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Alpha-linolenic acid suppresses dopaminergic neurodegeneration induced by 6-OHDA in C. elegans.

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Relation http://ir.cftri.com/13812/
http://dx.doi.org/10.1016/j.physbeh.2015.08.025
 
Title Alpha-linolenic acid suppresses dopaminergic neurodegeneration
induced by 6-OHDA in C. elegans.
 
Creator Shashikumar, S.
Pradeep, H.
Salim, Chinnu
Rajini, P. S.
 
Subject 17 Fatty Acid Chemistry
17 Toxicology
 
Description Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the specific
andmassive loss of dopamine (DA) containing neurons in the substantia nigra pars compacta (SNpc) and aggregation
of protein α-synuclein. There are a fewanimal 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 transgenicwormsweremonitored 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/30 s). 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 fromvisiblymarked 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.
 
Date 2015
 
Type Article
PeerReviewed
 
Format pdf
 
Language en
 
Identifier http://ir.cftri.com/13812/1/Physiology%20%26%20Behavior%20151%20%282015%29%20563%E2%80%93569.pdf
Shashikumar, S. and Pradeep, H. and Salim, Chinnu and Rajini, P. S. (2015) Alpha-linolenic acid suppresses dopaminergic neurodegeneration induced by 6-OHDA in C. elegans. Physiology and Behavior, 151. pp. 563-569.