Cellular compartmentalization of phosphorylated eIF2α and neuronal NOS in human temporal lobe epilepsy with hippocampal sclerosis

Theodor Petrov, José A. Rafols, Sarah S. Alousi, William J. Kupsky, Robert Johnson, Jagdish Shah, Aashit Shah, Craig Watson

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Hippocampal sclerosis (HS) is the most common neuropathologic finding in patients with medically refractory temporal lobe epilepsy (TLE). The mechanisms resulting in neuronal injury and cell loss in HS are incompletely understood, but inhibition of protein synthesis may play a pivotal role in these processes. This study examined the relationships between two molecules known to be involved in reduced protein synthesis in animals subjected to traumatic brain injury. Translational initiation of protein synthesis is inhibited when 2α (eIF2α) is phosphorylated. Recently, nitric oxide (NO) has been shown to reduce protein synthesis by inducing phosphorylation of eIF2α. We performed immunocytochemistry for eIF2α(P) and histochemistry (NADPH-D reaction) for nitric oxide synthase (NOS) to determine the distribution of these molecules in hippocampi removed from patients undergoing anterior temporal lobectomy (ATL) for medically intractable TLE due to HS. The greatest number of eIF2α(P) positive cells was in the CA1 sector of the hippocampus, followed by the hilus of the dentate gyrus. NADPH-D positive neurons were observed most often in the hilus. Labeling in both instances involved neuronal cell body cytoplasm and varicose processes. Combination of both staining procedures revealed close relationships between differentially labeled neurons within the hilus. The results suggest that NO participates in the phosphorylation of eIF2α since we demonstrated that nNOS processes are closely related to eIF2α(P) positive cells. This may occur through activation of kinases such as PERK, which was recently revealed. In human, TLE protein synthesis inhibition may occur at the translational level since the eIF2α (P) labeling is cytoplasmic. Protein synthesis inhibition may contribute to neuronal cell injury and death in HS.

Original languageEnglish (US)
Pages (from-to)31-39
Number of pages9
JournalJournal of the Neurological Sciences
Volume209
Issue number1-2
DOIs
StatePublished - May 15 2003
Externally publishedYes

Keywords

  • Glia
  • Hippocampus
  • Immunocytochemistry
  • NADPH-D
  • Neurons

ASJC Scopus subject areas

  • Aging
  • Clinical Neurology
  • Surgery
  • Developmental Neuroscience
  • Neurology
  • Neuroscience(all)

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