Reelin, tau phosphorylation and psychiatric complications in patients with hippocampal sclerosis and structural abnormalities in temporal lobe epilepsy

Epilepsy Behav. 2019 Jul:96:192-199. doi: 10.1016/j.yebeh.2019.04.052. Epub 2019 May 29.

Abstract

Introduction: Temporal lobe epilepsy (TLE) is the most common adult epileptic syndrome. About 30-70% of those cases have neuropsychiatric complications. More than 10% of patients have TLE because of focal cortical dysplasia (FCD) type IIIa.

Objectives: The objective of this study was to review the evidence of reelin (RELN) deficiency and tau phosphorylation role in the histopathological, neuropsychiatric, and hyperexcitability features in TLE because of dysplasia type IIIa.

Methods: The current literature was reviewed using Cochrane, EMBASE, PROSPERO, MEDLINE, and PubMed from 1995 to July 2018. Articles of interest were reviewed by one investigator (RAM).

Results: Reelin deficit is related to an abnormal migration of neurons in dentate gyrus, and its deficit causes dentate gyrus abnormalities, which in turn has been associated with memory deficits in patients with TLE. A decreased in the expression of RELN ribonucleic acid (RNA) was found in patients with TLE and dysplasia type IIIa compared with patients with TLE and isolated hippocampal sclerosis (HS). Reelin might affect the distribution and dynamic instability of microtubules within neurons in the cerebral cortex and their phosphorylation. Amyloid pathology, tauopathy, or phosphorylated tau (p-tau) overexpression has been reported in epileptic human brain and in animal models of epilepsy.

Conclusion: Reelin deficit may determine an abnormal cortical lamination and dentate gyrus dispersion and might be associated with an abnormal tau phosphorylation. These processes can be associated with an abnormal hyperexcitability, neuropsychiatric complications, and a myriad of typical histopathological features seen in patients with TLE because of dysplasia type IIIa.

Keywords: Depression; Dysplasia type IIIa; Psychosis; Reelin; Tau; Temporal lobe epilepsy.

Publication types

  • Review

MeSH terms

  • Brain / metabolism
  • Brain / pathology
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Epilepsy, Temporal Lobe / complications*
  • Epilepsy, Temporal Lobe / metabolism
  • Epilepsy, Temporal Lobe / pathology
  • Extracellular Matrix Proteins / metabolism*
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • Humans
  • Memory Disorders / complications*
  • Memory Disorders / metabolism
  • Memory Disorders / pathology
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism
  • Phosphorylation
  • Reelin Protein
  • Sclerosis / complications
  • Sclerosis / metabolism
  • Sclerosis / pathology
  • Serine Endopeptidases / metabolism*
  • tau Proteins / metabolism*

Substances

  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Reelin Protein
  • tau Proteins
  • RELN protein, human
  • Serine Endopeptidases