Neuroprotective Effects of Filgrastim in Rotenone-Induced Parkinson's Disease in Rats: Insights into its Anti-Inflammatory, Neurotrophic, and Antiapoptotic Effects.

Abstract

All current treatments of Parkinson's disease (PD) focus on enhancing the dopaminergic effects and providing symptomatic relief; however, they cannot delay the disease progression. Filgrastim, a recombinant methionyl granulocyte colony-stimulating factor, demonstrated neuroprotection in many neurodegenerative and neurological diseases. This study aimed to assess the neuroprotective effects of filgrastim in rotenone-induced rat model of PD and investigate the potential underlying mechanisms of filgrastim actions. The effects of two doses of filgrastim (20 and 40 μg/kg) on spontaneous locomotion, catalepsy, body weight, histology, and striatal dopamine (DA) content, as well as tyrosine hydroxylase (TH) and α-synuclein expression, were evaluated. Then, the effective dose was further tested for its potential anti-inflammatory, neurotrophic, and antiapoptotic effects. Filgrastim (40 μg/kg) prevented rotenone-induced motor deficits, weight reduction, striatal DA depletion, and histological damage. Besides, it significantly inhibited rotenone-induced decrease in TH expression and increase in α-synuclein immunoreactivity in the midbrains and striata of the rats. These effects were associated with reduction of rotenone-induced neuroinflammation, apoptosis, and brain-derived neurotrophic factor depletion. Collectively, these results suggest that filgrastim might be a good candidate for management of PD.

• Authors: Mariama S Azmy, Esther T Menze, Reem N El-Naga, Mariane G Tadros
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 55 Issue 8 Pg. 6572-6588 (Aug 2018) ISSN: 1559-1182 [Electronic] United States
• PMID: 29327204 (Publication Type: Journal Article, Retracted Publication)

Chemical References

• Anti-Inflammatory Agents
• Nerve Growth Factors
• Neuroprotective Agents
• alpha-Synuclein
• bcl-2-Associated X Protein
• Rotenone
• Tyrosine 3-Monooxygenase
• Filgrastim

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Apoptosis (drug effects)
• Body Weight
• Corpus Striatum (pathology)
• Filgrastim (pharmacology)
• Humans
• Inflammation (pathology)
• Male
• Mesencephalon (pathology)
• Microglia (drug effects, metabolism, pathology)
• Motor Activity (drug effects)
• Nerve Growth Factors (pharmacology)
• Neuroprotective Agents (pharmacology)
• Parkinson Disease (pathology, physiopathology)
• Rats, Wistar
• Rotenone
• Tyrosine 3-Monooxygenase (metabolism)
• alpha-Synuclein (metabolism)
• bcl-2-Associated X Protein (metabolism)