Transient expression of serotonin 5‐HT4 receptors in the mouse developing thalamocortical projections

Slaten, Erin R.; Hernandez, Melissa C.; Albay, Ricardo; Lavian, Rachel; Janušonis, Skirmantas

doi:10.1002/dneu.20775

Cited by 10 publications

(8 citation statements)

References 82 publications

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“…We have previously shown that the thalamocortical projections express 5-HT 4 -Rs in the embryonic mouse brain [Slaten et al, 2010]. However, it is unlikely that the observed upregulation was due to an increase in the mRNA levels in thalamocortical neurons, since our samples did not include the diencephalon and long-projection axons typically do not contain mRNA [Vilaro et al, 2005].…”

Section: Discussionmentioning

confidence: 94%

“…Studies have shown that 5-HT 4 -Rs and ␤ 2 -ARs may play important roles in the neurobiology of depressive disorders [Mongeau et al, 1997;Sastre et al, 2001;Duman, 2007;Lucas et al, 2007;Tamburella et al, 2009], Alzheimer's disease [Lezoualc'h, 2007;Yu et al, 2008Yu et al, , 2010, and autism spectrum disorders [Connors et al, 2005;Cheslack-Postava et al, 2007;Janušonis, 2008;Vincent et al, 2009;Slaten et al, 2010].…”

Section: Discussionmentioning

confidence: 99%

“…The RNA quality (the A260/A280 ratio) and concentration were measured with a NanoDrop spectrophotometer and the samples were stored at -75 ° C until further processing. Four embryos were analyzed at each developmental time-point (none of the collected samples overlapped with those used in our previous study [Slaten et al, 2010]). This experimental design allowed us to achieve good temporal resolution (every embryonic day was analyzed in the E13-E18 interval), at the cost of larger errors of the mean at each of the time-points.…”

Section: Collection Of Tissuementioning

confidence: 99%

“…The developing rodent forebrain exhibits a highly dynamic pattern of 5-HT 4 -R expression [Waeber et al, 1994[Waeber et al, , 1996Slaten et al, 2010], suggesting that factors interfering with this pattern may lead to functional brain abnormalities. Since 5-HT 4 -Rs receptors may interact with ␤ 2 -ARs during embryonic and fetal development and ␤ 2 -ARs can detect stress-related signals, the ontogeny of 5-HT 4 -R and ␤ 2 -AR levels in the developing forebrain has potentially important implications for understanding autism spectrum and other developmental disorders [Cheslack-Postava et al, 2007;Vincent et al, 2009;Yirmiya and Charman, 2010].…”

Section: Introductionmentioning

confidence: 99%

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Quantitative mRNA Analysis of Serotonin 5-HT4 and Adrenergic β2 Receptors in the Mouse Embryonic Telencephalon

Hernandez

Janušonis²

2010

Dev Neurosci

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The adrenergic β₂ receptor (β₂-AR) gene is embedded (nested) within the serotonin 5-HT₄ receptor (5-HT₄-R) gene and these two receptors can interact at the transcriptional and post-transcriptional levels. The mouse 5-HT₄-R gene contains a number of exons and codes at least four mRNA splice variants (5-HT_4(a)-R, 5-HT_4(b)-R, 5-HT_4(e)-R, 5-HT_4(f)-R), whereas the β₂-AR gene is intronless. Since 5-HT₄-Rs and β₂-ARs can form homodimers and heterodimers and they increase intracellular cAMP levels, these receptors may be important for integrating serotonergic and noradrenergic signals at the single-neuron level. Both 5-HT₄-R and β₂-AR have been implicated in autism spectrum disorders, depression, and Alzheimer’s disease. In the fetal brain, these receptors may mediate the effects of stress on neurodevelopmental processes. We used quantitative reverse-transcription PCR (qRT-PCR) to investigate the developmental expression of 5-HT₄-R and β₂-AR in the mouse telencephalon at embryonic days (E) 13–18. At E13–E14, the mRNA levels of all 5-HT₄-R splice variants were very low, but by E17–E18 they increased 7-fold (5- HT_4(a)-R), 5-fold (5-HT_4(b)-R), 9-fold (5-HT_4(e)-R), and 11-fold (5-HT_4(f)-R). The expression of 5-HT_4(a)-R and 5-HT_4(b)-R was rapidly upregulated between E14 and E15, at the time when the thalamocortical projections arrive in the telencephalon. This pattern was not observed in the expression of 5-HT_4(e)-R and 5-HT_4(f)-R, the mRNA levels of which showed a steady, gradual increase from E13 to E18. The β₂-AR mRNA levels were relatively high throughout the studied period of development and increased only by 70% from E13–E14 to E17–E18. These findings suggest that 5-HT₄-R splice variants and β₂-ARs are differentially regulated in the embryonic telencephalon and that their relative amounts may carry developmentally important information.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Collection Of Tissuementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Quantitative mRNA Analysis of Serotonin 5-HT4 and Adrenergic β2 Receptors in the Mouse Embryonic Telencephalon

Hernandez

Janušonis²

2010

Dev Neurosci

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“…Additionally, Slaten et al . () reported that 5‐HT4 receptor is transiently expressed in the mouse developing thalamocortical projections from E13 to E17. While these studies described a spatiotemporal pattern of 5‐HT receptor expression in the developing brain, there is a paucity of information regarding cellular localization of these receptors.…”

Section: Discussionmentioning

confidence: 99%

Exposure to serotonin adversely affects oligodendrocyte development and myelination in vitro

Fan

Bhatt

Tien

et al. 2015

Journal of Neurochemistry

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Serotonin (5-hydroxytraptamin, 5-HT) has been implicated to play critical roles in early neural development. Recent reports have suggested that perinatal exposure to selective serotonin reuptake inhibitors (SSRIs) resulted in cortical network miswiring, abnormal social behavior, callosal myelin malformation, as well as oligodendrocytes (OL) pathology in rats. To gain further insight into the cellular and molecular mechanisms underlying SSRIs-induced OL and myelin abnormalities, we investigated the effect of 5-HT exposure on OL development, cell death, and myelination in cell culture models. First, we showed that 5-HT receptor 1A and 2A subtypes were expressed in OL lineages, using immunocytochemistry, Western blot, as well as intracellular Ca2+ measurement. We then assessed the effect of serotonin exposure on the lineage development, expression of myelin proteins, cell death, and myelination, in purified OL and neuron-OL myelination cultures. For pure OL cultures, our results showed that 5-HT exposure led to disturbance of OL development, as indicated by aberrant process outgrowth and reduced myelin proteins expression. At higher doses, such exposure triggered a development-dependent cell death, as immature OLs exhibited increasing susceptibility to 5-HT treatment compared to OL progenitor cells (OPCs). We showed further that 5-HT-induced immature OL death was mediated at least partially via 5-HT2A receptor, since cell death could be mimicked by 5-HT2A receptor agonist DOI, but attenuated by pre-treatment with 5-HT2A receptor antagonist ritanserin. Utilizing a neuron-OL myelination co-culture model, our data showed that 5-HT exposure significantly reduced the number of myelinated internodes. In contrast to cell injury observed in pure OL cultures, 5-HT exposure did not lead to OL death or reduced OL density in neuron-OL co-cultures. However, abnormal patterns of contactin-associated protein (Caspr) clustering were observed at the sites of Node of Ranvier, suggesting that 5-HT exposure may affect other axon-derived factors for myelination. In summary, this is the first study to demonstrate that manipulation of serotonin levels affects OL development and myelination, which may contribute to altered neural connectivity noted in SSRIs-treated animals.

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The role of different serotonin receptor subtypes in seizure susceptibility

et al. 2013

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5-Hydroxytryptamine (5-HT) has the most diverse set of receptors in comparison with any other neurotransmitter or hormone in the body. To date, seven families of 5-HT receptors have been characterized. A great number of studies have been published regarding the role of 5-HT and its receptors in seizures. However, with a few exceptions, the net effect of activating or inhibiting each 5-HT receptor subtype on the development or severity of seizures remains controversial. Additionally, the results of studies, which have used knockout animals to investigate the role of 5-HT receptors in seizures, have sometimes been contradictory to those which have used pharmacological tools. The present study aims to review the available data regarding the influence of each receptor subtype on seizure development and, when possible, reconcile between the apparently different results obtained in these studies.

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Transient expression of serotonin 5‐HT₄ receptors in the mouse developing thalamocortical projections

Cited by 10 publications

References 82 publications

Quantitative mRNA Analysis of Serotonin 5-HT<sub>4</sub> and Adrenergic β<sub>2</sub> Receptors in the Mouse Embryonic Telencephalon

Quantitative mRNA Analysis of Serotonin 5-HT<sub>4</sub> and Adrenergic β<sub>2</sub> Receptors in the Mouse Embryonic Telencephalon

Exposure to serotonin adversely affects oligodendrocyte development and myelination in vitro

The role of different serotonin receptor subtypes in seizure susceptibility

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