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Loss of SIRT 4 decreases GLT ‐1‐dependent glutamate uptake and increases sensitivity to kainic acid
Author(s) -
Shih Jennifer,
Liu Lei,
Mason Andrew,
Higashimori Haruki,
Donmez Gizem
Publication year - 2014
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12942
Subject(s) - excitotoxicity , glutamate receptor , kainic acid , sirtuin , chemistry , microbiology and biotechnology , neurotransmission , biochemistry , neuroscience , biology , pharmacology , receptor , nad+ kinase , enzyme
Glutamate transport is a critical process in the brain that maintains low extracellular levels of glutamate to allow for efficient neurotransmission and prevent excitotoxicity. Loss of glutamate transport function is implicated in epilepsy, traumatic brain injury, and amyotrophic lateral sclerosis. It remains unclear whether or not glutamate transport can be modulated in these disease conditions to improve outcome. Here, we show that sirtuin ( SIRT )4, a mitochondrial sirtuin, is up‐regulated in response to treatment with the potent excitotoxin kainic acid. Loss of SIRT 4 leads to a more severe reaction to kainic acid and decreased glutamate transporter expression and function in the brain. Together, these results indicate a critical and novel stress response role for SIRT 4 in promoting proper glutamate transport capacity and protecting against excitotoxicity.Loss of sirtuin 4 (SIRT4) in mice leads to decreased glutamate transporter expression and function in the brain, which can ultimately cause increased excitotoxic effects. SIRT4 is up‐regulated in response to treatment with the potent excitotoxin kainic acid. These results indicate a critical and novel stress response role for SIRT4 in promoting proper glutamate transport capacity and protecting against excitotoxicity. GLT‐1, Glutamate Transporter 1, same as excitatory amino acid transporter 2; Glu, glutamate.