Elsevier

Neuroscience Letters

Volume 414, Issue 1, 27 February 2007, Pages 57-60
Neuroscience Letters

Kainic acid induces early and transient autophagic stress in mouse hippocampus

https://doi.org/10.1016/j.neulet.2006.12.025Get rights and content

Abstract

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 4–6 h 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.

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Acknowledgements

We wish to thank Dr. Liyan Qiao for scientific discussion, an award from the Batten Disease Support and Research Association (J.J.S.), UAB Neuroscience Core Facilities (NS4746 and NS57098), NIH grants NS35107 and NS41962 (K.A.R.) and a UAB Faculty Development Award and an Epilepsy Foundation award (J.Z.).

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