Session Information
Date: Monday, October 8, 2018
Session Title: Parkinson's Disease: Genetics
Session Time: 1:15pm-2:45pm
Location: Hall 3FG
Objective: This study aimed to investigate the therapeutic effect of mesencephalic astrocyte-derived neurotrophic factor (MANF) on the MPTP/MPP+-induced model of Parkinson’s disease (PD) and the potential mechanism.
Background: Currently, the most widely used treatment for PD is the dopamine replacement therapy, but long-term treatment can produce debilitating adverse effects and may not affect the progression of PD. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a novel neurotrophic factor and can selectively protect nigral dopaminergic neurons. It has been proven that MANF has neuroprotective and neurorestorative effects on PD in both in vitro and in vivo models.
Methods: Male C57BL/6 mice PD model with MPTP-induced were randomly injected bilaterally with MANF or PBS into the striatum. Two weeks later, Rotarod test, immunohistochemistry, and detection of dopamine (DA) and its metabolites, superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) were performed. A cell model of PD was established by incubating SH-SY5Y cells with MPP+, cells were pretreated for 2h with different concentrations of MANF before 24h incubation with MPP+. Cell viability, expression of Bax and Bcl-2, gene expression levels of Heme oxygenase 1 (HMOX1) and Superoxide dismutase 2 (SOD2), and mitochondrial transmembrane potential were detected.
Results: The latency reduction in PD mice was partially restored after MANF treatment (P<0.05); MANF significantly reduced the loss of tyrosine hydroxylase (TH)-positive dopaminergic neurons in the substantia nigra pars compacta (SNpc) (P<0.01); MANF significantly increased the striatal DA level in PD mice (P<0.05) and markedly increased the SOD activity (P<0.01) and GSH production (P<0.01). MANF pre-treatment significantly decreased the MPP+-induced reduction of cell viability (P<0.01), inhibited the ratio of Bax/Bcl-2 expression (P<0.01), activated gene expression levels of HMOX1 (P<0.01) and SOD2 (P<0.05), and reversed MPP+-induced loss of mitochondrial membrane potential (P<0.01).
Conclusions: MANF can attenuate the neuronal lesion in MPTP/MPP+-induced PD model, which may be related to the improvement of mitochondrial function and inhibition of oxidative stress.
To cite this abstract in AMA style:
Y. Liu, J. zhang, Q. Cai, H. Sun, L. Jin. MANF improves the MPP+/MPTP-induced Parkinson’s disease via improvement of mitochondrial function and inhibition of oxidative stress [abstract]. Mov Disord. 2018; 33 (suppl 2). https://www.mdsabstracts.org/abstract/manf-improves-the-mpp-mptp-induced-parkinsons-disease-via-improvement-of-mitochondrial-function-and-inhibition-of-oxidative-stress/. Accessed June 14, 2025.« Back to 2018 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/manf-improves-the-mpp-mptp-induced-parkinsons-disease-via-improvement-of-mitochondrial-function-and-inhibition-of-oxidative-stress/