Maternal stress induces long-lasting Purkinje cell developmental impairments in mouse offspring

A number of clinical studies suggest that prenatal stress can be a risk factor in the development of various psychopathologies, including schizophrenia, depression, anxiety, and autism. The cerebellar vermis has been shown to be involved in most of these disorders. In the present study, therefore, we evaluate the effect of maternal stress on long-term alterations in vermal Purkinje cell morphology. Furthermore, to discern whether these structural changes are associated with anxious behavior, the exploratory drive in the elevated plus maze was evaluated. Pregnant CF-1 mice were randomly assigned to control (n=14) or stressed (n=16) groups. Dams of the stressed group were subjected to restraint stress between gestational days 14 and 20, while control pregnant dams remained undisturbed in their home cages. Anxious behavior and Purkinje cell morphology were evaluated in three ontogenetic stages: postweaning, adolescence, and adulthood. Although exploratory behavior in the elevated plus maze was unaffected by prenatal stress, the Purkinje cell morphology showed a transient period of abnormal growth (at postweaning and juvenile stages) followed by dramatic dendritic atrophy in adulthood. In conclusion, prenatal stress induced significant long-lasting bimodal changes in the morphology of vermal Purkinje cells. These structural alterations, however, were not accompanied by anxious behaviors in the elevated plus maze.