Gene expression of glutamate metabolizing enzymes in the hippocampal formation in human temporal lobe epilepsy.
Gene expression of glutamate metabolizing enzymes in the hippocampal formation in human temporal lobe epilepsy.
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DOI：
10.1111/epi.12008
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发表时间：
2013-02
期刊：
影响因子：
5.6
通讯作者：
McCullumsmith RE
中科院分区：
文献类型：
--
作者：
Eid T;Lee TS;Wang Y;Perez E;Drummond J;Lauritzen F;Bergersen LH;Meador-Woodruff JH;Spencer DD;de Lanerolle NC;McCullumsmith RE
Increased interictal concentrations of extracellular hippocampal glutamate have been implicated in the pathophysiology of temporal lobe epilepsy (TLE) in humans. Recent studies suggest that perturbations of the glutamate metabolizing enzymes glutamine synthetase (GS) and phosphate activated glutaminase (PAG) may underlie the glutamate excess in TLE. However, the molecular mechanism of the enzyme perturbations remains unclear. A better understanding of the regulatory mechanisms of GS and PAG could facilitate the discovery of novel therapeutics for TLE. We used in situ hybridization on histological sections to assess the distribution and quantity of mRNA for GS and PAG in subfields of hippocampal formations from: (a) patients with TLE and concomitant hippocampal sclerosis, (b) patients with TLE and no hippocampal sclerosis, and (c) non-epilepsy autopsy subjects. GS mRNA was increased by approximately 50% in the CA3 in TLE patients without hippocampal sclerosis vs. in TLE patients with sclerosis and in non-epilepsy subjects. PAG mRNA was increased by more than 100% in the subiculum in both TLE patient categories vs. in non-epilepsy subjects. PAG mRNA was also increased in the CA1, CA2, CA3 and dentate hilus in TLE without hippocampal sclerosis vs. in TLE with sclerosis. Finally, PAG mRNA was increased in the dentate gyrus in TLE with sclerosis vs. in non-epilepsy subjects, and also increased in the hilus in TLE without sclerosis vs. in TLE with sclerosis. These findings demonstrate complex changes in the expression of mRNAs for GS and PAG in the hippocampal formation in TLE, and raise the possibility that both transcriptional and post-transcriptional mechanisms may underlie the regulation of GS and PAG proteins in the epileptic brain.
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影响因子：
3
作者：
Albrecht, Philipp;Lewerenz, Jan;Methner, Axel
通讯作者：
Methner, Axel
DOI：
10.1073/pnas.0409308102
发表时间：
2005-01-25
影响因子：
11.1
作者：
Eid, T;Lee, TSW;de Lanerolle, NC
通讯作者：
de Lanerolle, NC
影响因子：
7.4
作者：
Castegna, A;Aksenov, M;Butterfield, DA
通讯作者：
Butterfield, DA
影响因子：
3.3
作者：
EID, T;DU, F;SCHWARCZ, R
通讯作者：
SCHWARCZ, R
影响因子：
2.2
作者：
Bordey, A;Sontheimer, H
通讯作者：
Sontheimer, H