Melatonin synergizes with low doses of L-DOPA to improve dendritic spine density in the mouse striatum in experimental Parkinsonism

Amit Naskar, Thamilarasan Manivasagam, Joy Chakraborty, Raghavendra Singh, Bobby Thomas, Muralikrishnan Dhanasekaran, Kochupurackal P. Mohanakumar

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)304-312
Number of pages9
JournalJournal of Pineal Research
Volume55
Issue number3
DOIs
StatePublished - Oct 1 2013

Fingerprint

Dendritic Spines
Parkinsonian Disorders
Levodopa
Melatonin
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Corpus Striatum
Dopamine
Parkinson Disease
Drug-Induced Dyskinesia
Spine
Catalepsy
Neurons
Neurotoxins
Neurotransmitter Agents
Histology
Therapeutics
Pharmaceutical Preparations

Keywords

  • L-DOPA
  • MPTP
  • behavior
  • dendritic spines
  • spine density

ASJC Scopus subject areas

  • Endocrinology

Cite this

Naskar, A., Manivasagam, T., Chakraborty, J., Singh, R., Thomas, B., Dhanasekaran, M., & Mohanakumar, K. 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(3), 304-312. https://doi.org/10.1111/jpi.12076

Melatonin synergizes with low doses of L-DOPA to improve dendritic spine density in the mouse striatum in experimental Parkinsonism. / Naskar, Amit; Manivasagam, Thamilarasan; Chakraborty, Joy; Singh, Raghavendra; Thomas, Bobby; Dhanasekaran, Muralikrishnan; Mohanakumar, Kochupurackal P.

In: Journal of Pineal Research, Vol. 55, No. 3, 01.10.2013, p. 304-312.

Research output: Contribution to journalArticle

Naskar, A, Manivasagam, T, Chakraborty, J, Singh, R, Thomas, B, Dhanasekaran, M & Mohanakumar, KP 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, vol. 55, no. 3, pp. 304-312. https://doi.org/10.1111/jpi.12076
Naskar, Amit ; Manivasagam, Thamilarasan ; Chakraborty, Joy ; Singh, Raghavendra ; Thomas, Bobby ; Dhanasekaran, Muralikrishnan ; Mohanakumar, Kochupurackal P. / Melatonin synergizes with low doses of L-DOPA to improve dendritic spine density in the mouse striatum in experimental Parkinsonism. In: Journal of Pineal Research. 2013 ; Vol. 55, No. 3. pp. 304-312.
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