Send to

Choose Destination
Ann Neurosci. 2018 May;24(4):243-251. doi: 10.1159/000481551. Epub 2017 Oct 30.

1-Methyl-4-Phenylpyridinium-Induced Death of Differentiated SH-SY5Y Neurons Is Potentiated by Cholesterol.

Author information

Division of Cell Biology and Physiology, Kolkata, India.
Division of Chemistry, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, India.
Academy of Scientific and Innovative Research (AcSIR), CSIR Campus, CSIR Road, Taramani, Chennai, India.
Cellular and Molecular Neurobiology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar, India.
Inter University Centre for Biomedical Research and Super Speciality Hospital (IUCBR and SSH), Mahatma Gandhi University Campus at Thalappady, Kottayam, India.



Hypercholesterolemia is recently considered a risk factor for Parkinson's disease (PD), the most consistent neurodegenerative movement disorder. The study aimed to investigate the effect of exogenous cholesterol on 1-methyl-4-phenylpyridinium (MPP+) parkinsonian neurotoxin-induced cell death, loss of mitochondrial membrane potential, and dopaminergic deficiency in a cellular model of PD.


Cholesterol (50 μM) when added in the culture media alone or in combination with MPP+ was studied in SH-SY5Y neuroblastoma cells. There were 4 groups that were studied; SH-SY5Y cells treated with vehicle (control), cells that were treated with 1 mM MPP+ (MPP+), or cholesterol (chol) or both (M + chol). The loss of cell survival was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Dopamine depletion, microtubule-associated protein 2 (MAP-2), and tyrosine hydroxylase (TH)-positive neuronal loss were determined by HPLC-electrochemical detection and TH immunocytochemistry respectively. Mitochondrial membrane potential in cells stained by tetramethylrhodamine methyl ester dye was analysed by flow cytometry.


Cholesterol treatment potentiated a reduction of neuronal viability with loss of TH-positive neurons in cultures. MPP+-induced depletion of dopamine level in the post-mitotic MAP-2 immunoreactive neurons and loss of mitochondrial membrane potential were also heightened by cholesterol.


Apparently, changes in neuronal cholesterol content significantly influenced the neurotoxicity and the direct mitochondrial mechanisms involved in MPP+-induced cell death. Our observations demonstrate that high cholesterol incorporated into the differentiated human neuroblastoma cells worsened dopaminergic neuronal survivability through increased depolarization of mitochondrial membrane potential, which is a known mechanism of dopaminergic cell death by MPP+. The present findings support the hypothesis that hypercholesterolemia could be a risk factor for PD.


Cell viability; Cholesterol-induced neuronal death; Dopaminergic neurons; Mitochondrial membrane potential; Tyrosine hydroxylase

Supplemental Content

Full text links

Icon for S. Karger AG, Basel, Switzerland Icon for PubMed Central
Loading ...
Support Center