Improvement of synaptic plasticity by pharmacological activation of RXR nuclear receptors is PPARα dependent.
-
1
Université Catholique de Louvain, Belgium
-
2
Institute of Neuroscience, Catholic University of Leuven, Belgium
-
3
University of Mons, Belgium
-
4
University of Hasselt, Belgium
-
5
Free University of Brussels, Belgium
Retinoid X receptors (RXRs) are receptors belonging to the nuclear receptor superfamily of ligand-dependent transcription factors, containing different members including the Peroxisome Proliferator-Activated Receptors (PPARs). These receptors regulate the transcription of target genes through their binding with sequence-specific elements located in gene promoters. Activation of PPARs, which form obligatory heterodimers with RXRs, stimulates the transcription of specific target genes encoding proteins involved in numerous biological processes such as reproduction, development, adipogenesis, energy balance, lipid and glucose biosynthesis and inflammation. Interestingly, a potential involvement of RXRs in neuronal activity was recently proposed since activation of RXRs with specific ligands improves behaviour and cognition in various mouse models of neurodegenerative diseases. However, the mechanisms involved are not fully understood.
We have analyzed how bexarotene-mediated activation of RXRs nuclear receptors could modulate synaptic plasticity, an activity-dependent change in synaptic strength in the hippocampus considered as a prominent mechanism underlying learning and memory formation in the mammalian brain. By measuring long-term potentiation (LTP) at hippocampal CA3-CA1 synapses, we observed that activation of RXRs improved hippocampal synaptic plasticity in a transgenic mouse model with cognitive deficits by specifically increasing the expression of the GluA1 subunit of the AMPA receptors. This upregulation of GluA1 expression together with improvement of hippocampal synaptic plasticity induced by activation of RXRs were completely abolished in the absence of PPARalpha. These results indicate that improvement of synaptic functions induced by activation of RXRs is PPARalpha dependent.
Keywords:
Nuclear receptors (LXR, PPAR, RXR),
synaptic plasiticty,
LTP (Long Term Potentiation),
glutamate receptor,
Hippocampus
Conference:
Belgian Brain Congress 2018 — Belgian Brain Council, LIEGE, Belgium, 19 Oct - 19 Oct, 2018.
Presentation Type:
e-posters
Topic:
NOVEL STRATEGIES FOR NEUROLOGICAL AND MENTAL DISORDERS: SCIENTIFIC BASIS AND VALUE FOR PATIENT-CENTERED CARE
Citation:
PIERROT
N,
Ris
L,
STANCU
I,
Leroy
K,
Kienlen-Campard
P,
Gailly
P,
Brion
J,
Dewachter
I and
Octave
J
(2019). Improvement of synaptic plasticity by pharmacological activation of RXR nuclear receptors is PPARα dependent..
Front. Neurosci.
Conference Abstract:
Belgian Brain Congress 2018 — Belgian Brain Council.
doi: 10.3389/conf.fnins.2018.95.00017
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
30 Jul 2018;
Published Online:
17 Jan 2019.
*
Correspondence:
PhD. Nathalie PIERROT, Université Catholique de Louvain, Louvain-la-Neuve, Belgium, nathalie.pierrot@uclouvain.be
Prof. Ilse Dewachter, University of Hasselt, Hasselt, Limburg, 3500, Belgium, ilse.dewachter@uhasselt.be