Journal article
The neuronal nitric oxide synthase (nNOS) gene and neuroprotection against alcohol toxicity
Cellular and molecular neurobiology, Vol.35(4), pp.449-461
05/2015
DOI: 10.1007/s10571-015-0155-0
PMCID: PMC4380853
PMID: 25672665
Abstract
When a mother abuses alcohol during pregnancy, the offspring can suffer a myriad of abnormalities, collectively known as Fetal Alcohol Spectrum Disorder (FASD). Foremost among these abnormalities is central nervous system dysfunction, which commonly manifests itself as mental retardation, clumsiness, hyperactivity, and poor attention span. These behavior problems are due, in large part, to alcohol-induced neuronal losses in the developing fetal brain. However, not all fetuses are equally affected by maternal alcohol consumption during pregnancy. While some fetuses are severely affected and develop hallmarks of FASD later in life, others exhibit no evident neuropathology or behavioral abnormalities. This variation is likely due, at least in part, to differences in fetal genetics. This review focuses on one particular gene, neuronal nitric oxide synthase, whose mutation worsens alcohol-induced neuronal death, both
in vitro
and
in vivo
. In addition, ectopic expression of the nNOS gene protects neurons against alcohol toxicity. The gene encodes an enzyme that produces nitric oxide (NO), which facilitates the protective effects of neuronal growth factors and which underlies the ability of neurons to resist alcohol toxicity as they mature. Nitric oxide exerts its protective effects against alcohol via a specific signaling pathway, the NO-cGMP-PKG pathway. Pharmacologic manipulation of this pathway could be of therapeutic use in preventing or ameliorating FASD.
Details
- Title: Subtitle
- The neuronal nitric oxide synthase (nNOS) gene and neuroprotection against alcohol toxicity
- Creators
- Bahri Karaçay - Departments of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242Daniel J Bonthius - Departments of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- Cellular and molecular neurobiology, Vol.35(4), pp.449-461
- DOI
- 10.1007/s10571-015-0155-0
- PMID
- 25672665
- PMCID
- PMC4380853
- NLM abbreviation
- Cell Mol Neurobiol
- ISSN
- 0272-4340
- eISSN
- 1573-6830
- Language
- English
- Date published
- 05/2015
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984065835502771
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