Systemic Rotenone Administration Causes Extra-Nigral Alterations in C57BL/6 Mice.

Area of Science:

• Neuroscience
• Toxicology
• Neurodegenerative Diseases

Background:

• Systemic rotenone administration is a common model for Parkinson's disease (PD).
• Some PD features are not explained by nigrostriatal pathway deficits alone.

Purpose of the Study:

• To comprehensively analyze neurochemical alterations in the central nervous system (CNS) following systemic rotenone exposure.
• To evaluate the suitability of the rotenone model for studying extra-nigral defects in PD.

Main Methods:

• C57BL/6 mice received daily intraperitoneal injections of rotenone (1, 3, or 10 mg/kg) for 21 days.
• Locomotor and exploratory behaviors were assessed weekly.
• Molecular analyses included tyrosine hydroxylase (TH), dopamine transporter (DAT), dopamine receptors, brain-derived neurotrophic factor (BDNF), glial markers, mitochondrial function, oxidative stress, and neuroprotective peptides (PACAP, VIP, ADNP).

Main Results:

• Rotenone induced significant locomotor and exploratory impairments at 3 and 10 mg/kg.
• Reduced TH and DAT expression occurred in the midbrain, striatum, and spinal cord.
• Midbrain inflammation was observed, but mitochondrial dysfunction and oxidative stress were widespread.
• Alterations in dopamine receptors, BDNF, and neuroprotective peptides were identified.

Conclusions:

• Systemic rotenone intoxication in mice replicates key PD features, including extra-nigral neurochemical changes.
• The rotenone model is suitable for investigating PD aspects beyond nigrostriatal deficits.
• Widespread mitochondrial and oxidative stress alterations highlight the model's utility for studying complex PD pathology.