Excitatory amino acid transporters EAAT-1 and EAAT-2 in temporal lobe and hippocampus in intractable temporal lobe epilepsy.
Intractable temporal lobe epilepsy (TLE) is an invalidating disease and many patients are resistant to medical treatment. Increased glutamate concentration has been found in epileptogenic foci and may induce local over-excitation and cytotoxicity; one of the proposed mechanisms involves reduced extra-cellular clearance of glutamate by excitatory amino acid transporters (EAAT-1 to EAAT-5). EAAT-1 and EAAT-2 are mainly expressed on astroglial cells for the reuptake of glutamate from the extra-cellular space. We have studied the expression of EAAT-1 and EAAT-2 in the hippocampus and temporal lobe in 12 patients with TLE by immunohistochemistry and densitometry. The expression of EAAT-1 and EAAT-2 was reduced to approximately 40% and 25%, respectively, in CA1 of the hippocampus. In the same area, an increased expression of glial fibrillary acid protein (GFAP) at 90% reflected molecular rearrangements and upregulation of GFAP in the existing astrocytes as Ki-67 staining failed to demonstrate any signs of astrocytic proliferation. The aetiology of the reduced expression of EAAT-1 and EAAT-2 remains unclear. The downregulation of EAAT-1 and EAAT-2 may be an adaptive response to neuronal death or it may be a causative event contributing to neuronal death. Further studies of the EAATs and their function are needed to clarify the mechanisms and significance of EAAT-1 and EAAT-2 disappearance in TLE.
Sarac
Sinan
S
Laboratory of Neuropathology, Ringshospitalet, 9 Blegdamsvej, Copenhagen, Denmark.
Afzal
Shoaib
S
Broholm
Helle
H
Madsen
Flemming F
FF
Ploug
Thorkil
T
Laursen
Henning
H