Developmental manganese, lead, and barren cage exposure have adverse long-term neurocognitive, behavioral and monoamine effects in Sprague-Dawley rats

Sprowles, Jenna L.N.; Amos‐Kroohs, Robyn M.; Braun, Amanda A.; Sugimoto, Chiho; Vorhees, Charles V.; Williams, Michael T.

doi:10.1016/j.ntt.2018.04.001

Cited by 27 publications

(21 citation statements)

References 137 publications

(212 reference statements)

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“…This result indicates that Pb treatment may have affected the ability of the animals to learn or remember the location of the dark box earlier than expected after several trial period. This finding supported several earlier reports that implicated Pb EAHT exposure as an agent of cognitive impairment, particularly in a developing brain [13,[33][34][35]. This result further indicates that the treatment of Vitexin alongside Pb treatment will attenuate the possible cognitive impairment caused by Pb.…”

Section: Discussionsupporting

confidence: 91%

Lead acetate-induced neurodegenerative changes in the dorsolateral prefrontal cortex of mice: the role of Vitexin

Amedu

Omotoso

2020

Environ Anal Health Toxicol

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This study was aimed at investigating the neuroprotective effect of Vitexin against lead (Pb) induced neurodegenerative changes in the dorsolateral prefrontal cortex (DLPFC) and working memory in mice. Thirty-two adolescent male albino mice were divided into four groups (n=8). Control group received 0.2 mL of normal saline; Pb group received 100 mg/kg of Pb acetate for 14 days, Vitexin group received 1mg/kg of Vitexin for 14 days, and Pb+Vitexin group received 100 mg/kg of Pb acetate and 1 mgkg of Vitexin for 14 days. Barnes maze test and novel object recognition test were done to ascertain working memory. Histoarchitectural assessment of DLPFC was done with haematoxylin and eosin (H&E), cresyl fast violet and congo red stains. Furthermore, cell count and other morphometric measurements were done. There was significant decline in working memory in the Pb group, but a combination of Pb+Vitexin improved the working memory. Vitexin significantly reduced neuronal death and chromatolysis caused by Pb. Amyloid aggregation was not observed in any of the groups. This study has shown that concurrent administration of Vitexin and Pb will significantly reduce neurodegeneration and improve working memory. However, Pb treatment or Pb+Vitexin treatment does not have any effect on intercellular distance, neuronal length and the cross-sectional area of neurons in layer III of DLPFC.

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Section: Discussionsupporting

confidence: 91%

Lead acetate-induced neurodegenerative changes in the dorsolateral prefrontal cortex of mice: the role of Vitexin

Amedu

Omotoso

2020

Environ Anal Health Toxicol

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“…Performance in the CWM is largely mediated by dopamine since dopamine lesions of the striatum with 6-hydroxydopamine induce large learning deficits 25,48,49 . Drugs, pesticides, or metals that target the striatum also produce deficits in the CWM [50][51][52][53][54][55] . This is the first study to show long-term deficits in the CWM following irradiation.…”

Section: Discussionmentioning

confidence: 99%

Whole brain proton irradiation in adult Sprague Dawley rats produces dose dependent and non-dependent cognitive, behavioral, and dopaminergic effects

Williams

Sugimoto

Regan

et al. 2020

Sci Rep

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Proton radiotherapy causes less off-target effects than X-rays but is not without effect. To reduce adverse effects of proton radiotherapy, a model of cognitive deficits from conventional proton exposure is needed. We developed a model emphasizing multiple cognitive outcomes. Adult male rats (10/group) received a single dose of 0, 11, 14, 17, or 20 Gy irradiation (the 20 Gy group was not used because 50% died). Rats were tested once/week for 5 weeks post-irradiation for activity, coordination, and startle. Cognitive assessment began 6-weeks post-irradiation with novel object recognition (NOR), egocentric learning, allocentric learning, reference memory, and proximal cue learning. Proton exposure had the largest effect on activity and prepulse inhibition of startle 1-week post-irradiation that dissipated each week. 6-weeks post-irradiation, there were no effects on NOR, however proton exposure impaired egocentric (Cincinnati water maze) and allocentric learning and caused reference memory deficits (Morris water maze), but did not affect proximal cue learning or swimming performance. Proton groups also had reduced striatal levels of the dopamine transporter, tyrosine hydroxylase, and the dopamine receptor D1, effects consistent with egocentric learning deficits. This new model will facilitate investigations of different proton dose rates and drugs to ameliorate the cognitive sequelae of proton radiotherapy.

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“…Consequently, DA receptor upregulation that might result from reduced DA efflux cannot simply account for the lasting reductions in DA outflow in the STR. Other investigators examined elevated Mn exposure during early development in rats, measuring regional brain biogenic amine concentrations (Amos- Kroohs et al, 2016;Bailey et al, 2019;Sprowles et al, 2018;Vorhees et al, 2014). Results with those endpoints cannot be directly compared with the evoked outflow in extracellular fluid produced by microdialysis, but it is apparent in those studies that NE and DA are most sensitive to elevated Mn exposure and that in general, Mn-induced alterations in brain NE/DA concentrations observed in early development do not persist into adulthood.…”

Section: Discussionmentioning

confidence: 99%

Early Postnatal Manganese Exposure Reduces Rat Cortical and Striatal Biogenic Amine Activity in Adulthood

Lasley

Fornal

Mandal

et al. 2019

Toxicological Sciences

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Growing evidence from studies with children and animal models suggests that elevated levels of manganese during early development lead to lasting cognitive and fine motor deficits. This study was performed to assess presynaptic biogenic amine function in forebrain of adult Long-Evans rats exposed orally to 0, 25, or 50 mg Mn/kg/day over postnatal day 1–21 or continuously from birth to the end of the study (approximately postnatal day 500). Intracerebral microdialysis in awake rats quantified evoked outflow of biogenic amines in the right medial prefrontal cortex and left striatum. Results indicated that brain manganese levels in the early life exposed groups (postnatal day 24) largely returned to control levels by postnatal day 66, whereas levels in the lifelong exposed groups remained elevated 10%–20% compared with controls at the same ages. Manganese exposure restricted to the early postnatal period caused lasting reductions in cortical potassium-stimulated extracellular norepinephrine, dopamine, and serotonin, and reductions in striatal extracellular dopamine. Lifelong manganese exposure produced similar effects with the addition of significant decreases in cortical dopamine that were not evident in the early postnatal exposed groups. These results indicate that early postnatal manganese exposure produces persistent deficits in cortical and striatal biogenic amine function. Given that these same animals exhibited lasting impairments in attention and fine motor function, these findings suggest that reductions in catecholaminergic activity are a primary factor underlying the behavioral effects caused by manganese, and indicate that children exposed to elevated levels of manganese during early development are at the greatest risk for neuronal deficiencies that persist into adulthood.

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Developmental manganese, lead, and barren cage exposure have adverse long-term neurocognitive, behavioral and monoamine effects in Sprague-Dawley rats

Cited by 27 publications

References 137 publications

Lead acetate-induced neurodegenerative changes in the dorsolateral prefrontal cortex of mice: the role of Vitexin

Lead acetate-induced neurodegenerative changes in the dorsolateral prefrontal cortex of mice: the role of Vitexin

Whole brain proton irradiation in adult Sprague Dawley rats produces dose dependent and non-dependent cognitive, behavioral, and dopaminergic effects

Early Postnatal Manganese Exposure Reduces Rat Cortical and Striatal Biogenic Amine Activity in Adulthood

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