Olaf Schijns1, Ümit Karaca2, Pablo Andrade3, Laurence de Nijs2, Benno Küsters4, Andrea Peeters5, Jim Dings6, Heinz Pannek7, Alois Ebner8, Kim Rijkers6, Govert Hoogland3. 1. Departments of Neurosurgery, Maastricht University Medical Center, The Netherlands. Electronic address: o.schijns@mumc.nl. 2. Departments of School of Mental Health and Neuroscience, Maastricht University Medical Center, The Netherlands. 3. Departments of Neurosurgery, Maastricht University Medical Center, The Netherlands; Departments of School of Mental Health and Neuroscience, Maastricht University Medical Center, The Netherlands. 4. Departments of Pathology, Maastricht University Medical Center, The Netherlands. 5. Departments of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center, The Netherlands. 6. Departments of Neurosurgery, Maastricht University Medical Center, The Netherlands. 7. Departments of Neurosurgery, Epilepsy Center, Bielefeld, Germany. 8. Departments of Epileptology, Epilepsy Center, Bielefeld, Germany.
Abstract
PURPOSE: To determine hippocampal expression of neuronal GABA-transporter (GAT-1) and glial GABA-transporter (GAT-3) in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). METHODS: Hippocampal sections were immunohistochemically stained for GABA-transporter 1 and GABA-transporter-3, followed by quantification of the immunoreactivity in the hilus by optical density measurements. GABA-transporter 3 positive hilar cells were counted and GABA-transporter protein expression in sections that included all hippocampal subfields was quantified by Western blot. RESULTS: The hilar GABA-transporter 1 expression of patients with severe hippocampal sclerosis was about 7% lower compared to that in the mild hippocampal sclerosis/control group (p<0.001). The hilar GABA-transporter 3 expression was about 5% lower in the severe hippocampal sclerosis group than in the mild hippocampal sclerosis/control group (non-significant). Also, severe hippocampal sclerosis samples contained 34% less (non-significant) GABA-transporter 3 positive cells compared to that of controls. Protein expression as assessed by Western blot showed that GABA-transporter 1 was equally expressed in mild and severe hippocampal sclerosis samples, whereas GABA-transporter 3 was reduced by about 62% in severe hippocampal sclerosis samples (p<0.0001). CONCLUSION: These data confirm that GABA-transporter expression is spatially and isoform-specific reduced and GABA-transporter 3 positive cell numbers are unchanged in hippocampal sclerosis. Implications for the use of GABAergic antiepileptic therapies in hippocampal sclerosis vs non-hippocampal sclerosis patients remain to be studied.
PURPOSE: To determine hippocampal expression of neuronal GABA-transporter (GAT-1) and glial GABA-transporter (GAT-3) in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). METHODS: Hippocampal sections were immunohistochemically stained for GABA-transporter 1 and GABA-transporter-3, followed by quantification of the immunoreactivity in the hilus by optical density measurements. GABA-transporter 3 positive hilar cells were counted and GABA-transporter protein expression in sections that included all hippocampal subfields was quantified by Western blot. RESULTS: The hilar GABA-transporter 1 expression of patients with severe hippocampal sclerosis was about 7% lower compared to that in the mild hippocampal sclerosis/control group (p<0.001). The hilar GABA-transporter 3 expression was about 5% lower in the severe hippocampal sclerosis group than in the mild hippocampal sclerosis/control group (non-significant). Also, severe hippocampal sclerosis samples contained 34% less (non-significant) GABA-transporter 3 positive cells compared to that of controls. Protein expression as assessed by Western blot showed that GABA-transporter 1 was equally expressed in mild and severe hippocampal sclerosis samples, whereas GABA-transporter 3 was reduced by about 62% in severe hippocampal sclerosis samples (p<0.0001). CONCLUSION: These data confirm that GABA-transporter expression is spatially and isoform-specific reduced and GABA-transporter 3 positive cell numbers are unchanged in hippocampal sclerosis. Implications for the use of GABAergic antiepileptic therapies in hippocampal sclerosis vs non-hippocampal sclerosispatients remain to be studied.
Authors: Laurence de Nijs; Kyonghwan Choe; Hellen Steinbusch; Olaf E M G Schijns; Jim Dings; Daniel L A van den Hove; Bart P F Rutten; Govert Hoogland Journal: Clin Epigenetics Date: 2019-08-19 Impact factor: 6.551