5-HT2A receptors are concentrated in regions of the human infant medulla involved in respiratory and autonomic control

Paterson, David S.; Darnall, Ryan

doi:10.1016/j.autneu.2009.01.004

Cited by 21 publications

(14 citation statements)

References 90 publications

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“…14). Across the last part of human gestation, there was a sharp decline in 5-HT receptor binding as demonstrated with the broad radioligand 3 H-lysergic acid diethylamide (LSD); after birth, the only receptor binding change was an increases in the binding in the 5-HT 1A receptors in the hypoglossal nucleus (Paterson et al, 2004) and decreased binding in the 5-HT 2A receptors in the hypoglossal nucleus, principal inferior olive, and dorsal accessory olivary nucleus (Paterson et al, 2009). In contrast, there was a gradual increase in GABA Aα3 expression, as demonstrated by immunocytochemistry, in the raphé obscurus, paragigantocellularis lateralis, and arcuate nucleus from midgestation to the end of the first year, and a decrease in GABA Aα1 only in the raphé obscurus over the same time period (Fig.…”

Section: Resultsmentioning

confidence: 99%

Neuroanatomic relationships between the GABAergic and serotonergic systems in the developing human medulla

Broadbelt¹,

Paterson²,

Rivera³

et al. 2010

Autonomic Neuroscience

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Abstractγ-Amino butyric (GABA) critically influences serotonergic (5-HT) neurons in the raphé and extraraphé of the medulla oblongata. In this study we hypothesize there are marked changes in the developmental profile of markers of the human medullary GABAergic system relative to the 5-HT system in early life. We used single-and double-label immunocytochemistry and tissue receptor autoradiography in 15 human medullae from fetal and infant cases ranging from 15 gestational weeks to 10 postnatal months, and compared our findings with an extensive 5-HT-related database in our laboratory. In the raphé obscurus, we identified two subsets of GABAergic neurons using glutamic acid decarboxylase (GAD65/67) immunostaining: one comprised of small, round neurons; the other, medium, spindle-shaped neurons. In three term medullae cases, positive immunoflorescent neurons for both tryptophan hydroxylase and GAD65/67 were counted within the raphé obscurus. This revealed approximately 6% of the total neurons counted in this nucleus expressed both GAD65/67 and TPOH suggesting co-production of GABA by a subset of 5-HT neurons. The distribution of GABA A binding was ubiquitous across medullary nuclei, with highest binding in the raphé obscurus. GABA A receptor subtypes α1 and α3 were expressed by 5-HT neurons, indicating the site of interaction of GABA with 5-HT neurons. These receptor subtypes and KCC2, a major chloride transporter, were differentially expressed across early development, from mid-gestation (20wks) and thereafter. The developmental profile of GABAergic markers changed dramatically relative to the 5-HT markers. These data provide baseline information for medullary studies of human pediatric disorders, such as sudden infant death syndrome.

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Section: Resultsmentioning

confidence: 99%

Neuroanatomic relationships between the GABAergic and serotonergic systems in the developing human medulla

Broadbelt¹,

Paterson²,

Rivera³

et al. 2010

Autonomic Neuroscience

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“…These cell groups constitute the Medullary 5-HT System as defined by Kinney et al, (2007). Evidence from neuron tract tracing studies with the lipophilic fluorescent dye 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) indicates that these 5-HT neurons send projections to one another as well as to nuclei with respiratory-related function including the NTS and HG (Zec et al 1997; Zec et al 2001; Zec et al 2003); a hypothesis supported by the presence of serotonin transporter (5-HTT), 5-HT 1A receptor, and 5-HT 2A receptor binding sites in each of these regions (Paterson et al 2004; Paterson et al 2006b; Paterson et al 2009). Comparative anatomy indicates that the Arc is homologous to the respiratory chemosensitive fields at the ventral medullary surface of rodents and cats (Filiano et al 1990; Paterson et al 2006a).…”

Section: The Medullary 5-ht System In Humansmentioning

confidence: 99%

Medullary serotonin defects and respiratory dysfunction in sudden infant death syndrome

Paterson

Hilaire

Weese‐Mayer

2009

Respiratory Physiology & Neurobiology

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Sudden infant death syndrome (SIDS) is defined as the sudden and unexpected death of an infant less than 12 months of age that occurs during sleep and remains unexplained after a complete autopsy, death scene investigation, and review of the clinical history. It is the leading cause of postneonatal mortality in the developed world. The cause of SIDS is unknown, but is postulated to involve impairment of brainstem-mediated homeostatic control. Extensive evidence from animal studies indicates that serotonin (5-HT) neurons in the medulla oblongata play a role in the regulation of multiple aspects of respiratory and autonomic function. A subset of SIDS infants have several abnormalities in medullary markers of 5-HT function and genetic polymorphisms impacting the 5-HT system, informing the hypothesis that SIDS results from a defect in 5-HT brainstem-mediated control of respiratory (and autonomic) regulation. Here we review the evidence from postmortem human studies and animal studies to support this hypothesis and discuss how the pathogenesis of SIDS is likely to originate in utero during fetal development.

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“…5-HT immunostaining is present in the placenta and the ectoplacental cone (Yavarone et al, 1993). Raphe neuron differentiation and production of 5-HT starts by E10.5 in mice (Hendricks et al, 1999) and by the fifth gestational week in humans (Sundstrom et al, 1993;Verney et al, 2002;Paterson and Darnall, 2009). However, in cases where the embryo has deficient 5-HT production, maternal 5-HT can likely compensate during the embryonic phase of development.…”

Section: -Ht Sources During Developmentmentioning

confidence: 99%

Genetic Models of Serotonin (5‐HT) Depletion: What do They Tell Us About the Developmental Role of 5‐HT?

Trowbridge¹,

Narboux-Nême²,

Gaspar³

2010

The Anatomical Record

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A large number of hyposerotonergic genetic models have been generated over the past few years. Serotonin (5-HT) depletion has been obtained via targeting of genes involved in 5-HT synthesis (Tph1 and Tph2), specification and determination of the 5-HT phenotype during development (GATA3, Pet1, and Lmx1b), and 5-HT storage or clearance (Vmat2 and SERT). Here we review these various models from a developmental perspective, beginning with a description of the sources of 5-HT during development. We then summarize the neurological and behavioral alterations that have been observed in the genetic hyposerotonergic models. Although these models appear to have normal brain development and do not exhibit any gross morphological defects, problems in somatic growth and physiological functions have been observed. Abnormal adult behavior is also seen, although whether it results from depletion of 5-HT during development or functional 5-HT deficiencies in adult life remains unclear. Evidence from these hyposerotonergic models suggests that the developing brain may not need 5-HT for the establishment of general organization and structure. However, central 5-HT appears to be necessary for postnatal body growth, maturation of respiratory and vegetative control, and possibly for the development of normal adult behavior. Anat Rec, 294:1615Rec, 294: -1623Rec, 294: , 2011. V V C 2011 Wiley-Liss, Inc.

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5-HT2A receptors are concentrated in regions of the human infant medulla involved in respiratory and autonomic control

Cited by 21 publications

References 90 publications

Neuroanatomic relationships between the GABAergic and serotonergic systems in the developing human medulla

Neuroanatomic relationships between the GABAergic and serotonergic systems in the developing human medulla

Medullary serotonin defects and respiratory dysfunction in sudden infant death syndrome

Genetic Models of Serotonin (5‐HT) Depletion: What do They Tell Us About the Developmental Role of 5‐HT?

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