Behavioral and neurotoxicological effects of subchronic manganese exposure in rats

Vezér, Tünde; Papp, András; Hoyk, Zsófia; Varga, Csaba; Náray, Miklós; Nagymajtényi, László

doi:10.1016/j.etap.2004.12.046

Cited by 34 publications

(41 citation statements)

References 49 publications

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“…In those two studies, significant increase in amplitude and a non-significant change in the latency of the EP were found after acute parenteral Mn administration. Following subchronic oral Mn treatment, lengthening of the latency was detected by Vezér et al [35], as it was found in the present experiment.…”

Section: Discussionsupporting

confidence: 77%

Electrophysiological and biochemical response in rats on intratracheal instillation of manganese

et al. 2011

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Chronic exposure to excess manganese via inhalation of metal fumes causes central nervous system damage. For modelling Mn aerosol inhalation, male Wistar rats were intratracheally instilled with MnCl2 solution (0.5 mg/kg b.w. MnCl2; n=12) 5 days a week for 5 weeks. At the end of the treatment, somatosensory cortical evoked potentials, elicited by double-pulse stimulation, were recorded from the animals in urethane anaesthesia. Body weight gain, organ weights, and Mn level in brain, lung and blood samples were also measured. In brain samples, gene expression level of MnSOD (Mn superoxide dismutase) was determined. The effect of Mn was mainly seen on the evoked potential amplitudes, and on the second:first ratio of these. Tissue Mn concentration was elevated in brain and lungs, but changed hardly in the blood. Relative weight of heart, thymus, lungs and brain was significantly altered. The level of MnSOD transcript in brain tissue decreased. The observed effects showed that Mn had access to the brain and that somatosensory cortical responses evoked by double-pulse stimulation might be suitable biomarkers of Mn intoxication.

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Section: Discussionsupporting

confidence: 77%

Electrophysiological and biochemical response in rats on intratracheal instillation of manganese

et al. 2011

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“…From these data, counts, time, and run length of the activity forms were automatically calculated. It was known from our previous works (e.g., [36]) that OF test is suitable for investigating the impairment of higher nervous functions caused by Mn.…”

Section: Behavioral Investigationmentioning

confidence: 99%

Size-Dependent Toxicity Differences of Intratracheally Instilled Manganese Oxide Nanoparticles: Conclusions of a Subacute Animal Experiment

Máté

Horváth

Kozma

et al. 2015

Biol Trace Elem Res

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Incomplete information on toxicological differences of micro- and nanometer-sized particles raised concerns about the effects of the latter on health and environment. Besides chemical composition, size and surface-to-volume ratio of nanoparticles (NPs) can affect toxicity. To investigate size-dependent toxicity differences, we used particles made of dioxide of the neurotoxic heavy metal manganese (Mn), typically found in inhaled metal fumes, in three size ranges (size A, 9.14 ± 1.98 nm; size B, 42.36 ± 8.06 nm; size C, 118.31 ± 25.37 nm). For modeling the most frequent route of exposure to Mn, NPs were given to rats for 6 weeks by intratracheal instillation. Of each NP size, 3 or 6 mg/kg body weight was given while control animals were vehicle treated. Neurotoxicity was assessed by measuring spontaneous locomotor activity in an open field and by recording spontaneous and evoked electrical activity from the somatosensory cortical area. Mn content of brain, lung, and blood, measured by ICP-MS, were correlated to the observed functional alterations to see the relationship between Mn load and toxic effects. Body weight gain and organ weights were measured as general toxicological indices. The toxicity of size A and size B NPs proved to be stronger compared to size C NPs, seen most clearly in decreased body weight gain and altered spontaneous cortical activity, which were also well correlated to the internal Mn dose. Our results showed strong effect of size on NP toxicity, thus, beyond inappropriateness of toxicity data of micrometer-sized particles in evaluation of NP exposure, differentiation within the nano range may be necessary.

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“…Several reports address the effects of Mn exposure on behavioral tasks [67, 139, 149, 159–170]. Some of these effects are described on Table 5.…”

Section: Main Textmentioning

confidence: 99%

“Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies”

Peres

Schettinger

Chen

et al. 2016

BMC Pharmacol Toxicol

280

183

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Manganese (Mn) is an essential heavy metal. However, Mn’s nutritional aspects are paralleled by its role as a neurotoxicant upon excessive exposure. In this review, we covered recent advances in identifying mechanisms of Mn uptake and its molecular actions in the brain as well as promising neuroprotective strategies. The authors focused on reporting findings regarding Mn transport mechanisms, Mn effects on cholinergic system, behavioral alterations induced by Mn exposure and studies of neuroprotective strategies against Mn intoxication. We report that exposure to Mn may arise from environmental sources, occupational settings, food, total parenteral nutrition (TPN), methcathinone drug abuse or even genetic factors, such as mutation in the transporter SLC30A10. Accumulation of Mn occurs mainly in the basal ganglia and leads to a syndrome called manganism, whose symptoms of cognitive dysfunction and motor impairment resemble Parkinson’s disease (PD). Various neurotransmitter systems may be impaired due to Mn, especially dopaminergic, but also cholinergic and GABAergic. Several proteins have been identified to transport Mn, including divalent metal tranporter-1 (DMT-1), SLC30A10, transferrin and ferroportin and allow its accumulation in the central nervous system. Parallel to identification of Mn neurotoxic properties, neuroprotective strategies have been reported, and these include endogenous antioxidants (for instance, vitamin E), plant extracts (complex mixtures containing polyphenols and non-characterized components), iron chelating agents, precursors of glutathione (GSH), and synthetic compounds that can experimentally afford protection against Mn-induced neurotoxicity.

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Behavioral and neurotoxicological effects of subchronic manganese exposure in rats

Cited by 34 publications

References 49 publications

Electrophysiological and biochemical response in rats on intratracheal instillation of manganese

Electrophysiological and biochemical response in rats on intratracheal instillation of manganese

Size-Dependent Toxicity Differences of Intratracheally Instilled Manganese Oxide Nanoparticles: Conclusions of a Subacute Animal Experiment

“Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies”

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