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Mitochondrial uncoupling protein‐2 protects the immature brain from excitotoxic neuronal death
Author(s) -
Sullivan Patrick G.,
Dubé Celine,
Dorenbos Kristina,
Steward Oswald,
Baram Tallie Z.
Publication year - 2003
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.10543
Subject(s) - excitotoxicity , neuroprotection , biology , neuroscience , mitochondrion , programmed cell death , population , uncoupling protein , microbiology and biotechnology , endocrinology , apoptosis , medicine , biochemistry , environmental health , brown adipose tissue , obesity
Excitotoxic cell death is the fundamental process responsible for many human neurodegenerative disorders, yet the basic mechanisms involved are not fully understood. Here, we exploited the fact that the immature brain is remarkably resistant to seizure‐induced excitotoxic cell death and examined the underlying protective mechanisms. We found that, unlike in the adult, seizures do not increase the formation of reactive oxygen species or result in mitochondrial dysfunction in neonatal brain, because of high levels of the mitochondrial uncoupling protein (UCP2). UCP2 expression and function were basally increased in neonatal brain by the fat‐rich diet of maternal milk, and substituting a low‐fat diet reduced UCP2, restored mitochondrial coupling, and permitted seizure‐induced neuronal injury. Thus, modulation of UCP2 expression and function by dietary fat protects neonatal neurons from excitotoxicity by preventing mitochondrial dysfunction. This mechanism offers novel neuroprotective strategies for individuals, greater than 1% of the world's population, who are affected by seizures. Ann Neurol 2003