Developmental Changes in [3H]Lysergic Acid Diethylamide ([3H]LSD) Binding to Serotonin Receptors in the Human Brainstem

Zec, Natasa; Filiano, James J.; Panigrahy, Ashok; White, William F.; Kinney, Hannah C.

doi:10.1097/00005072-199601000-00012

Cited by 29 publications

(24 citation statements)

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“…Serotonergic receptor-binding was found to be increased in the brainstem nuclei in RTT, which may reflect decreased serotonergic input with a compensatory upregulation of receptor binding and/or binding affinity [20].…”

Section: Csf Neurotransmitters In Rtt and Rdmentioning

confidence: 92%

Evaluation of CSF neurotransmitters and folate in 25 patients with Rett disorder and effects of treatment

Temudo

Ríos

Prior

et al. 2009

Brain and Development

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Background: Rett disorder (RD) is a progressive neurodevelopmental entity caused by mutations in the MECP2 gene. It has been postulated that there are alterations in the levels of certain neurotransmitters and folate in the pathogenesis of this disease. Here we re-evaluated this hypothesis. Patients and methods: We evaluated CSF folate, biogenic amines and pterines in 25 RD patients. Treatment with oral folinic acid was started in those cases with low folate. Patients were clinically evaluated and videotaped up to 6 months after therapy. Results: CSF folate was below the reference values in 32% of the patients. Six months after treatment no clinical improvement was observed. Three of the four patients with the R294X mutation had increased levels of a dopamine metabolite associated to a particular phenotype. Three patients had low levels of a serotonin metabolite. Two of them were treated with fluoxetine and one showed clinical improvement. No association was observed between CSF folate and these metabolites, after adjusting for the patients age and neopterin levels. Conclusion: Our results support that folinic acid supplementation has no significant effects on the course of the disease. We report discrete and novel neurotransmitter abnormalities that may contribute to the pathogenesis of RD highlighting the need for further studies on CSF neurotransmitters in clinically and genetically well characterized patients.

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Section: Csf Neurotransmitters In Rtt and Rdmentioning

confidence: 92%

Evaluation of CSF neurotransmitters and folate in 25 patients with Rett disorder and effects of treatment

Temudo

Ríos

Prior

et al. 2009

Brain and Development

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“…Our procedures for tissue preparation have been described in detail previously (Panigrahy et al, 2000;Zec et al, 1996). Unfixed brainstem sections were stored frozen at -70°C, and subsequently sectioned at 20 m on a Leitz motorized cryostat.…”

Section: Clinical Databasementioning

confidence: 99%

“…Alternate sections from each infant case were used for binding analysis with the radioligands for the selected 5-HT receptor subtypes and SERT. The procedure for 3 H-LSD binding to 5-HT receptors was based on previously described methods (Zec et al, 1996). Unfixed slide-mounted sections of the medulla were preincubated in 300 mM Tris-maleate buffer (pH 7.4) for 30 minutes at room temperature (RT).…”

Section: Clinical Databasementioning

confidence: 99%

“…We tested the following specific hypotheses: 1) there are significant age-related changes in the first 6 postnatal months in 5-HT receptor and/or SERT binding in nuclei that compose the medullary 5-HT system, and/or in their medullary projection sites, which are indicative of ongoing postnatal development of the medullary 5-HT system; and 2) 5-HT 1A -receptor binding is distributed principally in the medullary nuclei that contain 5-HT cell bodies, given the predominant localization and function of 5-HT 1A receptors as presynaptic autoreceptors (Barnes and Sharp, 1999), while the distribution and density of SERT and 3 H-LSD binding to 5-HT 1A-D and 5-HT 2 receptors are more heterogeneous within the medulla. Of note, we previously examined the ontogeny of the binding profiles of 3 H-LSD to 5-HT 1A-1D and 5-HT 2 receptors in the human fetal (n ϭ 3) and infant (n ϭ 5) brainstem (Zec et al, 1996). Since that time, however, we have increased our normative infant brainstem dataset 5-fold, allowing us now to examine developmental changes in 3 H-LSD binding across infancy (i.e., the first year of life) rather than grouping all infant values together (Zec et al, 1996).…”

mentioning

confidence: 99%

“…Of note, we previously examined the ontogeny of the binding profiles of 3 H-LSD to 5-HT 1A-1D and 5-HT 2 receptors in the human fetal (n ϭ 3) and infant (n ϭ 5) brainstem (Zec et al, 1996). Since that time, however, we have increased our normative infant brainstem dataset 5-fold, allowing us now to examine developmental changes in 3 H-LSD binding across infancy (i.e., the first year of life) rather than grouping all infant values together (Zec et al, 1996). Thus, the expanded database provides the opportunity to uncover potentially more subtle developmental changes during this period.…”

mentioning

confidence: 99%

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Differential development of 5‐HT receptor and the serotonin transporter binding in the human infant medulla

Paterson

Belliveau

Trachtenberg

et al. 2004

J of Comparative Neurology

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Tissue receptor autoradiography with 3H-lysergic acid diethylamide (3H-LSD), 3H-8-hydroxy-2-[di-N-propylamine] tetralin (3H-8-OH-DPAT), and 125I-RTI-55 was used to map the distribution and developmental profile of 5-HT(1A-1D) and 5-HT2 receptors, 5-HT1A receptors, and the serotonin (5-HT) transporter (SERT), respectively, to nuclei with cardiorespiratory function in the human medulla from midgestation to maturity. The distribution pattern of the 5-HT markers was heterogeneous, with variable densities of binding of each observed both in nuclei with and without 5-HT cell bodies. The highest density of binding for each marker was observed in the raphé nuclei, the site of the highest density of 5-HT cell bodies. A significant reduction in 5-HT receptor binding measured with 3H-LSD was observed between midgestation and infancy, and between infancy and maturity in multiple nuclei, but no changes were observed across infancy. A significant increase in 5-HT1A receptor binding density was observed across infancy in the hypoglossal nucleus (regression slope coefficient = 0.008 +/- 0.002, P = 0.02), and a marginally significant increase was observed in the raphé obscurus (regression slope coefficient = 0.061 +/- 0.026 [mean +/- SEM], P = 0.05). No significant age-related changes in SERT binding were observed at any time. With the exception of the hypoglossal nucleus, where 5-HT1A receptor binding increases while SERT binding remains stable, the medullary 5-HT markers analyzed in the study are essentially "in place" at birth. This study provides important baseline data that serve as a foundation for future work in pediatric 5-HT brainstem disorders, including sudden infant death syndrome.

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Developmental changes in heterogeneous patterns of neurotransmitter receptor binding in the human interpeduncular nucleus

et al. 1998

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The interpeduncular nucleus (IPN) exhibits many complex features, including multiple subnuclei, widespread projections with the forebrain and brainstem, and neurotransmitter heterogeneity. Despite the putative importance of this nucleus, very little is known about its neurochemical development in the human. The human IPN is cytoarchitectonically simple, unlike the rat IPN, which displays considerable heterogeneity. In the following study, we hypothesized that the developing human IPN is neurochemically heterogeneous despite its cytological simplicity. The chemoarchitecture in this study was defined by neurotransmitter receptor binding patterns by using quantitative tissue autoradiography for the muscarinic, nicotinic, serotoninergic, opioid, and kainate receptors. We examined neurotransmitter receptor binding in the developing human IPN in a total of 15 cases. The midbrains of five midgestational fetuses (19-26 gestational weeks) and six infants (38-74 postconceptional weeks) were examined. The midbrain of one child (4 years) and three adults (20-68 years) were analyzed as indices of maturity. At all ages examined, high muscarinic binding was localized to the lateral subdivision of the IPN, high serotoninergic binding was localized to the dorsal IPN, and high opioid receptor binding was localized to the medial IPN. The developmental profile was unique for each radioligand. We report a heterogenous distribution of neurotransmitter receptor binding in the developing human IPN, which supports a complex role for it in human brain function.

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Developmental Changes in [3H]Lysergic Acid Diethylamide ([3H]LSD) Binding to Serotonin Receptors in the Human Brainstem

Cited by 29 publications

References 0 publications

Evaluation of CSF neurotransmitters and folate in 25 patients with Rett disorder and effects of treatment

Evaluation of CSF neurotransmitters and folate in 25 patients with Rett disorder and effects of treatment

Differential development of 5‐HT receptor and the serotonin transporter binding in the human infant medulla

Developmental changes in heterogeneous patterns of neurotransmitter receptor binding in the human interpeduncular nucleus

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