Activity, Motor Control & Coordination
Pain - Thermal Allodynia / Hyperalgesia
Pain - Spontaneous Pain - Postural Deficit
Pain - Mechanical Allodynia / Hyperalgesia
Anxiety & Depression Disorder
Learning/Memory - Attention - Addiction
Physiology & Respiratory Research
Metabolism - Food & Drink Intake
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Central Nervous System (CNS)
Neurodegeneration
Sensory system
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Muscular system
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Cross-disciplinary subjects
Preclinical studies and opioids: role in crisis management in the United States Authors
F Zhao, Q Austria, W Wang et al
Lab
Department of Pathology, Case Western Reserve University, Cleveland, OH, USA3
Journal
International Journal of Molecular Sciences
Abstract
Mitochondrial dysfunction represents a critical event in the pathogenesis of Parkinson's disease (PD). Increasing evidence demonstrates that disturbed mitochondrial dynamics and quality control play an important role in mitochondrial dysfunction in PD. Our previous study demonstrated that MPP+Êinduces mitochondrial fragmentation in vitro. In this study, we aimed to assess whether blocking MPTP-induced mitochondrial fragmentation by overexpressing Mfn2 affords neuroprotection in vivo. We found that the significant loss of dopaminergic neurons in the substantia nigra (SN) induced by MPTP treatment, as seen in wild-type littermate control mice, was almost completely blocked in mice overexpressing Mfn2 (hMfn2 mice). The dramatic reduction in dopamine neuronal fibers and dopamine levels in the striatum caused by MPTP administration was also partially inhibited in hMfn2 mice. MPTP-induced oxidative stress and inflammatory response in the SN and striatum were significantly alleviated in hMfn2 mice. The impairment of motor function caused by MPTP was also blocked in hMfn2 mice. Overall, our work demonstrates that restoration of mitochondrial dynamics by Mfn2 overexpression protects against neuronal toxicity in an MPTP-based PD mouse model, which supports the modulation of mitochondrial dynamics as a potential therapeutic target for PD treatment.
BIOSEB Instruments Used:
Grip strength test (BIO-GS3)
