Yonsei Med J.  2010 Sep;51(5):653-660. 10.3349/ymj.2010.51.5.653.

The Ketogenic Diet Suppresses the Cathepsin E Expression Induced by Kainic Acid in the Rat Brain

• Jeong HJ
• Kim H
• Kim YK
• Park SK
• Kang DW
• Yoon D

• KMID: 1071415
• DOI: http://doi.org/10.3349/ymj.2010.51.5.653

Abstract

PURPOSE
The ketogenic diet has long been used to treat epilepsy, but its mechanism is not yet clearly understood. To explore the potential mechanism, we analyzed the changes in gene expression induced by the ketogenic diet in the rat kainic acid (KA) epilepsy model.
MATERIALS AND METHODS
KA-administered rats were fed the ketogenic diet or a normal diet for 4 weeks, and microarray analysis was performed with their brain tissues. The effects of the ketogenic diet on cathepsin E messenger ribonucleic acid (mRNA) expression were analyzed in KA-administered and normal saline-administered groups with semi-quantitative and real-time reverse transcription polymerase chain reaction (RT-PCR). Brain tissues were dissected into 8 regions to compare differential effects of the ketogenic diet on cathepsin E mRNA expression. Immunohistochemistry with an anti-cathepsin E antibody was performed on slides of hippocampus obtained from whole brain paraffin blocks.
RESULTS
The microarray data and subsequent RT-PCR experiments showed that KA increased the mRNA expression of cathepsin E, known to be related to neuronal cell death, in most brain areas except the brain stem, and these increases of cathepsin E mRNA expression were suppressed by the ketogenic diet. The expression of cathepsin E mRNA in the control group, however, was not significantly affected by the ketogenic diet. The change in cathepsin E mRNA expression was greatest in the hippocampus. The protein level of cathepsin E in the hippocampus of KA-administered rat was elevated in immunohistochemistry and the ketogenic diet suppressed this increase.
CONCLUSION
Our results showed that KA administration increased cathepsin E expression in the rat brain and its increase was suppressed by the ketogenic diet.

Keyword

Cathepsin E; epilepsy; kainic acid; ketogenic diet; neuroprotection

MeSH Terms

3-Hydroxybutyric Acid/blood
Animals
Cathepsin E/genetics/*metabolism
Enzyme Activators/pharmacology
*Gene Expression Regulation, Enzymologic/drug effects
Hippocampus/*drug effects/*metabolism
Immunohistochemistry
Kainic Acid/*pharmacology
*Ketogenic Diet
Male
Oligonucleotide Array Sequence Analysis
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction