HEИндивидуална стипендия2023–2025

SeRBoMo · Serotoninergic Regulation of Body Axis Morphology

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период: 2023-06-21 → 2025-06-20
Финансиране от ЕС: 195 915 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Серотониновите неврони и тяхната роля при изкривяването на гръбначния стълб се изучават чрез модели с зебрни рибки. Разбирането на тези механизми ще помогне за по-добра диагностика и подобряване на живота на хората с идиопатична сколиоза.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Serotoninergic Regulation of Body Axis Morphology

Idiopatic scoliosis (IS) is a human pathology that affects 1-4% of adolescents worldwide, who suffer from spine deformities that arise during puberty. At present, evidence for genetic causes of IS exist, but the aetiology of this pathology is still not understood. As of now, no effective treatment is available for IS. This is partly due to the impossibility of early diagnosis, as IS can be detected only when spine curvatures are already visible in patients. This leads to painful treatment and life conditions, which are often not improved after bracing, as well as costly surgery and expensive orthopaedic equipment. The combination of these two factors induces only ~3K patients/year in Europe to undergo surgery, out of a total number of ~20K severe cases who would need treatment. For these reasons, understanding the fundamental caused of IS will help informing clinical research, ultimately ameliorating the life condition of patients. The longterm goal of this research project is to gain insights into novel physiological mechanisms leading to a defective body axis alignment, which are also present in IS patients. To this end, zebrafish has proven to be a powerful organism to model human pathologies that entail body axis misalignment as, by swimming in a viscous liquid, its spine is subject to forces similar to the ones acting on the spine in bipedal position. Surprisingly, a scoliotic-like phenotype arises in the tph2ct817/817 mutant zebrafish. Tph2 is one of the rate-limiting enzymes for serotonin synthesis, so that the mutant fish are genetically depleted of serotonin in some neurons of the CNS (Central Nervous System). The overarching aim of this research project is to unravel how the neuronal activity of serotoninergic neurons can control the maintenance of a straight longitudinal body axis during the zebrafish post embryonic life.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Idiopatic scoliosis (IS) is a human pathology that affects 1-4% of adolescents worldwide, who suffer from spine deformities for which an effective treatment is not currently available. At present, evidence for genetic causes of IS exist, but the aetiology of this pathology is still not understood. The zebrafish is a powerful organism to model human pathologies that entail body axis misalignment as, by swimming in a viscous liquid, its spine is subject to forces similar to the ones acting on the spine in bipedal position. One essential player in the establishment of embryonic zebrafish longitudinal axis is the Reissner Fibre (RF). The RF consists of SCO-spondin protein, which, during post embryonic life, is secreted by a paraventricular organ, the SCO. Zebrafish scospondin mutants lack the RF and exhibit severe scoliotic phenotype. Remarkably, a similar scoliotic phenotype is observed in the tph2-/- zebrafish, genetically depleted of serotonin. Preliminary observations have shown that serotoninergic projections reach the SCO, in mammals and in the zebrafish. My research objective is to unravel how the neuronal activity of serotoninergic neurons can control the maintenance of a straight longitudinal body axis during the zebrafish post embryonic life. Firstly, a detailed characterisation of spine alignment in correlation to RF assembly will be carried out in the tph2-/- zebrafish. Secondly, the serotoninergic neurons projecting to the SCO will be anatomically located and mapped. Thirdly, the neuronal mechanism by which serotoninergic neurons regulate RF maintenance will be functionally investigated. The long-term goal of this research project is to gain insights in the progression of IS, and to inform preclinical research on the development of diagnostic tools, which are currently lacking.

Оригинален текст от CORDIS (на английски).

Участници

INSTITUT DU CERVEAU ET DE LA MOELLE EPINIERE · ParisКоординаторФранция