Selective Lesions by Manganese and Extensive Damage by Iron After Injection into Rat Striatum or Hippocampus

Sloot, W.N.; Sluijs-Gelling, Alita J. van der; Gramsbergen, Jan Bert

doi:10.1046/j.1471-4159.1994.62010205.x

Cited by 68 publications

(23 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1), reaching one of the highest concentrations in brain parenchyma (just comparable to those reached in the basal ganglia) and, therefore, a preferential candidate for Mn 2+ intoxication. However, it must be also noted that high endogenous Fe 3+ and/or catecholamine levels potentiate the neurotoxicity of Mn 2+ [31], and therefore, Mn 2+ accumulation could differentially alter cellular physiology in areas enriched with those substances, like the basal ganglia or the substantia nigra. Indeed, this toxic potentiation is proposed to play a role in human manganism [7] and could also help to explain the motor deficits found in our experiments (Fig.…”

Section: Discussionmentioning

confidence: 99%

Behavioral, electrophysiological and histopathological consequences of systemic manganese administration in MEMRI

Eschenko

Canals

Simanova

et al. 2010

Magnetic Resonance Imaging

View full text Add to dashboard Cite

Manganese (Mn 2+ )-enhanced magnetic resonance imaging (MEMRI) offers the possibility to generate longitudinal maps of brain activity in unrestrained and behaving animals. However, Mn 2+ is a metabolic toxin and a competitive inhibitor for Ca 2+ , and therefore, a yet unsolved question in MEMRI studies is whether the concentrations of metal ion used may alter brain physiology. In the present work we have investigated the behavioral, electrophysiological and histopathological consequences of MnCl 2 administration at concentrations and dosage protocols regularly used in MEMRI. Three groups of animals were sc injected with saline, 0.1 and 0.5 mmol/kg MnCl 2 , respectively. In vivo electrophysiological recordings in the hippocampal formation revealed a mild but detectable decrease in both excitatory postsynaptic potentials (EPSP) and population spike (PS) amplitude under the highest MnCl 2 dose. The EPSP to PS ratio was preserved at control levels, indicating that neuronal excitability was not affected. Experiments of pair pulse facilitation demonstrated a dose dependent increase in the potentiation of the second pulse, suggesting presynaptic Ca 2+ competition as the mechanism for the decreased neuronal response. Tetanization of the perforant path induced a long-term potentiation of synaptic transmission that was comparable in all groups, regardless of treatment. Accordingly, the choice accuracy tested on a hippocampal-dependent learning task was not affected. However, the response latency in the same task was largely increased in the group receiving 0.5 mmol/kg of MnCl 2 . Immunohistological examination of the hippocampus at the end of the experiments revealed no sign of neuronal toxicity or glial reaction. Although we show that MEMRI at 0.1 mmol/Kg MnCl 2 may be safely applied to the study of cognitive networks, a detailed assessment of toxicity is strongly recommended for each particular study and Mn 2+ administration protocol.

show abstract

Section: Discussionmentioning

confidence: 99%

Behavioral, electrophysiological and histopathological consequences of systemic manganese administration in MEMRI

Eschenko

Canals

Simanova

et al. 2010

Magnetic Resonance Imaging

View full text Add to dashboard Cite

show abstract

“…Its properties have led to its extensive use in studies assessing the negative effects of Mn on the basal ganglia (Bird et al, 1984;Sloot et al, 1994;Cano et al, 1997;Takeda, 2003). However, the basis for the use of MnSO 4 and MnPO 4 in this study lies in the fact that they are the two major combustion products of MMT, a gasoline additive used in certain countries and approved for use in the U.S. (Lynam et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Direct effects of manganese compounds on dopamine and its metabolite Dopac: An in vitro study

Sistrunk

Ross

Filipov

2007

Environmental Toxicology and Pharmacology

View full text Add to dashboard Cite

Following combustion of fuel containing the additive methylcyclopentadienyl-manganesetricarbonyl (MMT), manganese phosphate (MnPO 4 ) and manganese sulfate (MnSO 4 ) are emitted in the atmosphere. Manganese chloride (MnCl 2 ), another Mn 2+ species, is widely used experimentally. Using rat striatal slices, we found that MnPO 4 decreased tissue and media dopamine (DA) and media Dopac (a DA metabolite) levels substantially more than either MnCl 2 or MnSO 4 ; antioxidants were partially protective. Also, both MnCl 2 and MnPO 4 (more potently) oxidized DA and Dopac even in the absence of tissue in the media, suggesting a direct interaction between Mn and DA/Dopac. Because aminochrome is a major oxidation product of DA, we next determined whether MnPO 4 will be more potent in forming aminochrome than MnCl 2 or MnSO 4 which, indeed, was the case. Thus, a potential additional mechanism for the neurotoxic effects of environmentally-relevant forms of Mn, MnPO 4 in particular, is the generation of reactive DA intermediates.

show abstract

“…This method was validated in models of cell death such as kainic acid (27), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (28), or multivalent metals (29) in vivo and showed similar results as quantification of cell death using conventional hematoxylin and eosin, Nissl, or de Olmos' cupric-staining methodologies (30). Typically, Fluoro-Jade-positive neurons also present a condensation of the chromatin, a disruption of the plasma membrane, and nuclear membrane integrity.…”

Section: Treatment With Diaminothiazole Kinase Inhibitors Exerts Neurmentioning

confidence: 99%

Diaminothiazoles Modify Tau Phosphorylation and Improve the Tauopathy in Mouse Models*

Zhang

Hernández

Rei

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Tau is hyperphosphorylated in the tauopathies. Targeting Tau kinases CDK5 and GSK3␤ represents a potential therapeutic approach. Results: Inhibitors of Tau kinases are neuroprotective, decrease PHF-1 immunoreactivity, and induce recovery of memory by fear conditioning. Conclusion: Diaminothiazoles as CDK5 and GSK3␤ inhibitors improve the tauopathy in mouse models. Significance: Dual kinase inhibition can be critical for efficacy when treating tauopathies.

show abstract

Selective Lesions by Manganese and Extensive Damage by Iron After Injection into Rat Striatum or Hippocampus

Cited by 68 publications

References 53 publications

Behavioral, electrophysiological and histopathological consequences of systemic manganese administration in MEMRI

Behavioral, electrophysiological and histopathological consequences of systemic manganese administration in MEMRI

Direct effects of manganese compounds on dopamine and its metabolite Dopac: An in vitro study

Diaminothiazoles Modify Tau Phosphorylation and Improve the Tauopathy in Mouse Models*

Contact Info

Product

Resources

About