Sex-regulated gene dosage effect of PPARα on synaptic plasticity
| Autor: | Karelle Leroy, Pascal Kienlen-Campard, Eric Bauge, Jean-Noël Octave, Philippe Gailly, Ilie-Cosmin Stancu, Donatienne Tyteca, Liza Malong, Anna Doshina, Floriane Ribeiro, Ilse Dewachter, Bart Staels, Nathalie Pierrot, Laurence Ris, Jean Pierre Brion, Olivier Schakman, Fanny Lalloyer |
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| Přispěvatelé: | 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, UCL - SSS/DDUV/CELL - Biologie cellulaire, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Health Toxicology and Mutagenesis Long-Term Potentiation Gene Dosage Alpha (ethology) Hippocampus Mice Transgenic Plant Science AMPA receptor Retinoid X receptor Biology Hippocampal formation Biochemistry Genetics and Molecular Biology (miscellaneous) Mice 03 medical and health sciences Sex Factors 0302 clinical medicine Animals Cognitive Dysfunction PPAR alpha Receptors AMPA Rats Wistar Cells Cultured Research Articles Benzoxazoles Neuronal Plasticity Ecology Médecine pathologie humaine Généralités Long-term potentiation Neuropathologie Sciences bio-médicales et agricoles Sciences biomédicales Rats Cell biology Butyrates Retinoid X Receptors 030104 developmental biology Nuclear receptor Gene Knockdown Techniques Synaptic plasticity Female 030217 neurology & neurosurgery Signal Transduction Research Article |
| Zdroj: | Article Life science alliance, 2 (2 Life science alliance, Vol. 2, no. 2, p. e201800262 [1-15] (2019) Life Science Alliance |
| Popis: | 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-3hydroxy-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. SCOPUS: ar.j info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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