Tobacco Nitrosamine Exposures Contribute to Fetal Alcohol Spectrum Disorder Associated Cerebellar Dysgenesis
- Edward Re
- Ming Tong
- Suzanne de la Monte
Abstract
Variability in the phenotypic features and severity of fetal alcohol spectrum disorder (FASD) is not fully linked to alcohol dose. We hypothesize that FASD-type neurodevelopmental abnormalities may be caused by exposures to the tobacco-specific nitrosamine, NNK, since a high percentage of pregnant women who drink also smoke. In vitro experiments using PNET2 human cerebellar neuronal cultures examined ethanol and NNK effects on viability and mitochondrial function. Early postnatal rat cerebellar slice cultures were used to examine effects of ethanol and NNK on cerebellar histology and neuroglial and stress protein expression. Ethanol (50 mM) decreased viability and ATP content and increased mitochondrial mass, while NNK (100 uM or higher) selectively inhibited mitochondrial function. The slice culture studies demonstrated striking adverse effects of ethanol, NNK and ethanol+NNK exposures manifested by architectural disorganization of the cortex with relative reductions of internal granule cells, increases in external granule cells, and loss of Purkinje cells. Ethanol, NNK, and ethanol+NNK inhibited expression of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), and increased levels of 4-hydroxynonenal (HNE). In addition, ethanol increased activated Caspase 3, NNK decreased tau and phospho-tau, and ethanol+NNK inhibited expression of Aspartyl-beta-hydroxylase (ASPH), which mediates neuronal migration. In conclusion, ethanol and NNK were shown to exert independent but overlapping adverse effects on cerebellar cortical development, neuronal viability, function, and neuroglial protein expression. These findings support our hypothesis that NNK exposures via tobacco smoking in pregnancy can contribute to FASD-associated neurodevelopmental abnormalities.
- Full Text:
PDF
- DOI:10.5539/ijb.v8n3p10
Journal Metrics
h-index (December 2021 ): 37
i10-index (December 2021 ): 149
h5-index (December 2021 ): N/A
h5-median (December 2021 ): N/A
Index
- ACNP
- AGRICOLA
- BASE (Bielefeld Academic Search Engine)
- CAB Abstracts
- CiteFactor
- CNKI Scholar
- CrossRef
- DTU Library
- Elektronische Zeitschriftenbibliothek (EZB)
- Excellence in Research for Australia (ERA)
- Google Scholar
- Infotrieve
- LIVIVO (ZB MED)
- LOCKSS
- Max Planck Institutes
- MIAR
- PKP Open Archives Harvester
- Qualis/CAPES
- ResearchGate
- ROAD
- SafetyLit
- SHERPA/RoMEO
- Technische Informationsbibliothek (TIB)
- Universe Digital Library
- WorldCat
Contact
- Ryan JonesEditorial Assistant
- ijb@ccsenet.org