Abstract
Reduced activity of CNS serotonin is reported in unipolar depression and serotonin is the major target of recent antidepressant drugs. However, an acute depletion of serotonin in healthy individuals does not induce depressive symptoms suggesting that depression does not correlate with the serotonin system only. Neuronal plasticity (structural adaptation of neurons to functional requirements) includes synthesis of microtubular proteins such as tyrosinated isoform of α-tubulin and presence of serotonin as regulator of synaptogenesis. In depression neuronal plasticity is modified.Here, in rats submitted to a behavioural test widely used to predict the efficacy of antidepressant drugs (forced swimming test: FST) a significant decrease of both cerebral tyrosinated α-tubulin expression and serotonin levels is monitored. Moreover, treatment with para-chlorophenylalanine (PCPA, compound that specifically depletes brain serotonin) but not alpha-methyl para tyrosine (α-MPT, compound that blocks synthesis of catechols: chemicals also implicated in depression) significantly reduced tyrosinated α-tubulin. Thus, a direct relationship between serotonin and tyrosinated α-tubulin appears to be present both in “physiological” and in “pathological” states. In addition, data obtained in animals submitted to FST and/or treated with the selective serotonin reuptake inhibitor (SSRI) fluoxetine further support the interrelationship between central serotonin and cytoskeleton. These data propose that direct relationship between serotonin and tyrosinated α-tubulin could be considered within the mechanism(s) involved in the pathogenesis of depression.
Highlights
The cytoskeleton is the structural component of neurones and three polymers, i.e. microtubules, intermediate filaments and microfilaments are their components [1].Microtubules derive from the polymerisation of tubulin proteins, they are abundant in neurones and exhibit high heterogeneity of components
Pharmacological Treatments i) PCPA treatment resulted in a significant decrease of Tyr-Tub expression in the whole brain (approximately 75% of vehicle treated rats (NaCl 0.9% 600 l i.p., control rats) (Fig. 1 TOP)
Concomitant DPV measurements in the same homogenate resulted in a large decrease to approximately 45% or 12% of control values of both the catecholaminergic (Peak 1) and the 5-HT (Peak 2) related signals, respectively (Fig. 1 right, see Fig. 2 for technicality)
Summary
The cytoskeleton is the structural component of neurones and three polymers, i.e. microtubules, intermediate filaments and microfilaments are their components [1].Microtubules derive from the polymerisation of tubulin proteins (heterodimers consisting of - and - sub-units), they are abundant in neurones and exhibit high heterogeneity of components. Microtubules are highly dynamic polymers as they exchange rapidly the polymerised tubulin dimers with soluble sub-unit pools. This feature is involved in fundamental cellular functions such as cell division, motility and transport, maintenance of cell shape and signal transduction [2]. The -tubulin sub-unit of the microtubule is expressed in mammalian species in various isoforms related to different primary sequences and several post-translational modifications One of these modifications is the cyclic tyrosination / detyrosination of the C-terminus, cycle that has been shown to occur in many cell types and to be related to the microtubule dynamic [3]. Stable microtubules are detyrosinated [4], whilst the highly dynamic microtubules show to be highly tyrosinated [3]
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