Temporal lobe epilepsy associated up-regulation of metabotropic glutamate receptors: correlated changes in mGluR1 mRNA and protein expression in experimental animals and human patients.
Neuropeptide Y (NPY) has anticonvulsant and anti-epileptogenic properties in animal models of temporal lobe epilepsy when delivered by an adeno-associated viral (AAV) vector.
Current evidences suggest that inhibiting BDNF-TrkB signaling and reinforcing the NPY system could represent a potential therapeutic strategy for epilepsy, especially for temporal lobe epilepsy.
These results suggest that loss of somatostatin and neuropeptide Y interneurones occurs in proportion to overall hilar cell loss, and therefore the hypothesis of a selective loss of these interneurones in temporal lobe epilepsy seems unlikely.
We investigated Y1 and Y2 receptor binding and NPY immunoreactivity in hippocampal specimens that were obtained at surgery from patients with temporal lobe epilepsy and in autopsy controls.
Our research showed that downregulation of KCC2 and microstructural abnormalities might contribute to the observed refractoriness in temporal lobe epilepsy.
To clarify whether these abnormalities are specific to the epileptogenic zone (EZ), we characterized in vivo whole-brain mGluR5 availability in MTLE patients using positron emission tomography (PET) and [<sup>11</sup> C]ABP688, a radioligand that binds specifically to the mGluR5 allosteric site.
The neuronal specific K<sup>+</sup>/Cl<sup>-</sup> co-transporter 2 (KCC2) is a critical determinant of the efficacy of GABAergic inhibition and deficits in its activity are observed in mTLE patients and animal models of epilepsy.
We conclude that the anomalous expression of both Cl(-) transporters, NKCC1 and KCC2 [corrected] in TLE hippocampal subiculum probably causes altered Cl(-) transport in the "epileptic" neurons, as revealed in the microtransplanted Xenopus oocytes, and renders GABA aberrantly "exciting," a feature that may contribute to the precipitation of epileptic seizures.
Here, we have analyzed the hippocampal distribution and mRNA expression of mGluR1 and mGluR5 in two rat models of limbic seizures, i.e. electrical kindling and intraperitoneal kainate injections, as well as in human TLE.
P2X7 receptor levels were increased in hippocampal subfields in the mice and in resected hippocampus from patients with pharmacoresistant temporal lobe epilepsy.
In this study, 150 controls and 82 patients with temporal lobe epilepsy (TLE) were genotyped for five common VDR polymorphisms (Cdx-2, FokI, BsmI, ApaI and TaqI) by the polymerase chain reaction-ligase detection reaction method.
We assessed the protein expression levels of VEGF-A, VEGF-B, and VEGF-C, their specific receptors VEGFR-2 and -3, their accessory receptors neuropilins 1 and 2, and PI3 and Akt kinases, in temporal neocortex from pharmacoresistant TLE (PR-TLE) patients and control subjects by western blotting.
We conclude that the anomalous expression of both Cl(-) transporters, NKCC1 and KCC2 [corrected] in TLE hippocampal subiculum probably causes altered Cl(-) transport in the "epileptic" neurons, as revealed in the microtransplanted Xenopus oocytes, and renders GABA aberrantly "exciting," a feature that may contribute to the precipitation of epileptic seizures.
Immunolabeling demonstrated that EAAT3/EAAC1 protein expression was enhanced in dentate granule cells from both rats and humans with TLE as well as in dysplastic neurons from human cortical dysplasia tissue.
With the intention to test if RNA editing plays a role in pathological processes, which contribute to seizure maintenance, we examined the ratio of the unedited (Q) to edited (R) form of the AMPA receptor subunit GluR2 and kainate receptor subunits GluR5 and GluR6 in the hippocampus and temporal cerebral cortex, both excised from patients with pharmacoresistant temporal lobe epilepsies.
We investigated Y1 and Y2 receptor binding and NPY immunoreactivity in hippocampal specimens that were obtained at surgery from patients with temporal lobe epilepsy and in autopsy controls.
Inhibition of the mammalian target of rapamycin (mTOR) pathway could be antiepileptogenic in temporal lobe epilepsy (TLE), possibly via anti-inflammatory actions.
We found significantly increased expression of phospho-mTOR (Ser2448), phospho-S6 (Ser235/236), phospho-S6 (Ser240/244), and phospho-Akt (Ser473) in TLE samples compared to controls, consistent with activation of both mTORC1 and mTORC2.