Lipin1 mediates cognitive impairment in fld mice via PKD-ERK pathway

Biochem Biophys Res Commun. 2020 Apr 30;525(2):286-291. doi: 10.1016/j.bbrc.2020.02.070. Epub 2020 Feb 20.

Abstract

Lipin1 is important in lipid synthesis because of its phosphatidate phosphatase activity, and it also functions as transcriptional coactivators to regulate the expression of genes involved in lipid metabolism. We found that fld mice exhibit cognitive impairment, and it is related to the DAG-PKD-ERK pathway. We used fld mice to explore the relationship between lipin1 and cognitive function. Our results confirmed the presence of cognitive impairment in the hippocampus of lipin1-deficient mice. As shown in behavioral test, the spatial learning and memory ability of fld mice was much worse than that of wild-type mice. Electron microscopy results showed that the number of synapses in hippocampus of fld mice was significantly reduced. BDNF,SYP, PSD95 were significantly reduced. These results suggest that lipin1 impairs synaptic plasticity. Hence,a deficiency of lipin1 leads to decreased DAG levels and inhibits PKD activation, thereby affecting the phosphorylation of ERK and the CREB.

Keywords: Lipin1; cognitive dysfunction; fld mice; protein kinase D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cognitive Dysfunction / metabolism*
  • Diacylglycerol Kinase / metabolism*
  • Hippocampus / metabolism
  • Humans
  • Infant
  • MAP Kinase Signaling System / physiology*
  • Memory
  • Mice
  • Neuronal Plasticity
  • Phosphatidate Phosphatase / deficiency
  • Phosphatidate Phosphatase / physiology*
  • Phosphorylation
  • Protein Kinase C / metabolism*
  • Synapses

Substances

  • Diacylglycerol Kinase
  • protein kinase D
  • Protein Kinase C
  • Lpin1 protein, mouse
  • Phosphatidate Phosphatase