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Evidence reveals that gut dysbiosis is involved in bidirectional interactions in gut-brain axis and participates in the progress of multiple disorders like anxiety. Gut microbes in early life are crucial for establishment of host health. We aimed to investigate whether early life probiotics Lactobacillus rhamnosus GG (LGG) colonization could relieve anxiety in adulthood through regulation of gut-brain axis. Live or fixed LGG was gavaged to C57BL/6 female mice from day 18 of pregnancy until natural birth, and newborn mice from day 1 to day 5 respectively. In this study, we found that live LGG could be effectively colonized in the intestine of offspring. LGG colonization increased intestinal villus length and colonic crypt depth, accompanied with barrier function protection before weaning. Microbiota composition by 16S rRNA sequencing showed that some beneficial bacteria, such as Akkermansia and Bifidobacteria, were abundant in LGG colonization group. The protective effect of LGG on gut microbiota persisted from weaning to adulthood. Intriguingly, behavioral results assessed by elevated plus mazed test and open field test demonstrated relief of anxiety-like behavior in adult LGG-colonized offspring. Mechanically, LGG colonization activated epithelial growth factor receptor (EGFR) and enhanced serotonin transporter (SERT) expression and modulated serotonergic system in the intestine, and increased brain-derived neurotrophic factor and γ-aminobutyric acid receptor levels in the hippocampus and amygdala. Blocking EGFR blunted LGG-induced the increased SERT and zonula occludens-1 expression. Collectively, early life LGG colonization could protect intestinal barrier of offspring and modulate gut-brain axis in association with relief of anxiety-like behavior in adulthood.

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RESUMEN

Nowadays the pathogenesis of early-onset depression is still uncertain. Only SSRIs are currently approved for clinical use as antidepressants in children and adolescents, indicating that 5-HT is the most important neurotransmitter involved in the dis-ease. Current studies with regard to central 5-HTergic system in early-onset depression mainly focus on 5-HT synthesis deficien-cy, 5-HT transportation dysregulation, as well as the earlier mat-uration of 5-HT system than norepinephrine system. 5-HT precur-sor tryptophan malabsorption and dysregulation of 5-HT synthesis can contribute to 5-HT deficiency. Moreover, the 5-HTTLPR low-expressing genotypes may increase the risk of early-onset de-pression. It is necessary to make preclinical and clinical studies more widely and deeply about the effect of central 5-HTergic sys-tem in early-onset depression in future.

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The present article reviews the role of the serotoninergic system in the regulation of the sodium appetite. Data from the peripheral and icv administration of serotoninergic (5-HTergic) agents showed the participation of 5-HT2/3 receptors in the modulation of sodium appetite. These observations were extended with the studies carried out after brain serotonin depletion, lesions of DRN and during blockade of 5-HT2A/2C receptors in lateral parabrachial nucleus (LPBN). Brain serotonin depletion and lesions of DRN increased the sodium appetite response, in basal conditions, after sodium depletion and hypovolemia or after beta-adrenergic stimulation as well. These observations raised the hypothesis that the suppression of ascending pathways from the DRN, possibly, 5-HTergic fibers, modifies the angiotensinergic or sodium sensing mechanisms of the subfornical organ involved in the control of the sodium appetite. 5-HTergic blockade in LPBN induced to similar results, particularly those regarded to the natriorexigenic response evoked by volume depletion or increase of the hypertonic saline ingestion induced by brain angiotensinergic stimulation. In conclusion, many evidences lead to acceptation of an integrated participation resulting of an interaction, between DRN and LPBN, for the sodium appetite control.

Este artigo revisa o papel do sistema serotoninérgico no controle do apetite ao sódio. Dados derivados da administração periférica e icv de agentes serotoninérgicos demonstraram a participação de receptores 5-HT2/3 na modulação do apetite ao sódio. Estas observações foram estendidas com os estudos realizados após a depleção cerebral de serotonina, lesões do NDR e durante o bloqueio 5-HT2A/2C no núcleo parabraquial lateral (NPBL). A depleção cerebral de serotonina e as lesões do NDR aumentaram o apetite ao sódio, em condições basais, após depleção de sódio, durante a hipovolemia ou após a estimulação beta-adrenérgica. Estas evidências suscitaram a hipótese de que a supressão de vias ascendentes do NDR, possivelmente 5-HT, alteram os mecanismos angiotensinérgicos e a atividade dos sensores de sódio do órgão subfornicial envolvidos no controle do apetite ao sódio. O bloqueio serotoninérgico no NPBL induziu a resultados similares, particularmente aqueles relacionados com a resposta natriorexigênica provocada pela depleção de volume ou o aumento da ingestão de salina hipertônica induzida pela estimulação angiotensinérgica cerebral. Em resumo, as evidências convergem para a admissão de uma participação integrada resultante da interação recíproca entre NDR e NPBL objetivando controlar o apetite ao sódio.

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