PhD Scientific Days 2020

Theoretical and Translational II. Lectures

Lymph Flow Induces the Postnatal Formation of Mature and Functional Meningeal Lymphatic Vessels.

Előadó neve

Bálint, László

Előadó munkahelye

Department of Physiology, Semmelweis University

Előadó telefonszáma

+36307108654

Előadó e-mail címe

balint.laszlo@med.semmelweis-univ.hu

Az előadás címe

Lymph Flow Induces the Postnatal Formation of Mature and Functional Meningeal Lymphatic Vessels.

Szerző(k) neve és munkahelye

László Bálint [1,2]
Zsombor Ocskay [1,2]
Bálint András Deák [1,2]
Petra Aradi [1,2]
Zoltán Jakus [1,2]

Affiliations:
1 - Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary
2 - MTA-SE “Lendület” Lymphatic Physiology Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary

Szekció

Theoretical and Translational II. Lectures

Language of the presentation

English

Section, first choice

Theoretical and Translational Medicine

Section, second choice

Molecular Sciences

Összefoglaló szövege

Introduction
Recently, the presence of lymphatics has been demonstrated and characterized in the dura mater, which is in contrast to the well-accepted view indicating the lack of a classical lymphatic drainage system of the central nervous system. Moreover, the role of meningeal lymphatics in the pathogenesis of Alzheimer's disease and multiple sclerosis was suggested. However, the possible regulators of the developmental program and function of meningeal lymphatics remain unclear.
Aims
We aimed at characterizing the lymph flow dependence of the developmental program and function of the meningeal lymphatic vessels.
Methods
C57BL/6 wild type and lymphatic reporter mice Prox1GFP and Flt4YFP from different ages were used to investigate the developmental program of the meningeal lymphatics. Lymphatic vessels were visualized by whole-mount immunostaining. Lymphatic function was assessed by injection of fluorescently labelled macromolecules and lipids. Flow dependence of the developmental program and function of the meningeal lymphatic vessels was studied in PLCγ2-deficient mice.
Results
First, we demonstrated that lymphatics present in the dura mater are involved in the uptake and transport of macromolecules from the CNS. Meningeal lymphatics develop during the postnatal period which process involves the maturation and structural remodeling of the vessels. The formation of mature meningeal lymphatics coincides with the increase of the drainage of macromolecules from the CNS to the deep cervical lymph nodes. Importantly, the structural remodeling and maturation of meningeal lymphatics is impaired in Plcγ2-/- mice with reduced lymph flow. Furthermore, macromolecule uptake and transport by the meningeal lymphatics are also affected in Plcγ2-/- mice.
Conclusions
Collectively, our results indicate that the meningeal lymphatics are involved in the uptake and transport of macromolecules from the CNS. A postnatal structural remodeling of meningeal lymphatics induces the uptake and drainage of macromolecules from CNS. Lymph flow-induced mechanical forces are required for the postnatal formation of mature and functional meningeal lymphatic vessels. Defining lymph flow-dependence of the development and function of meningeal lymphatics may lead to better understanding of the pathogenesis of neurological diseases including Alzheimer's disease and multiple sclerosis.

Additional Information

Supervisor: Zolán Jakus
E-mail: jakus.zoltan@med.semmelweis-univ.hu

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1231

Start

12:05

End

12:20

Authors (legacy)

László Bálint [1,2]
Zsombor Ocskay [1,2]
Bálint András Deák [1,2]
Petra Aradi [1,2]
Zoltán Jakus [1,2]

Affiliations:
1 - Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary
2 - MTA-SE “Lendület” Lymphatic Physiology Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary