4.7 Article

Altered mRNA and Protein Expression of Monocarboxylate Transporter MCT1 in the Cerebral Cortex and Cerebellum of Prion Protein Knockout Mice

Journal

Publisher

MDPI
DOI: 10.3390/ijms22041566

Keywords

cellular prion protein; prionprotein knockout; MCT1; MCT4; Na+; K+ ATPase; cortex; qRT-PCR; Western blot

Funding

  1. Department of Physiology, University of Lausanne
  2. program IdEx Bordeaux [ANR-10-IDEX-03-02]

Ask authors/readers for more resources

This study investigated the impact of cellular prion protein deficiency on neuroenergetics by analyzing the expression of genes involved in lactate/pyruvate metabolism. The results show that the absence of PrP(C) leads to altered MCT1 and MCT4 expression levels in different brain regions, indicating a potential role of PrP(C) in the regulation of monocarboxylate transport.
The effect of a cellular prion protein (PrP(C)) deficiency on neuroenergetics was primarily analyzed via surveying the expression of genes specifically involved in lactate/pyruvate metabolism, such as monocarboxylate transporters (MCT1, MCT2, MCT4). The aim of the present study was to elucidate a potential involvement of PrP(C) in the regulation of energy metabolism in different brain regions. By using quantitative real-time polymerase chain reaction (qRT-PCR), we observed a marked reduction in MCT1 mRNA expression in the cortex of symptomatic Zurich I Prnp(-/-) mice, as compared to their wild-type (WT) counterparts. MCT1 downregulation in the cortex was accompanied with significantly decreased expression of the MCT1 functional interplayer, the Na+/K+ ATPase alpha 2 subunit. Conversely, the MCT1 mRNA level was significantly raised in the cerebellum of Prnp(-/-) vs. WT control group, without a substantial change in the Na+/K+ ATPase alpha 2 subunit expression. To validate the observed mRNA findings, we confirmed the observed change in MCT1 mRNA expression level in the cortex at the protein level. MCT4, highly expressed in tissues that rely on glycolysis as an energy source, exhibited a significant reduction in the hippocampus of Prnp(-/-) vs. WT mice. The present study demonstrates that a lack of PrP(C) leads to altered MCT1 and MCT4 mRNA/protein expression in different brain regions of Prnp(-/-) vs. WT mice. Our findings provide evidence that PrP(C) might affect the monocarboxylate intercellular transport, which needs to be confirmed in further studies.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available