Prenatal nicotine exposure in mice induces sex-dependent anxiety-like behavior, cognitive deficits, hyperactivity, and changes in the expression of glutamate receptor associated-genes in the prefrontal cortex

Polli, Filip S.; Scharff, Malthe B.; Ipsen, Theis H.; Aznar, Susana; Kohlmeier, Kristi A.; Andreasen, Jesper T.

doi:10.1016/j.pbb.2020.172951

Cited by 29 publications

(14 citation statements)

References 103 publications

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“…Specifically, muscimol application was associated with a significantly lower mean amplitude in the PNEs when decreases were elicited; whereas, application of 1 was associated with a significantly higher amplitude in the young PNE males when decreases were induced. Treatment-based differences between results obtained with muscimol and 1 were unsurprising at they suggest differential alterations in subunit composition of membrane GABA A R associated with early life nicotine exposure, which is similar to findings noted in the PNE animal in the hippocampus, prefrontal cortex and brain stem in the subunit composition of AMPA and NMDA glutamate receptors (Parameshwaran et al, 2012;, 2019aPolli, Scharff, et al, 2020). Although we did not use more subunit-specific agonists of the GABA A R, future studies can be designed to elucidate which subunits were altered, which would likely have differential effects on the kinetics of membrane currents mediated by the GABA A R.…”

Section: Gaba Aρ Rsupporting

confidence: 57%

“…Every two days, pups underwent a health assessment based on appearance, and at no point during this study were any health issues in pups of either treatment group apparent. The presence of cotinine levels, which is a well-established marker of nicotine exposure during pregnancy, has been detected in our laboratory in pups exposed to nicotine in this model (Polli, Scharff, et al, 2020). Specifically, we have shown that PNE pups had a plasma concentration average of 152 ng/ml of cotinine, whereas, cotinine was not detected in controls (Polli, Scharff, et al, 2020).…”

Section: Prenatal Nicotine Modelmentioning

confidence: 50%

“…The presence of cotinine levels, which is a well-established marker of nicotine exposure during pregnancy, has been detected in our laboratory in pups exposed to nicotine in this model (Polli, Scharff, et al, 2020). Specifically, we have shown that PNE pups had a plasma concentration average of 152 ng/ml of cotinine, whereas, cotinine was not detected in controls (Polli, Scharff, et al, 2020). We did not implement controls for the effects of saccharine, but in other mouse studies, saccharine is routinely added to the drinking water to enhance palatability of the nicotine solution, and as controls are exposed to saccharine as well, differences are ascribed to effects of nicotine (Alkam et al, 2017;Pauly, Sparks, Hauser, & Pauly, 2004).…”

Section: Prenatal Nicotine Modelmentioning

confidence: 63%

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Sex‐specific alterations in GABA receptor‐mediated responses in laterodorsal tegmentum are associated with prenatal exposure to nicotine

Eliasen

Krall

Frølund

et al. 2020

Developmental Neurobiology

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Smoking during pregnancy is associated with deleterious physiological and cognitive effects on the offspring, which are likely due to nicotine‐induced alteration in the development of neurotransmitter systems. Prenatal nicotine exposure (PNE) in rodents is associated with changes in behaviors controlled in part by the pontine laterodorsal tegmentum (LDT), and LDT excitatory signaling is altered in a sex and age‐dependent manner by PNE. As effects on GABAergic LDT signaling are unknown, we used calcium imaging to evaluate GABAA receptor‐ (GABAAR as well as GABAA‐ρR) and GABAB receptor (GABABR)‐mediated calcium responses in LDT brain slices from female and male PNE mice in two different age groups. Overall, in older PNE females, changes in calcium induced by stimulation of GABAAR and GABABR, including GABAA‐ρR were shifted toward calcium rises. In both young and old males, PNE was associated with alterations in calcium mediated by all three receptors; however, the GABAAR was the most affected. These results show for the first time that PNE is associated with alterations in GABAergic transmission in the LDT in a sex‐ and age‐dependent manner, and these data are the first to show PNE‐associated alterations in functionality of GABA receptors in any nucleus. PNE‐associated alterations in LDT GABAergic transmission within the LDT would be expected to alter output to target regions and could play a role in LDT‐implicated, negative behavioral outcomes following gestational exposure to smoking. Accordingly, our data provide further supportive evidence of the importance of eliminating the consumption of nicotine during pregnancy.

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Section: Gaba Aρ Rsupporting

confidence: 57%

Section: Prenatal Nicotine Modelmentioning

confidence: 50%

Section: Prenatal Nicotine Modelmentioning

confidence: 63%

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Sex‐specific alterations in GABA receptor‐mediated responses in laterodorsal tegmentum are associated with prenatal exposure to nicotine

Eliasen

Krall

Frølund

et al. 2020

Developmental Neurobiology

Self Cite

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show abstract

“…Validation of the PNE NMRI model via maternal drinking water model was provided by evaluation and detection of high cotinine levels in newborn PNE pups, confirming the gestational nicotine exposure of the fetus following maternal ingestion of nicotine via the drinking water[ 116 ]. Behavioral tasks were also employed in order to characterize the behavioral phenotype associated with early-life exposure to nicotine via the drinking water[ 116 ].…”

Section: Pne Effects On Cognitive-based Behaviors That Could Involve ...mentioning

confidence: 91%

Prenatal nicotine alters development of the laterodorsal tegmentum: Possible role for attention-deficit/hyperactivity disorder and drug dependence

Polli¹,

Kohlmeier²

2022

WJP

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As we cycle between the states of wakefulness and sleep, a bilateral cholinergic nucleus in the pontine brain stem, the laterodorsal tegmentum (LDT), plays a critical role in controlling salience processing, attention, behavioral arousal, and electrophysiological signatures of the sub- and microstates of sleep. Disorders involving abnormal alterations in behavioral and motivated states, such as drug dependence, likely involve dysfunctions in LDT signaling. In addition, as the LDT exhibits connectivity with the thalamus and mesocortical circuits, as well as receives direct, excitatory input from the prefrontal cortex, a role for the LDT in cognitive symptoms characterizing attention-deficit/hyperactivity disorder (ADHD) including impulsivity, inflexibility, and dysfunctions of attention is suggested. Prenatal nicotine exposure (PNE) is associated with a higher risk for later life development of drug dependence and ADHD, suggesting alteration in development of brain regions involved in these behaviors. PNE has been shown to alter glutamate and cholinergic signaling within the LDT. As glutamate and acetylcholine are major excitatory mediators, these alterations would likely alter excitatory output to target regions in limbic motivational circuits and to thalamic and cortical networks mediating executive control. Further, PNE alters neuronal development and transmission within prefrontal cortex and limbic areas that send input to the LDT, which would compound effects of differential processing within the PNE LDT. When taken together, alterations in signaling in the LDT are likely to play a role in negative behavioral outcomes seen in PNE individuals, including a heightened risk of drug dependence and ADHD behaviors.

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“…It is unclear whether the cardiovascular effects that have been observed in adult offspring following prenatal exposure to CNS stimulants result from a direct effect of these drugs on the developing heart and vasculature or if they are secondary to stimulant-induced changes in the CNS. Previous work has demonstrated that prenatal exposure to cocaine (5), nicotine (124,125), and methamphetamine (2, 3) lead to sex-dependent changes in the CNS of adult rodents. The ability of these drugs to induce sex-dependent changes in the developing nervous system that subsequently impact cardiovascular function could potentially provide a mechanism by which CNS stimulants induce sex dependent changes in the adult heart and vasculature.…”

Section: Unanswered Questions and Future Directionsmentioning

confidence: 99%

Does Prenatal Exposure to CNS Stimulants Increase the Risk of Cardiovascular Disease in Adult Offspring?

Rorabaugh

2021

Front. Cardiovasc. Med.

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Prenatal exposure to an adverse uterine environment can have long lasting effects on adult offspring through DNA methylation, histone acetylation, and other epigenetic effects that alter gene expression and physiology. It is well-known that consumption of CNS stimulants such as caffeine, nicotine, amphetamines, and cocaine during pregnancy can adversely impact the offspring. However, most work in this area has focused on neurological and behavioral outcomes and has been limited to assessments in young offspring. The impact of prenatal exposure to these agents on the adult cardiovascular system has received relatively little attention. Evidence from both animal and human studies indicate that exposure to CNS stimulants during the gestational period can negatively impact the adult heart and vasculature, potentially leading to cardiovascular diseases later in life. This review discusses our current understanding of the impact of prenatal exposure to cocaine, methamphetamine, nicotine, and caffeine on the adult cardiovascular system.

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Prenatal nicotine exposure in mice induces sex-dependent anxiety-like behavior, cognitive deficits, hyperactivity, and changes in the expression of glutamate receptor associated-genes in the prefrontal cortex

Cited by 29 publications

References 103 publications

Sex‐specific alterations in GABA receptor‐mediated responses in laterodorsal tegmentum are associated with prenatal exposure to nicotine

Sex‐specific alterations in GABA receptor‐mediated responses in laterodorsal tegmentum are associated with prenatal exposure to nicotine

Prenatal nicotine alters development of the laterodorsal tegmentum: Possible role for attention-deficit/hyperactivity disorder and drug dependence

Does Prenatal Exposure to CNS Stimulants Increase the Risk of Cardiovascular Disease in Adult Offspring?

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