Dual effect of serotonin on the dendritic growth of cultured hippocampal neurons: Involvement of 5-HT1A and 5-HT7 receptors

Rojas, Paulina S.; Aguayo, Felipe I.; Neira, David; Tejos, Macarena; Aliaga, Esteban; Muñoz, Juan Pablo; Parra, C.; Fiedler, Jenny L.

doi:10.1016/j.mcn.2017.09.009

Cited by 21 publications

(16 citation statements)

References 70 publications

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“…Alzheimer's disease [5,66], indicating the important role of neurogenesis of hippocampus in the brain. 5-HT1AR has been reported to regulate the neurogenesis of hippocampus [67,68]. Moreover, lines of evidence showed that 5-HT1AR was involved in the pathology of neurological diseases such as Parkinson's disease and depression [64,[69][70][71][72][73].…”

Section: Discussionmentioning

confidence: 99%

Signaling transduction regulated by 5-hydroxytryptamine 1A receptor and orexin receptor 2 heterodimers

Wang

Cheng

et al. 2019

Cellular Signalling

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As G-protein-coupled receptors (GPCRs), 5-hydroxytryptamine 1A receptor (5-HT1AR) and orexin receptor 2 (OX2R) regulate the levels of the cellular downstream molecules. The heterodimers of different GPCRs play important roles in various of neurological diseases. Moreover, 5-HT1AR and OX2R are involved in the pathogenesis of neurological diseases such as depression with deficiency of hippocampus plasticity. However, the direct interaction of the two receptors remains elusive. In the present study, we firstly demonstrated the heterodimer formation of 5-HT1AR and OX2R. Exchange protein directly activated by cAMP (Epac) cAMP bioluminescence resonance energy transfer (BRET) biosensor analysis revealed that the expression levels of cellular cAMP significantly increased in HEK293T cells transfected with the two receptors compared with the 5-HT1AR group. Additionally, the cellular level of calcium was upregulated robustly in HEK293T cells co-transfected with 5-HT1AR and OX2R group after agonist treatment. Furthermore, western blotting data showed that 5-HT1AR and OX2R heterodimer decreased the levels of phosphorylation of extracellular signal-regulated kinase (ERK) and cAMP-response element-binding protein (CREB). These results not only unraveled the formation of 5-HT1AR and OX2R heterodimer but also suggested that the heterodimer affected the downstream signaling pathway, which will provide new insights into the function of the two receptors in the brain.

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Section: Discussionmentioning

confidence: 99%

Signaling transduction regulated by 5-hydroxytryptamine 1A receptor and orexin receptor 2 heterodimers

Wang

Cheng

et al. 2019

Cellular Signalling

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“…Downstream of Dab1, PI3K, and AKT are activated (Jossin and Goffinet, 2007). A study by Rojas et al (2017) showed that the number and length of long primary dendrites (≻40 mm) and the number of secondary dendrites were reduced by 5-HT 1A R by activating PI3K; however, the activation of PI3K did not change the phosphorylation state of GSK3b in Ser 9 . MiR-17-92 cluster-elevated MSC exosome treatment significantly increased neurite branching and spine density.…”

Section: Discussionmentioning

confidence: 99%

DL‐3‐n‐butylphthalide promotes dendrite development in cortical neurons subjected to oxygen‐glucose deprivation/reperfusion

Zhang

Guo

et al. 2018

Cell Biology International

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The limited degree of functional recovery is closely associated with the condition of the periinfarct cortex after ischemic stroke. The model of oxygen-glucose deprivation in cultured neurons could partly simulate this condition. Proper dendritic morphology is crucial for the correct wiring of neuronal function. Hence, the question of how to facilitate the plasticity of neural dendrites is of great significance. DL-3-n-butylphthalide is an efficient medication for ischemic stroke. In this study, in addition to having neuroprotective effects, DL-3-n-butylphthalide could increase the number of primary and secondary dendrites and of dendritic tips as confirmed by Sholl analysis. This study further demonstrated that DL-NBP inactivates PI3K/AKT signaling to positively regulate dendritic branching.

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“…Considering the antagonistic action of the 5-HT 7 R and 5-HT 1A R in regulating the cAMP concentration, the question arose about the specific functional impact of the formation of hetero-over homo-oligomers. This is of particular importance because the balance of the expression level of the 5-HT 7 R and 5-HT 1A R, and thus the balance between the homo-and hetero-oligomer formation, changes during neuronal development (Kobe et al, 2012;Rojas et al, 2017), which could provide further downstream regulatory consequences. Therefore, we co-expressed 5-HT 7 R and 5-HT 1A R together with CEpac in various 5-HT 7 R:5-HT 1A R plasmid concentration ratios to investigate the downstream signaling in relation to 5-HTR oligomerization.…”

Section: Functional Role Of Heterodimerizationmentioning

confidence: 99%

“…Cell culturing of murine N1E-115 neuroblastoma (N1E) cells (American Type Culture Collection), which are known not to express any G-protein coupled 5-HTR (Richelson, 1990), was undertaken as described previously (Renner et al, 2012). Cells were plated on 18 mm glass coverslips and transfected using Lipofectamine 2000 reagent (Life Technologies, Darmstadt, Germany) according to the manufacturer's instruction.…”

Section: Cell Culture and Transfectionmentioning

confidence: 99%

Serotonin receptor oligomerization regulates cAMP-based signaling

Prasad

Ponimaskin

Zeug

2019

Journal of Cell Science

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Protein-protein interaction is often investigated using quantitative molecular microscopy with Förster resonant energy transfer (FRET). Here, we combined 'linear unmixing FRET' (lux-FRET) with the simultaneous application of a FRET-based biosensor for cAMP to investigate the oligomerization between the 5-HT 7 receptor (5-HT 7 R, also known as HTR7) and the 5-HT 1A receptor (5-HT 1A R, also known as HTR1A) and its importance for cAMP signaling. We found that the 5-HT 7 R not only stimulates cAMP production, but also forms heterooligomers with 5-HT 1A R, which blocks the inhibitory effect of the latter. 5-HT 7 R signaling, however, is not affected by this heterooligomerization. By modeling the kinetics of intracellular cAMP level changes in relation to the 5-HT 7 R:5-HT 1A R stoichiometry, we were able to decipher the complex signaling characteristics of endogenous serotonin receptors in cultured hippocampal neurons. Our findings indicate that serotonergic signaling is not only modulated by the concentration of an individual receptor but also by its specific interaction with other receptors in endogenous systems. We conclude that the regulated ratio of serotonin receptors in immature and mature neurons may be critically involved in both the onset and response to treatments of psychiatric diseases, such as anxiety and depression.

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Dual effect of serotonin on the dendritic growth of cultured hippocampal neurons: Involvement of 5-HT1A and 5-HT7 receptors

Cited by 21 publications

References 70 publications

Signaling transduction regulated by 5-hydroxytryptamine 1A receptor and orexin receptor 2 heterodimers

Signaling transduction regulated by 5-hydroxytryptamine 1A receptor and orexin receptor 2 heterodimers

DL‐3‐n‐butylphthalide promotes dendrite development in cortical neurons subjected to oxygen‐glucose deprivation/reperfusion

Serotonin receptor oligomerization regulates cAMP-based signaling

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