Resumo

FLORES CRUZ, María Guadalupe  e  ESCOBAR IZQUIERDO, Alfonso. 5-Hydroxytryptaminie and plasticity in rodents. Salud Ment [online]. 2006, vol.29, n.3, pp.18-23. ISSN 0185-3325.

The attributes that characterize a molecule as neurotransmitter at CNS are: i . neuronal synthesis, ii . being present at presynapsis, iii. Ca2+-dependent release, iv. postsynaptic actions mediated by receptors, v. an elimination mechanism at synapse. Since 1964, 5-hydroxytryptamine (5-HT) was included as a neurotransmitter and is part of a set of neurotransmitters named biogenic amines.

In rodents, the 5-hydroxytryptaminergic system is constituted by nine nuclei at brainstem, and divided in two groups, rostral and caudal by ther localization. The rostral group projects mainly to the telencephalon and diencephalon, while the caudal group does it to the spinal cord. 5-HT innervation to brainstem and cerebellar nuclei have been also described.

The most well-known function of 5-hydroxytryptamine (5-HT) in the CNS is neuromodulation, in processes such as memory, learning, mood, sleep-wake cycle; all of these are regulated by this biogenic amine through a wide family of receptors. All the receptors are metabotropic with the sole exception of 5-HT1, which is an ionotropic receptor.

The 5-HT system differentiates early in ontogenesis; 5-HT immunoreactive neurons are evident in rat fetuses at embryonic day 12 (E12), when almost any other neuronal lineage possesses a cellular commitment. This fact highlights the importance 5-HT has at neurodevelopment.

Scientific works are focused in the 5-HT auto-regulatory signalling for neuropil outgrowth at ontogeny, another remarkable trait of the 5-HT system. In addition, 5-HT releases astrocyte neurotrophic factor S-100 beta, necessary for dendritic maintenance. The 5-HT set point at different stages during ontogeny remains unknown.

Several target structures of the 5-HT system are dependent on the level of 5-HT activity in newborn rodents; e.g. the somatosensory cortex where proper barrel field arrangement requires an active 5-HT innervation.

Moreover, besides the 5-HT level, other factors, such as the level of reelin, are determinant for the proper cytoarchitectonic organization of the neocortex. The use of 5-methoxytryptamine, an unespecific 5-HT agonist, in the prenatal period, which negatively affects the reelin level, leads to cytoarchitectonic derangement, as it has been described to occur in the presubicular cortex.

5-HT and plasticity are also related to neurogenesis in adulthood. Neurogenesis in adulthood is influenced by several factors. Some of them, such as exercise and an enriched environment, increase the rate of newly born neurons in the dentate gyrus and olfactory bulb; while others, such as mood depression (in humans), low 5-HT levels, 5-HT1A receptor blockade by antagonists, or down-regulation, account for a poor neurogenesis rate.

Chronic administration of 5-HT reuptake inhibitors, such as fluoxetine, increases the number of bromodeoxiuridine- labelled (BrdU) granule cells at the dentate gyrus and hilus versus control rats. This means that fluoxetine increases the neurogenesis rate. Newly born granule cells at dentate gyrus are more likely to survive, thus contributing to maintaining the hippocampal volume unchanged.

On the contrary, following chronic 5-HT antagonist administration, specifically 5-HT1A receptor blockade BrdU-labelled granule cells in dentate gyrus are 30% reduced.

Reduced hippocampal volume develops in humans affected by major depression, concomitant in some cases with a decrease in 5-HT neurotransmiter level. Recent studies linking 5-HT neurogenesis stimulation in dentate gyrus explain why plastic phenomena associated to pathology could be reversed by 5-HT reuptake inhibitors like fluoxetine. These works contribute to a better understanding of both depression etiology and clinical approach.

Palavras-chave : 5-Hydroxytrypamine; neurodevelopment; neurogenesis; fluoxetine; BrdU.

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