Objective: To investigate the neurodegenerative facets of Manganese (Mn) in rat model in rat model of Parkinson’s disease.
To study the neuroprotective effect of luteolin in Mn induced neurodegeneration.

Background: Parkinson’s disease (PD) is a neurodegenerative characterized by behavioural, motor and nonmotor dysfunctions. Over-exposure of Mn due to occupational/environmental sources is detrimental and cause neurodegeneration. Mn overaccumulation leads to generation of ROS (reactive oxygen species), mitochondrial failure, calcium-dyshomeostasis, excitotoxicity, inflammation, α-synuclein misfolding and enzymes hypoactivity which produce an extrapyramidal-effect like PD. Neuroprotective mechanism of luteolin proceeds via inhibition of inflammatory mediators, suppression of lipid peroxidation and antioxidant enzymes activation which makes them ideal therapeutic representative for PD treatment.

Method: I will divide the animals in 4 groups (7 rats in each). I will administered Control (saline), toxin (MnCl2 15mg/kg i.p), drug (luteolin 50mg/kg+ MnCl2 15mg/kg i.p) and standard (levodopa 36 mg/kg p.o + MnCl₂ 15mg/kg i.p) for 28 days. Their after i will assess the behavioral by rotarod, grip strength, Actophotometer, narrow beam walk, string test and biochemical  such as LPO, GSH, nitrite, SOD, LDH by chemical methods and neurotransmitter level by HPLC in straitum region.

Results: Behavioral parameters such as locomotor activity, muscle coordination, grip strength will be analyzed. Effect of luteolin in biochemical parameters like reduced glutathione, lipid peroxidation, MAO-B, nitrite, metal ion will be estimate. Furthermore, inflammatory markers like IL-12, IL-1, TNF-, NF-kb, and neurotransmitters level(dopamine, glutamate and GABA) will also analysed by HPLC.

Conclusion: Till now, we analyse the body weight (BW) of animals and we found that the BW of toxin control animal was decrease as compare to control group and it was improve at day 14th in drug treated group as compare to toxin control group. we also analyse behavioural parameters and  found that mean time spent by animals on rota rod, narrow beam walk, string test appratus was decrease in toxin control group as compare to control group and mean time spent by drug treated animasl was improve as compare to toxin control group. while, i did not found any significant change in locomotion and grip strength of animals.

References: [1] Parkinson, J. (2002). An essay on the shaking palsy. The Journal of neuropsychiatry and clinical neurosciences, 14(2), 223-236.
[2] Gavin, C. E., Gunter, K. K., & Gunter, T. E. (1999). Manganese and calcium transport in mitochondria: implications for manganese toxicity. Neurotoxicology, 20(2-3), 445–453.
[3] Kempuraj, D., Thangavel, R., Kempuraj, D. D., Ahmed, M. E., Selvakumar, G. P., Raikwar, S. P., … & Zaheer, A. (2021). Neuroprotective effects of flavone luteolin in neuroinflammation and neurotrauma. Biofactors, 47(2), 190-197.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/therapeutic-potential-of-luteolin-in-manganese-induced-parkinsons-disease-targeting-neuroinflammation-and-oxidative-stress/