliance, 2 (2) (Art N° ARTN e201800262) | Abstract: | Mechanisms driving cognitive improvements following nuclear receptor activation are poorly understood. The peroxisome proliferator-activated nuclear receptor alpha (PPARα) forms heterodimers with the nuclear retinoid X receptor (RXR). We report that PPARα mediates the improvement of hippocampal synaptic plasticity upon RXR activation in a transgenic mouse model with cognitive deficits. This improvement results from an increase in GluA1 subunit expression of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, eliciting an AMPA response at the excitatory synapses. Associated with a two times higher PPARα expression in males than in females, we show that male, but not female, PPARα null mutants display impaired hippocampal long-term potentiation. Moreover, PPARα knockdown in the hippocampus of cognition-impaired mice compromises the beneficial effects of RXR activation on synaptic plasticity only in males. Furthermore, selective PPARα activation with pemafibrate improves synaptic plasticity in male cognition-impaired mice, but not in females. We conclude that striking sex differences in hippocampal synaptic plasticity are observed in mice, related to differences in PPARα expression levels. | Document URI: | http://hdl.handle.net/1942/30332 | DOI: | 10.26508/lsa.201800262 | ISI #: | 000466600900015 | Rights: | 2019 Pierrot et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/ licenses/by/4.0/). | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2020 |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
e201800262.full.pdf | Published version | 2.63 MB | Adobe PDF | View/Open |
SCOPUSTM
Citations
1
checked on Sep 5, 2020
WEB OF SCIENCETM
Citations
18
checked on Sep 27, 2024
Page view(s)
44
checked on Sep 7, 2022
Download(s)
18
checked on Sep 7, 2022
Google ScholarTM
Check
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.