Related Experiment Video
Updated: Jun 13, 2026
Rapid Golgi Stain for Dendritic Spine Visualization in Hippocampus and Prefrontal Cortex
Published on: December 3, 2021
L-methionine decreases dendritic spine density in mouse frontal cortex
Patricia Tueting1, John M Davis, Marin Veldic
1Department of Psychiatry, Psychiatric Institute, College of Medicine, University of Illinois at Chicago, USA. ptueting@psych.uic.edu
Abstract:
Schizophrenia postmortem brain is characterized by gamma aminobutyric acid downregulation and by decreased dendritic spine density in frontal cortex. Protracted L-methionine treatment exacerbates schizophrenia symptoms, and our earlier work (Tremolizzo et al. and Dong et al.) has shown that L-methionine decreases reelin and GAD67 transcription in mice which is prevented by co-administration of valproate. In this study, we observed a decrease in spine density following L-methionine treatment, which was prevented by co-administration of valproate. Together with our earlier findings conducted under the same experimental conditions, we suggest that downregulation of spine density in L-methionine-treated mice may be because of the decreased expression of reelin and that valproate may prevent spine downregulation by inhibiting the methylation induced decrease in reelin.
Insights
Protracted L-methionine treatment in mice decreased brain dendritic spine density, a key feature of schizophrenia. Co-administration of valproate prevented this effect, suggesting a potential therapeutic mechanism for schizophrenia.
Area of Science:
- Neuroscience
- Psychiatry
- Molecular Biology
Background:
- Schizophrenia is linked to reduced gamma-aminobutyric acid and dendritic spine density in the brain.
- L-methionine exacerbates schizophrenia symptoms and has been shown to decrease reelin and GAD67 transcription.
- Valproate can prevent L-methionine-induced decreases in reelin and GAD67 transcription.
Purpose of the Study:
- To investigate the effect of L-methionine on dendritic spine density in mice.
- To determine if valproate can prevent L-methionine-induced changes in dendritic spine density.
- To explore the role of reelin in L-methionine-induced neurobiological alterations.
Main Methods:
- Administered L-methionine to mice to observe effects on brain structure.
- Co-administered valproate with L-methionine to assess protective effects.
- Quantified dendritic spine density in the frontal cortex of treated mice.
Main Results:
- L-methionine treatment led to a significant decrease in dendritic spine density.
- Co-administration of valproate prevented the reduction in dendritic spine density caused by L-methionine.
- These findings align with previous observations on reelin and GAD67 expression.
Conclusions:
- L-methionine-induced downregulation of dendritic spine density may be mediated by decreased reelin expression.
- Valproate may protect against spine loss by inhibiting methylation-induced decreases in reelin.
- These findings suggest a potential therapeutic role for valproate in conditions involving L-methionine-induced neurotoxicity.
