Role of JNK isoforms in the kainic acid experimental model of epilepsy and neurodegeneration

Front Biosci (Landmark Ed). 2017 Jan 1;22(5):795-814. doi: 10.2741/4517.

Abstract

Chemoconvulsants that induce status epilepticus in rodents have been widely used over the past decades due to their capacity to reproduce with high similarity neuropathological and electroencephalographic features observed in patients with temporal lobe epilepsy (TLE). Kainic acid is one of the most used chemoconvulsants in experimental models. KA administration mainly induces neuronal loss in the hippocampus. We focused the present review inthe c-Jun N-terminal kinase-signaling pathway (JNK), since it has been shown to play a key role in the process of neuronal death following KA activation. Among the three isoforms of JNK (JNK1, JNK2, JNK3), JNK3 is widely localized in the majority of areas of the hippocampus, whereas JNK1 levels are located exclusively in the CA3 and CA4 areas and in dentate gyrus. Disruption of the gene encoding JNK3 in mice renders neuroprotection to KA, since these animals showed a reduction in seizure activity and a diminution in hippocampal neuronal apoptosis. In light of this, JNK3 could be a promising subcellular target for future therapeutic interventions in epilepsy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Anticonvulsants / pharmacology
  • Disease Models, Animal
  • Epilepsy / chemically induced
  • Epilepsy / enzymology*
  • Epilepsy / pathology
  • Hippocampus / drug effects
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Humans
  • Isoenzymes / metabolism
  • JNK Mitogen-Activated Protein Kinases / deficiency
  • JNK Mitogen-Activated Protein Kinases / genetics
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Kainic Acid / toxicity
  • MAP Kinase Signaling System / drug effects
  • Mice
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase 10 / metabolism
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / enzymology*
  • Nerve Degeneration / pathology

Substances

  • Adaptor Proteins, Signal Transducing
  • Anticonvulsants
  • Isoenzymes
  • Mitogen-Activated Protein Kinase 10
  • JNK Mitogen-Activated Protein Kinases
  • Kainic Acid