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Effects of paternal nicotine taking on gene expression in dorsal hippocampus of drug naïve male offspring

ABSTRACT: Effects of paternal nicotine taking on gene expression in dorsal hippocampus of drug naïve male offspring

PROVIDER: PRJNA821090 | ENA |

REPOSITORIES: ENA

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Effects of paternal nicotine taking on gene expression in dorsal hippocampus of drug naïve male offspring

Project description:Nicotine intake, whether through tobacco smoking or e-cigarettes, remains a global health concern. An emerging preclinical literature indicates that parental nicotine exposure produces behavioral, physiological, and molecular changes in subsequent generations. However, the heritable effects of voluntary parental nicotine taking are unknown. Here, we show increased acquisition of nicotine taking in male and female offspring of sires that self-administered nicotine. In contrast, self-administration of sucrose and cocaine were unaltered in male and female offspring suggesting that the intergenerational effects of paternal nicotine taking may be reinforcer specific. Further characterization revealed memory deficits and increased anxiety-like behaviors in drug-naïve male, but not female, offspring of nicotine-experienced sires. Using an unbiased, genome-wide approach, we discovered that these phenotypes were associated with decreased expression of Satb2, a transcription factor known to play important roles in synaptic plasticity and memory formation, in the hippocampus of nicotine-sired male offspring. This effect was sex-specific as no changes in Satb2 expression were found in nicotine-sired female offspring. Finally, increasing Satb2 levels in the hippocampus prevented the escalation of nicotine intake and rescued the memory deficits associated with paternal nicotine taking in male offspring. Collectively, these findings indicate that paternal nicotine taking produces heritable sex-specific molecular changes that promote addiction-like phenotypes and memory impairments in male offspring. To characterize the molecular changes associated with the heritable effects of paternal nicotine taking, an unbiased, whole-genome analysis was used to characterize the hippocampal transcriptome of drug-naïve F1 males

2022-04-01 | GSE199661 | GEO

Paternal nicotine exposure promotes hepatic fibrosis in offspring

Project description:Paternal nicotine exposure can alter phenotypes in future generations. To explore whether paternal nicotine exposure affects the hepatic repair to chronic injury which would lead to hepatic fibrosis in offspring, we establish a paternal effect model based on nicotine exposure in mice.

2020-07-31 | GSE155308 | GEO

Paternal nicotine exposure alters hepatic xenobiotic metabolism in offspring

Project description:Although it is increasingly accepted that some paternal environmental conditions can influence phenotypes in future generations, it remains unclear whether phenotypes induced in offspring represent specific responses to particular aspects of the paternal exposure history, or whether they represent a more generic response to paternal “quality of life”. To establish a paternal effect model based on a specific ligand-receptor interaction and thereby enable pharmacological interrogation of the offspring phenotype, we explored the effects of paternal nicotine administration on offspring phenotype in mouse. We show that paternal exposure to chronic nicotine induced a broad protective response to xenobiotic exposure in the next generation. This effect manifested as increased survival following an injection of toxic levels of nicotine, was specific to male offspring, and was only observed after these offspring were first acclimated to low levels of nicotine for a week. Importantly, offspring xenobiotic resistance was documented not only for toxic nicotine challenge, but also for toxic cocaine challenge, indicating that paternal nicotine exposure reprograms offspring to become broadly resistant to environmental toxins. Mechanistically, the reprogrammed state was characterized by enhanced clearance of nicotine in drug-acclimated animals, and we found that isolated hepatocytes displayed upregulation of enzymes that metabolize xenobiotics. Taken together, our data show that paternal nicotine exposure induces a protective phenotype in offspring by enhancing metabolic tolerance to xenobiotics in the environment.

2017-02-02 | GSE92240 | GEO

Paternal nicotine enhances fear memory, reduces nicotine administration and alters hippocampal genetic and neural function in offspring [Bisulfite-seq]

Project description:We tested the effects of chronic paternal nicotine exposure in C57BL6/J mice on hippocampal DNA methylation in F1 offspring.

2019-11-25 | GSE140904 | GEO

Paternal nicotine enhances fear memory, reduces nicotine administration and alters hippocampal genetic and neural function in offspring [RNA-seq]

Project description:We tested the effects of chronic paternal nicotine exposure in C57BL6/J mice on hippocampal RNA expression in F1 offspring.

2019-11-25 | GSE140903 | GEO

Paternal nicotine exposure promotes hepatic fibrosis in offspring

Project description:Paternal nicotine exposure promotes hepatic fibrosis in offspring

| PRJNA649278 | ENA

Intergenerational programming of hepatic xenobiotic response by paternal Nicotine exposure

Project description:Although it is increasingly accepted that some paternal environmental conditions can influence phenotypes in future generations, it generally remains unclear whether the phenotypes induced in offspring represent specific responses to particular aspects of the paternal exposure history, or whether they represent a more generic response to paternal “quality of life”. To establish a paternal effect model based on a known ligand-receptor interaction and thereby enable pharmacological interrogation of the specificity of the offspring response, we explored the effects of paternal nicotine administration on offspring phenotype in mouse. We show that chronic paternal exposure to nicotine prior to reproduction induced a broad protective response to multiple xenobiotics in the next generation. This effect manifested as increased survival following an injection of toxic levels of either nicotine or of cocaine, was specific to male offspring, and was only observed after offspring were first acclimated to sublethal doses of nicotine or cocaine. Mechanistically, the reprogrammed state was characterized by enhanced clearance of nicotine in drug-acclimated animals, accompanied by hepatic upregulation of genes involved in xenobiotic metabolism. Surprisingly, this protective effect could also be induced by paternal exposure to a nicotinic receptor antagonist as well as to nicotine, suggesting that paternal xenobiotic exposure, rather than nicotinic receptor signaling, is likely to be responsible for programming of offspring drug resistance. Taken together, our data show that paternal drug exposure can induce a protective phenotype in offspring by enhancing metabolic tolerance to xenobiotics in the environment.

2017-02-01 | GSE94059 | GEO

miRNA expression profiles in the dorsal striatum of a mouse model of nicotine withdrawal

Project description:Nicotine withdrawal can diversely affect brain gene expression patterns. In the brain, the dorsal striatum is a hub of nicotine dependence. Previous studies have shown that nicotine dependence leads to functional alterations in the dorsal striatum. miRNAs are small non-coding RNAs that regulates cellular functions and dysfunctions. Here, we performed small RNA sequencing from the dorsal striatum of mice at 7 days after nicotine withdrawal. Our results show that nicotine withdrawal does not notably impact miRNA expression profile in the dorsal striatum, but a few miRNAs were significantly altered in response to nicotine withdrawal. These results suggest that nicotine withdrawal has a small but significant impact on the miRNA expression profile in the mouse dorsal striatum.

2024-10-31 | GSE280738 | GEO

Paternal nicotine enhances fear memory, reduces nicotine administration and alters hippocampal genetic and neural function in offspring

Project description:Paternal nicotine enhances fear memory, reduces nicotine administration and alters hippocampal genetic and neural function in offspring

| PRJNA591361 | ENA

Paternal nicotine enhances fear memory, reduces nicotine administration and alters hippocampal genetic and neural function in offspring [RNA-seq]

Project description:Paternal nicotine enhances fear memory, reduces nicotine administration and alters hippocampal genetic and neural function in offspring [RNA-seq]

| PRJNA591365 | ENA

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