Cytoskeletal changes in the hippocampus following restraint stress: Role of serotonin and microtubules

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Abstract
The aetiology of depression is associated with depletion in central levels of serotonin (5‐HT). Hence, a major effect of antidepressant drugs is to increase synaptic 5‐HT levels. Stressful conditions have also been shown to affect neuronal plasticity and 5‐HT neurotransmission in the hippocampus. Neuronal plasticity, which is typically referred to as a structural adaptation of neurons to functional requirements, requires more dynamic forms of microtubules (cytoskeletal component). The α‐tubulin, which is the major component of microtubules, can be postranslationally modified and both the tyrosinated (tyr‐tub) and acetylated (acet‐tub) forms are considered markers of more dynamic or more stable microtubules, respectively. The aim of the present work was to investigate the expression of tyr‐tub and acet‐tub in the hippocampus of rats submitted to either acute (6 h for 1 day) or sub‐chronic (6 h for 4 days every day) restraint stress. In addition, ex vivo hippocampal 5‐HT levels were monitored by differential pulse voltammetry to analyse the influence of both stress conditions upon 5‐HT levels. Our results showed that the expression of tyr‐tub in the hippocampus was significantly decreased to 70 ± 7% following sub‐chronic restraint stress (P < 0.01). In contrast, acute and sub‐chronic restraint stress increased the hippocampal expression of acet‐tub to 139 ± 11% and 145 ± 11% of control, respectively. Finally, 5‐HT levels were significantly increased (P < 0.05) to 142 ± 15% and 135 ± 11% following acute and sub‐chronic restraint stress, respectively. The stress‐induced cytoskeletal changes observed in the present study suggest that the microtubular network is a potential new pathway that may increase our understanding of stress‐related events. Synapse 49:188–194, 2003.