Developmental nicotine exposure causes persistent changes in cortical neuron morphology and in behavior. We used microarray screening to identify master transcriptional or epigenetic regulators mediating these effects of nicotine and discovered increases in Ash2l mRNA, encoding a component of a histone methyltransferase complex. We therefore examined genome-wide changes in trimethylation of histone H3 on Lys4 (H3K4me3), a mark induced by the Ash2l complex associated with increased gene transcription. A large proportion of regulated promoter sites were involved in synapse maintenance. We found that Mef2c interacts with Ash2l and mediates changes in H3K4me3. Knockdown of Ash2l or Mef2c abolished nicotine-mediated alterations of dendritic complexity in vitro and in vivo, and attenuated nicotine-dependent changes in passive avoidance behavior. In contrast, overexpression mimicked nicotine-mediated alterations of neuronal structure and passive avoidance behavior. These studies identify Ash2l as a target induced by nicotinic stimulation that couples developmental nicotine exposure to changes in brain epigenetic marks, neuronal structure and behavior.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4925298 | PMC |
| http://dx.doi.org/10.1038/nn.4315 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Embryonic exposure to acetamiprid insecticide induces CD68-positive microglia and Purkinje cell arrangement abnormalities in the cerebellum of neonatal rats.
Toxicol Appl Pharmacol
December 2024
Department of Applied Chemistry and Life Sciences, Graduate School of Engineering, Toyohashi University of Technology, Toyohashi, Aichi 441-8580, Japan; Center for Diversity and Inclusion, Toyohashi University of Technology, Toyohashi, Aichi, 441-8580, Japan. Electronic address:
Concerns have been raised regarding acetamiprid (ACE), a neonicotinoid insecticide, due to its potential neurodevelopmental toxicity. ACE, which is structurally similar to nicotine, acts as an agonist of nicotinic acetylcholine receptors (nAChRs) and resists degradation by acetylcholinesterase. Furthermore, ACE has been reported to disrupt neuronal transmission and induce developmental neurotoxicity and ataxia in animal models.
View Article and Find Full Text PDFE-cigarette Quit Attempts in Emerging Adults: Motivations for Attempts and Predictors of Cessation Barriers.
Nicotine Tob Res
November 2024
Department of Psychological Sciences, William & Mary, VA, USA.
Introduction: Although young adults use electronic nicotine delivery systems (ENDS) more often than any other demographic group, most are interested in cessation; however, little is known about their cessation experiences. The present study examined characteristics associated with quit attempts, reasons for quitting and resources utilized, and psychological symptoms [i.e.
View Article and Find Full Text PDFImpact of Intrauterine Insults on Fetal and Postnatal Cerebellar Development in Humans and Rodents.
Cells
November 2024
Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands.
Many children suffer from neurodevelopmental aberrations that have long-term effects. To understand the consequences of pathological processes during particular periods in neurodevelopment, one has to understand the differences in the developmental timelines of brain regions. The cerebellum is one of the first brain structures to differentiate during development but one of the last to achieve maturity.
View Article and Find Full Text PDFGeneral and Specific Risk and Protective Factors for Cigarette and Electronic Nicotine Delivery System (ENDS) Use.
Prev Sci
December 2024
Social Development Research Group, School of Social Work, University of Washington, Seattle, USA.
Article Synopsis
- The research highlights that the prevalence of electronic nicotine delivery systems (ENDS) among young adults matches that of traditional cigarettes, indicating a need for tailored prevention strategies that address specific risk and protective factors (RPFs) for each.
- Using data from the Community Youth Development Study involving over 4,000 participants, the study explores how general protective factors and substance-specific RPFs influence young adult use of both cigarettes and ENDS from early adolescence to young adulthood.
- Findings reveal that while general protective factors can indirectly affect young adult nicotine use, targeted interventions focusing on cigarette-specific beliefs and peer substance use are necessary for effective prevention of both cigarette and ENDS use.
Molecular impact of nicotine and smoking exposure on the developing and adult mouse brain.
bioRxiv
November 2024
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA.
Article Synopsis
- - Maternal smoking during pregnancy has notable negative effects on the cognitive and behavioral development of offspring, with this study specifically comparing the impacts of nicotine and cigarette smoke on gene expression in developing brains.
- - Researchers found a significant number of differentially expressed genes (1,010 for nicotine and 4,165 for smoking) linked to prenatal exposure, indicating different neurodevelopmental pathways affected by each substance.
- - The findings suggest that while both prenatal nicotine exposure and maternal smoking have specific and overlapping effects on the developing brain, these effects are not replicated in the adult brain, highlighting developmental-stage sensitivity to smoke-related changes.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!