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Cholesterol Lowering: Boon for the Heart, Bane for the Brain..?

CC BY 4.0 · Indian J Med Paediatr Oncol 2024; 45(S 01): S1-S16

DOI: DOI: 10.1055/s-0044-1788228

*Corresponding author: (e-mail: ankur@tifr.res.in).

Abstract

Background: Neurons communicate through a crucial process known as exocytosis. Cholesterol, a lipid found in both secretory vesicles and cell plasma membranes, has the potential to influence this process. We are probing the effect of reducing membrane cholesterol on biophysical properties of lipid bilayers and the dynamics of fusion pore formation.

Material and Methods: Nile red G/R and FLIP-TR Lifetime to measure the order of the membrane. Atomic force microscopy was used to measure the indentation force. Lipid mixing of vesicles using FRET assay while content mixing using TbCl3 and DPA filled vesicles. Measurement of vesicle fusion using total internal reflection fluorescence microscopy (TIRF).

Results: Membrane order measured using shift in polarity-sensitive dye Nile red and change is lifetime of Flip-TR shows an increase with increase in cholesterol content. High cholesterol facilitates the production of pores in the composition of synaptic vesicles composition (PC:PE:PS::3:5:2), according to an increase in AFM force recorded on a supported lipid bilayer to evaluate the membrane's ability to do so. In synaptic vesicles, cholesterol speeds up the pace of lipid mixing as well as content mixing. It also speeds up the rate fusion of vesicles with lipid bilayer measured using TIRF.

Conclusion: Vesicle association and fusion increases with cholesterol despite an increase in the membrane order. Vesicle fusion with the supported bilayer also increases with high cholesterol. After this, our next target will be to probe whether blood cholesterol lowering drugs like statins can hamper the process of signaling in neuronal cell.

Publication History

Article published online:
08 July 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India


*Corresponding author: (e-mail: ankur@tifr.res.in).

Abstract

Background: Neurons communicate through a crucial process known as exocytosis. Cholesterol, a lipid found in both secretory vesicles and cell plasma membranes, has the potential to influence this process. We are probing the effect of reducing membrane cholesterol on biophysical properties of lipid bilayers and the dynamics of fusion pore formation.

Material and Methods: Nile red G/R and FLIP-TR Lifetime to measure the order of the membrane. Atomic force microscopy was used to measure the indentation force. Lipid mixing of vesicles using FRET assay while content mixing using TbCl3 and DPA filled vesicles. Measurement of vesicle fusion using total internal reflection fluorescence microscopy (TIRF).

Results: Membrane order measured using shift in polarity-sensitive dye Nile red and change is lifetime of Flip-TR shows an increase with increase in cholesterol content. High cholesterol facilitates the production of pores in the composition of synaptic vesicles composition (PC:PE:PS::3:5:2), according to an increase in AFM force recorded on a supported lipid bilayer to evaluate the membrane's ability to do so. In synaptic vesicles, cholesterol speeds up the pace of lipid mixing as well as content mixing. It also speeds up the rate fusion of vesicles with lipid bilayer measured using TIRF.

Conclusion: Vesicle association and fusion increases with cholesterol despite an increase in the membrane order. Vesicle fusion with the supported bilayer also increases with high cholesterol. After this, our next target will be to probe whether blood cholesterol lowering drugs like statins can hamper the process of signaling in neuronal cell.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
08 July 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India