The NR1 N-methyl-D-aspartate subunit and brain-derived neurotrophic factor in temporal lobe epilepsy hippocampus: a comparison of patients with and without coexisting psychiatric symptoms.
OBJECTIVE
The glutamate N-methyl-D-aspartate (NMDA) receptor and the neurotrophin brain-derived neurotrophic factor have been implicated in the pathophysiology of schizophrenia and depression. Since these psychiatric disorders are common in temporal lobe epilepsy (TLE), a comparison of TLE patients with and without coexisting psychiatric symptoms may be useful to unravel pathophysiologic mechanisms for psychosis or depression.


METHODS
We used immunoautoradiography to assess the NR1 NMDA receptor subunit and brain-derived neurotrophic factor in resected TLE hippocampus.


RESULTS
No changes relative to comparison controls were found for TLE patients with schizophrenia-like psychosis or depression. Increased NR1 was found in the dentate molecular layer in the dysphoria group and unmedicated depressed patients.


CONCLUSIONS
An increase in NR1 protein in the dentate molecular layer suggests an upregulation of NMDA receptors in granule cells in TLE patients with dysphoria and depression. This finding is compatible with the theory that increased NMDA receptor function is involved in the pathogenesis of depression and that antidepressants may act by opposing this mechanism.
Toro
Carla Tatiana
CT
Neuroscience and Psychiatry Unit, University of Manchester, Manchester, UK. carla.t.toro@manchester.ac.uk
Hallak
Jaime E
JE
Dunham
Jason S
JS
Leite
João P
JP
Sakamoto
Américo C
AC
Guarnieri
Ricardo
R
Fong
Vivian
V
Deakin
John F W
JF
D000328:Adult; D000704:Analysis of Variance; D001345:Autoradiography; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis*; D015897:Comorbidity; D018891:Dentate Gyrus / Q000737:chemistry / Q000378:metabolism; D003865:Major Depressive Disorder / Q000453:epidemiology / Q000378:metabolism; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000601:surgery; D005260:Female; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism* / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D001523:Mental Disorders / Q000453:epidemiology / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis*; D012559:Schizophrenia / Q000453:epidemiology / Q000378:metabolism; D012565:Schizophrenic Psychology
D019208:Brain-Derived Neurotrophic Factor; C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate