Neuroinflammatory and Behavioral Outcomes Measured in Adult Offspring of Mice Exposed Prenatally to E-Cigarette Aerosols

产前暴露于电子香烟气溶胶的小鼠成年后代的神经炎症和行为结果测量

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作者:Jamie S Church, Fiona Chace-Donahue, Jason L Blum, Jill R Ratner, Judith T Zelikoff, Jared J Schwartzer

Background

In an effort to decrease the rates of smoking conventional tobacco cigarettes, electronic cigarettes (e-cigarettes) have been proposed as an effective smoking cessation tool. However, little is known about their toxicological impacts. This is concerning given that e-cigarette use is perceived as less harmful than conventional tobacco cigarettes during pregnancy for both the mother and fetus.

Discussion

These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.

Methods

Pregnant female CD-1 mice were randomly assigned to one of three treatment groups (n=8−10pergroupn=8-10pergroup<math><mrow><mi>n</mi><mo>=</mo><mn>8</mn><mo>-</mo><mn>10</mn><mtext> </mtext><mtext>per</mtext><mtext> </mtext><mtext>group</mtext></mrow></math>) and exposed daily to either filtered air, propylene glycol and vegetable glycerol (50:50 PG/VG vehicle), or to PG/VG with 16mg/mL16mg/mL<math><mrow><mn>16</mn><mspace></mspace><mi>mg</mi><mo>/</mo><mi>mL</mi></mrow></math> nicotine (+Nic+Nic<math><mrow><mo>+</mo><mtext>Nic</mtext></mrow></math>). Whole-body exposures were carried out for 3 h/d, 7 d/week, from gestational day (GD)0.5 until GD17.5. Adult male and female offspring (8 weeks old) were assessed across a battery of behavioral assessments followed by region-specific quantification of brain cytokines using multiplex immunoassays.

Objective

The goal of this study was to test the neurodevelopmental consequences of maternal e-cigarette use on adult offspring behavior and neuroimmune outcomes.

Results

Adult offspring of both sexes exposed to +Nic+Nic<math><mrow><mo>+</mo><mtext>Nic</mtext></mrow></math> exhibited elevated locomotor activity in the elevated plus maze and altered stress-coping strategies in the forced swim task. Moreover, male and female offspring exposed to PG/VG with and without nicotine had a 5.2% lower object discrimination score in the novel object recognition task. In addition to differences in offspring behavior, maternal e-cigarette exposure with nicotine led to a reduction in interleukin (IL)-4 and interferon-gamma (IFNγIFNγ<math><mrow><mtext>IFN</mtext><mi>γ</mi></mrow></math>) in the diencephalon, as well as lower levels of hippocampal IFNγIFNγ<math><mrow><mtext>IFN</mtext><mi>γ</mi></mrow></math> (females only). E-cigarette exposure without nicotine resulted in a 2-fold increase of IL-6 in the cerebellum.

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