Developmental Neurotoxicity of Tobacco Smoke Directed Toward Cholinergic and Serotonergic Systems: More Than Just Nicotine

Introduction:
This text discusses a study analyzing the developmental neurotoxicity of tobacco smoke extract (TSE) compared to nicotine alone in pregnant rats and their offspring. The study aimed to distinguish the effects of nicotine from those of other chemicals in tobacco smoke and to evaluate the impact of TSE exposure on brain regions involved in acetylcholine (aCh) and serotonin (5hT) systems. The researchers also compared the effects of TSE and nicotine on cholinergic and serotonergic synaptic markers in male and female offspring.

Key Points:

* The study used TSE prepared from Kentucky Reference cigarettes and administered it to pregnant rats via osmotic mini-pumps, along with two different dose levels of nicotine bitartrate.
* The TSE and low-dose nicotine treatments were chosen to produce maternal nicotine plasma levels comparable to low levels seen with second-hand smoke exposure.
* The researchers assessed the impact on aCh and 5hT synaptic markers in multiple brain regions from adolescence to full adulthood.
* TSE exposure impaired presynaptic cholinergic activity, which was exacerbated by a decrement in nicotinic cholinergic receptor concentrations.
* Both nicotine doses produced presynaptic cholinergic deficits, but these were partially compensated by hyperinnervation and receptor upregulation, effects that were absent with TSE.
* TSE produced deficits in serotonin receptors in females that were not seen with nicotine.
* Regression analysis showed a profound sex difference in the degree to which nicotine could account for overall TSE effects, with nicotine accounting for 36%-46% of TSE effects in males but only 7%-13% in females.

Main Message:
The study highlights that the adverse effects of TSE on neurodevelopment exceed those that can be attributed to just the nicotine present in the mixture. These effects are evident even at second-hand smoke exposure levels. The researchers also found that nicotine itself evoked deficits at low exposures, indicating that "harm reduction" nicotine products do not eliminate the potential for neurodevelopmental damage. The sex differences in the impact of TSE on brain development suggest differing contributions of nicotine in males and females, with TSE components exacerbating the impact of nicotine in males but not females. Overall, the findings emphasize the importance of avoiding second-hand smoke exposure during pregnancy and the potential risks associated with nicotine alternatives, such as e-cigarettes.

Slotkin, Theodore a., Samantha Skavicus, Jennifer Card, ashley Stadler, Edward D. Levin, and Frederic J. Seidler. “Developmental Neurotoxicity of Tobacco Smoke Directed Toward Cholinergic and Serotonergic Systems: More Than Just Nicotine.” Toxicological Sciences 147, no. 1 (September 2015): 178–89. https://doi.org/10.1093/toxsci/kfv123.