Abstract
The maturational changes in the brain and spinal cord do not linearly proceed from
immature in infants to mature in adults. Dendrites dynamically extend or retract as
neurotrophic factors fluctuate. In certain cases mature neurons can be seen soon after
birth, and in other cases immature neurons can be identified in the aged brain. Monoamine
‘neurotransmitter’; such as serotonin (5-HT), dopamine and norepinephrine appear to
function as Maintenance Growth Factors since they must be present in order to produce
their maturational actions. Serotonin neurons contain TRK-B receptors and are sensitive
to availability of the trophic factor, BDNF. 5-HT also functions by promoting the
release of the glial extension factor, S-100β. 5-HT and S-100β can provide maturational
signals to a variety of neurons, in both cortical and subcortical areas, and appear
to be involved in regulating the maturation and release of acetylcholine and dopamine.
We have shown that activation of the 5-HT1A receptor is particularly effective in
inducing growth of stunted neurons. The mechanism of action of the 5-HT1A receptor
involves both a direct inhibition on c-AMP and pCREB formation in postsynaptic neurons
and a release of S-100β from glial cells. Both these events are capable of stabilization
and elaboration of the cytoskeleton of the neuron and inhibition of apoptosis. 5-HT1A
receptors have been shown to effectively reverse stunted neurons and microencephaly
produced in animal models of fetal alcohol syndrome and prenatal cocaine administration.
I discuss the implications for regressive disorders such as Rett's syndrome and autism,
and the feasibility of treatments with 5-HT1A agonists in children with developmental
disorders.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Brain and DevelopmentAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- S-100 beta protects cultured neurons against glutamate- and staurosporine-induced damage and is involved in the antiapoptotic action of the 5 HT(1A)-receptor agonist, Bay x 3702.Brain Res. 2000; 858: 121-128
- Prenatal cocaine decreases the trophic factor S-100 beta and induced microcephaly: reversal by postnatal 5-HT1A receptor agonist.Neurosci Lett. 1994; 170: 141-144
- The 5-HT1A receptor: signaling, desensitization, and gene transcription.Neuropsychopharmacology. 1996; 14: 19-25
- Cloning, functional expression, and mRNA tissue distribution of the rat 5-hydroxytryptamine1A receptor gene.J Biol Chem. 1990; 265: 5825-5832
- Plasticity in brain development.Sci Am. 1988; 259: 56-64
- Organ growth in Rett syndrome: a postmortem examination analysis.Pediatr Neurol. 1999; 20: 125-129
- Cellular localization of the 5-HT1A receptor in primate brain neurons and glial cells.Neuropsychopharmacology. 1996; 14: 35-46
Azmitia EC. Serotonin (Enclycolpedia of Life Science, www.els.com; Nature Publishing Group).
- Chpt. 1: Development and neuroplasticity of central serotonergic neurons.in: Baumgarten H.G. Gothert M. Handbook Of Experimental Pharmacology: Serotonergic Neurons and 5-HT Receptors in the CNS. Springer–Verlag, Berlin, Heidelberg, New York, 1997: 1-39
- Dexamethasone reverses adrenalectomy-induced neuronal de-differentiation in midbrain raphe –hippocampal axis.Ann NY Acad Sci. 1994; 746: 180-194
- 5-HT1A agonist and dexamethasone reversal of para-chloroamphetamine induced loss of MAP-2 and synaptophysin immunoreactivity in adult rat brain.Brain Res. 1995; 677: 181-192
- Interactions between the microtubule-associated tau proteins and S100b regulate tau phosphorylation by the Ca2+/calmodulin-dependent protein kinase II.J Biol Chem. 1988; 263: 5876-5883
- A comparison of pattern formation by thalamocortical and serotonergic afferents in the rat barrel field cortex.Cereb Cortex. 1991; 1: 380-389
- Colchicine induced cytoskeletal collapse and apoptosis in N-18 neuroblastoma cultures is rapidly reversed by exogenously applied S-100β.Brain Res. 2001; (In Press)
- Buspirone in the management of anxiety and irritability in children with pervasive developmental disorders: results of an open-label study.J Clin Psychiatry. 1998; 59: 56-59
- Evoking communication in Rett syndrome: comparisons with conversations and games in mother-infant interaction.Eur Child Adolesc Psychiatry. 1997; 6: 26-30
- Neuron theory or reticular theory.Arch Neurobiol Madrid. 1933; 13: 1-144
- PCPA reduces both monoaminergic afferents and non- monoaminergic synapses in the cerebral cortex.Neurosci Res. 1994; 19: 111-115
- Effect of serotonin on the growth and differentiation of the cellular elements of the hippocampus during cultivation.Arkh Anat Gistol Embriol. 1978; 74: 98-106
- Prenatal cocaine delays astroglial maturation: immunodensitometry shows increased markers of immaturity (vimentin and GAP-43) and decreased proliferation and production of the growth factor S-100.Dev Brain Res. 1996; 91: 268-273
- Developmental regression in autism: maternal perception.J Autism Dev Disord. 2000; 30: 113-119
- Early localization of mRNA coding for 5-HT1A receptors in human brain during development.Mol Brain Res. 1998; 60: 123-126
- An increase in phosphorylation of microtubule-associated protein 2 accompanies dendrite extension during the differentiation of cultured hippocampal neurones.Eur J Biochem. 1995; 15: 68-77
- Perspectives in S-100 protein biology.Cell Calcium. 1991; 12: 713-726
- Interaction between S-100 proteins and steady-state and taxol-stabilized microtubules in vitro.J Neurochem. 1989; 52: 1010-1017
- Effects of in utero ethanol exposure and maternal treatment with a 5-HT(1A) agonist on S100B-containing glial cells.Dev Brain Res. 2000; 121: 133-143
- Synaptogenesis in the postnatal rat fascia dentata is influenced by 5-HT1a receptor activation.Dev Brain Res. 1999; 114: 245-252
- Characterization of glial trkB receptors: differential response to injury in the central and peripheral nervous systems.Proc Natl Acad Sci. 1993; 90: 4971-4975
- Fenfluramine blocks low-Mg2+-induced epileptiform activity in rat entorhinal cortex.Epilepsia. 2000; 41: 925-928
- Hippocampal serotonin levels influence the expression of S-100β detected by immunocytochemistry.Brain Res. 1993; 631: 119-123
- Dentate granule cell function after neonatal treatment with parachloroamphetamine or 5,7-dihydroxytryptamine.Dev Brain Res. 1999; 114: 269-272
- Evidence that S100b proteins regulate microtubule assembly and stability in rat brain extracts.Int J Biochem. 1986; 18: 691-695
- Homologous regulation of 5-HT1A receptor mRNA in adult rat hippocampal dentate gyrus.Neurosci Lett. 1999; 270: 5-8
- 5-HT1A receptor agonist reverses adrenalectomy-induced loss of granule neuronal morphology in the rat dentate gyrus.Neurochem Res. 1997; 22: 1329-1337
- Activity and injury-dependent expression of inducible transcription factors, growth factors and apoptosis-related genes within the central nervous system.Prog Neurobiol. 1999; 57: 421-450
- Is there a basis for novel pharmacotherapy of autism?.Life Sci. 2000; 67: 1667-1682
- Modification of microtubule steady-state dynamics by phosphorylation of the microtubule-associated proteins.Proc Natl Acad Sci USA. 1981; 78: 3413-3417
- The role of microtubule-associated protein 2 (MAP-2) in neuronal growth, plasticity, and degeneration.J Neurosci Res. 1992; 33: 505-512
- Abnormalities in neuronal maturation in Rett syndrome neocortex: preliminary molecular correlates.Eur Child Adolesc Psychiatry. 1997; 6: 75-77
- Protective effects of maternal buspirone treatment on serotonin reuptake sites in ethanol-exposed offspring.Brain Res Dev Brain Res. 1996; 92: 190-198
- Microtubule dynamics.Nature. 1986; 324: 621-623
- The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3.Cell. 1991; 66: 395-403
- Purification and characterization of neurite extension factor from bovine brain.Proc Natl Acad Sci. 1985; 482: 7136-7139
- Neurotransmitters as growth regulatory signals: role of receptors and second messengers.Trends Neurosci. 1993; 16: 233-240
- Effects of p-chlorophenylalanine on time of neuronal origin during embryogenesis in the rat.Brain Res. 1976; 107: 638-644
- Immunohistochemical study of the development of serotonergic neurons in the rat CNS.Brain Res Bull. 1982; 9: 559-604
- Role of serotonin for scoliotic deformity in pinealectomized chicken.Spine. 1997; 22: 1297-1301
- Brain-derived neurotrophic factor promotes the survival and sprouting of serotonergic axons in rat brain.J Neurosci. 1995; 16: 7929-7939
- Microtubule-associated protein 2 as an early indicator of ischemia-induced neurodegeneration in the gerbil forebrain.J Neurochem. 1994; 63: 1012-1020
- Serotonin and acetylcholine are crucial to maintain hippocampal synapses and memory acquisition in rats.Neurosci Lett. 1997; 230: 13-16
- Serotonin depletion during synaptogenesis leads to decreased synaptic density and learning deficits in the adult rat: a possible model of neurodevelopmental disorders with cognitive deficits.Brain Res. 1997; 760: 68-73
- A cosmid clone for the 5HT1A receptor (HTR1A) reveals a TaqI RFLP that shows tight linkage to DNA loci D5S6, D5S39, and D5S76.Genomics. 1991; 11: 767-769
- Outcome in schizophrenia: beyond symptom reduction.J Clin Psychiatry. 1999; 60: 3-7
- Molecular cloning of rat trkC and distribution of cells expressing messenger RNAs for members of the trk family in the rat central nervous system.Neuroscience. 1992; 51: 513-532
- Expression of serotonin receptors in human fetal astrocytes and glioma cell lines: a possible role in glioma cell proliferation and migration.Mol Brain Res. 1996; 41: 1-7
- Regulation by serotonin of tooth-germ morphogenesis and gene expression in mouse mandibular explant cultures.Arch Oral Biol. 1998; 43: 789-800
- Rett syndrome: natural history and underlying disease mechanisms.Eur Child Adolesc Psychiatry. 1997; 6: 14-17
- Agonist- and antagonist-induced plasticity of rat 5-HT1A receptor in hippocampal cell culture.Synapse. 1999; 31: 186-195
- S100beta promotes the extension of microtubule associated protein2 (MAP2)-immunoreactive neurites retracted after colchicine treatment in rat spinal cord culture.Neurosci Lett. 1997; 229: 212-214
- Trophic interactions between brain-derived neurotrophic factor and s100beta on cultured serotonergic neurons.Brain Res. 2000; 868: 113-118
- Brain derived neurotrophic factor and S100β trophic interactions on cultured serotonergic neurons.Neurosci Net. 1996; (www.neuroscience.com): 10003
- Rett syndrome: an early catecholamine and indolamine deficient disorder?.Brain Dev. 1985; 7: 334-341
- Genomic organization of adrenergic and serotonin receptors in the mouse: linkage mapping of sequence-related genes provides a method for examining mammalian chromosome evolution.Genomics. 1991; 10: 338-344
- A biogenic amine-synapse mechanism for mental retardation and developmental disabilities.Brain Dev. 2001; 23: S11-S15
- The molecular evolution of G protein-coupled receptors: focus on 5-hydroxytryptamine receptors.Neuropharmacology. 1994; 33: 319-324
- Cerebrospinal fluid values for monoamine metabolites, gamma-aminobutyric acid, and other amino compounds in Rett syndrome.J Pediatr. 1988; 112: 234-238
- Auditory brainstem response findings in Rett syndrome: stability over time.J Pediatr. 2000; 137: 393-396
- The pharmacotherapy of target symptoms associated with autistic disorder and other pervasive developmental disorders.Harv Rev Psychiatry. 2000; 8: 45-63
- Neurotrophic effects of ipsapirone and other 5-HT1A receptor agonists on septal cholinergic neurons in culture.Dev Brain Res. 1994; 82: 245-258
- Neurochemical aspects of the Rett syndrome.Brain Dev. 1985; 7: 351-360
- BDNF-activated signal transduction in rat cortical glia.Eur J Neurosci. 1995; 7: 849-863
- Citalopram, a selective serotonin reuptake inhibitor, improves symptoms of Friedreich's ataxia.Pharmacopsychiatry. 1999; 32: 113-114
- Glial-derived S100b protein selectively inhibits recombinant protein kinase C (PKC) phosphorylation of neuron-specific protein F1/GAP43.Mol Brain Res. 1994; 21: 62-66
- The occurrence, metabolism and functions of amines in plants.Biol Rev Camb Philos Soc. 1971; 46: 201-241
- Effects of BDNF on dopaminergic, serotonergic, and GABAergic neurons in cultures of human fetal ventral mesencephalon.Exp Neurol. 1995; 133: 50-63
- Neurochemical differentiation of human bulbospinal monoaminergic neurons during the first trimester.Brain Res Dev Brain Res. 1993; 7: 1-12
- Rett's syndrome: report of 5 cases in Tunisia.Rev Neurol (Paris). 1999; 155: 955-959
- Neurotrophic factors in cerebrospinal fluid and serum of patients with Rett syndrome.J Child Neurol. 1998; 13: 429-433
- Pharmacologic treatment of anxiety disorders in children and adolescents.Child Adolesc Psychiatr Clin N Am. 2000; 9: 119-133
- Immunoreactivity of sera to a peptide derived from the serotonin 5-HT1A receptor in a group of children with developmental disorders: possible role in non-autistic epilepsy.Int J Mol Med. 1998; 1: 185-189
- Development of the serotonergic system in the rat embryo: an immunocytochemical study.Brain Res Bull. 1983; 10: 459-479
- Serotonin depletion in the adult rat causes loss of the dendritic marker MAP-2: A new animal model of schizophrenia?.Neuropsychopharmacology. 1995; 12: 269-272
- Localization of 5-HT1A receptors to astroglial cells in adult rats: implications for neuronal-glial interactions and psychoactive drug mechanism of action.Synapse. 1993; 14: 201-211
- Stimulation of astroglial 5-HT1A receptors releases the serotonergic growth factor, protein S100b, and alters astroglial morphology.Brain Res. 1990; 528: 155-158
- Treatment of apneustic respiratory disturbance with a serotonin-receptor agonist.J Pediatr. 1997; 130: 89-94
- Serotonin regulates synaptic connections in the dentate molecular layer of adult rats via 5-HT1a receptors: evidence for a glial mechanism.Brain Res. 1998; 782: 235-239
- 5-HT1a receptors mediate the neurotrophic effect of serotonin on developing dentate granule cells.Dev Brain Res. 1997; 98: 185-190
Article info
Identification
Copyright
© 2001 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
