title: The synergistic effect between β-amyloid(1-42) and α-synuclein on the synapses dysfunction in hippocampal neurons.
abstract: OBJECTIVE
  This study was to explore the molecular mechanisms underpinning the synergetic effect between β-amyloid (Aβ) and α-synuclein (α-syn) on synapses dysfunction during the development of neurodegenerative disorders including Parkinson's disease (PD), dementia with Lewy bodies (DLB) and Alzheimer disease (AD).
  
  
  METHODS
  The primary cultured hippocampal neurons prepared from the fetal tissue of mice were divided into six groups and treated with DMSO, Aβ(42-1), α-syn, Aβ(1-42), α-syn plus Aβ(42-1) and α-syn plus Aβ(1-42), respectively. After incubation for 24 h, the synapsin I content was calculated by immunofluorescence and the synaptic vesicle recycling was monitored by FM1-43 staining. Furthermore, the expression of cysteine string protein-α (CSPα) detected by western blot was also conducted.
  
  
  RESULTS
  Either Aβ(1-42) or α-syn alone could induce a significant synapses dysfunction through reducing the content of synapsin I, inhibiting the synaptic vesicle recycling as well as down-regulating the expression of CSPα compared with the controls (P<0.05). However, simultaneous intervention with both α-syn and Aβ(1-42) aggravated these effects in cultured hippocampal neurons compared with the treatment with α-syn (synapsin I content: P<0.001; synaptic vesicle recycling: P=0.007; CSPα expression: P<0.001) or Aβ(1-42) (synapsin I number: P<0.001; synaptic vesicle recycling: P=0.007 CSPα expression: P<0.001) alone.
  
  
  CONCLUSIONS
  There was synergistic effect between Aβ and α-syn on synapses dysfunction through reducing the synapsin I content, inhibiting the synaptic vesicle recycling and down-regulating the expression of CSPα in several neurodegenerative diseases.
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China; Department & Institute of Neurology, Shanghai Medical College, Fudan University, Shanghai 200040, China.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China; Department & Institute of Neurology, Shanghai Medical College, Fudan University, Shanghai 200040, China.
authors.forename: Zheming
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China; Department & Institute of Neurology, Shanghai Medical College, Fudan University, Shanghai 200040, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China; Department & Institute of Neurology, Shanghai Medical College, Fudan University, Shanghai 200040, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China; Department & Institute of Neurology, Shanghai Medical College, Fudan University, Shanghai 200040, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China; Department & Institute of Neurology, Shanghai Medical College, Fudan University, Shanghai 200040, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China; Department & Institute of Neurology, Shanghai Medical College, Fudan University, Shanghai 200040, China. Electronic address: dingzhengtong123@163.com.
authors.forename: Zhengtong
authors.initials: Z
authors.lastname: Ding
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D050956:HSP40 Heat-Shock Proteins / Q000096:biosynthesis / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D008565:Membrane Proteins / Q000096:biosynthesis / Q000187:drug effects; D051379:Mice; D019636:Neurodegenerative Diseases / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects*; D016704:Synapsins / Q000096:biosynthesis / Q000187:drug effects; D013572:Synaptic Vesicles / Q000187:drug effects; D051844:alpha-Synuclein / Q000633:toxicity*
chemical_list: D016229:Amyloid beta-Peptides; D050956:HSP40 Heat-Shock Proteins; D008565:Membrane Proteins; D016704:Synapsins; D051844:alpha-Synuclein; C088460:cysteine string protein
keywords: Hippocampal neuron; Synapse; α-Synuclein; β-Amyloid(1–42)