Melatonin synergizes with low doses of L-DOPA to improve dendritic spine density in the mouse striatum in experimental Parkinsonism
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Title |
Melatonin synergizes with low doses of L-DOPA to improve dendritic spine density in the mouse striatum in experimental Parkinsonism |
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Creator |
Naskar, Amit
Manivasagam, Thamilarasan Chakraborty, Joy Singh, Raghavendra Thomas, Bobby Dhanasekaran, Muralikrishnan Mohanakumar, Kochupurackal P |
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Subject |
Cell Biology & Physiology
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Description |
The dopamine precursor, L-3,4-dihydroxyphenylalanine (L-DOPA), is the preferred drug for Parkinson’s disease, but long-term treatment results in the drug-induced dyskinesias and other side effects. This study was undertaken to examine whether melatonin could potentiate low dose L-DOPA effects in 1-methyl-4 phenyl-1,2,3,6- tetrahydropyridine (MPTP)-induced experimental parkinsonism. Mice were treated with the parkinsonian neurotoxin, MPTP, and different doses of melatonin and low doses of L-DOPA. Behavior, striatal histology, and dopamine metabolism were evaluated on the 7th day. MPTP-induced striatal dopamine loss was not modified by melatonin administration (10–30 mg/kg; i.p. at 10-hr intervals, 6 times; or at 2-hr intervals, by day). However, low doses of L-DOPA (5 mg/kg, by oral gavage) administered alone or along with melatonin (10 mg/kg, i.p.) twice everyday for 2 days, 10 hr apart, after two doses of MPTP significantly attenuated striatal dopamine loss and provided improvements in both catalepsy and akinesia. Additionally, Golgi-impregnated striatal sections showed preservation of the medium spiny neurons, which have been damaged in MPTP-treated mouse. The results demonstrated that melatonin, but not L-DOPA, restored spine density and spine morphology of medium spiny neurons in the striatum and suggest that melatonin could be an ideal adjuvant to L-DOPA therapy in Parkinson’s disease, and by the use of this neurohormone, it is possible to bring down the therapeutic doses of L-DOPA. |
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Publisher |
Blackwell Publishing
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Date |
2013
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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/2432/1/JOURNAL_OF_PINEAL_RESEARCH__Vol.__55_(__3_)_304%2D312;2013.pdf
Naskar, Amit and Manivasagam, Thamilarasan and Chakraborty, Joy and Singh, Raghavendra and Thomas, Bobby and Dhanasekaran, Muralikrishnan and Mohanakumar, Kochupurackal P (2013) Melatonin synergizes with low doses of L-DOPA to improve dendritic spine density in the mouse striatum in experimental Parkinsonism. Journal of Pineal Research, 55. pp. 304-312. |
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Relation |
http://dx.doi.org/10.1111/jpi.12076
http://www.eprints.iicb.res.in/2432/ |
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