Alternative splicing of glutamate transporter EAAT2 RNA in neocortex and hippocampus of temporal lobe epilepsy patients

• Published in: Epilepsy research Vol. 59; no. 2; pp. 75 - 82
• Main Authors: Hoogland, G, van Oort, R.J, Proper, E.A, Jansen, G.H, van Rijen, P.C, van Veelen, C.W.M, van Nieuwenhuizen, O, Troost, D, de Graan, P.N.E
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01-04-2004; Elsevier
• Subjects: Adult; Aged; Alternative Splicing - genetics; Alternative Splicing - physiology; Biological and medical sciences; Chi-Square Distribution; EAAT2; Epilepsy; Epilepsy, Temporal Lobe - genetics; Epilepsy, Temporal Lobe - metabolism; Excitatory Amino Acid Transporter 2 - genetics; Excitatory Amino Acid Transporter 2 - metabolism; Glutamate; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Hippocampus - metabolism; Humans; Medical sciences; Middle Aged; Neocortex - metabolism; Nervous system (semeiology, syndromes); Neurology; Protein Isoforms - genetics; Protein Isoforms - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Splicing; Temporal lobe; Transporter; Temporal lobe; EAAT2; Splicing; Glutamate; Transporter; Epilepsy; Alternative splicing; Motor pathway; Motor neuron disease; Central nervous system; Complex partial epilepsy; Motor cortex; Deletion; Degenerative disease; Human; Nervous system diseases; GLT-1 glutamate transporter; Amyotrophic lateral sclerosis; Protein; Cerebral disorder; Case study; Central nervous system disease; Excitatory aminoacid; Neurotransmitter; Temporal lobe epilepsy; Spinal cord disease; Hippocampus
• ISSN: 0920-1211; 1872-6844
• DOI: 10.1016/j.eplepsyres.2004.03.003

Rationale: Altered expression of glutamate transporter EAAT2 protein has been reported in the hippocampus of patients with temporal lobe epilepsy (TLE). Two alternative EAAT2 mRNA splice forms, one resulting from a partial retention of intron 7 (I7R), the other from a deletion of exon 9 (E9S), were previously implicated in the loss of EAAT2 protein in patients with amyotrophic lateral sclerosis.
Methods: By RT–PCR we studied the occurrence of I7R and E9S in neocortical and hippocampal specimens from TLE patients and non-neurological controls.
Results: Both splice forms were found in all neocortical specimens from TLE patients (100% I7R, 100% E9S). This was significantly more than in controls (67% I7R, 60% E9S;
P<0.05). We also detected I7R and E9S in all seven motor cortex post-mortem samples from patients with amyotrophic lateral sclerosis. Within the TLE patient group, both splice variants appeared significantly more in non-sclerotic (100%), than in sclerotic hippocampi (69%,
P<0.05).
Conclusion: These data indicate that the epileptic brain, especially that of TLE patients without hippocampal sclerosis, is highly prone to alternative EAAT2 mRNA splicing. Our data confirm that the presence of alternative EAAT2 splice forms is not disease specific.