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.

Conclusion: 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.

Keywords: Hippocampal neuron; Synapse; α-Synuclein; β-Amyloid(1–42).