Modulation of cell adhesion systems by prenatal nicotine exposure in limbic brain regions of adolescent female rats.
Maternal smoking during pregnancy (MS) has long-lasting neurobehavioural effects on the offspring. Many MS-associated psychiatric disorders begin or change symptomatology during adolescence, a period of continuous development of the central nervous system. However, the underlying molecular mechanisms are largely unknown. Given that cell adhesion molecules (CAMs) modulate various neurotransmitter systems and are associated with many psychiatric disorders, we hypothesize that CAMs are altered by prenatal treatment of nicotine, the major psychoactive component in tobacco, in adolescent brains. Pregnant Sprague-Dawley rats were treated with nicotine (3 mg/kg.d) or saline via osmotic mini-pumps from gestational days 4 to 18. Female offspring at postnatal day 35 were sacrificed, and several limbic brain regions (the caudate putamen, nucleus accumbens, prefrontal cortex, and amygdala) were dissected for evaluation of gene expression using microarray and quantitative RT-PCR techniques. Various CAMs including neurexin, immunoglobulin, cadherin, and adhesion-GPCR superfamilies, and their intracellular signalling pathways were modified by gestational nicotine treatment (GN). Among the CAM-related pathways, GN has stronger effects on cytoskeleton reorganization pathways than on gene transcription pathways. These effects were highly region dependent, with the caudate putamen showing the greatest vulnerability. Given the important roles of CAMs in neuronal development and synaptic plasticity, our findings suggest that alteration of CAMs contributes to the neurobehavioural deficits associated with MS. Further, our study underscores that low doses of nicotine produce substantial and long-lasting changes in the brain, implying that nicotine replacement therapy during pregnancy may carry many of the same risks to the offspring as MS.
Cao
Junran
J
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, USA.
Dwyer
Jennifer B
JB
Mangold
Jamie E
JE
Wang
Ju
J
Wei
Jinxue
J
Leslie
Frances M
FM
Li
Ming D
MD
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005731:Ganglionic Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D020869:Gene Expression Profiling; D008032:Limbic System / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
D015815:Cell Adhesion Molecules; D005731:Ganglionic Stimulants; D009538:Nicotine