Fig 10.

Sex differences in- and sex dependent stress effects on- cellular architecture across mPFC. Left panel. Males show more complex dendritic arbors in layers 1 and 2/3 in mPFC compared to females. Likewise, astrocyte structure is more complex in layers 2/3 and 5/6. Activated microglia can prune synapses and remodel dendritic architecture. In line with this, males show reduced microglial density or activation state across all layers compared to females. Top left. In males, T and/or E regulate basal aspects of microglial morphology across mPFC. Top right: Chronic stress effects on neuronal morphology differ by dendritic location and cortical layer. Stress induces apical – but not basilar – dendritic retraction and spine loss in layers 1 and 2/3 in males (44, 62), yet has little effect on dendritic arborization in layer 5/6 (73). Perhaps mediating these effects, chronic stress increases microglia-neuron contact and microglial engulfment of dendritic spines near layers 1 and 2/3 – but not layer 5/6, suggesting layer-specific microglia-mediated neuronal remodeling (12). Shifts in microglial morphology were not detected in this study. Astrocytes undergo stress-induced atrophy in layers 2/3 and 5/6; this appears to be mediated – in part – by either T or E. Bottom left. Gonadal hormones do not regulate basal microglial or astrocyte morphology in mPFC in females. Bottom right. Chronic stress has either no effect on- or increases dendritic complexity in layers 2/3 in females. This may be due to a significant decrease in microglial density/activation and – in turn – reduced microglial maintenance or pruning across mPFC. Stress-induced neuronal and microglial remodeling is estradiol dependent. Chronic stress leads to astrocytic growth or reorganization (i.e. increased process complexity) across mPFC. As ovariectomy or hormone replacement disrupts stress effects on astrocyte morphology, it is possible that gonadal hormones regulate aspects of stress-induced astrocyte remodeling in females. Light tan: layer 1, medium tan: layer 2/3, dark tan: layer 5/6. Purple: pyramidal neurons, blue: astrocytes, green: microglia.