The interaction between microglia and astrocytes exhibits a relatively balanced state in order to maintain homeostasis in the healthy central nervous system (CNS). Disease stimuli alter microglia–astrocyte interaction patterns and elicit cell-type-specific responses, resulting in their contribution to various pathological processes. Here, we review the similarities and differences in the activation modes between microglia and astrocytes in various scenarios, encompassing different stages of neural development and a wide range of neural disorders. The aim is to provide a comprehensive understanding of their roles in neural development and regeneration and guiding new strategies for restoring CNS homeostasis.

Maternal obesity or exposure to a high-fat diet (HFD) has an irreversible impact on the structural and functional development of offspring brains. This study aimed to investigate whether maternal HFD during pregnancy and lactation impairs dentate gyrus (DG) neurogenesis in offspring by altering neural stem cells (NSCs) behaviors. Pregnant Sprague-Dawley rats were fed a chow diet (CHD) or HFD (60% fat) during gestation and lactation. Pups were collected on postnatal day 1 (PND 1), PND 10 and PND 21. Changes in offspring body weight, brain structure and granular cell layer (GCL) thickness in the hippocampus were analyzed. Hippocampal NSCs behaviors, in terms of proliferation and differentiation, were investigated after immunohistochemical staining with Nestin, Ki67, SOX2, Doublecortin (DCX) and NeuN. Maternal HFD accelerated body weight gain and brain structural development in offspring after birth. It also reduced the number of NSCs and their proliferation, leading to a decrease in NSCs pool size. Furthermore, maternal HFD intensified NSCs depletion and promoted neuronal differentiation in the early postnatal development period. These findings suggest that maternal HFD intake significantly reduced the amount and capability of NSCs via reducing type–2 NSCs and promoting premature neuronal differentiation during postnatal hippocampal development.