Rat striatal dopamine tetrahydrobiopterin content following an intrastriatal injection of manganese chloride

Lista, Alvaro; Abarca, Jorge; Ramos, Camila de Oliveira; Daniels, Alejandro J.

doi:10.1016/0024-3205(86)90211-0

Cited by 26 publications

(11 citation statements)

References 13 publications

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“…In order to expound the behavior change after injection of Mn in rats, we tested the dopamine levels, DA receptor and TH protein expression after Mn injection. It had been proved that dopamine levels decreased in the basal ganglia of monkey intoxicated with manganese and in rat striatum directly injected with manganese(Bird et al 1984; Lista et al 1986), our experimental results also proved that the dopamine levels and DA receptor protein expression were significantly decreased (Figs. 1, 2).…”

Section: Discussionsupporting

confidence: 79%

The Role of Autophagy Dysregulation in Manganese-Induced Dopaminergic Neurodegeneration

et al. 2013

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The etiological role of dysregulated autophagy in neurodegenerative diseases has been a subject of intense investigation. While manganese (Mn) is known to cause dopaminergic (DAergic) neurodegeneration, it has yet to be determined whether the dysregulation of autophagy plays a role in Mn-induced neuronal injury. In this study, we investigated the effect of Mn on autophagy in a rat model of manganism, a neurodegenerative disease associated with excessive exposure to Mn. After a single intrastriatal injection of Mn, the short- (4–12 h) and long-term (1–28 days) effect of Mn on DAergic neurons and autophagy were examined. Marked reduction in the number of TH-immunoreactive neurons in the substantia nigra pars compacta (SNpc) as well as TH protein expression, and a significant increase of apomorphine-induced rotations were observed in rats after Mn injection. Manganese also induced the down-regulation of dopamine levels and D1 dopamine receptor expression. In addition, autophagy was dysregulated and inhibited, as evidenced by increased number of abnormal lysosomes, decreased protein expression of Beclin1, and decreased ratio of microtubule-associated protein 1 light chain 3 (LC3) II over LC3 I, concomitant with activated mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70s6k) signaling. In contrast, in the early phase of Mn exposure, the level of autophagy was not be suppressed but compensatorily activated. Although the morphology of the DAergic neuron was intact in the early phase, Mn caused a significant decrease in TH-immunoreactivity and a significant increase in apomorphine-induced rotations in the presence of wortmannin, an inhibitor of autophagy. Taken together, these results demonstrate, for the first time, that autophagy may play a protective role against Mn-induced neuronal damage, whilst dysregulation of autophagy at later phases may mediate DAergic neurodegeneration.

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Section: Discussionsupporting

confidence: 79%

The Role of Autophagy Dysregulation in Manganese-Induced Dopaminergic Neurodegeneration

et al. 2013

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“…In experimental animals, manganese is selectively neurotoxic to pathways intrinsic to the basal ganglia. Dopamine levels decreased in the basal ganglia of monkeys intoxicated with manganese (Bird et al, 1984;Eriksson et al, 1992) and in rat striatum directly injected with manganese (Lista et al, 1986;Brouillet et al, 1993). In cultured cells, manganese induces apoptosis, as judged by changes in cell morphology, caspase-3 activation, and DNA fragmentation/TUNEL staining (Desole et al, 1996;Hirata et al, 1998;Schrantz et al, 1999;Oubrahim et al, 2001).…”

Section: Introductionmentioning

confidence: 95%

The role of dopamine transporter in selective toxicity of manganese and rotenone

et al. 2008

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“…The fall in dopamine levels may result from a rapid replacement of the amine from its storage sites by manganese followed by a decrease in the rate of dopamine synthesis caused by the drop in biopterin cofactor levels. 63 In the adrenal gland, reserpine increased tyrosine hydroxylase protein threefold, but cellular tyrosine hydroxylase activity measured in tissue slices increased sixfold. This differences may be due to increased biopterin cofactor levels induced by r e~e r p i n e .~~ Repeated subcutaneous injection of thyrotropin-releasing hormone (TRH) and its analog, y-butyrolactone-y-carbonyl-L-prolinamide citrate (DN 1417) reduced biopterin levels in the raphe nucleus 70%) but cellular tryptophan hydroxylase activity in raphe tissue slices was reduced by 30%.…”

Section: B Regulation Of Aromatic Amino Acid Hydroxylases By the Tetmentioning

confidence: 98%

Physiological and clinical chemistry of biopterin

Nagatsu

Matsuura

Sugimoto

1989

Medicinal Research Reviews

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Rat striatal dopamine tetrahydrobiopterin content following an intrastriatal injection of manganese chloride

Cited by 26 publications

References 13 publications

The Role of Autophagy Dysregulation in Manganese-Induced Dopaminergic Neurodegeneration

The Role of Autophagy Dysregulation in Manganese-Induced Dopaminergic Neurodegeneration

The role of dopamine transporter in selective toxicity of manganese and rotenone

Physiological and clinical chemistry of biopterin

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