Differential development of central dopaminergic and serotonergic systems across select mouse strains

Abstract

Although the etiology of autism is unclear, disruptions of the dopaminergic and serotonergic systems have been associated with the disorder. Based upon behavioral differences observed in the BALB/c strain of mice in comparison to other strains, notably, C57BL/6J mice, it has been suggested that the BALB/c strain may serve as an animal model of autism. However, to date, most work investigating neural and behavioral abnormalities in this strain has been performed in adult animals. Therefore, experiment 1 was conducted to examine the development of the central dopaminergic and serotonergic systems of BALB/c mice as compared to C57BL/6J mice. Levels of dopamine, serotonin, and their metabolites in several different brain regions and at three ages during development were measured. Alterations in both monoaminergic systems associated with age and strain were detected across brain regions indicating that there are neurochemical differences between these strains early in life. However, despite these differences in the development of brain monoaminergic systems, it remains difficult to declare this strain as a valid model of autism. Glutathione is an endogenous antioxidant, and gene mutations affecting glutathione have been linked to autism. One such gene mutation involves the altered expression of glutathione-S-transferase M1 (GSTM1). An animal model of autism incorporating this genetic mutation may be useful in studying the disorder. Therefore, experiment 2 was performed to investigate the neurochemical development of GSTM1 wildtype and knockout animals. Like experiment 1, dopamine, serotonin, and their metabolites were measured in several brain regions at three developmental time points. Neurochemical analysis revealed alterations in both dopaminergic and serotonergic systems associated with age and genotype. An understanding of these mice may help to further develop this animal model of autism.