Gender influence on manganese induced depression-like behavior and Mn and Fe deposition in different regions of CNS and excretory organs in intraperitoneally exposed rats

Yamagata, A.; Guimarães, Natália Carvalho; Santana, David Filipe de; Gonçalves, Marialva; Souza, Vanessa Aparecida Feijó de; Júnior, Fernando Barbosa; Pandossio, José Eduardo; Santos, Virgínia Souza

doi:10.1016/j.tox.2016.05.012

Cited by 14 publications

(10 citation statements)

References 32 publications

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“…Sexual dimorphism in the association between Mn and neurodevelopment may be related to biological differences in neurochemistry and hormone activity (Ngun et al 2011), such as testosterone, which has been shown to improve visuospatial performance in animals (Lund and Lephart 2001) and humans (Mueller et al 2008). Animal studies have demonstrated sex differences in the accumulation of Mn in body tissues (Dorman et al 2004; Yamagata et al 2017), neuron morphology (Madison et al 2011), and performance on tests of behavior and motor function (Yamagata et al 2017).…”

Section: Discussionmentioning

confidence: 99%

Uncovering neurodevelopmental windows of susceptibility to manganese exposure using dentine microspatial analyses

Henn

Austin

Coull

et al. 2018

Environmental Research

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Section: Discussionmentioning

confidence: 99%

Uncovering neurodevelopmental windows of susceptibility to manganese exposure using dentine microspatial analyses

Henn

Austin

Coull

et al. 2018

Environmental Research

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“…Behavioral damage associated with Mn exposure in rats showed a sex-specific response where male rats were more severely impacted, and female rats did not experience as severe motor damage until the dose was increased (Yamagata et al, 2016). However, to date, limited human research has studied the potential for effect modification by sex on the associations between perinatal Mn exposure and neuromotor functions.…”

Section: Introductionmentioning

confidence: 99%

Sex differences in sensitivity to prenatal and early childhood manganese exposure on neuromotor function in adolescents

Chiu

Henn

Hsu

et al. 2017

Environmental Research

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Introduction While studies have suggested that exposure to manganese (Mn) may be associated with neurodevelopment in school-age children, there is limited information on prenatal and postnatal Mn exposures and tremor or motor function in children. Methods We measured Mn levels in dentine of shed teeth, representing prenatal, early postnatal, and cumulative childhood exposure windows, from 195 children in Italy. Pursuit Aiming, Luria Nebraska Motor Battery, as well as Tremor and Sway system from Computerized Adaptive Testing System (CATSYS) were administered at 11–14 years old. We examined the relationships of tooth Mn (ln-transformed) with motor function using generalized linear models and generalized additive models, adjusting for age, sex, and socioeconomic status index. Effect modification by sex was also examined. Results We found that higher prenatal Mn was associated with better body stability in boys in a number of sway tests (including mean sway, transversal sway, sagittal sway, sway area, and sway intensity), while Mn was associated with poorer performance in girls on all of these metrics (all p for Mn × sex interaction <0.05). Higher prenatal Mn was also modestly associated with better hand/finger and eye-hand coordination in boys compared to girls in sex-stratified analyses, although interaction models did not reach statistical significance. For tremor, on the other hand, higher early postnatal Mn was associated with increased center frequency in girls (p for interaction<0.01), but increased Mn level at the later postnatal period was associated with increased center frequency in boys (p for interaction=0.01). Conclusions This study, which used a direct measure of prenatal and childhood Mn exposure, suggested sex-specific critical windows of early life Mn exposure in relation to neuromotor function in adolescents. The sex-specific associations might be strongest with measures of whole body stability, for which the critical exposure window was during the prenatal period.

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“…Guilarte et al 64 demonstrated increased Mn accumulation in the frontal cortex of male Cynomolgus macaques . Finally, Mn levels increased in the hippocampus and cerebellum of exposed male and female rats after Mn exposure 65 . Additionally, we measured levels of other essential metals included Fe, Cu, and Zn, after Mn exposure.…”

Section: Discussionmentioning

confidence: 97%

“…Finally, Mn levels increased in the hippocampus and cerebellum of exposed male and female rats after Mn exposure. 65 Additionally, we measured levels of other essential metals included Fe, Cu, and Zn, after Mn exposure. We observed no overt and consistent influence on Mn administration on these metals.…”

Section: Discussionmentioning

confidence: 99%

Sex‐dependent metal accumulation and immunoexpression of Hsp70 and Nrf2 in rats' brain following manganese exposure

Ijomone

Iroegbu

Morcillo

et al. 2022

Environmental Toxicology

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Manganese (Mn), although important for multiple cellular processes, has posed environmental health concerns due to its neurotoxic effects. In recent years, there have been extensive studies on the mechanism of Mn‐induced neuropathology, as well as the sex‐dependent vulnerability to its neurotoxic effects. Nonetheless, cellular mechanisms influenced by sex differences in susceptibility to Mn have yet to be adequately characterized. Since oxidative stress is a key mechanism of Mn neurotoxicity, here, we have probed Hsp70 and Nrf2 proteins to investigate the sex‐dependent changes following exposure to Mn. Male and female rats were administered intraperitoneal injections of MnCl2 (10 mg/kg and 25 mg/kg) 48 hourly for a total of eight injections (15 days). We evaluated changes in body weight, as well as Mn accumulation, Nrf2 and Hsp70 expression across four brain regions; striatum, cortex, hippocampus and cerebellum in both sexes. Our results showed sex‐specific changes in body‐weight, specifically in males but not in females. Additionally, we noted sex‐dependent accumulation of Mn in the brain, as well as in expression levels of Nrf2 and Hsp70 proteins. These findings revealed sex‐dependent susceptibility to Mn‐induced neurotoxicity corresponding to differential Mn accumulation, and expression of Hsp70 and Nrf2 across several brain regions.

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Gender influence on manganese induced depression-like behavior and Mn and Fe deposition in different regions of CNS and excretory organs in intraperitoneally exposed rats

Cited by 14 publications

References 32 publications

Uncovering neurodevelopmental windows of susceptibility to manganese exposure using dentine microspatial analyses

Uncovering neurodevelopmental windows of susceptibility to manganese exposure using dentine microspatial analyses

Sex differences in sensitivity to prenatal and early childhood manganese exposure on neuromotor function in adolescents

Sex‐dependent metal accumulation and immunoexpression of Hsp70 and Nrf2 in rats' brain following manganese exposure

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