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Cholinergic Differentiation of Human Neuroblastoma SH-SY5Y Cell Line and Its Potential Use as an In vitro Model for Alzheimer’s Disease Studies
- Source :
- Molecular Neurobiology. 56:7355-7367
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- Cholinergic transmission is critical to high-order brain functions such as memory, learning, and attention. Alzheimer's disease (AD) is characterized by cognitive decline associated with a specific degeneration of cholinergic neurons. No effective treatment to prevent or reverse the symptoms is known. Part of this might be due to the lack of in vitro models that effectively mimic the relevant features of AD. Here, we describe the characterization of an AD in vitro model using the SH-SY5Y cell line. Exponentially growing cells were maintained in DMEM/F12 medium and differentiation was triggered by the combination of retinoic acid (RA) and BDNF. Both acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) enzymatic activities and immunocontent were determined. For mimicking tau and amyloid-β pathology, RA + BDNF-differentiated cells were challenged with okadaic acid (OA) or soluble oligomers of amyloid-β (AβOs) and neurotoxicity was evaluated. RA + BDNF-induced differentiation resulted in remarkable neuronal morphology alterations characterized by increased neurite density. Enhanced expression and enzymatic activities of cholinergic markers were observed compared to RA-differentiation only. Combination of sublethal doses of AβOs and OA resulted in decreased neurite densities, an in vitro marker of synaptopathy. Challenging RA + BDNF-differentiated SH-SY5Y cells with the combination of sublethal doses of OA and AβO, without causing considerable decrease of cell viability, provides an in vitro model which mimics the early-stage pathophysiology of cholinergic neurons affected by AD.
- Subjects :
- 0301 basic medicine
SH-SY5Y
Neurite
Neuroscience (miscellaneous)
Tretinoin
Models, Biological
Neuroblastoma
03 medical and health sciences
Cellular and Molecular Neuroscience
chemistry.chemical_compound
0302 clinical medicine
Alzheimer Disease
Cell Line, Tumor
Neurites
medicine
Humans
Cholinergic neuron
Cognitive decline
Brain-Derived Neurotrophic Factor
Neurotoxicity
Cell Differentiation
medicine.disease
Acetylcholinesterase
Choline acetyltransferase
Cholinergic Neurons
Cell biology
030104 developmental biology
Gene Expression Regulation
Neurology
chemistry
Synapses
Cholinergic
Biomarkers
030217 neurology & neurosurgery
Signal Transduction
Subjects
Details
- ISSN :
- 15591182 and 08937648
- Volume :
- 56
- Database :
- OpenAIRE
- Journal :
- Molecular Neurobiology
- Accession number :
- edsair.doi.dedup.....9c6223d9731cc8ea0331e8acc2a82db2