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 language | English |
|---|---|
| Pages (from-to) | 711-717 |
| Number of pages | 7 |
| Journal | Annals of Neurology |
| Volume | 53 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 1 2003 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Mitochondrial uncoupling protein-2 protects the immature brain from excitotoxic neuronal death
AU - Sullivan, Patrick G.
AU - Dubé, Celine
AU - Dorenbos, Kristina
AU - Steward, Oswald
AU - Baram, Tallie Z.
PY - 2003/6/1
Y1 - 2003/6/1
N2 - 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.
AB - 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.
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U2 - 10.1002/ana.10543
DO - 10.1002/ana.10543
M3 - Article
VL - 53
SP - 711
EP - 717
JO - Annals of Neurology
JF - Annals of Neurology
SN - 0364-5134
IS - 6
ER -