Neurobiology of Disease (Apr 2019)

Cell injury and receptor expression in the epileptic human amygdala

  • Maryam Jafarian,
  • Sayed Mostafa Modarres Mousavi,
  • Fatemeh Alipour,
  • Hadi Aligholi,
  • Farshid Noorbakhsh,
  • Masoud Ghadipasha,
  • Jaber Gharehdaghi,
  • Christoph Kellinghaus,
  • Stjepana Kovac,
  • Maryam Khaleghi Ghadiri,
  • Sven G. Meuth,
  • Erwin-Josef Speckmann,
  • Walter Stummer,
  • Ali Gorji

Journal volume & issue
Vol. 124
pp. 416 – 427

Abstract

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Neuropathological findings in the amygdala obtained from patients with mesial temporal lobe epilepsy (MTLE) indicate varying degrees of histopathological alterations, such as neuronal loss and gliosis. The mechanisms underlying cellular damage in the amygdala of patients with MTLE have not been fully elucidated. In the present study, we assess cellular damage, determine the receptor expression of major inhibitory and excitatory neurotransmitters, and evaluate the correlation between the expression of various receptors and cell damage in the basolateral complex and the centromedial areas in the amygdala specimens resected during brain surgery on 30 patients with medically intractable MTLE. Our data reveal an increased rate of cell damage and apoptosis as well as decreased expression levels of several GABAergic receptor subunits (GABAARα1, GABAARβ3, and GABABR1) and GAD65 in the amygdalae obtained during epilepsy surgery compared to autopsy specimens. Analyses of the expression of glutamate excitatory receptor subunits (NR1, NR2B, mGluR1α, GluR1, and GluR2) reveal no significant differences between the epileptic amygdalae and autopsy control tissues. Furthermore, the increased occurrence of apoptotic cells in the amygdala is negatively correlated with the reduced expression of the studied GABAergic receptor subunits and GAD65 but is not correlated with the expression of excitatory receptors. The present data point to the importance of GABAergic neurotransmission in seizure-induced cell injury in the amygdala of patients with MTLE and suggest several GABA receptor subunits as potential druggable target structures to control epilepsy and its comorbid disorders, such as anxiety.

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