Skip to content
DraconiticResearch
Search Sources API
203,234 studies31 sourcesUpdated 43 min ago
Peer-reviewedCC BY-NC-ND 4.0Journal of Neurochemistry

Examining the Impact of Neurodevelopmental Nicotine Exposure on Cortical Excitation/Inhibition Homeostasis Markers in a Cerebral Organoid Model of Schizophrenia

  • Kuralay Zhaksylyk1,2
  • Mohammed H. Sarikahya1,2
  • Enzo Pérez‐Valenzuela1,2
  • Daniel B. Hardy3,4,5
  • Walter J. Rushlow1,2,3
  • Steven R. Laviolette1,2,3,6
6 affiliations
  1. 1Addiction Research Group University of Western Ontario London Ontario Canada
  2. 2Department of Anatomy and Cell Biology University of Western Ontario London Ontario Canada
  3. 3Lawson Health Research Institute University of Western Ontario London Ontario Canada
  4. 4Department of Physiology and Pharmacology University of Western Ontario London Ontario Canada
  5. 5Division of Maternal, Fetal and Newborn Health, Childrens Health Research Institute (CHRI) University of Western Ontario London Ontario Canada
  6. 6Department of Psychiatry University of Western Ontario London Ontario Canada
Read full textPDFDOICite

Abstract

Schizophrenia (SCZ) is a severe neuropsychiatric disorder thought to arise from an interplay between genetic susceptibility and environmental risk factors, including prenatal nicotine exposure (PNE). Although PNE has been associated with increased risk for SCZ, the underlying mechanisms remain poorly understood. Both SCZ and PNE have independently been linked to excitation/inhibition (E/I) imbalance, suggesting that PNE may exacerbate neurodevelopmental disruptions associated with SCZ. This study employed a cerebral organoid model derived from human induced pluripotent stem cells to examine the impact of PNE on E/I‐related pathways in SCZ. Organoids were chronically exposed to nicotine and analyzed using immunofluorescence and quantitative polymerase chain reaction. Results revealed disease‐associated differences between SCZ and control organoids in a neural progenitor cell marker and several GABAergic, glutamatergic and cholinergic markers. Specifically, SCZ‐derived organoids showed reduced SOX2 and GABAergic differentiation and synthesis markers (LHX6, GAD1/GAD67 and SST), increased select GABAergic and glutamatergic markers (GABRA1, GABRA2, GABBR2 and GRIA1), and alterations in multiple cholinergic synthesis, degradation and receptor markers. Effects of nicotine were more modest and limited to CCK, SLC6A1 and SST. These findings support a role for E/I imbalance in SCZ pathophysiology and offer insights into how early‐life exposures may influence disease risk.

Related

  1. Examining the links between vitamin C and schizophrenia spectrum disorders: a systematic review and meta-analysis on circulating levels and supplementation outcomes.
    Gaatha Suresh, Jeevitha Gada Chengaiyan, Fatemeh Dabaghzadeh +1
    Frontiers in nutritionPeer-reviewedCC BYFull textPsychiatry & mental healthEurope PMCPMC
  2. Rethinking childhood-onset schizophrenia: neurodevelopmental comorbidities shape the psychopathological profile
    Michelangelo Di Luzio, Maria Pontillo, Barbara D’Aiello +5
    Frontiers in PsychiatryPeer-reviewedCC BY 4.0Full textPsychiatry & mental healthPMCCrossrefEurope PMC
  3. Neurophysiological excitation/inhibition imbalance in young adults burdened with childhood interpersonal trauma
    Alejandro Orozco Valero, Natalia Kopiś-Posiej, Víctor Rodríguez-González +6
    Translational PsychiatryPeer-reviewedCC BY-NC-ND 4.0Full textPsychiatry & mental healthCrossref
  4. Convergent multidimensional neural phenotypes in human patients and schizophrenia-relevant mouse models identify reduced recurrent excitation in cortical circuits
    K. Wengler, J. P. Hamm, Y. Shymkiv +3
    medRxivPreprintCC BY-NC-NDFull textPsychiatry & mental healthmedRxiv
  5. Transcranial photobiomodulation rebalances cortical excitation/inhibition in young adults with attention deficit/hyperactivity disorder
    X. Yuan, Y. Wang, C. Dang +5
    medRxivPreprintCC BY-NC-NDFull textPsychiatry & mental healthmedRxiv

Cite

BibTeXRIS
BibTeX
@article{zhaksylyk2026examining,
  title = {{Examining the Impact of Neurodevelopmental Nicotine Exposure on Cortical Excitation/Inhibition Homeostasis Markers in a Cerebral Organoid Model of Schizophrenia}},
  author = {Kuralay Zhaksylyk and Mohammed H. Sarikahya and Enzo Pérez‐Valenzuela and Daniel B. Hardy and Walter J. Rushlow and Steven R. Laviolette},
  journal = {Journal of Neurochemistry},
  year = {2026},
  month = oct,
  doi = {10.1111/jnc.70548},
  url = {https://doi.org/10.1111/jnc.70548},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Examining the Impact of Neurodevelopmental Nicotine Exposure on Cortical Excitation/Inhibition Homeostasis Markers in a Cerebral Organoid Model of Schizophrenia
AU  - Kuralay Zhaksylyk
AU  - Mohammed H. Sarikahya
AU  - Enzo Pérez‐Valenzuela
AU  - Daniel B. Hardy
AU  - Walter J. Rushlow
AU  - Steven R. Laviolette
PY  - 2026
DA  - 2026/10/27
JO  - Journal of Neurochemistry
DO  - 10.1111/jnc.70548
UR  - https://doi.org/10.1111/jnc.70548
AB  - Schizophrenia (SCZ) is a severe neuropsychiatric disorder thought to arise from an interplay between genetic susceptibility and environmental risk factors, including prenatal nicotine exposure (PNE). Although PNE has been associated with increased risk for SCZ, the underlying mechanisms remain poorly understood. Both SCZ and PNE have independently been linked to excitation/inhibition (E/I) imbalance, suggesting that PNE may exacerbate neurodevelopmental disruptions associated with SCZ. This study employed a cerebral organoid model derived from human induced pluripotent stem cells to examine the impact of PNE on E/I‐related pathways in SCZ. Organoids were chronically exposed to nicotine and analyzed using immunofluorescence and quantitative polymerase chain reaction. Results revealed disease‐associated differences between SCZ and control organoids in a neural progenitor cell marker and several GABAergic, glutamatergic and cholinergic markers. Specifically, SCZ‐derived organoids showed reduced SOX2 and GABAergic differentiation and synthesis markers (LHX6, GAD1/GAD67 and SST), increased select GABAergic and glutamatergic markers (GABRA1, GABRA2, GABBR2 and GRIA1), and alterations in multiple cholinergic synthesis, degradation and receptor markers. Effects of nicotine were more modest and limited to CCK, SLC6A1 and SST. These findings support a role for E/I imbalance in SCZ pathophysiology and offer insights into how early‐life exposures may influence disease risk.
SN  - 0022-3042
SN  - 1471-4159
ER  -