Central myelin gene expression during postnatal development in rats exposed to nicotine gestationally

Abstract

Abnormal myelin gene expression in the central nervous system (CNS) is associated with many mental illnesses, including psychiatric disorders and drug addiction. We have previously shown that prenatal exposure to nicotine, the major psychoactive component in cigarette smoke, alters myelin gene expression in the CNS of adolescent rats. To examine whether this effect is specific for adolescents, we examined myelin gene expression in the CNS of juveniles and adults. Pregnant Sprague-Dawley rats were treated with nicotine (3 mg/kg/day; GN) or saline (GS) via osmotic mini pumps from gestational days 4-18. Both male and female offspring were sacrificed at postnatal day P20-21 (juveniles), P35-36 (adolescents), or P59-60 (adults). Three limbic brain regions, the prefrontal cortex (PFC), caudate putamen (CPu), and nucleus accumbens (NAc), were dissected. The expression of genes encoding major myelin components was evaluated using quantitative RT-PCR. We found that GN altered myelin gene expression in juveniles with brain region and sex differences. The pattern of alteration was different from that observed in adolescents. Although these genes were expressed normally in male adults, we observed decreased expression in GN-treated female adults, especially in the CPu. Thus, GN altered myelin gene expression throughout postnatal development and adulthood. The effect on adolescents was quite different from that at other ages, which correlated with the unique symptoms of many psychiatric disorders during adolescence.

Keywords: Development; Gestational; Myelin; Nicotine; Sex; Smoking.

Figure 1

Fold change in mRNA expression of eight myelin genes in the PFC in juvenile, adolescent, and adult rats exposed to gestational nicotine (GN; solid lines) or saline (GS; dotted lines). Data from males and females are presented separately. Data are expressed as means ± SEM (N = 4 or 5). *p <0.05; **p <0.01; ***p <0.001 significantly different from GS controls. Abbreviations for Figures 1–3: Aspa = aspartoacylase; Cnp = 2′,3′-cyclic nucleotide 3′ phosphodiesterase; Gjc3 = gap junction protein, gamma 3; Mal = T-cell differentiation protein; Mbp = myelin basic protein; Mobp = myelin-associated oligodendrocytic basic protein; Mog = myelin oligodendrocyte glycoprotein; and Plp1 = proteolipid protein 1.

Figure 2

Fold change in mRNA expression of eight myelin genes in the CPu in juvenile, adolescent and adult rats exposed to gestational nicotine (GN; solid lines) or saline (GS; dotted lines). Data for males and females are presented separately. Data are expressed as means ± SEM (N = 4 or 5). *p <0.05; **p <0.01; ***p <0.001 significantly different from GS controls.

Figure 3

Fold change in mRNA expression of eight myelin genes in the NAc in juvenile, adolescent, and adult rats exposed to gestational nicotine (GN; solid lines) or saline (GS; dotted lines). Data from males and females are presented separately. Data are expressed as means ± SEM (N = 4 or 5). *p <0.05; **p <0.01; ***p <0.001 significantly different from GS controls.