Mitochondrial uncoupling protein-2 protects the immature brain from excitotoxic neuronal death

Patrick G. Sullivan, Celine Dubé, Kristina Dorenbos, Oswald Steward, Tallie Z. Baram

Research output: Contribution to journalArticle

187 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)711-717
Number of pages7
JournalAnnals of Neurology
Volume53
Issue number6
DOIs
StatePublished - Jun 1 2003
Externally publishedYes

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Seizures
Brain
Cell Death
Fat-Restricted Diet
Dietary Fats
Neurodegenerative Diseases
Reactive Oxygen Species
Milk
Fats
Mothers
Diet
Neurons
Uncoupling Protein 2
Wounds and Injuries
Population

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Mitochondrial uncoupling protein-2 protects the immature brain from excitotoxic neuronal death. / Sullivan, Patrick G.; Dubé, Celine; Dorenbos, Kristina; Steward, Oswald; Baram, Tallie Z.

In: Annals of Neurology, Vol. 53, No. 6, 01.06.2003, p. 711-717.

Research output: Contribution to journalArticle

Sullivan, Patrick G. ; Dubé, Celine ; Dorenbos, Kristina ; Steward, Oswald ; Baram, Tallie Z. / Mitochondrial uncoupling protein-2 protects the immature brain from excitotoxic neuronal death. In: Annals of Neurology. 2003 ; Vol. 53, No. 6. pp. 711-717.
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