Effect of intranasal manganese administration on neurotransmission and spatial learning in rats

Blecharz-Klin, Kamilla; Piechal, Agnieszka; Joniec-Maciejak, Ilona; Pyrzanowska, Justyna; Widy-Tyszkiewicz, Ewa

doi:10.1016/j.taap.2012.09.015

Cited by 40 publications

(29 citation statements)

References 69 publications

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“…Likewise, the MWM test results of this study showed that the escape latency increased as Mntreated dose increased; by contrast, the number of platform crossings decreased as Mn-treated dose increased. Therefore, Mn exposure significantly impaired the spatial learning and memory of Mn-treated rats; this finding is consistent with that in a previous study (Blecharz-Klin et al, 2012) The cAMP signaling pathway in the hippocampus is involved in the formation of spatial memories (Mizuno et al, 2002). In the present study, the hippocampal levels of cAMP, protein kinase A, pCREB, and BDNF of the Mn-treated rats decreased dose-dependently.…”

Section: Discussionsupporting

confidence: 93%

“…Chronic Mn exposure can lead to an excessive accumulation of Mn in different brain regions, including the cerebral cortex (Guilarte et al, 2006) and the hippocampus (Blecharz-Klin et al, 2012), where Mn likely elicits a toxic effect. It is well known that the hippocampus plays an important role in learning-and memoryrelated processes (Clark et al, 2000;Eichenbaum, 2004;Sutherland et al, 1982).…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, Mn exposure significantly impairs spatial learning and memory in Mn-treated rats or non-human primates (Blecharz-Klin et al, 2012;Oner and Sentürk, 1995;Schneider et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Effects of chronic manganese exposure on the learning and memory of rats by observing the changes in the hippocampal cAMP signaling pathway

Liang

Zhang

et al. 2015

Food and Chemical Toxicology

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Effects of chronic manganese exposure on the learning and memory of rats by observing the changes in the hippocampal cAMP signaling pathway

Liang

Zhang

et al. 2015

Food and Chemical Toxicology

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“…For example, a similar study by Blecharz-Klin, et al (2012) used an intranasal dose route for 2 weeks instead of 4 weeks in slightly older animals; they did not observe a difference in either STR DA or DOPAC, but noted a decreased level of STR HVA and decreased DA turnover. Autissier et al (1982) also used an i.p.…”

Section: Discussionmentioning

confidence: 99%

Subacute manganese exposure in rats is a neurochemical model of early manganese toxicity

et al. 2014

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Manganese (Mn) is an essential trace element, but excess exposure leads to accumulation in biological tissues, including the brain. Chronically high Mn levels in the brain are neurotoxic and can result in a progressive, irreversible neurological disorder known as manganism. Manganism has signs and symptoms similar to, but distinguishable from idiopathic Parkinson’s disease, which include both psychological and motor disturbances. Evidence suggests that Mn exposure impacts neurotransmitter levels in the brain. However, it remains unclear if subacute, low-level Mn exposure resulted in alterations in neurotransmitter systems with concomitant behavioral deficits. The current study used high performance liquid chromatography to quantify neurotransmitter levels in rat striatum (STR), substantia nigra (SN), and hippocampus (HP). Subacute Mn exposure via i.p. injection of 15 mg Mn/kg as MnCl2 caused significantly increased dopamine (DA) levels in the STR. The enhancement was accompanied by significantly elevated levels of the DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the STR. In addition, levels of HVA were significantly increased in the SN and HP. These data indicate that subacute, low-level Mn exposure disrupts multiple neurotransmitter systems in the rat brain which may be responsible, in part, for observed locomotor deficits.

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“…Several studies reported that Mn exposure causes cognitive deficits and decreased learning ability [120,250,251] [252]. Therefore, it is possible that Hfe deficiency could modify the distribution of Mn within the brain along with the uptake of the metal into the brain through two different pathways, namely, through the air-brain barrier (intranasal) and the BBB (drinking water).…”

Section: Discussionmentioning

confidence: 99%

Effect of hemochromatosis on manganese neurotoxicity

Alsulimani¹

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ABSTRACT:Manganese (Mn) is an essential element for normal brain function, but excess levels of Mn in the brain are associated with a number of behavioral problems, including motor dysfunction, memory loss and psychiatric disorders. While Mn is known to share iron transporters for cellular uptake, deficiency in the Hfe (hemochromatosis), a cellular iron regulatory protein, affects the activities of iron transporters and impairs iron metabolism. Previously it was shown that Mn uptake into the brain is increased after intranasal exposure to Mn in Hfe-deficient mice, a mouse model of iron overload hereditary hemochromatosis. However, there is limited information about the effect of Hfe deficiency on Mn toxicity after exposure by other routes. Mn exposure is common through ingestion and inhalation in both environmental and occupational settings. Because Hfe deficiency alters iron transporters, and since Mn shares iron transporters, I hypothesize that Hfe deficiency increases Mn toxicity by modulating Mn uptake from the absorption site and deposition into the target organ for Mn toxicity which is the brain after gastric exposure in drinking water and pulmonary exposure to Mn particles. Specific aims are focused on the effect of Hfe deficiency on 1) the expression levels of metal transporters in the brain, gut and lung including alveolar macrophages, 2) levels of Mn, 3) Mn-associated neurobehavioral impairments, and 4) mechanisms of Mn neurotoxicity. This research will enhance the knowledge of Mn exposure and uptake in Hfe-related hemochromatosis, a prevalent iron disorder in the world.

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Effect of intranasal manganese administration on neurotransmission and spatial learning in rats

Cited by 40 publications

References 69 publications

Effects of chronic manganese exposure on the learning and memory of rats by observing the changes in the hippocampal cAMP signaling pathway

Effects of chronic manganese exposure on the learning and memory of rats by observing the changes in the hippocampal cAMP signaling pathway

Subacute manganese exposure in rats is a neurochemical model of early manganese toxicity

Effect of hemochromatosis on manganese neurotoxicity

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