INTRODUCTION: Dendritic spines are the primary sites of excitatory synaptic input, and their intact morphology is critical for the effective signal transmission. Prolonged elevation of corticosterone (CORT) is one of the factors that affects spine structure and, consequently, dysregulates synaptic function; however, the underlying mechanisms remain unclear.

AIM(S): Therefore, we investigated whether focal adhesion kinase (FAK)—known to influence spine remodeling and respond to CORT stimulation—contributes to CORT-induced structural changes of spines.

METHOD(S): Primary cortical and hippocampal cultures, rich in FAK and sensitive to chronic CORT, were exposed to 250 nM CORT for 72 h to induce and assess its effects on spine morphology. Additionally, a FAK inhibitor or activator was co-applied with CORT for 72 h to determine whether altering FAK activity could mimic or counteract CORT-driven remodeling. Finally, FAK mRNA and protein levels were measured after 48 h and 72 h of CORT to clarify FAK’s involvement in the CORT-related signaling pathways that lead to spine remodeling.

RESULTS: 72 h of elevated CORT affected spines of cortical and hippocampal neurons differently, resulting in mild elongation of cortical spines and shortening of hippocampal spines. In contrast, the spine head width decreased in both types of neurons. FAK inhibition replicated these CORT-induced changes in cortical neurons but did not affect hippocampal spines. Conversely, FAK activation blocked all CORT effects on cortical spines and prevented the reduction in hippocampal spine head width, but not in length. After 72 h, but not 48 h of CORT, cortical FAK mRNA increased, while FAK protein remained unchanged. Hippocampal FAK mRNA and protein were stable at both time points.

CONCLUSIONS: Our results revealed a potential use of FAK activity modulation in preventing CORT-induced spine alterations. However, FAK is unlikely to mediate CORT signaling, which leads to spine remodeling.

FINANCIAL SUPPORT: Supported by the Polish National Science Center, Preludium 20, No. 2021/41/N/NZ4/01845