A cDNA microarray analysis of gene expression profiles in rat hippocampus following a ketogenic diet.
The ketogenic diet (KD) is an effective therapy for medically intractable epilepsy, but its anticonvulsant mechanisms are unknown. Few studies to date have addressed the molecular changes following treatment with a KD. In the present study, we fed juvenile rats either a standard diet or a KD for 1 month, and then determined changes in hippocampal gene expression using cDNA microarray analysis (Clontech). To validate the microarray expression results, we also performed Northern blot and RT-PCR analysis on a small subset of affected genes. Among a total of 1176 cDNAs, 42 genes were strongly up- or down-regulated (>2-fold change over controls) by a KD. We found that the expression of mitochondrial ATP synthase beta subunit, mitochondrial ATP synthase D subunit (ATP5H) and mitochondrial ATP synthase beta subunit precursor (ATP5F) were especially increased in KD-treated group, whereas the KD down-regulated protein kinase C (PKC) beta and epsilon isoforms. Thus, the most prominent changes were seen in genes encoding proteins involved in mitochondrial metabolic and intracellular signal transduction pathways. Our data provide some insights into the complex cascade of cellular changes in the hippocampus induced by a KD, some of which may contribute to its anticonvulsant effects.
Department of Anatomy and Neurobiology, College of Medicine, Gyeongsang National University, 92 Chilam-dong, Chinju, Kyungnam 660-751, Korea.
Hae Sook
HS
Noh
Hee Po
HP
Lee
Dong Wook
DW
Kim
Sang Soo
SS
Kang
Gyeong Jae
GJ
Cho
Jong M
JM
Rho
Wan Sung
WS
Choi
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000818:Animals; D001835:Body Weight; D004032:Diet; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000502:physiology*; D007659:Ketones / Q000378:metabolism*; D007662:Ketosis / Q000097:blood; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D007659:Ketones; D020155:3-Hydroxybutyric Acid