Melatonin enhances L-DOPA therapeutic effects, helps to reduce its dose, and protects dopaminergic neurons in 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in mice
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Melatonin enhances L-DOPA therapeutic effects, helps to reduce its dose, and protects dopaminergic neurons in 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in mice
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| Creator |
Naskar, Amit
Prabhakar, Visakh Singh, Raghavendra Dutta, Debashis Mohanakumar, Kochupurackal P. Mohanakumar |
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| Subject |
Cell Biology & Physiology
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| Description |
L-3,4-dihydroxyphenylalanine (L-DOPA) reduces symptoms of
Parkinson’s disease (PD), but suffers from serious side effects on long-term use.
Melatonin (10–30 mg/kg, 6 doses at 10 hr intervals) was investigated to
potentiate L-DOPA therapeutic effects in 1-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine (MPTP)-induced parkinsonism in mice. Striatal tyrosine
hydroxylase (TH) immunoreactivity, TH, and phosphorylated ser 40 TH
(p-TH) protein levels were assayed on 7th day. Nigral TH-positive neurons
stereology was conducted on serial sections 2.8 mm from bregma rostrally to
3.74 mm caudally. MPTP caused 39% and 58% decrease, respectively, in
striatal fibers and TH protein levels, but 2.5-fold increase in p-TH levels. About
35% TH neurons were lost between 360 and 600 lm from 940 lm of the entire
nigra analyzed, but no neurons were lost between 250 lm rostrally and 220 lm
caudally. When L-DOPA in small doses (5–8 mg/kg) failed to affect MPTPinduced
akinesia or catalepsy, co-administration of melatonin with L-DOPA
attenuated these behaviors. Melatonin administration significantly attenuated
MPTP-induced loss in striatal TH fibers (82%), TH (62%) and p-TH protein
(100%) levels, and nigral neurons (87–100%). Melatonin failed to attenuate
MPTP-induced striatal dopamine depletion. L-DOPA administration (5 mg/kg,
once 40 min prior to sacrifice, p.o.) in MPTP- and melatonin-treated mice
caused significant increase in striatal dopamine (31%), as compared to
L-DOPA and MPTP-treated mice. This was equivalent to 8 mg/kg L-DOPA
administration in parkinsonian mouse. Therefore, prolonged, effective use of
L-DOPA in PD with lesser side effects could be achieved by treating with 60%
lower doses of L-DOPA along with melatonin.
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| Publisher |
Blackwell Publishing
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| Date |
2015
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/2236/1/JOURNAL_OF_PINEAL_RESEARCH__V._58(_3_)_262%2D274;2015[35].pdf
Naskar, Amit and Prabhakar, Visakh and Singh, Raghavendra and Dutta, Debashis and Mohanakumar, Kochupurackal P. Mohanakumar (2015) Melatonin enhances L-DOPA therapeutic effects, helps to reduce its dose, and protects dopaminergic neurons in 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in mice. Journal Of Pineal Research, 58 (3). pp. 262-274. |
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| Relation |
http://dx.doi.org/10.1111/jpi.12212
http://www.eprints.iicb.res.in/2236/ |
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