Long-term effects of prenatal stress on the development of prefrontal cortex in the adolescent offspring

Abstract

Exposure to stress during pregnancy consequently prompts long-lasting effects on fetal brain development and predisposes the offspring to mental illnesses in later life. Adolescence is a vulnerable period of prefrontal cortex (PFC) development and coincident with the onset of neuropsychiatric symptoms. The medial PFC (mPFC) is the brain area that plays a significant role in emotional processing, and stress alters the function of this brain area leading to emotional disorders. Microglia not only play a role in neuroinflammatory responses but also play a crucial role in brain development, especially during synaptic development and pruning. Previous studies have revealed the long-term effects of prenatal stress (PS) on microglia activation and neuroinflammation in the hippocampus of the offspring. However, there is still a need to investigate how PS alters the mPFC development during adolescence. This study examines the effects of maternal stress during the last week of gestation on microglia activation and neuroimmune response in the mPFC of adolescent offspring. Morphological study demonstrated that PS increased the density of activated microglia in the prelimbic region of the mPFC of adolescent offspring. Besides, PS significantly increased the levels of microglia marker (Iba1), interleukin-6 (IL-6), and brain-derived neurotrophic factor (BDNF) in the mPFC of the adolescent offspring. In conclusion, PS-induced microglia activation and neuroinflammation in the mPFC might increase the risk for neuropsychiatric disorders in the offspring in later years.