medigraphic.com
ISSN 0185-3325 (Print)
Órgano Oficial del Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz

2006, Number 3

<< Back Next >>

Salud Mental 2006; 29 (3)

5-hydroxytryptamine and plasticity in rodents

Flores CMG, Escobar IA

Language: Spanish
References: 36
Page: 18-23
PDF size: 0. Kb.


ABSTRACT

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, 5hydroxytryptamine (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 (5HT) 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 BrdUlabelled 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 5HT 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.


REFERENCES

  1. AZMITIA EC, DOLAN K, WHITAKER APM: S-100β² but not NGF, EGF, insulin or calmodulin is a CNS serotonergic growth factor. Brain Res, 516:354-356, 1990.

  2. AZMITIA EC: Modern views on an ancient chemical: Serotonin effects on cell proliferation, maturation and apoptosis. Brain Res Bull, 56:413-424, 1992.

  3. BANASR M, HERY M, PRINTEMPS R, DASZUTA A: Serotonin-induced increases in adult cell proliferation and neurogenesis are mediated through different and common 5HT receptor subtypes in the dentate gyrus and the subventricular zone. Neuropsychopharm, 29:450-460, 2004.

  4. BREZUN JM, DASZUTA A: Depletion in serotonin decreases neurogenesis in the dentate gyrus and the subventricular zone of adult rats. Neurosci, 89:999-1002, 1999.

  5. BREZUN JM, DASZUTA A: Serotonin may stimulate granule cell proliferation in the adult hippocampus, as observed in rats grafted with foetal raphe neurons. Eur J Neurosci, 12:391-396, 2000.

  6. CHALMERS DT, KWAK SP, MANSOUR A, AKIL H, WATSON SJ: Corticosteroids regulate brain hippocampal 5HT1A receptor mRNA expression. J Neurosci, 13:914-923, 1993.

  7. CHAOULOFF F: Physiopharmacological interactions between stress hormones and central serotonergic systems. Brain Res Rev, 18:1-32, 1993.

  8. DAHLSTRÖM A, FUXE K: Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demostration of monoamines in cell bodies of brainstem neurons. Acta Physiol Scand, 62:13-55, 1964.

  9. FRAZER A, HENSLER JG: Serotonin. En: Siegel GJ, Agranoff BW, Albers RW, Fisher SK, Uhler MD (eds). Basic Neurochemistry: Molecular, Cellular and Medical Aspects. Lippincott Raven Publishers, 263-292, Philadelphia, 1996.

  10. GASPAR P, CASES O, MAROTEAUX L: The developmental role of serotonin: News from mouse molecular genetics. Nature Rev Neurosci, 4:1002-1012, 2003.

  11. GOULD E: Serotonin and hippocampal neurogenesis. Neuropsychopharma, 21:46S-49S, 1999.

  12. JACOBS BL, AZMITIA EC: Structure and function of the brain serotonin system. Physiol Rev, 72:165-229, 1992.

  13. JANUSNNIS SS, GLUNCIC V, RAKIC P: Early serotonergic projections to Cajal-Retzius cells: Relevance to cortical development. J Neurosci, 24:1652-1659, 2004.

  14. KONNO J, NARITA M, NARITA N: Migration and differentiation disorder of serotonergic neuron in the embryonic thalidomide/valproic acid exposed autism model rats. En: Treinta y cuatro Revisión Annual de la Society for Neuroscience. Poster, noviembre, 2004.

  15. LARSEN PJ, HAY-SCHMIDT A, VRANG N, MIKKELSEN JD: Origin of the projections from the midbrain raphe nuclei to the hypothalamic paraventricular nucleus in the rat: a combined retrograde and anterograde tracing study. Neurosci, 70:963-988, 1996.

  16. LAVDAS AA, BLUE ME,LINCOLN J,PARNAVELAS JG: Serotonin promotes the differentiation of glutamate neurons in organotypic slice cultures of the developing cerebral cortex. J Neurosci, 17:7872-7880, 1997.

  17. LIDOV HG, MOLLIVER ME: An histochemical study of serotonin neuron development in the rat: ascending pathways and terminal fields. Brain Res Bull, 8:389-430, 1982.

  18. LUO X, PERSICO AM, LAUDER JM: Serotonergic regulation of somatosensory cortical development: Lessons from genetic mouse models. Develop Neurosci, 25:173-183, 2003.

  19. MALBERG JE, EISCH AJ, NESTLER EJ, DUMAN RS: Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci, 20:9104-9110, 2000.

  20. MARIN-PADILLA M: Cajal-Retzius cells and the development of the neocortex. TINS, 21:64-71, 1998.

  21. MUNEOKA K, MIKUNI M, OGAWA T, KITERA K y cols.: Prenatal dexamethasone exposure alters brain monoamine metabolism and adrenocortical response in rat offspring. Am J Physiol, 273:R1669-R1675, 1997.

  22. NARITA N, KATO M, TAZOE M, MIYAZAKI K y cols.: Increased monoamine concentration in the brain and blood of fetal thalidomide- and valproic acid-exposed rat: Putative animal models for autism. Ped Res, 52:576-579, 2002.

  23. NICHOLLS JG: Neurotransmitters in the central nervous system. En: Nicholls JG, Martin RA, Wallace BG, Fuchs PA (eds). From Neuron to Brain. Sinauer Associates, Sunderland, 271-288, 2001.

  24. PETERS DAV: Maternal stress increases fetal brain and neonatal cerebral cortex 5-hydroxitryptamine synthesis in rats: a possible mechanism by which stress influences brain development. Pharmacol Biochem Behav, 35:943-947, 1990.

  25. PETERS DAV: Prenatal stress: effects on brain biogenic amine and plasma corticosterone levels. Pharmacol Biochem Behav, 17:721-725, 1982.

  26. RADLEY JJ, JACOBS BL: 5-HT 1A receptor antagonist administration decreases cell proliferation in the dentate gyrus. Brain Res, 995:264-267, 2002.

  27. RAKIC P, VERNE SC: Cortical development: View from neurological mutants two decades later. Neuron, 14:11011104, 1995.

  28. SAPER CB: Regulación de la sensibilidad, el movimiento y la conciencia por el tronco encefálico. En: Kandel ER, Schwartz JH, Jessell TM (eds). Principios de Neurociencia. Mc Graw Hill/Interamericana, 889-909, 2001.

  29. UEDA S, HOU XP, WHITAKER-AZMITIA PM, AZMITIA EC: Neuro-glial interaction in the S-100² retarded mutant mouse (Polydactyly Nagoya). II. Co-cultures study. Brain Res, 633:284-288, 1994.

  30. WALLACE JA, LAUDER JM: Development of serotonergic system in the rat embryo: an immunocytochemical study. Brain Res Bull, 10:459-479, 1983.

  31. WHITAKER-AZMITIA PM, CLARKE C, AZMITIA EC: Localization of 5-HT receptors to astroglial cells in adult 1A rats: Implications for neuronal-glial interactions and psychoactive drug mechanism of action. Synapse, 14:201205, 1993.

  32. WHITAKER-AZMITIA PM, DRUSE M, WALKER P, LAUDER JM: Serotonin as a developmental signal. Behav Brain Res, 73:19-29, 1996.

  33. WHITAKER-AZMITIA PM, MURPHY R, AZMITIA EC: Stimulation of astroglial 5-HT receptors releases the 1A serotonergic growth factor, protein S-100, and alters astroglial morphology. Brain Res, 528:155-158, 1990.

  34. WHITAKER-AZMITIA PM: Role of serotonin and other neurotransmitter receptors in brain development: Basis for developmental pharmacology. Pharmacol Rev, 43:553-561, 1991.

  35. WHITAKER-AZMITIA PM: Serotonin and brain development: role in human developmental diseases. Brain Res Bull, 56: 479-485, 2001.

  36. WHITAKER-AZMITIA PM: Serotonin as a developmental signal. Behav Brain Res, 73:19-29, 1996.




2020     |     www.medigraphic.com