Melatonin increases striatal dopaminergic function in 6-OHDA-lesioned rats

Joo, Wan Seok; Jin, Byung Kwan; Park, Chan W.; Maeng, Sung H.; Kim, Yong-Sik

doi:10.1097/00001756-199812210-00022

Cited by 45 publications

(36 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These effects may be due to the antioxidant properties of TBHQ. These data are in agreement with a similar study reported by Joo et al [33] in which the antioxidant melatonin was able to protect the lesioned striatum induced by 6-hydroxyedopamine through free radical generation.…”

Section: Discussionsupporting

confidence: 93%

Potential neuroprotective effect of t‐butylhydroquinone against neurotoxicity—Induced by 1‐methyl‐4‐(2′‐methylphenyl)‐1,2,3,6‐tetrahydropyridine (2′‐methyl‐MPTP) in mice

Abdel-Wahab

2005

J Biochem & Molecular Tox

View full text Add to dashboard Cite

Dopaminergic damage inducing Parkinson's disease (PD) is ubiquitous neurodegenerative disorder, characterized by the progressive loss of dopaminergic neurons in the nigrostriatal pathways. The etiology and pathogenic factors implicated in dopaminergic damage are still unexplored to develop causal therapeutic strategies aimed to halt its progressive loss. The neurotoxicity induced by 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'CH3-MPTP), which is more potent neurotoxic than MPTP in mice, is one of the most valuable models for analyzing pathological feature of dopaminergic damage. Herein, we investigated the neuroprotective effect of the potent antioxidant tertiary butylhydroquinone (TBHQ) against 2'CH3-MPTP-induced neurotoxicity in mice as well as the possible mechanism underlying such neurotoxicity. Male albino mice were injected with two doses of 2'CH3-MPTP (20 mg/kg, i.p.) for two consecutive days. Animals were killed after 2 weeks from the last dose of 2'CH3-MPTP. Control animals received 10 mL/kg body weight i.p. of distilled water. In both groups, brain stems containing the nigrostriatal pathways were dissected and reduced glutathione (GSH), malonyldialdehyde (MDA) contents, and superoxide dismutase (SOD) activity were estimated. Also, brain stem histopathological and histochemical changes were examined. The results of this study revealed that i.p. injection of 2'CH3-MPTP caused decrease in the brain stem content of GSH. On the other hand, the content of MDA and SOD activity was increased as compared with control groups. Also, 2'CH3-MPTP showed severe histopathological changes including swelling of cytoplasm, interstitial edema, and complete loss of the neurons with reactive microglial proliferation and gliosis. Furthermore, histochemical examination of brain stem qualitatively showed depletion of dopaminergic neurons of nigrostriatum. Oral administration of TBHQ (100 mg/kg) prior to 2'CH3-MPTP for 7 days caused normalization of GSH content and SOD activity and ameliorated the MDA content but still above the control value. Pretreatment with TBHQ slightly mitigated the histopathological and histochemical changes observed in 2'CH3-MPTP-treated mice. Based on these observations, it can be concluded that the antioxidant TBHQ has the ability to reverse the oxidative stress caused by 2'CH3-MPTP in mice while failed to challenge the histopathological and histochemical changes induced by that toxicant.

show abstract

Section: Discussionsupporting

confidence: 93%

Potential neuroprotective effect of t‐butylhydroquinone against neurotoxicity—Induced by 1‐methyl‐4‐(2′‐methylphenyl)‐1,2,3,6‐tetrahydropyridine (2′‐methyl‐MPTP) in mice

Abdel-Wahab

2005

J Biochem & Molecular Tox

View full text Add to dashboard Cite

show abstract

“…Other investigators have shown that in vitro exposure to 6-OHDA increases oxidative stress and may lead to apoptosis (Kumar et al, 1995,Park et al, 2002,Soto-Otero et al, 2002,Holtz and O'Malley, 2003,Salinas et al, 2003,Ugarte et al, 2003,Zhuo et al, 2003,Datla et al, 2004,Elkon et al, 2004,Mazzio et al, 2004, and some elements of apoptosis and degeneration occur shortly after in vivo administration of 6-OHDA (Jeon et al, 1995,Joo et al, 1998,Zuch et al, 2000,Kramer and Mytilineou, 2004,Mladenovic et al, 2004. However, little has been reported on in vivo markers of oxidative stress after 6-OHDA administration.…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress and dopamine depletion in an intrastriatal 6-hydroxydopamine model of Parkinson’s disease

Smith

Cass

2007

Neuroscience

View full text Add to dashboard Cite

Although the etiology of Parkinson's disease (PD) is unknown, a common element of most theories is the involvement of oxidative stress, either as a cause or effect of the disease. There have been relatively few studies that have characterized oxidative stress in animal models of PD. In the present study a 6-hydroxydopamine (6-OHDA) rodent model of PD was used to investigate the in vivo production of oxidative stress after administration of the neurotoxin. 6-OHDA was injected into the striatum of young adult rats and the production of protein carbonyls and 4-hydroxynonenal (HNE) was measured at 1, 3, 7, and 14 days after administration. A significant increase in both markers was found in the striatum 1 day after neurotoxin administration, and this increase declined to basal levels by day 7. There was no significant increase found in the substantia nigra at any of the time points investigated. This same lesion paradigm produced dopamine depletions of 90-95% in the striatum and 63-80% in the substantia nigra by 14 to 28 days post 6-OHDA. Protein carbonyl and HNE levels were also measured in middle-aged and aged animals 1 day after striatal 6-OHDA. Both protein carbonyl and HNE levels were increased in the striatum of middle-aged and aged animals treated with 6-OHDA, but the increases were not as great as those observed in the young adult animals. Similar to the young animals, there were no increases in either marker in the substantia nigra of the middle-aged and aged animals. There was a trend for an age-dependent increase in basal amounts of oxidative stress markers when comparing the non-lesioned side of the brains of the three age groups. These results support that an early event in the course of dopamine depletion following intrastriatal 6-OHDA administration is the generation of oxidative stress. Keywordsreactive oxygen species; protein carbonyls; 4-hydroxynonenal; striatum; substantia nigra; aging; Fischer-344 rat Parkinson's disease (PD) stems from the loss of dopamine (DA) caused by the degeneration of the dopaminergic neurons of the substantia nigra. The nature of this degeneration remains unclear, although current theories suggest that reactive oxygen species (ROS) are involved in some capacity early in the disease process (Jenner, 2003). One of the earliest changes in patients with PD and incidental Lewy body disease is the loss of glutathione (Sian et al., 1994,Owen et al., 1996. Post mortem tissue from PD patients has been shown to contain elevated levels Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (Yoritaka et al., 1996), protein carbonyls (Alam et...

show abstract

“…Pharmacological doses of melatonin have been shown to be neuroprotective in the 6-OHDA and in the MPTP models of PD (Joo et al, 1998;Thomas and Mohanakumar, 2004). Delivery of melatonin at physiological doses by mini-pump also protects against a 6-OHDA-induced decrease in mitochondrial complex I activity (Dabbeni-Sala et al, 2001).…”

Section: Immunophilin Ligandsmentioning

confidence: 99%