| Maternal cigarette smoking produces profound effects on developmental. Studies in both animals and humans have shown nicotine can act as a neurobehavioral teratogen in a sex-dependent fashion. Despite these effects, and all the public health warnings, some 25% of pregnant women still smoke. Many who agree to quit smoking are placed on nicotine replacement therapies (e.g. nicotine patch). However, chronic exposure to nicotine might be even more detrimental than smoking, particularly to some aspects of brain development. Results of previous studies indicate that the hippocampus and striatum are particularly vulnerable to the disruptive effects of nicotine. In contrast to in utero exposure to nicotine, very little is known about the effects of nicotine exposure during the peripuberal or “adolescent” period on brain development, the time when most people begin to smoke. The brain continues to develop and mature until early adulthood, and limited data suggest that adolescence is another vulnerable period.; The purpose of the study is to assess the effects of nicotine on the developing brain by measuring changes in brain neurochemistry in animals exposed to nicotine prenatally, and/or during the adolescent period as measured by proton magnetic resonance spectroscopy (1H-MRS). 1H-MRS is an imaging tool that allows the measurement of several major brain metabolites. These metabolites are different from those typically measured in biochemical assays. Some of these metabolites include n-acetyl aspartate (NAA), glutamate, gamma amino butyric acid, total creatine, choline containing compounds, alanine, taurine, and myo-inositol. NAA is of particular interest since it is a putative marker of neuronal integrity. Although others have reported marked changes in brain neurochemistry stemming from prenatal or peripuberal nicotine, no changes in NAA concentrations were found, although some other brain metabolites were affected. It is possible that alterations in NAA might have occurred earlier in time, but had normalized by adulthood. Alternatively, the lack of effect of nicotine on NAA might be due to its neuroprotective properties. Since 1H MRS can be performed not only on tissue ex vivo, as performed herein, but also on human brain in vivo, the results of this study will provide the foundation for helping to optimize the design of studies in humans exposed to nicotine during various developmental periods. |
