Activation of PPARγ Ameliorates Spatial Cognitive Deficits through Restoring Expression of AMPA Receptors in Seipin Knock-Out Mice

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Libin ZhouLing Chen

Abstract

A characteristic phenotype of congenital generalized lipodystrophy 2 (CGL2) that is caused by loss-of-function of seipin gene is mental retardation. Here, we show that seipin deficiency in hippocampal CA1 pyramidal cells caused the reduction of peroxisome proliferator-activated receptor gamma (PPARγ). Twelve-week-old systemic seipin knock-out mice and neuronal seipin knock-out (seipin-nKO) mice, but not adipose seipin knock-out mice, exhibited spatial cognitive deficits as assessed by the Morris water maze and Y-maze, which were ameliorated by the treatment with the PPARγ agonist rosiglitazone (rosi). In addition, seipin-nKO mice showed the synaptic dysfunction and the impairment of NMDA receptor-dependent LTP in hippocampal CA1 regions. The density of AMPA-induced current (IAMPA) in CA1 pyramidal cells and GluR1/GluR2 expression were significantly reduced in seipin-nKO mice, whereas the NMDA-induced current (INMDA) and NR1/NR2 expression were not altered. Rosi treatment in seipin-nKO mice could correct the decrease in expression and activity of AMPA receptor (AMPAR) and was accompanied by recovered synaptic function and LTP induction. Furthermore, hippocampal ERK2 and CREB phosphorylation in seipin-nKO mice were reduced and th...Continue Reading

Citations

Oct 1, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Maria Grazia MorgeseStefania Schiavone
Dec 6, 2018·Frontiers in Cellular Neuroscience·Nuria Del Olmo, Mariano Ruiz-Gayo
Oct 5, 2018·Frontiers in Molecular Neuroscience·Laura B FergusonIgor Ponomarev
Nov 8, 2018·International Journal of Cell Biology·Aquiles Sales Craveiro SarmentoJulliane Tamara Araújo de Melo Campos
Nov 22, 2020·Aging Cell·Lingyan XuElisabetta Mueller
May 1, 2021·Journal of Clinical Medicine·Sofía Sánchez-IglesiasDavid Araújo-Vilar

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