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Related Concept Videos

CNS Depressants: Alcohol and Nicotine01:27

CNS Depressants: Alcohol and Nicotine

137
Ethanol, a clear colorless alcohol, has been consumed by humans for millennia, but its effects on the body are far from benign. At lower doses, it induces decreased inhibitions and loquaciousness, leading to its social appeal. However, it can cause severe consequences at higher doses, such as coma and respiratory depression, due to its zero-order elimination kinetics. Chronic ethanol abuse wreaks havoc on multiple organ systems, particularly the CNS and the liver. Abrupt cessation of ethanol...
137

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Chronic nicotine exposure induces molecular and transcriptomic endophenotypes associated with mood and anxiety

Emma K Proud1,2,3, Mar Rodríguez-Ruiz1,2,3, Dana M Gummerson1,2,3

  • 1Addiction Research Group, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.

Frontiers in Pharmacology
|January 7, 2025
PubMed
Summary

Prenatal nicotine exposure disrupts fetal brain development, leading to long-term mood and anxiety issues. This study models these effects using human organoids to reveal molecular and transcriptomic changes.

Keywords:
anxietydepressionhuman cerebral organoidsprenatal developmentprenatal nicotine exposure

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Genetics

Background:

  • Prenatal nicotine exposure (PNE) from maternal smoking is linked to long-term behavioral impairments, including mood and anxiety disorders.
  • The precise molecular and transcriptomic mechanisms underlying PNE's effects on neurodevelopment remain unclear.

Purpose of the Study:

  • To investigate the molecular and transcriptomic consequences of PNE on human brain development.
  • To establish and validate an in vitro model for studying PNE's impact on neuropsychiatric endophenotypes.

Main Methods:

  • Utilized human cerebral organoids for chronic nicotine exposure modeling.
  • Performed molecular analyses and RNA sequencing on organoids at different developmental stages.

Main Results:

  • Short-term nicotine exposure altered neural identity markers, mood/anxiety-related genes, and cortical excitatory/inhibitory balance.
  • RNA sequencing identified transcriptomic changes in genes related to embryonic development, neurogenesis, and DNA binding.
  • Long-term exposure in mature organoids showed persistent disruptions in excitatory/inhibitory balance, reduced neural markers, and altered dopamine receptor expression.

Conclusions:

  • Nicotine-induced neurodevelopmental alterations occur early and persist throughout development.
  • The study validates a human cerebral organoid model for investigating PNE's effects on neuropsychiatric conditions.
  • Findings provide insights into the molecular and transcriptomic basis of neurodevelopmental disorders linked to gestational nicotine exposure.