The serotonergic system dysfunction in diabetes mellitus

Yan, Cheng; Li, Xiaolong; Zhou, Hongli; Zhou, Jiyin

doi:10.3389/fncel.2022.899069

Cited by 13 publications

(4 citation statements)

References 113 publications

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“…Likewise, although disruption of the A. aegypti 5HT2B receptor resulted in reduced larval size 38 , this phenotype was not observed following the silencing of 5-HTR1 in any of the mosquito larval species. These data suggest that this receptor does not impact insulin signaling as reported in other 5-HTR subtypes 49 – 52 . When 5-HTR.426 yeast was supplied beginning in the late third instar, no significant larval death was observed (P > 0.05), suggesting that treatment beginning in early larval development is critical for 5-HTR.426 larvicidal activity.…”

Section: Resultssupporting

confidence: 66%

Characterization of a novel RNAi yeast insecticide that silences mosquito 5-HT1 receptor genes

Mysore,

Njoroge,

Stewart

et al. 2023

Sci Rep

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G protein-coupled receptors (GPCRs), which regulate numerous intracellular signaling cascades that mediate many essential physiological processes, are attractive yet underexploited insecticide targets. RNA interference (RNAi) technology could facilitate the custom design of environmentally safe pesticides that target GPCRs in select target pests yet are not toxic to non-target species. This study investigates the hypothesis that an RNAi yeast insecticide designed to silence mosquito serotonin receptor 1 (5-HTR1) genes can kill mosquitoes without harming non-target arthropods. 5-HTR.426, a Saccharomyces cerevisiae strain that expresses an shRNA targeting a site specifically conserved in mosquito 5-HTR1 genes, was generated. The yeast can be heat-inactivated and delivered to mosquito larvae as ready-to-use tablets or to adult mosquitoes using attractive targeted sugar baits (ATSBs). The results of laboratory and outdoor semi-field trials demonstrated that consumption of 5-HTR.426 yeast results in highly significant mortality rates in Aedes, Anopheles, and Culex mosquito larvae and adults. Yeast consumption resulted in significant 5-HTR1 silencing and severe neural defects in the mosquito brain but was not found to be toxic to non-target arthropods. These results indicate that RNAi insecticide technology can facilitate selective targeting of GPCRs in intended pests without impacting GPCR activity in non-targeted organisms. In future studies, scaled production of yeast expressing the 5-HTR.426 RNAi insecticide could facilitate field trials to further evaluate this promising new mosquito control intervention.

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Section: Resultssupporting

confidence: 66%

Characterization of a novel RNAi yeast insecticide that silences mosquito 5-HT1 receptor genes

Mysore,

Njoroge,

Stewart

et al. 2023

Sci Rep

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“…However, during the fetal and early postnatal development of the brain, the blood-brain barrier is not fully formed, and the two systems can freely communicate [12]. Considering the role of 5-HT in neurodevelopment [13] and prenatal programming [14], genetic or environmental disruption of optimal serotonin concentrations can affect serotonin homeostasis in both compartments, leading to an increased vulnerability to behavioral and/or metabolic disorders [15,16]. One of the measurable signs of 5HT homeostasis disruption is hyperserotonemia-a state of elevated blood 5HT levels.…”

Section: Introductionmentioning

confidence: 99%

Beyond the Brain: Perinatal Exposure of Rats to Serotonin Enhancers Induces Long-Term Changes in the Jejunum and Liver

Gračan,

Blažević,

Brižić

et al. 2024

Biomedicines

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Serotonin (5-hydroxytryptamine, 5HT) homeostasis is essential for many physiological processes in the central nervous system and peripheral tissues. Hyperserotonemia, a measurable sign of 5HT homeostasis disruption, can be caused by 5HT-directed treatment of psychiatric and gastrointestinal diseases. Its impact on the long-term balance and function of 5HT in the peripheral compartment remains unresolved and requires further research due to possible effects on human health. We explored the effects of perinatal 5HT imbalance on the peripheral organs responsible for serotonin metabolism—the jejunum, a synthesis site, and the liver, a catabolism site—in adult rats. Hyperserotonemia was induced by subchronic treatment with serotonin precursor 5-hydroxytryptophan (5HTP) or serotonin degradation inhibitor tranylcypromine (TCP). The jejunum and liver were collected on postnatal day 70 and analyzed histomorphometrically. Relative mRNA levels of 5HT-regulating proteins were determined using qRT-PCR. Compared to controls, 5HTP- and TCP-treated rats had a reduced number of 5HT-producing cells and expression of the 5HT-synthesising enzyme in the jejunum, and an increased expression of 5HT-transporter accompanied by karyomegaly in hepatocytes, with these differences being more pronounced in the TCP-treated animals. Here, we report that perinatal 5HT disbalance induced long-term cellular and molecular changes in organs regulating 5HT-metabolism, which may have a negative impact on 5HT availability and function in the periphery. Our rat model demonstrates a link between the developmental abnormalities of serotonin homeostasis and 5HT-related changes in adult life and may be suitable for exploring the neurobiological substrates of vulnerability to behavioral and metabolic disorders, as well as for modeling the adverse effects of the prenatal exposure to 5HT enhancers in the human population.

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“…Disrupted 5-HT homeostasis is a widely recognized feature of various mental health conditions [ 15 ] and an emerging component of metabolic disorders such as obesity and diabetes [ 16 , 17 ]. The DOHaD (Developmental Origins of Health and Disease) concept posits DNA methylation and other epigenetic mechanisms as pivotal mediators linking prenatal adversity to lifelong risk for various chronic diseases [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence

Bečeheli,

Horvatiček,

Perić

et al. 2024

Clin Epigenet

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Background Serotonin (5-hydroxytryptamine, 5-HT) signaling is involved in neurodevelopment, mood regulation, energy metabolism, and other physiological processes. DNA methylation plays a significant role in modulating the expression of genes responsible for maintaining 5-HT balance, such as 5-HT transporter (SLC6A4), monoamine oxidase A (MAOA), and 5-HT receptor type 2A (HTR2A). Maternal metabolic health can influence long-term outcomes in offspring, with DNA methylation mediating these effects. We investigated associations between maternal metabolic parameters—pre-pregnancy body mass index (pBMI), gestational weight gain (GWG), and glucose tolerance status (GTS), i.e., gestational diabetes mellitus (GDM) versus normal glucose tolerance (NGT)—and cord blood methylation of SLC6A4, MAOA, and HTR2A in participants from our PlaNS birth cohort. CpG sites (15, 9, and 2 in each gene, respectively) were selected based on literature and in silico data. Methylation levels were quantified by bisulfite pyrosequencing. We also examined the stability of methylation patterns in these genes in circulating blood cells from birth to adolescence using longitudinal DNA methylation data from the ARIES database. Results None of the 203 PlaNS mothers included in this study had preexisting diabetes, 99 were diagnosed with GDM, and 104 had NGT; all neonates were born at full term by planned Cesarean section. Methylation at most CpG sites differed between male and female newborns. SLC6A4 methylation correlated inversely with maternal pBMI and GWG, while methylation at HTR2A site -1665 correlated positively with GWG. None of the maternal metabolic parameters statistically associated with MAOA methylation. DNA methylation data in cord blood and peripheral blood at ages 7 and 15 years were available for 808 participants from the ARIES database; 4 CpG sites (2 in SLC6A4 and 2 in HTR2A) overlapped between the PlaNS and ARIES cohorts. A positive correlation between methylation levels in cord blood and peripheral blood at 7 and 15 years of age was observed for both SLC6A4 and HTR2A CpG sites. Conclusions Methylation of 5-HT regulating genes in cord blood cells is influenced by neonatal sex, with maternal metabolism playing an additional role. Inter-individual variations present in circulating blood cells at birth are still pronounced in childhood and adolescence.

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The serotonergic system dysfunction in diabetes mellitus

Cited by 13 publications

References 113 publications

Characterization of a novel RNAi yeast insecticide that silences mosquito 5-HT1 receptor genes

Characterization of a novel RNAi yeast insecticide that silences mosquito 5-HT1 receptor genes

Beyond the Brain: Perinatal Exposure of Rats to Serotonin Enhancers Induces Long-Term Changes in the Jejunum and Liver

Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence

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