Objective: To observe therapeutic effect of MANF in the attenuation of neurotoxin MPTP/MPP+-induced model of Parkinson’s disease

Background: Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a novel neurotrophic factors and had proved that MANF has neuroprotective and neurorestorative effect. 

Methods: 1. Male C57BL/6 mice were treated with MPTP intraperitoneal injection, MPTP-induced mice were randomly divided. mice were injected bilaterally into striatum with MANF (10 μg/side) or phosphate buffered saline 2 μl/side. 2. Rotarod test was used to record the latency on the rotor. Immunohistochemistry was used to detect the tyrosine hydroxylase (TH) positive cells in SNpc. Dopamine (DA) and its metabolites 3,4-dihydroxyphenylaceticacid (DOPAC) and homovanillic acid (HVA) were determined by high performance liquid chromatography (HPLC) analysis. Superoxide dismutase (SOD), Glutathione (GSH), and Malondialdehyde (MDA) in substantial nigra were evaluated using assay kits. 3. A cell model of PD was structured by incubating SH-SY5Y cells with MPP+, cells were pretreated with different concentrations of MANF before incubation in medium containing  MPP+, then the cell viability was measured by MTT assay. JC-1 was used to detect mitochondrial transmembrane potential changes in SH-SY5Y cells under a flow cytometry.

Results: 1. The latency reduction caused by MPTP injection were partially rescued in the MANF-treatment group relative to PBS-treatment group after two weeks. 2. MANF significantly reduced the number of TH-positive dopaminergic neurons loss in MANF-treatment group relative to PBS-treatment group in the SNpc. 3.Mice that received MANF injection had significantly higher striatal DA, DOPAC and HVA levels than mice that received PBS injection. 4.Compared with PBS-treatment group, MANF-treatment group increased the activity of SOD and the yield of GSH, and decreased the yield of MDA. 5. MANF for 2 h followed by 2mM MPP+ for 24 h significantly decreased MPP+-induced loss of cell viability . MANF alone did not cause a significant affect in cell viability in SH-SY5Y cells after 24 h treatment. 6. Pretreatment with MANF reversed MPP+-induced mitochondrial membrane potential loss.

Conclusions: MANF can attenuate the neuronal lesion in MPTP/MPP+-induced model of Parkinson’s disease; MANF may play a role in improving mitochondrial function and inhibiting oxidative stress.

« Back to 2017 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/the-therapeutic-effect-of-manf-in-the-mptpmpp-induced-model-of-parkinsons-disease/