التفاصيل البيبلوغرافية
العنوان: |
Membrane cholesterol depletion in cortical neurons highlights altered NMDA receptor functionality in a mouse model of amyotrophic lateral sclerosis |
المؤلفون: |
Luana Saba, Silvia Biocca, Nadia Canu, Alessia Antonini, Giulia Vindigni, Silvia Caioli, Cristina Zona |
المصدر: |
Biochimica et biophysica acta. Molecular basis of disease 1864 (2018): 509–519. doi:10.1016/j.bbadis.2017.11.008 info:cnr-pdr/source/autori:Antonini A.; Caioli S.; Saba L.; Vindigni G.; Biocca S.; Canu N.; Zona C./titolo:Membrane cholesterol depletion in cortical neurons highlights altered NMDA receptor functionality in a mouse model of amyotrophic lateral sclerosis/doi:10.1016%2Fj.bbadis.2017.11.008/rivista:Biochimica et biophysica acta. Molecular basis of disease/anno:2018/pagina_da:509/pagina_a:519/intervallo_pagine:509–519/volume:1864 |
بيانات النشر: |
Elsevier Science Publishers, Amsterdam , Paesi Bassi, 2018. |
سنة النشر: |
2018 |
مصطلحات موضوعية: |
Cortical neurons, Male, Proteomics, 0301 basic medicine, ALS, Electrophysiology, Lipid rafts, Methyl-?-cyclodextrin, NMDA receptor, Mice, chemistry.chemical_compound, Superoxide Dismutase-1, 0302 clinical medicine, Amyotrophic lateral sclerosis, Lipid raft, Methyl-β-cyclodextrin, Motor Neurons, beta-Cyclodextrins, Glutamate receptor, Cell biology, Cholesterol, Molecular Medicine, Female, lipids (amino acids, peptides, and proteins), Signal Transduction, N-Methylaspartate, Cell Survival, Glutamic Acid, Mice, Transgenic, AMPA receptor, Biology, Settore BIO/09, Receptors, N-Methyl-D-Aspartate, 03 medical and health sciences, Membrane Microdomains, Cell surface receptor, medicine, Animals, Humans, Receptors, AMPA, Molecular Biology, Amyotrophic Lateral Sclerosis, Cell Membrane, Neurotoxicity, medicine.disease, Disease Models, Animal, 030104 developmental biology, chemistry, nervous system, 030217 neurology & neurosurgery |
الوصف: |
Amyotrophic Lateral Sclerosis (ALS) is a chronic neurodegenerative disease affecting upper and lower motor neurons, with unknown aetiology. Lipid rafts, cholesterol enriched microdomains of the plasma membrane, have been linked to neurodegenerative disorders like ALS. The NMDA-receptor subcellular localization in lipid rafts is known to play many roles, from modulating memory strength to neurotoxicity. In this study, performed on the widely used G93A mouse model of ALS, we have shown an equal content of total membrane cholesterol in Control and G93A cortical cultures. Moreover, by electrophysiological studies, we have recorded NMDA- and AMPA-evoked currents which were not significantly different between the two neuronal populations. To study the role of membrane cholesterol on glutamate receptor functionality, we have analysed NMDA and AMPA receptors following cholesterol membrane depletion by methyl-β-cyclodextrin (MβCD). Interestingly, MβCD chronic treatment has provoked a significant reduction of NMDA-evoked currents in both cellular populations which was dose- and time-dependent but significantly higher in ALS neurons compared to Control. The different MβCD effect on NMDA-evoked currents was not due to a different membrane receptor subunit composition but seemed to cause in both neuronal populations a NMDA receptor membrane redistribution. MβCD treatment effect was receptor-specific since no alterations in the two neuronal populations were detected on AMPA receptors. These results lead us to speculate for an altered proteomic composition of lipid rafts in cortical mutated neurons and suggest the need for further studies on the lipid rafts composition and on their interaction with membrane receptors in ALS cortices. |
اللغة: |
English |
DOI: |
10.1016/j.bbadis.2017.11.008 |
URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6a6b84ba4c21054600f5b04133ab73a8 |
Rights: |
OPEN |
رقم الانضمام: |
edsair.doi.dedup.....6a6b84ba4c21054600f5b04133ab73a8 |
قاعدة البيانات: |
OpenAIRE |