Prenatal Nicotine Exposure and Molecular Mechanisms of Memory Impairment

Abstract

Prenatal nicotine exposure in the form of active maternal smoking is a major risk factor for several harmful effects in the children. These effects include reduced motor skills, poor IQ scores and most importantly learning and memory deficits. Several animal studies have also shown that these harmful effects could arise due to prenatal nicotine exposure. However, the physiological mechanisms underlying the learning and memory deficits have poorly been studied. In this study a rat model of prenatal nicotine exposure, in which pregnant dams received a subcutaneous dose of 6 mg/kg/day nicotine throughout gestation via osmotic mini pumps implanted beneath shoulder skin, was utilized. Birth weights and body weights of rats after 2 weeks were measured. In addition surface righting reflex, negative geotaxis, open field activity, rotorod test, forced swim test and Y maze test were performed in young rats to assess motor coordination, activity and hippocampal based memory acquisition. Lipid peroxide, protein carbonyl and reactive oxygen species were also analyzed to assess any neurochemical changes in the hippocampus. To specifically address hippocampus dependent memory impairments observed in the young animals, detailed electrophysiological analyses were performed. The electrophysiological analyses included assessment of basal synaptic transmission and long tem potentiation (LTP) in Shaffer collateral-CA1 synapses, AMPA receptor mediated whole cell currents from CA1 pyramidal neurons and single channel synaptic AMPA receptor currents from hippocampus. Result of these studies revealed that prenatal nicotine exposure results in reduced body weight, motor coordination and strength and hippocampal memory. Results of electrophysiological studies showed decreased basal synaptic transmission, LTP, AMPA receptor mediated whole cell currents and single channel currents providing support that decreased synaptic function in the hippocampus could be a mechanism underlying cognitive deficits due to prenatal nicotine exposure. To test whether these synaptic impairments are long lasting, LTP, basal synaptic transmission, AMPA receptor mediated whole cell currents and single channel currents were analyzed in 2 months old young adult rats which showed deficits in these electrophysiological measures. This suggests that compromise in hippocampal synaptic function could be long lasting. Overall this study provides evidence for physiological mechanisms that could potently diminish memory processes in prenatal nicotine exposed animals.