Corticosterone induced morphological changes of hippocampal and amygdaloid cell lines are dependent on 5-HT7 receptor related signal pathway

Stress is an unavoidable life experience. It induces mood, cognitive dysfunction and plasticity changes in chronically stressed individuals. Among the various brain regions that have been studied, the hippocampus and amygdala have been observed to have different roles in controlling the limbic-hypothalamic-pituitary-adrenal axis (limbic-HPA axis). This study investigated how the stress hormone corticosterone (CORT) affects neuronal cells. The first aim is to test whether administration of CORT to hippocampal and amygdaloid cell lines induces different changes in the 5-HT receptor subtypes. The second goal is to determine whether stress induced morphological changes in these two cell lines were involved in the 5-HT receptor subtypes expression. We now show that 5-HT7 receptor mRNA levels were significantly upregulated in HT-22 cells, but downregulated in AR-5 cells by exposure to a physiologically relevant level of CORT (50 μM) for 24 h, which was later confirmed by primary hippocampal and amygdaloid neuron cultures. Additionally, pretreatment of cells with 5-HT7 antagonist SB-269970 or agonist LP-44 reversed CORT induced cell lesion in a dose-dependent manner. Moreover, CORT induced different changes in neurite length, number of neurites and soma size in HT-22 and AR-5 cells were also reversed by pretreatment with either SB-269970 or LP-44. The different effects of 5-HT7 receptors on cell lines were observed in two members of the Rho family small GTPase expression: the Cdc-42 and RhoA. These observed results support the hypothesis that 5-HT may differentially modulate neuronal morphology in the hippocampus and amygdala depending on the expression levels of the 5-HT receptor subtypes during stress hormone insults.

▶CORT induces differential changes of 5-HT7 receptor in HT-22 and AR-5 cell lines. ▶Different morphological changes were found in these cell lines after CORT exposure. ▶5-HT7 receptor antagonist or agonist prevents the morphological changes. ▶The signal cascade depends on 5-HT7 receptor related Cdc-42 and RhoA expression.