Sex-selective hippocampal alterations after adolescent nicotine administration: effects on neurospecific proteins.
Nicotine is a neuroteratogen that targets cell development and synaptic function into adolescence, when smoking typically commences. We used a rat model of adolescent nicotine exposure to characterize the types of cells involved in hippocampal alterations. Nicotine was given to adolescent rats by minipump infusions from postnatal day (PN) 30 to PN47.5, using a dose rate (6 mg/kg/day) that replicates the plasma nicotine levels found in smokers. We examined specific neuronal and astrocyte proteins in the posttreatment period (PN50, PN60), when deficits in neurotransmission first appear: glial fibrillary acidic protein (GFAP), a marker for astrocytes; neurofilament 68-kDa protein (NF68), which is concentrated in the neuronal perikaryon and proximal neurites; and neurofilament 200-kDa protein (NF200), which is found in axonal projections distal to the perikaryon. Adolescent nicotine treatment evoked a significant decrease across all three markers, with the effect restricted to females and showing intensification between PN50 and PN60. These changes correspond to the sex-selectivity and temporal course over which other biomarkers indicate hippocampal cell damage and alterations in synaptic function. We conclude that administration of nicotine to adolescent rats alters neuroproteins in the female hippocampus during withdrawal, effects that could contribute to neurobehavioral deficits.
Xu, Z; Seidler, FJ; Tate, CA; Garcia, SJ; Slikker, W; Slotkin, TA
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