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Effects of Nicotine on Brain Development

Institution: Cedars-Sinai Medical Center
Investigator(s): Christine Cloak,
Award Cycle: 1999 (Cycle 8) Grant #: 8DT-0170 Award: $55,404
Subject Area: Nicotine Dependence
Award Type: Dissertation Awards
Abstracts

Initial Award Abstract
Maternal cigarette smoking produces profound health effects including premature labor, low birth weight, stillbirth, and neonatal death. Postnatal growth and behavior also are affected. For example, several researchers have reported a possible association between hyperactivity in children and exposure to nicotine, due to maternal cigarette smoking. Despite all the public health warnings, some 25% of pregnant women still smoke. Many who agree to quit smoking are placed on nicotine replacement therapies such as the patch. Nicotine is well known as an important component of cigarette smoke and has been implicated in many of the adverse effects of smoking, on fetal development. A few animal studies support the notion that many effects of cigarette smoking on the brain are due to nicotine and/or its metabolite(s). Thus, chronic exposure to nicotine via the patch might be even more detrimental than smoking to some aspects of brain development. We use a relatively new imaging procedure called proton magnetic resonance spectroscopy ('H-MRS), which can be performed safely on humans. With this technology, we have shown that chronic exposure to nicotine in rats (using a procedure similar to that of the patch) produces long-term effects on the brain. We propose to study this issue further.

Although data clearly show that prenatal exposure to nicotine can be harmful, considerably less is known about the effects of nicotine on the brain during other developmental periods, particularly during puberty. The brain is still maturing rapidly during puberty and, most likely, remains vulnerable to the detrimental effects of nicotine during this period as well. We propose to extend our studies to determine if the "window" of vulnerability that exists during very early development extends into adolescence.

Final Report
Maternal cigarette smoking produces profound health effects including premature labor, low birth weight, stillbirth, and neonatal death. Postnatal growth and behavior also are affected. Despite all the public health warnings many pregnant women still smoke or are placed on nicotine replacement therapies such as the patch. Nicotine is well known as an important component of cigarette smoke and has been implicated in many of the adverse effects of smoking, on fetal development. Although data clearly show that prenatal exposure to nicotine is bad, considerably less is known about the effects of nicotine on the brain during other developmental periods, particularly during puberty. The brain is still maturing rapidly during puberty and, most likely; it remains vulnerable to the detrimental effects of nicotine during this period as well. We extended our studies to determine if the "window" of vulnerability that exists during very early development extends into adolescence. We used a relatively new imaging procedure called proton magnetic resonance spectroscopy (1 H MRS), which can be performed safely on humans. One of the brain metabolites measured by 1 H MRS is the compound n-acetyl-aspartate (NAA). In animals with brain damage or humans with neurodegenerative diseases, NAA concentrations are reduced, in a regionally specific manner. The concentration of this brain metabolite reflects the health and viability of neurons. We hypothesized that developmental nicotine exposure would result in a decrease in NAA concentrations. Our data indicated that NAA concentrations were not reduced in adult offspring exposed to nicotine during development, however other brain metabolites were affected. The primary focus of the study (long-term effects of developmental nicotine exposure) has been completed and written up as the Ph.D. dissertation for Christine Cloak. We are in the process of converting the dissertation into journal, articles for publication. Tissue has been collected but not yet analyzed for the progressive developmental effects of nicotine exposure (early developmental time points). Although our hypotheses concerning the long-term effects of nicotine during development on NAA concentrations in the brain were not supported, other measurable metabolites were effected such as glutamate and myo-inositol. Future studies will focus more on these metabolites.
Publications

Effects on peripuberal nicotine exposure on the brain as detected by 1H-MRS
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Cloak CC, Poland RE ABS
Yr: 2000 Vol: Nbr: Abs: 589 Pg: