Molecular Sciences IV.
Dr. Ocskay, Zsombor
Semmelweis University Department of Physiology
06205802280
zsombor.ocskay@med.semmelweis-univ.hu
CCBE1 regulates the development and prevents the age-dependent degradation of meningeal lymphatics
Zsombor Ocskay1, László Bálint1, Carolin Christ1, Zoltán Jakus1
1 Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary
Szóbeli
Molecular Sciences IV.
English
Molecular Sciences
The mLVs (meningeal lymphatic vessels) develop postnatally and are degraded by aging. For this developmental program and maintenance, VEGFC/VEGFR3 signaling is essential.
Recent in vitro works have suggested that the collagen- and calcium-binding EGF domains 1 (CCBE1) protein promotes lymphogenic VEGFC maturing and binding.
We aimed to investigate the organ-specific role of the CCBE1 in developmental lymphangiogenesis and maintenance of lymphatic vessels during aging.
Lymphatic endothelial cell-specific immunostainings were used to characterize the meningeal lymphatic structures in wild-type and CCBE1 deficient mice at different ages, including young and old animals. The lymphatic function was monitored by injecting labeled macromolecules into the CNS, then assessing uptake and drainage to the cervical lymph nodes.
We have demonstrated that the CCBE1 inducible deletion impaired the postnatal development of the meningeal lymphatics and decreased macromolecule drainage from the CNS. We revealed that the structural integrity and density of mLV vessels gradually altered during aging. Surprisingly, in adult mice, the LVs showed regression after CCBE1 deletion.
Our results indicate the importance of lymphangiogenic mechanisms in developing and preventing the age-related degradation of meningeal lymphatics.
The degradation of meningeal lymphatic structures in aging may play an essential role in the pathophysiology of Alzheimer's disease.
Funding:
This work was supported by the National Research, Development and Innovation Office (NVKP_16-2016-1-0039, K 139165, TKP2021-EGA-29, TKP2021-EGA-24 to Z.J.), the European Union and the Hungarian Government (VEKOP-2.3.2-16-2016-00002 to Z.J. and EFOP-3.6.3-VEKOP-16-2017-00009 to O.Z.), and the Higher Education Institutional Excellence Program of the Ministry for Innovation and Technology in Hungary, within the framework of the Molecular Biology thematic program of the Semmelweis University.
Semmelweis University, Doctoral School of Molecular Medicine
Zoltán Jakus MD,PhD
I do not give consent to the publication of my abstract on the website of the congress.
Szabad
elfogadva
szóbeli
nem rendelkezett róla
4805
15:45
16:00
Zsombor Ocskay1, László Bálint1, Carolin Christ1, Zoltán Jakus1
1 Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary