Kainic acid induces early and transient autophagic stress in mouse hippocampus

Neurosci Lett. 2007 Feb 27;414(1):57-60. doi: 10.1016/j.neulet.2006.12.025. Epub 2006 Dec 27.


Kainic acid (KA) treatment is a well-established model of hippocampal neuron death mediated in large part by KA receptor-induced excitotoxicity. KA-induced, delayed neuron death has been shown previously to follow the induction of seizures and exhibit characteristics of both apoptosis and necrosis. Growing evidence supports a role of autophagic stress-induced death of neurons in several in vitro and in vivo models of neuron death and neurodegeneration. However, whether autophagic stress also plays a role in KA-induced excitotoxicity has not been previously investigated. To examine whether KA alters the levels of proteins associated with or known to regulate the formation of autophagic vacuoles, we isolated hippocampal extracts from control mice and in mice following 2-16 h KA injection. KA induced a significant increase in the amount of LC3-II, a specific marker of autophagic vacuoles, at 4-6h following KA, which indicates a transient induction of autophagic stress. Levels of autophagy-associated proteins including ATG5 (conjugated to ATG12), ATG6 and ATG7 did not change significantly after treatment with KA. However, ratios of phospho-mTOR/mTOR were elevated from 6 to 16 h, and ratios of phospho-Akt/Akt were elevated at 16 h following KA treatment, suggesting a potential negative feedback loop to inhibit further stimulation of autophagic stress. Together these data indicate the transient induction of autophagic stress by KA which may serve to regulate excitotoxic death in mouse hippocampus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / drug effects
  • Autophagy / physiology*
  • Autophagy-Related Protein 5
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Epilepsy / chemically induced
  • Epilepsy / metabolism*
  • Epilepsy / physiopathology
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Hippocampus / physiopathology
  • Kainic Acid / toxicity
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microtubule-Associated Proteins / drug effects
  • Microtubule-Associated Proteins / metabolism
  • Molecular Chaperones / drug effects
  • Molecular Chaperones / metabolism
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / metabolism*
  • Nerve Degeneration / physiopathology
  • Neurotoxins / toxicity*
  • Oncogene Protein v-akt / drug effects
  • Oncogene Protein v-akt / metabolism
  • Stress, Physiological / chemically induced
  • Stress, Physiological / metabolism*
  • Stress, Physiological / physiopathology
  • Ubiquitins / drug effects
  • Ubiquitins / metabolism
  • Up-Regulation / drug effects
  • Up-Regulation / physiology


  • Atg5 protein, mouse
  • Autophagy-Related Protein 5
  • Biomarkers
  • Dyt1 protein, mouse
  • Gabarapl1 protein, mouse
  • Microtubule-Associated Proteins
  • Molecular Chaperones
  • Neurotoxins
  • Ubiquitins
  • Oncogene Protein v-akt
  • Kainic Acid