Melatonin protects against behavioural dysfunctions and dendritic spine damage in 3-nitropropionic acid-induced rat model of Huntington's disease

Chakraborty, J.; Nthenge-Ngumbau, Dominic Ngima; Rajamma, Usha; Mohanakumar, Kochupurackal P.

doi:10.1016/j.bbr.2014.01.048

Cited by 42 publications

(28 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, melatonin is shown to protect nigral dopaminergic neurons in MPTP‐induced parkinsonism . This effect is shown to be mediated via controlling oxidative stress, upregulating neurotropic factors, anti‐apoptotic activity, anti‐inflammatory activity, and restoring mitochondrial homeostasis by melatonin . Here, we demonstrate upregulation of striatal TH levels, regulation of p‐TH levels, and recovery of immunoreactive dopaminergic fibers in the striatum of mouse treated with MPTP and melatonin.…”

Section: Discussionmentioning

confidence: 60%

“…It is a critical fact that melatonin exerts most of its protective effects at pharmacological concentrations, whereas only few studies could show any antioxidant effects of this neurohormone at physiological concentration . Consistent with this observation, melatonin at higher concentration shows a high potency to counteract neurons and astrocytes death in the brain in view of its (i) trophic value , (ii) anti‐apoptotic activity , (iii) antioxidant actions , (iv) anti‐inflammatory activity , and (iv) as a mitochondrial rejuvenator . Not only melatonin, but also its metabolites including N1‐acetyl‐N‐2‐formyl‐5‐methoxykynuramine and N′‐acetyl‐5‐methoxykynuramine are proven free radicals scavengers .…”

Section: Introductionmentioning

confidence: 87%

See 1 more Smart Citation

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

Naskar

Prabhakar

Singh

et al. 2015

Journal of Pineal Research

View full text Add to dashboard Cite

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 μm from 940 μm of the entire nigra analyzed, but no neurons were lost between 250 μm rostrally and 220 μm caudally. When L-DOPA in small doses (5-8 mg/kg) failed to affect MPTP-induced 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.

show abstract

Section: Discussionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 87%

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

Naskar

Prabhakar

Singh

et al. 2015

Journal of Pineal Research

View full text Add to dashboard Cite

show abstract

“…Previous studies have shown early treatment of creatine, which could enhance phosphocreatine levels and protect mitochondrial functions. Melatonin, which is an antioxidant, or anti‐mutant HTT antibodies, could improve the pathological and behavioral phenotypes of HD . These results suggest that removal of abnormal aggregate proteins at early stages might offer better results.…”

Section: Discussionmentioning

confidence: 93%

The Differential Profiling of Ubiquitin‐Proteasome and Autophagy Systems in Different Tissues before the Onset of Huntington's Disease Models

Her

Lin

et al. 2014

Brain Pathology

View full text Add to dashboard Cite

Huntington's disease (HD) is a genetic and neurodegenerative disease, leading to motor and cognitive dysfunction in HD patients. At cellular level, this disease is caused by the accumulation of mutant huntingtin (HTT) in different cells, and finally results in the dysfunction of different cells. To clean these mutant proteins, ubiquitin-proteasome system (UPS) and autophagy system are two critical pathways in the brain; however, little is known in other peripheral tissues. As mutant HTT affects different tissues progressively and might influence the UPS and autophagy pathways at early stages, we attempted to examine two clearance systems in HD models before the onset. Here, in vitro results showed that the accumulation of UPS signals with time was observed obviously in neuroblastoma and kidney cells, not in other cells. In HD transgenic mice, we observed the impairment of UPS, but not autophagy, over time in the cortex and striatum. In heart and muscle tissues, disturbance of autophagy was observed, whereas dysfunction of UPS was displayed in liver and lung. These results suggest that two protein clearance pathways are disturbed differentially in different tissues before the onset of HD, and enhancement of protein clearance at early stages might provide a potential stratagem to alleviate the progression of HD.

show abstract

“…Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder, characterized by motor dysfunction, emotional disturbances, abnormal involuntary movements, dementia, and weight loss [ 1 , 2 ]. The neuropathological changes associated with these physical symptoms of HD include progressive neuronal degeneration and atrophy primarily affecting the striatum and cerebral cortex [ 3 , 4 ]. This neurodegenerative disorder is believed to be caused by an expanded trinucleotide CAG sequence in exon 1 of the Huntingtin gene (Htt), which encodes a stretch of glutamines in the Huntingtin protein [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Aqueous Extract ofLuehea divaricataagainst Behavioral and Oxidative Changes Induced by 3-Nitropropionic Acid in Rats

Courtes

Arantes

Barcelos

et al. 2015

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease. Accordingly, 3-nitropropionic acid (3-NP) has been found to effectively produce HD-like symptoms. Luehea divaricata (L. divaricata), popularly known in Brazil as “açoita-cavalo,” may act as a neuroprotective agent in vitro and in vivo. We evaluated the hypothesis that the aqueous extract of L. divaricata could prevent behavioral and oxidative alterations induced by 3-NP in rats. 25 adult Wistar male rats were divided into 5 groups: (1) control, (2) L. divaricata (1000 mg/kg), (3) 3-NP, (4) L. divaricata (500 mg/kg) + 3-NP, and (5) L. divaricata (1000 mg/kg) + 3-NP. Groups 2, 4, and 5 received L. divaricata via intragastric gavage daily for 10 days. Animals in groups 3, 4, and 5 received 20 mg/kg 3-NP daily from days 8–10. At day 10, parameters of locomotor activity and biochemical evaluations were performed. Indeed, rats treated with 3-NP showed decreased locomotor activity compared to controls. Additionally, 3-NP increased levels of reactive oxygen species and lipid peroxidation and decreased ratio of GSH/GSSG and acetylcholinesterase activity in cortex and/or striatum. Our results suggest that rats pretreated with L. divaricata prior to 3-NP treatment showed neuroprotective effects when compared to 3-NP treated controls, which may be due to its antioxidant properties.

show abstract

Melatonin protects against behavioural dysfunctions and dendritic spine damage in 3-nitropropionic acid-induced rat model of Huntington's disease

Cited by 42 publications

References 69 publications

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

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

The Differential Profiling of Ubiquitin‐Proteasome and Autophagy Systems in Different Tissues before the Onset of Huntington's Disease Models

Protective Effects of Aqueous Extract ofLuehea divaricataagainst Behavioral and Oxidative Changes Induced by 3-Nitropropionic Acid in Rats

Contact Info

Product

Resources

About