Cellular defence mechanisms in the striatum of young and aged rats subchronically exposed to manganese

Desole, Maria Speranza; Esposito, Giovanni; Migheli, Rossana; Fresu, Luigia Grazia; Sircana, S.; Zangani, Danilo; Miele, Maddalena; Miele, E

doi:10.1016/0028-3908(94)00140-n

Cited by 58 publications

(32 citation statements)

References 15 publications

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“…On the other hand, an increase in urate oxidase activity would lead to an increase in damage caused by H 2 O 2 with a concomitant lower antioxidant status. One report described an increase in uric acid levels in striatal synaptosomes in aged rats compared with young [52], suggesting a lower urate oxidase activity. However, the same study demonstrated that total striatal uric acid levels are decreased in these same aged rats.…”

Section: Review Articlementioning

confidence: 99%

The role of peroxisomes in aging

Périchon¹,

Bourre

Kelly³

et al. 1998

Cellular and Molecular Life Sciences (CMLS)

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Reactive oxygen species and alterations in membrane lipid homeostasis are thought to be important events in aging process and aging-related degenerative diseases. The peroxisome is a small cellular organelle involved in both oxygen and lipid metabolism, and defects in peroxisomal function are associated with major, and often fatal, changes at the neurological level during human development. Recent reports of aging-related changes in peroxisomal function raised the hypothesis that peroxisomes may also have a significant role in the aging process and aging-related degenerative diseases. This review presents the current data on changes in peroxisomal function during aging and discusses the implications of these changes for health.

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Section: Review Articlementioning

confidence: 99%

The role of peroxisomes in aging

Périchon¹,

Bourre

Kelly³

et al. 1998

Cellular and Molecular Life Sciences (CMLS)

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“…One mechanism proposed for manganese neurotoxicity is oxidative stress (19)(20)(21). In support of this mechanism, pathological concentration of manganese have been shown to produce reactive oxygen species (ROS) in vivo (22), in isolated rat brain mitochondria (23) and in cultured astrocytes (24).…”

Section: Introductionmentioning

confidence: 98%

Combined Effects of Ammonia and Manganese on Astrocytes in Culture

et al. 2004

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Ammonia has been strongly implicated in the pathogenesis of hepatic encephalopathy (HE), and astrocytes appear to be the primary target of ammonia neurotoxicity. Recent work has shown that manganese also plays a role in the pathogenesis of HE and causes astrocyte morphologic and functional changes similar to ammonia. We therefore investigated whether a combination of these compounds could produce additive/synergistic effects. Cultured astrocytes treated with 5 mM ammonia (NH4Cl) along with 100 microM manganese acetate (MnAc) for 3 h showed a 55-65% increase in free radical production over ammonia or manganese alone (P < 0.05). There was also a 50% decrease in the mitochondrial membrane potential (beta psi(m)) at 24 h following treatment with NH4Cl (5 mM) plus MnAc (50 microM) (P < 0.05), as compared to ammonia or manganese alone. Astrocytes treated with ammonia or manganese alone for 24 h showed no cell death, as determined by LDH release and light microscopic examination. However, cultures treated with ammonia plus manganese showed 80-90% necrotic cell death as estimated by light microscopy and 59% cell death as determined by LDH release. LDH release by ammonia plus manganese was blocked by the antioxidant superoxide dismutase (25 units/ml) as well as by the nitric oxide synthase inhibitor N(omega)-nitro-L-argininemethyl ester (500 microM). In conclusion, ammonia plus manganese exert additive/synergetic effects on the induction free radicals, mitochondrial inner membrane depolarization and cellular integrity, which may contribute to the tissue injury associated with chronic forms of HE.

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“…Altogether, experimental data on DA levels in the striatum of Mn-exposed animals suggest that Mn depletes DA only at elevated concentrations (See Gwiazda et al 2007 for a review). Additionally, Desole et al (1995) reported a biphasic response depending on Mn dose, resulting in increased DA and its metabolites at low doses and decreased levels at high doses. In rats treated chronically with oral MnCl 2 the activity of striatal tyrosine hydroxylase was increased at the beginning of the experiment and decreased after 6 months of treatment (Bonilla 1980).…”

Section: Manganese and Dopaminergic System Disturbancesmentioning

confidence: 96%

“…Several mechanisms of Mn neurotoxicity have been proposed, including the disruption of mitochondrial metabolism , oxidative stress (Zhang et al 2004), alteration of iron homeostasis (Kwik-Uribe and Smith 2006), inflammation Zhao et al 2009), altered glutamate and dopamine (DA) metabolism (Desole et al 1995;Erikson et al 2008;Gwiazda et al 2007;Normandin and Hazell 2002), among others. The brain areas mainly affected by Mn are the globus pallidus and the substantia nigra pars reticulata, with damage extending less prominently to the caudate nucleus and the putamen Olanow et al 1996;Stanwood et al 2009;Yamada et al 1986).…”

Section: Introductionmentioning

confidence: 99%

Manganese accumulation in the CNS and associated pathologies

2011

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Manganese (Mn) is an essential metal for life. It is a key constituent of clue enzymes in the central nervous system, contributing to antioxidant defenses, energetic metabolism, ammonia detoxification, among other important functions. Until now, Mn transport mechanisms are partially understood; however, it is known that it shares some mechanisms of transport with iron. CNS is susceptible to Mn toxicity because it possesses mechanisms that allow Mn entry and favor its accumulation. Cases of occupational Mn exposure have been extensively reported in the literature; however, there are other ways of exposure, such as long-term parental nutrition and liver failure. Manganism and hepatic encephalopathy are the most common pathologies associated with the effects of Mn exposure. Both pathologies are associated with motor and psychiatric disturbances, related in turn to mechanisms of damage such as oxidative stress and neurotransmitters alterations, the dopaminergic system being one of the most affected. Although manganism and Parkinson's disease share some characteristics, they differ in many aspects that are discussed here. The mechanisms for Mn transport and its participation in manganism and hepatic encephalopathy are also considered in this review. It is necessary to find an effective therapeutic strategy to decrease Mn levels in exposed individuals and to treat Mn long term effects. In the case of patients with chronic liver failure it would be worthwhile to test a low-Mn diet in order to ameliorate symptoms of hepatic encephalopathy possibly related to Mn accumulation.

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Cellular defence mechanisms in the striatum of young and aged rats subchronically exposed to manganese

Cited by 58 publications

References 15 publications

The role of peroxisomes in aging

The role of peroxisomes in aging

Combined Effects of Ammonia and Manganese on Astrocytes in Culture

Manganese accumulation in the CNS and associated pathologies

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