RESUMEN
Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and subsequent depletion of dopamine in the striatum. Solanesol, an alcohol that acts as a precursor to coenzyme Q10, possesses potential applications in managing neurological disorders with antioxidant, anti-inflammatory, and neuromodulatory potential. In this study, a zebrafish model was employed to investigate the effects of solanesol in tramadol induced PD like symptoms. Zebrafish were administered tramadol injections (50 mg/kg) over a 20-day period. Solanesol was administered at doses of 25, 50, and 100 mg/kg, three hours prior to tramadol administration from day 11 to day 20. Behavioral tests assessing motor coordination were conducted on a weekly basis using open field and novel diving tank apparatus. On day 21, the zebrafish were euthanized, and brain tissues were examined for markers of oxidative stress, inflammation, and neurotransmitters level. Chronic tramadol treatment resulted in motor impairment, reduced antioxidant enzyme levels, enhanced release of proinflammatory cytokines in the striatum, and disrupted neurotransmitter balance. However, solanesol administration mitigated these effects and exhibited a neuroprotective effect against neurodegenerative alterations in the zebrafish model of PD. This was evident through improvements in behavior, modulation of biochemical markers, attenuation of neuroinflammation, restoration of neurotransmitters level, and enhancement of mitochondrial activity. The histopathological study also confirmed that solanesol dose dependently restored neuronal cell density which confirmed its neuroprotective potential. Further investigations are required to elucidate the underlying mechanisms of solanesol neuroprotective effects and evaluate its efficacy in human patients.
Neuroprotective effects: Solanesol has shown significant neuroprotective effects in a zebrafish model of Parkinson's disease induced by chronic tramadol usage.Improved behavioral performance: Administration of solanesol resulted in improved motor coordination in the open field test (OFT) and novel diving apparatus in the tramadol-induced zebrafish model of PD.Decreased inflammation: Solanesol treatment significantly reduced pro-inflammatory cytokine levels in the tramadol-induced zebrafish model of PD, indicating its anti-inflammatory properties.Restored oxidative parameters: Solanesol administration restored oxidative stress parameters, as well as catecholamine and neurotransmitter levels in the tramadol-induced zebrafish model of PD.Histopathological improvement: Solanesol administration prevented histopathological alterations induced by tramadol, indicating its ability to protect against neuronal damage in the zebrafish model of PD.
RESUMEN
Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, resulting in motor and non-motor symptoms. Although levodopa is the primary medication for PD, its long-term use is associated with complications such as dyskinesia and drug resistance, necessitating novel therapeutic approaches. Recent research has highlighted the potential of targeting opioid and cannabinoid receptors as innovative strategies for PD treatment. Modulating opioid transmission, particularly through activating µ (MOR) and δ (DOR) receptors while inhibiting κ (KOR) receptors, shows promise in preventing motor complications and reducing L-DOPA-induced dyskinesia. Opioids also possess neuroprotective properties and play a role in neuroprotection and seizure control. Similar to this, endocannabinoid signalling via CB1 and CB2 receptors influences the basal ganglia and may contribute to PD pathophysiology, making it a potential therapeutic target. In addition to opioid and cannabinoid receptor targeting, the NLRP3 pathway, implicated in neuroinflammation and neurodegeneration, emerges as another potential therapeutic avenue for PD. Recent studies suggest that targeting this pathway holds promise as a therapeutic strategy for PD management. This comprehensive review focuses on neuromodulation and novel therapeutic approaches for PD, specifically highlighting the targeting of opioid and cannabinoid receptors and the NLRP3 pathway. A better understanding of these mechanisms has the potential to enhance the quality of life for PD patients.