Cytoskeletal changes in the hippocampus following restraint stress: role of serotonin and microtubules.
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 alpha-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.
Bianchi
Massimiliano
M
Center of Excellence for Drug Discovery in Psychiatry, Department of Biology, GlaxoSmithKline Pharmaceuticals, 37135 Verona, Italy. massimiliano.m.bianchi@gsk.com
Heidbreder
Christian
C
Crespi
Francesco
F
D000818:Animals; D015153:Blotting, Western; D003599:Cytoskeleton / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D008870:Microtubules / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D012701:Serotonin / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism*
D012701:Serotonin