title: Alpha-linolenic acid suppresses dopaminergic neurodegeneration induced by 6-OHDA in C. elegans.
abstract: Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the specific and massive loss of dopamine (DA) containing neurons in the substantia nigra pars compacta (SNpc) and aggregation of protein α-synuclein. There are a few animal studies, which indirectly implicate the neuroprotective action of omega-3 polyunsaturated fatty acids in neurodegenerative diseases. In this study, we exposed Caenorhabditis elegans (both wild type N2, and transgenic strain, UA44) to 6-hydroxydopamine (6-OHDA, the model neurotoxicant) and evaluated the extent of protection offered by alpha-linolenic acid (ALA). Larval stage worms (L1/L2) of N2 and transgenic strains were exposed to 6-OHDA (25 mM) with or without ALA (10, 50 and 100 μM) for 48 h at 20 °C. After 48 h, while the N2 worms were assessed for their responses in terms of locomotion, pharyngeal pumping, lifespan and AChE activity, the transgenic worms were monitored for dopaminergic neuronal degeneration. Worms exposed to 6-OHDA exhibited a significant reduction (48%) in the locomotion rate. Interestingly, supplementation with ALA increased the locomotion rate in 6-OHDA treated worms. A marked decrease (45%) in thrashing was evident in worms exposed to 6-OHDA while thrashing was slightly improved in worms co-exposed to 6-OHDA and higher concentrations of ALA. Interestingly, worms co-exposed to 6-OHDA with ALA (100 μM) exhibited a significant increase in thrashing (66 ± 1.80 thrashes/30s). The pharyngeal pumping rate declined significantly in the case of worms exposed to 6-OHDA (35%). However, the worms co-treated with ALA exhibited significant recovery in pharyngeal pumping. The mean survival for the control worms was 26 days, while the worms exposed to 6-OHDA, showed a marked reduction in survival (21 days). Worms co-exposed to 6-OHDA and ALA showed a concentration-dependent increase in lifespan compared to those exposed to 6-OHDA alone (23, 25 and 26 days respectively). Transgenic worms treated with 6-OHDA showed significant loss of processes of CEP and ADE neurons as evident from visibly marked reduction in GFP expression. Worms co-exposed to 6-OHDA and ALA showed visibly significant reduction in neuronal degeneration in both CEP and ADE. However, worms exposed to 6-OHDA together with ALA showed increased GFP expression within processes of CEP and ADE neurons. Overall, our results demonstrate that ALA significantly suppresses the dopaminergic neurodegeneration and movement disorder induced by 6-OHDA in C. elegans.
authors: National Institute of Technology (NIT), Calicut, Kerala 673601, India.
authors: S
authors: S
authors: Shashikumar
authors: National Institute of Technology (NIT), Calicut, Kerala 673601, India.
authors: H
authors: H
authors: Pradeep
authors: CSIR-Central Food Technological Research Institute, Mysuru, Karnataka 570020, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
authors: Salim
authors: S
authors: Chinnu
authors: CSIR-Central Food Technological Research Institute, Mysuru, Karnataka 570020, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
authors: P S
authors: PS
authors: Rajini
authors: National Institute of Technology (NIT), Calicut, Kerala 673601, India. Electronic address: rajanikant@nitc.ac.in.
authors: G K
authors: GK
authors: Rajanikant
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine; D016019:Survival Analysis; D016896:Treatment Outcome; D017962:alpha-Linolenic Acid / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D017962:alpha-Linolenic Acid; D049452:Green Fluorescent Proteins; D016627:Oxidopamine; D000110:Acetylcholinesterase
keywords: 6-Hydroxydopamine; Alpha linolenic acid (ALA); C. elegans; Dopamine; Lifespan; Neurodegeneration