Effect of ethanol and cocaine on [11C]MPC-6827 uptake in SH-SY5Y cells

Microtubules (MTs) are structural units in the cytoskeleton. In brain cells they are responsible for axonal transport, information processing, and signaling mechanisms. Proper function of these processes is critical for healthy brain functions. Alcohol and substance use disorders (AUD/SUDs) affects...

Full description

Saved in:
Bibliographic Details
Published in:Molecular biology reports 2021-04, Vol.48 (4), p.3871-3876
Main Authors: Damuka, Naresh, Orr, Miranda, Czoty, Paul W., Weiner, Jeffrey L., Martin, Thomas J., Nader, Michael A., Bansode, Avinash H., Liyana Pathirannahel, Buddhika S., Mintz, Akiva, Macauley, Shannon L., Craft, Suzanne, Solingapuram Sai, Kiran Kumar
Format: Article
Language:English
Subjects:
Alzheimer's disease
Animal Anatomy
Animal Biochemistry
Animal models
Axonal transport
Biomedical and Life Sciences
Brain
Carbon Radioisotopes
Cell Line, Tumor
Central Nervous System Agents - pharmacology
Cocaine
Cocaine - pharmacology
Cognitive ability
Cytoskeleton
Ethanol
Ethanol - pharmacology
Histology
Humans
Information processing
Life Sciences
Microtubules
Microtubules - drug effects
Microtubules - metabolism
Monomers
Morphology
Neuroblastoma cells
Neurodegenerative diseases
Neuroimaging
Neurons - drug effects
Neurons - metabolism
Positron emission tomography
Protein Binding
Quinazolines - pharmacology
Radiopharmaceuticals - pharmacology
Short Communication
Tubulin
Tubulin - metabolism
Tubulin Modulators - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Microtubules (MTs) are structural units in the cytoskeleton. In brain cells they are responsible for axonal transport, information processing, and signaling mechanisms. Proper function of these processes is critical for healthy brain functions. Alcohol and substance use disorders (AUD/SUDs) affects the function and organization of MTs in the brain, making them a potential neuroimaging marker to study the resulting impairment of overall neurobehavioral and cognitive processes. Our lab reported the first brain-penetrant MT-tracking Positron Emission Tomography (PET) ligand [ 11 C]MPC-6827 and demonstrated its in vivo utility in rodents and non-human primates. To further explore the in vivo imaging potential of [ 11 C]MPC-6827, we need to investigate its mechanism of action. Here, we report preliminary in vitro binding results in SH-SY5Y neuroblastoma cells exposed to ethanol (EtOH) or cocaine in combination with multiple agents that alter MT stability. EtOH and cocaine treatments increased MT stability and decreased free tubulin monomers. Our initial cell-binding assay demonstrated that [ 11 C]MPC-6827 may have high affinity to free/unbound tubulin units. Consistent with this mechanism of action, we observed lower [ 11 C]MPC-6827 uptake in SH-SY5Y cells after EtOH and cocaine treatments (e.g., fewer free tubulin units). We are currently performing in vivo PET imaging and ex vivo biodistribution studies in rodent and nonhuman primate models of AUD and SUDs and Alzheimer's disease.
ISSN:0301-4851
1573-4978
DOI:10.1007/s11033-021-06336-7