Chronic Nicotine Exposure Systemically Alters microRNA Expression Profiles During Post-Embryonic Stages in Caenorhabditis Elegans.

Chronic nicotine exposure systemically alters microRNA expression profiles during post-embryonic stages in Caenorhabditis elegans.

J Cell Physiol. 2013 Jun 14;
Taki FA, Pan X, Zhang B

Tobacco smoking is associated with many diseases. Addiction is of the most notorious tobacco-related syndrome and is majorly attributed to nicotine. In this study, we employed C. elegans as a biological model to systemically investigate the effect of chronic nicotine exposure on microRNA (miRNA) expression profile and their regulated biochemical pathways. Nicotine treatment (20?µM and 20?mM) was limited to the post-embryonic stage from L1-L4 (?31?hours) period after which worms were collected for genome-wide miRNA profiling. Our results show that nicotine significantly altered the expression patterns of 40 miRNAs. The effect was proportional to the nicotine dose and was expected to have an additive, more robust response. Based on pathway enrichment analyses coupled with nicotine-induced miRNA patterns, we inferred that miRNAs as a system mediates “regulatory hormesis”, manifested in biphasic behavioral and physiological phenotypes. We proposed a model where nicotine addiction is mediated by miRNAs’ regulation of fos-1 and is maintained by epigenetic factors. Thus, our study offers new insights for a better understanding of the sensitivity of early developmental stages to nicotine. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc. HubMed – addiction


Neonatal hypocalcemia, neonatal seizures, and intellectual disability in 22q11.2 deletion syndrome.

Genet Med. 2013 Jun 13;
Cheung EN, George SR, Andrade DM, Chow EW, Silversides CK, Bassett AS

Purpose:Hypocalcemia is a common endocrinological condition in 22q11.2 deletion syndrome. Neonatal hypocalcemia may affect neurodevelopment. We hypothesized that neonatal hypocalcemia would be associated with rare, more severe forms of intellectual disability in 22q11.2 deletion syndrome.Methods:We used a logistic regression model to investigate potential predictors of intellectual disability severity, including neonatal hypocalcemia, neonatal seizures, and complex congenital heart disease, e.g., interrupted aortic arch, in 149 adults with 22q11.2 deletion syndrome. Ten subjects had moderate-to-severe intellectual disability.Results:The model was highly significant (P < 0.0001), showing neonatal seizures (P = 0.0018) and neonatal hypocalcemia (P = 0.047) to be significant predictors of a more severe level of intellectual disability. Neonatal seizures were significantly associated with neonatal hypocalcemia in the entire sample (P < 0.0001), regardless of intellectual level. There was no evidence for the association of moderate-to-severe intellectual disability with other factors such as major structural brain malformations in this sample.Conclusion:The results suggest that neonatal seizures may increase the risk for more severe intellectual deficits in 22q11.2 deletion syndrome, likely mediated by neonatal hypocalcemia. Neonatal hypocalcemia often remains unrecognized until the postseizure period, when damage to neurons may already have occurred. These findings support the importance of early recognition and treatment of neonatal hypocalcemia and potentially neonatal screening for 22q11.2 deletions.Genet Med advance online publication 13 June 2013Genetics in Medicine (2013); doi:10.1038/gim.2013.71. HubMed – addiction


Clozapine Toxicity and Hepatitis.

J Clin Psychopharmacol. 2013 Jun 12;
Brown CA, Telio S, Warnock CA, Wong AH

HubMed – addiction