Cholinergic Differentiation of Human Neuroblastoma SH-SY5Y Cell Line and Its Potential Use as an In vitro Model for Alzheimer's Disease Studies

被引：178

作者：

de Medeiros, Liana M. ^{[1
,2
,3
]}

De Bastiani, Marco A. ^{[1
,2
,3
]}

Rico, Eduardo P. ^{[4
]}

Schonhofen, Patricia ^{[1
,2
,3
]}

Pfaffenseller, Bianca ^{[1
,2
,5
]}

Wollenhaupt-Aguiar, Bianca ^{[1
,2
,5
]}

Grun, Lucas ^{[3
,6
]}

Barbe-Tuana, Florencia ^{[3
,6
]}

Zimmer, Eduardo R. ^{[3
,7
,8
]}

Castro, Mauro A. A. ^{[9
]}

Parsons, Richard B. ^{[10
]}

Klamt, Fabio ^{[1
,2
,3
]}

机构：

[1] Univ Fed Rio Grande do Sul, ICBS, Dept Biochem, Lab Cellular Biochem, 2600 Ramiro Barcelos St, BR-90035003 Porto Alegre, RS, Brazil

[2] Natl Inst Sci & Technol Translat Med INCT TM, Porto Alegre, RS, Brazil

[3] Univ Fed Rio Grande do Sul, ICBS, Dept Biochem, Postgrad Program Biochem, BR-90035003 Porto Alegre, RS, Brazil

[4] Univ Extremo Sul Catarinense UNESC, Unidade Acad Ciencias Saude, Programa Posgrad Ciencias Saude, BR-88806000 Criciuma, SC, Brazil

[5] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada

[6] Univ Fed Rio Grande do Sul, ICBS, Dept Biochem, Lab Mol Biol & Bioinformat, BR-90035003 Porto Alegre, RS, Brazil

[7] Pontifical Catholic Univ Rio Grande Sul PUCRS, Brain Inst Rio Grande Sul BraIns, Porto Alegre, RS, Brazil

[8] Univ Fed Rio Grande do Sul, ICBS, Dept Pharmacol, Porto Alegre, RS, Brazil

[9] Fed Univ Parana UFPR, Polytech Ctr, Bioinformat & Syst Biol Lab, BR-81520260 Curitiba, PR, Brazil

[10] Kings Coll London, Sch Canc & Pharmaceut Sci, 150 Stamford St, London SE1 9NH, England

来源：

MOLECULAR NEUROBIOLOGY | 2019年 / 56卷 / 11期

基金：

巴西圣保罗研究基金会;

关键词：

Retinoic acid; BDNF; Cholinergic neurons; SH-SY5Y; RETINOIC ACID; BASAL FOREBRAIN; A-BETA; OLIGOMERS; MODULATION; EXPRESSION; NEURONS; SYSTEM; TAU; BRAIN;

D O I：

10.1007/s12035-019-1605-3

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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-beta pathology, RA + BDNF-differentiated cells were challenged with okadaic acid (OA) or soluble oligomers of amyloid-beta (A beta Os) 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 A beta Os 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 A beta O, without causing considerable decrease of cell viability, provides an in vitro model which mimics the early-stage pathophysiology of cholinergic neurons affected by AD.

引用

页码：7355 / 7367

页数：13

共 58 条

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