INTRODUCTION: The majority of excitatory chemical synapses in the brain are formed on dendritic spines, and even subtle alterations in dendritic spine morphology may impair neuronal network function. Therefore, identifying the biological factors that regulate dendritic spine structure is of major importance. One such factor is chronically elevated corticosterone (CORT). Chronic CORT has been associated with reduced dendritic spine number and structural alterations in cortical and hippocampal neurons.

AIM(S): However, it remains unclear whether CORT directly drives these morphological changes and, if so, to what extent and which specific structural parameters are altered by prolonged CORT elevation.

METHOD(S): To address this, we employed a simplified in vitro approach using mouse primary cells isolated from the cortex and hippocampus, and exposed primary cells to CORT for 72 h.

RESULTS: First, we experimentally identified a CORT concentration sufficient to induce a glucocorticoid signaling response without compromising primary cell viability or overall neuronal morphology. Next, we showed that prolonged CORT exposure differentially affects dendritic spine morphology in primary hippocampal and cortical neurons. In cortical neurons, we observed an increase in spine length, whereas in hippocampal neurons, mean spine length was reduced. In addition, primary cells from both regions exhibited decreased spine head width. Finally, we examined whether these CORT-induced structural alterations in dendritic spines are dependent on glucocorticoid receptor (GR) signaling by using CORT108297, a GR-selective antagonist.

CONCLUSIONS: Prolonged CORT exposure directly alters dendritic spine morphology in primary mouse neurons in a region-specific manner. Together, these findings suggest that CORT may directly affect dendritic spines and provide a detailed characterization of the associated structural alterations.

FINANCIAL SUPPORT: Supported by the Polish National Science Center, No. 2021/41/N/NZ4/01845