Effects of maternal nicotine injections on brain development in the rat: ornithine decarboxylase activity, nucleic acids and proteins in discrete brain regions.

Fetal exposure to nicotine via maternal cigarette smoking produces intrauterine growth retardation and postnatal behavioral abnormalities. In this study, biochemical characteristics of brain development were compared in normal rats and in rats whose mothers received chronic nicotine injections throughout pregnancy. Nicotine exposure produced a persistent elevation of fetal ornithine decarboxylase activity preferentially in brain; in keeping with this selectivity, there was no evidence of the sparing of brain growth which ordinarily accompanies non-specific toxic insult. After birth, DNA synthesis was suppressed throughout the brain and there was a subsequent rebound during the phase of "catch-up" growth. Evidence was also obtained for regional selectivity of the adverse effects of maternal nicotine injections: the effects on DNA synthesis and levels were most profound in cerebellum (a region which matures postnatally) and growth-impairment was least evident in midbrain & brainstem, an early-maturing region. The maternal nicotine group also displayed desynchronization of the ontogenetic patterns of DNA, RNA and proteins in every brain region. These data indicate that maternally-injected nicotine compromises early biochemical events which delineate brain cell replication and differentiation; these alterations are eventually translated into abnormalities in development of specific brain regions.

Duke Scholars

Author Theodore Alan Slotkin Pharmacology & Cancer Biology

Author Frederic J. Seidler Pharmacology & Cancer Biology