Melatonin Reduces Projection Neuronal Injury Induced by 3-Nitropropionic Acid in the Rat Striatum

Mu, Shuhua; Lin, Er-jian; Liu, Bingbing; Ma, Yuxin; Ouyang, Liang; Li, Youlan; Chen, Si; Zhang, Jian; Lei, Wanlong

doi:10.1159/000365891

Cited by 20 publications

(8 citation statements)

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“…Also, HD is a destructive neurodegenerative disorder and indicates dysfunction in the neurons that may eventually lead to death of selected brain regions; especially, the striatum and cerebral cortex [ 5 ]. In recent studies, the dendritic spine density of striatal projection neurons was reported to be seriously decreased after 3-nitropropionic acid treatment [ 23 ]. This finding is in conformity with the results of the present study where dopamine levels increased in cortex, striatum and cerebellum/medulla oblongata regions of animals that received 3-nitropropionic acid treatment.…”

Section: Discussionmentioning

confidence: 99%

Riboflavin and pyridoxine restore dopamine levels and reduce oxidative stress in brain of rats

et al. 2018

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BackgroundNeurological disorders suggest that the excitotoxicity involves a drastic increase in intracellular Ca2+ concentrations and the formation of reactive oxygen species. The presence of these free radicals may also affect the dopaminergic system. The aim of this work was to determine if riboflavin (B2) and pyridoxine (B6) provide protection to the brain against free radicals generated by 3-nitropropionic acid (3-NPA) by measuring the levels of dopamine (DA) and selected oxidative stress markers.MethodsMale Fisher rats were grouped (n = 6) and treated as follows: group 1, control (NaCl 0.9%); group 2, 3-NPA (20 mg/kg); group 3, B2 (10 mg/kg); group 4, B2 (10 mg/kg) + 3-NPA (20 mg/kg); group 5, B6 (10 mg/kg) and group 6, B6 + 3-NPA. All treatments were administered every 24 h for 5 days by intraperitoneal route. After sacrifice, the brain was obtained to measure DA, GSH, and lipid peroxidation, Ca2+, Mg2+, ATPase and H2O2.Main findingsLevels of dopamine increased in cortex, striatum and cerebellum/medulla oblongata of animals that received 3-NPA alone. The lipid peroxidation increased in cortex, striatum, and cerebellum/medulla oblongata, of animals treated with B2 vitamin alone. ATPase dependent on Ca+2, Mg+2 and H2O2 increased in all regions of animals that received 3-NPA alone.ConclusionThe results confirm the capacity of 3-NPA to generate oxidative stress. Besides, the study suggests that B2 or B6 vitamins restored the levels of DA and reduced oxidative stress in brain of rats. We believe that these results would help in the study of neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

Riboflavin and pyridoxine restore dopamine levels and reduce oxidative stress in brain of rats

et al. 2018

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“…This protection applies to DNA, proteins, and lipids . There is certainly no shortage of studies that have unequivocally documented the ability of this molecule to attenuate the accumulation of free radical‐damaged molecules, for example, in ischemia–reperfusion injury , toxin exposure , inflammation , and many other clinically relevant situations . These benefits are apparent in both plants and animals .…”

Section: Melatonin Reduces Oxidative Stress: the Machinery And The Mementioning

confidence: 99%

Melatonin: an ancient molecule that makes oxygen metabolically tolerable

Manchester

Coto‐Montes

Boga

et al. 2015

Journal of Pineal Research

824

650

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Melatonin is remarkably functionally diverse with actions as a free radical scavenger and antioxidant, circadian rhythm regulator, antiinflammatory and immunoregulating molecule, and as an oncostatic agent. We hypothesize that the initial and primary function of melatonin in photosynthetic cyanobacteria, which appeared on Earth 3.5-3.2 billion years ago, was as an antioxidant. The evolution of melatonin as an antioxidant by this organism was necessary as photosynthesis is associated with the generation of toxic-free radicals. The other secondary functions of melatonin came about much later in evolution. We also surmise that mitochondria and chloroplasts may be primary sites of melatonin synthesis in all eukaryotic cells that possess these organelles. This prediction is made on the basis that mitochondria and chloroplasts of eukaryotes developed from purple nonsulfur bacteria (which also produce melatonin) and cyanobacteria when they were engulfed by early eukaryotes. Thus, we speculate that the melatoninsynthesizing actions of the engulfed bacteria were retained when these organelles became mitochondria and chloroplasts, respectively. That mitochondria are likely sites of melatonin formation is supported by the observation that this organelle contains high levels of melatonin that are not impacted by blood melatonin concentrations. Melatonin has a remarkable array of means by which it thwarts oxidative damage. It, as well as its metabolites, is differentially effective in scavenging a variety of reactive oxygen and reactive nitrogen species. Moreover, melatonin and its metabolites modulate a large number of antioxidative and pro-oxidative enzymes, leading to a reduction in oxidative damage. The actions of melatonin on radical metabolizing/producing enzymes may be mediated by the Keap1-Nrf2-ARE pathway. Beyond its direct free radical scavenging and indirect antioxidant effects, melatonin has a variety of physiological and metabolic advantages that may enhance its ability to limit oxidative stress.

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“…The methods for Golgi staining were previously described in detail (26). At 4 weeks following the 6OHDA lesions, all the rats were deeply anesthetized with sodium pentobarbital (50 mg/kg, i.p.)…”

Section: Methodsmentioning

confidence: 99%

Partial�decortication ameliorates dopamine depletion‑induced striatal neuron lesions in rats

et al. 2019

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The balance between glutamate (cortex and thalamus) and dopamine (substantia nigra) inputs on striatal neurons is of vital importance. Dopamine deficiency, which breaks this balance and leads to the domination of cortical glutamatergic inputs, plays an important role in Parkinson's disease (PD). However, the exact impact on striatal neurons has not been fully clarified. Thus, the present study aimed to characterize the influence of corticostriatal glutamatergic inputs on striatal neurons after decortication due to dopamine depletion in rats. 6-Hydroxydopamine was injected into the right medial forebrain bundle to induce dopamine depletion, and/or ibotenic acid into the primary motor cortex to induce decortication. Subsequently, the grip strength test and Morris water maze task indicated that decortication significantly shortened the hang time and the latency that had been increased in the rats subjected to dopamine depletion. Golgi staining and electron microscopy analysis showed that the total dendritic length and dendritic spine density of the striatal neurons were decreased in the dopamine-depleted rats, whereas decortication alleviated this damage. Immunohistochemistry analysis demonstrated that decortication decreased the number of caspase-3-positive neurons in the dopamine-depleted rats. Moreover, reverse transcription-quantitative PCR and western blot analyses showed that decortication offset the upregulation of caspase-3 at both the protein and mRNA levels in the dopamine-depleted rats. In conclusion, the present study demonstrated that a relative excess of cortical glutamate inputs had a substantial impact on the pathological processes of striatal neuron lesions in PD.

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Melatonin Reduces Projection Neuronal Injury Induced by 3-Nitropropionic Acid in the Rat Striatum

Cited by 20 publications

References 53 publications

Riboflavin and pyridoxine restore dopamine levels and reduce oxidative stress in brain of rats

Riboflavin and pyridoxine restore dopamine levels and reduce oxidative stress in brain of rats

Melatonin: an ancient molecule that makes oxygen metabolically tolerable

Partial�decortication ameliorates dopamine depletion‑induced striatal neuron lesions in rats

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