L-methionine decreases dendritic spine density in mouse frontal cortex

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.

Figure 1

Microscope digital photographs of Golgi stained layer III pyramidal neurons in mouse frontal cortex. Top panel: 10x objective; Middle panel: 20x Bottom panel: 100x. Vehicle (VEH); L-methionine (MET)

Figure 2

Mean spine density per micron as a function of distance from the pyramidal cell body shown separately for the apical and basilar dendrites. (Vehicle (VEH) n=13; L-methionine (MET) n=12). The dose of L-methioinine was 5.2. mmol/kg s.c. twice daily for seven days.