Paternal nicotine taking elicits heritable sex-specific phenotypes that are mediated by hippocampal Satb2

Maurer, John J.; Wimmer, Mathieu E.; Turner, Cortney A.; Herman, Rae J.; Zhang, Yafang; Ragnini, Kael; Ferrante, Julia; Kimmey, Blake A.; Crist, Richard C.; Pierce, R. Christopher; Schmidt, Heath D.

doi:10.1038/s41380-022-01622-7

Cited by 8 publications

(8 citation statements)

References 66 publications

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“…Our findings are consistent with other reports in the literature on heritable effects of paternal nicotine exposure on offspring behavior in multiple generations that are associated with nicotine-induced epigenetic changes in the spermatozoa of the founder males in animal models (Hawkey et al, 2019; Maurer et al, 2022; McCarthy et al, 2022; McCarthy & Bhide, 2021; Wang et al, 2022; Zeid et al, 2021; Zeid & Gould, 2023; M. Zhang et al, 2020).…”

Section: Transgenerational Transmission Of Adhd-associated Traits In ...supporting

confidence: 93%

“…Accumulating evidence from multiple fields of biology demonstrates that environmental exposures can impact the directly exposed individuals as well as their descendants in multiple generations. In other words, the impact of the environmental exposures can manifest as traits transmitted transgenerationally along maternal and paternal lines of descent, and these environment-induced traits can linger in multiple generations even after the termination of the environmental exposures (Bell & Hellmann, 2019; Bohacek & Mansuy, 2015; Donelan et al, 2020; Goldberg & Gould, 2019; Maurer et al, 2022; McCarthy & Bhide, 2021; Nilsson et al, 2018; Skinner, 2014; Vassoler et al, 2014). Under this scenario, maternal smoking or vaping during pregnancy could produce adverse effects not only for the mother and her children, but also in multiple generations of her descendants.…”

Section: Transgenerational Transmission Of Adhd-associated Traits In ...mentioning

confidence: 99%

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Preclinical Models of Attention Deficit Hyperactivity Disorder: Neurobiology, Drug Discovery, and Beyond

McCarthy,

Spencer,

Bhide

2023

J Atten Disord

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Objective: We offer an overview of ADHD research using mouse models of nicotine exposure. Method: Nicotine exposure of C57BL/6 or Swiss Webster mice occurred during prenatal period only or during the prenatal and the pre-weaning periods. Behavioral, neuroanatomical and neurotransmitter assays were used to investigate neurobiological mechanisms of ADHD and discover candidate ADHD medications. Results: Our studies show that norbinaltorphimine, a selective kappa opioid receptor antagonist is a candidate novel non-stimulant ADHD treatment and that a combination of methylphenidate and naltrexone has abuse deterrent potential with therapeutic benefits for ADHD. Other studies showed transgenerational transmission of ADHD-associated behavioral traits and demonstrated that interactions between untreated ADHD and repeated mild traumatic brain injury produced behavioral traits not associated with either condition alone. Conclusion: Preclinical models contribute to novel insights into ADHD neurobiology and are valuable tools for drug discovery and translation to benefit humans with ADHD.

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Section: Transgenerational Transmission Of Adhd-associated Traits In ...supporting

confidence: 93%

Section: Transgenerational Transmission Of Adhd-associated Traits In ...mentioning

confidence: 99%

Preclinical Models of Attention Deficit Hyperactivity Disorder: Neurobiology, Drug Discovery, and Beyond

McCarthy,

Spencer,

Bhide

2023

J Atten Disord

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“…Recent evidence suggests that a variety of environmental factors produce phenotypes that are inherited by multiple generations descending from the directly exposed individuals ( 55 – 66 ). Whether the anxiety produced by aspartame exposure shows heritability was not known.…”

Section: Resultsmentioning

confidence: 99%

“…These data do not merely add anxiety to the long list of aspartame’s adverse effects, but also raise the previously unrecognized possibility that aspartame’s adverse effects are not limited to the individuals who consume it but persist for generations to come. Therefore, aspartame deserves a place on the list of environmental agents such as hormones, insecticides, and drugs of abuse whose adverse effects are not limited to the exposed individuals but manifest in multiple generations of descendants ( 55 – 66 , 77 ).…”

Section: Discussionmentioning

confidence: 99%

Transgenerational transmission of aspartame-induced anxiety and changes in glutamate-GABA signaling and gene expression in the amygdala

Jones

McCarthy

Vied

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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We report the effects of aspartame on anxiety-like behavior, neurotransmitter signaling and gene expression in the amygdala, a brain region associated with the regulation of anxiety and fear responses. C57BL/6 mice consumed drinking water containing 0.015% or 0.03% aspartame, a dose equivalent of 8 to 15% of the FDA recommended maximum human daily intake, or plain drinking water. Robust anxiety-like behavior (evaluated using open field test and elevated zero maze) was observed in male and female mice consuming the aspartame-containing water. Diazepam, an allosteric modulator of the GABA-A receptor, alleviated the anxiety-like behavior. RNA sequencing of the amygdala followed by KEGG biological pathway analysis of differentially expressed genes showed glutamatergic and GABAergic synapse pathways as significantly enriched. Quantitative PCR showed upregulation of mRNA for the glutamate NMDA receptor subunit 2D ( Grin2d ) and metabotropic receptor 4 ( Grm4 ) and downregulation of the GABA-A receptor associated protein ( Gabarap ) mRNA. Thus, taken together, our diazepam and gene expression data show that aspartame consumption shifted the excitation-inhibition equilibrium in the amygdala toward excitation. Even more strikingly, the anxiety-like behavior, its response to diazepam, and changes in amygdala gene expression were transmitted to male and female offspring in two generations descending from the aspartame-exposed males. Extrapolation of the findings to humans suggests that aspartame consumption at doses below the FDA recommended maximum daily intake may produce neurobehavioral changes in aspartame-consuming individuals and their descendants. Thus, human population at risk of aspartame’s potential mental health effects may be larger than current expectations, which only include aspartame-consuming individuals.

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“…METH is commonly abused illicit drugs among men of reproductive age. Emerging evidences have found that paternal drugs exposure heightened the risk of susceptibility to drugs in the subsequent generations (26–29). Consistent with previous studies, we found that subthreshold doses of METH effectively induced METH-preferred behaviors in METH-sired male mice, indicating an enhanced sensitivities to drugs in F1 mice paternally exposed to METH.…”

Section: Discussionmentioning

confidence: 99%

Paternal methamphetamine exposure induces higher sensitivity to methamphetamine in male offspring through driving ADRB1 on CaMKII-positive neurons in mPFC

Zheng

Wen

et al. 2022

Preprint

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As a highly addictive psychostimulant drug, paternal methamphetamine (METH) exposure enhances the risk of developing addiction to drugs in descendants, however the underlying mechanism remains unclear. Medial prefrontal cortex (mPFC) is a key brain region that implicated in susceptibility to drugs. Here, male adult mice were exposed to METH for 30 days, followed by mating with naive female mice to create the first-generation (F1) mice. In METH-sired mice, baseline levels of c-Fos were decreased but β1-adrenergic receptor (ADRB1) were increased in mPFC by paternal METH exposure. Trained with subthreshold-dosed administration of METH, METH-sired mice exhibited significant METH-preferred behaviors, accompanied with higher levels of c-Fos, ADRB1 and dendritic spines density in mPFC. Importantly, local blocking ADRB1 activity or specific knockdown of ADRB1 on excitatory neurons of mPFC, both efficiently inhibited METH-preferred behaviors in METH-sired mice. In parallel, levels of p-ERK1/2 and ΔFosB, as well as dendritic spine density were reduced by knocking-down mPFC ADRB1 in METH-sired mice. Collectively, these findings suggested that targeting ADRB1 signals in mPFC may represent a promising therapeutic strategy for preventing drug addiction, particularly in progeny with a history of paternal drugs exposure.

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Paternal nicotine taking elicits heritable sex-specific phenotypes that are mediated by hippocampal Satb2

Cited by 8 publications

References 66 publications

Preclinical Models of Attention Deficit Hyperactivity Disorder: Neurobiology, Drug Discovery, and Beyond

Preclinical Models of Attention Deficit Hyperactivity Disorder: Neurobiology, Drug Discovery, and Beyond

Transgenerational transmission of aspartame-induced anxiety and changes in glutamate-GABA signaling and gene expression in the amygdala

Paternal methamphetamine exposure induces higher sensitivity to methamphetamine in male offspring through driving ADRB1 on CaMKII-positive neurons in mPFC

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