IADR Abstract Archives
The Effects of Altered GABA Synthesis in Tooth Enamel Formation
Objectives: During development ameloblasts are sensitive to genetic and physical stressors that influence the quality of the tooth crown. Recent studies suggest enamel biosignatures can be used as predictors of psychological health. Although this potential use of teeth as diagnostic tools, is an exciting possibility, a critical barrier towards this goal is the lack of understanding the biological mechanisms by which neurodevelopmental pathways are linked to structural and functional changes in the enamel matrix. In this study, we focus on a mouse model lacking synthesis of Gamma-Aminobutyric Acid (GABA), a critical neurotransmitter that promotes a balanced mood by inhibiting overall neural excitability. The objective of this study is to characterize the tooth enamel phenotype in a GAD65 knockout mouse (GAD65-KO) model where GABA synthesis is impaired.
Methods: Adult wild type (WT) and GAD65-KO mice were imaged by uCT in 10 micron increments at the Center for High-Throughput Phenogenomics at the University of British Columbia. Dicom files were uploaded into Amira 6.5 software (ThermoFisher) where enamel volume, shape and relative intensity were characterized in the mandibular molars and incisors of WT and GAD65-KO mice.
Results: Gross morphology of GAD65-KO mouse molars showed evidence of incomplete cusp formation. MicroCT analysis showed a significant increase in average enamel thickness, and reduction in enamel volume and surface area as compared to WT molars. In the mandibular incisors, matrix mineralization began earlier as compared to WT mice. These findings are consistent with an early enamel matrix mineralization in mice with impaired GABA synthesis.
Conclusions: Mice with impaired GABA synthesis have altered tooth enamel formation as compared to WT controls. These results indicate that the GABA neurotransmitter can influence tooth enamel maturation and supports the possibility for teeth to permanently store measurable information in the enamel matrix generated from prenatal stress and other conditions during development.
Methods: Adult wild type (WT) and GAD65-KO mice were imaged by uCT in 10 micron increments at the Center for High-Throughput Phenogenomics at the University of British Columbia. Dicom files were uploaded into Amira 6.5 software (ThermoFisher) where enamel volume, shape and relative intensity were characterized in the mandibular molars and incisors of WT and GAD65-KO mice.
Results: Gross morphology of GAD65-KO mouse molars showed evidence of incomplete cusp formation. MicroCT analysis showed a significant increase in average enamel thickness, and reduction in enamel volume and surface area as compared to WT molars. In the mandibular incisors, matrix mineralization began earlier as compared to WT mice. These findings are consistent with an early enamel matrix mineralization in mice with impaired GABA synthesis.
Conclusions: Mice with impaired GABA synthesis have altered tooth enamel formation as compared to WT controls. These results indicate that the GABA neurotransmitter can influence tooth enamel maturation and supports the possibility for teeth to permanently store measurable information in the enamel matrix generated from prenatal stress and other conditions during development.