Methylphenidate alleviates cognitive dysfunction caused by early manganese exposure: Role of catecholaminergic receptors

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2024, Volume and Issue: 131, P. 110949 - 110949

Published: Jan. 22, 2024

Environmental manganese (Mn) exposure is associated with impaired attention and psychomotor functioning, as well impulsivity/hyperactivity in children adolescents. We have shown previously that developmental Mn can cause these same dysfunctions a rat model. Methylphenidate (MPH) lessens impairments attention, impulse control, function children, but it unknown whether MPH ameliorates when induced by exposure. Here, we sought to (1) determine oral treatment the lasting sensorimotor caused exposure, (2) elucidate mechanism(s) of neurotoxicity effectiveness. Rats were given 50 mg Mn/kg/d orally over PND 1-21 assessed adults series control tasks during (0, 0.5, 1.5, or 3.0 mg/kg/d). Subsequently, selective catecholaminergic receptor antagonists administered gain insight into action MPH. Developmental persistent impairments. at 0.5 mg/kg/d completely ameliorated attentional dysfunction, whereas deficits dose. Notably, benefit on was only apparent after prolonged treatment, while efficacy for emerged early treatment. Selectively antagonizing D1, D2, α2

Language: Английский

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Maternal choline supplementation lessens the behavioral dysfunction produced by developmental manganese exposure in a rodent model of ADHD

Neurotoxicology and Teratology, Journal Year: 2024, Volume and Issue: 102, P. 107337 - 107337

Published: Feb. 27, 2024

Language: Английский

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Developmental Manganese Exposure Causes Lasting Attention Deficits Accompanied by Dysregulation of mTOR Signaling and Catecholaminergic Gene Expression in Brain Prefrontal Cortex

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 18, 2023

Elevated manganese (Mn) exposure is associated with attentional deficits in children, and an environmental risk factor for attention deficit hyperactivity disorder (ADHD). We have shown that developmental Mn causes lasting sensorimotor a rat model of early childhood exposure, these are hypofunctioning catecholaminergic system the prefrontal cortex (PFC), though mechanistic basis not well understood. To address this, male Long-Evans rats were exposed orally to (50 mg/kg/d) over PND 1-21 function was assessed adulthood using 5-Choice Serial Reaction Time Task. Targeted epigenetic gene expression, followed by unbiased differential DNA methylation regulation expression transcriptomics PFC, performed young adult littermates. Results show focused reduced tyrosine hydroxylase, dopamine transporter, methyltransferase 3a. Further, broader dysregulation regulation, inflammation, cell development, neuronal systems. Pathway enrichment analyses uncovered mTOR Wnt signaling pathway genes as significant transcriptomic regulators altered transcriptome, Western blot total, C1 C2 phospho-mTOR confirmed dysregulation. Our findings deepen our understanding how leads dysfunction deficits, which may aid future therapeutic interventions disorders.Attention (ADHD) factors, including neurotoxic agents. Here we used rodent producing broad changes cortex, identify disrupted pathways novel mechanism induce impairments. Importantly, establish development critical period susceptibility caused elevated toxicant exposure. Given health threats disproportionately impact communities color low socioeconomic status, can studies assess vulnerable populations.

Language: Английский

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Interaction of prenatal maternal selenium and manganese levels on child neurodevelopmental trajectories-the Shanghai birth cohort study

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 915, P. 170095 - 170095

Published: Jan. 16, 2024

The fetal brain is particularly plastic, and may be concurrently affected by chemical exposure malnutritional factors. Selenium essential for the developing brain, excess manganese exert neurotoxic effects. However, few epidemiological studies have evaluated interaction of selenium assessed in different prenatal stages on postnatal neurodevelopmental trajectories. This study contained 1024 mother-child pairs Shanghai-birth-cohort from 2013 to 2016 recruited since early/before pregnancy with complete data levels infant Whole blood early around birth were measured inductively-coupled-plasma-mass-spectrometry (ICP-MS), children's cognitive development was at 6, 12, 24 months age using Age & Stage-Questionnaire (ASQ)-3 Bayley-III. Multiple linear regression used investigate 1.82 ± 0.98 μg/dL 13.53 2.70 maternal pregnancy, 5.06 1.67 11.81 3.35 umbilical cord blood, respectively. Higher Se associated better neurocognitive performances or consistently-high-level trajectory (P < 0.05), more significant associations observed than birth. such positive relationships became non-significant even adverse high (vs. low) status, effect differences between low pregnancy. Prenatal positively child neurodevelopment, but mitigate favorable effects mainly earlier stage.

Language: Английский

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Invited Perspective: Studying Metal Impacts on Neurobehavior during the Critical but Challenging Window of Adolescence

Environmental Health Perspectives, Journal Year: 2024, Volume and Issue: 132(2)

Published: Feb. 1, 2024

Language: Английский

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Association between Autism Spectrum Disorder, Trace Elements, and Intracranial Fluid Spaces

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8050 - 8050

Published: July 24, 2024

(1) Autism spectrum disorder (ASD) belongs to the group of complex developmental disorders. Novel studies have suggested that genetic and environmental factors equally affect risk ASD. Identification involved in development ASD is therefore crucial for a better understanding its etiology. Whether there causal link between trace elements, brain magnetic resonance imaging (MRI), remains matter debate requires further studies. (2) In prospective part study, we included 194 children, including an age-matched control group; retrospective 28 children with available MRI were included. All had urine analysis elements performed. those MRI, linear indexes ventricular volumes measured calculated. (3) We found highest vanadium, rubidium, thallium, silver levels These also correlated estimated volume based on subanalysis. However, severity deficits did not correlate our except negatively magnesium. (4) Trace impact ASD, but multi-centric are needed explain pathophysiological mechanisms.

Language: Английский

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Methylphenidate alleviates cognitive dysfunction from early Mn exposure: Role of catecholaminergic receptors

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 30, 2023

ABSTRACT Environmental manganese (Mn) exposure is associated with impaired attention and psychomotor functioning, as well impulsivity/hyperactivity in children adolescents. We have shown previously that developmental Mn can cause these same dysfunctions a rat model. Methylphenidate (MPH) lessens impairments attention, impulse control, sensorimotor function children, but it unknown whether MPH ameliorates when induced by exposure. Here, we sought to (1) determine oral treatment the lasting caused exposure, (2) elucidate mechanism(s) of neurotoxicity effectiveness. Rats were given 50 mg Mn/kg/d orally over PND 1-21 assessed adults series control tasks during (0, 0.5, 1.5, or 3.0 mg/kg/d). Subsequently, selective catecholaminergic receptor antagonists administered gain insight into action MPH. Developmental persistent impairments. at 0.5 mg/kg/d completely ameliorated attentional dysfunction, whereas deficits dose. Notably, benefit on was only apparent after prolonged treatment, while efficacy for emerged early treatment. Selectively antagonizing D1, D2, α2 A receptors had no effect Mn-induced dysfunction this domain. However, antagonism D2R attenuated deficits, ameliorate those diminished D1R antagonism. These findings demonstrate effective alleviating they clarify mechanisms underlying efficacy. Given often unknown, implications environmentally-induced more broadly. Highlights dose varied functional domain The No specific singly mediates inattention Dopamine 1 2 moderated improve behavioral an environmental toxicant

Language: Английский

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Sensorimotor dysfunction due to developmental manganese exposure is less severe in adult female than male rats and partially improved by acute methylphenidate treatment

Neurotoxicology and Teratology, Journal Year: 2024, Volume and Issue: 102, P. 107330 - 107330

Published: Feb. 1, 2024

Language: Английский

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Time course of lead-induced dyslipidemia in male albino rats

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 19, 2024

Background Lead has been shown to induce dyslipidemia in rats although the attendant mechanisms have not clearly elucidated. Methods In order investigate time-course of lead-induced perturbations lipid metabolism, male Wistar were exposed 200, 300 and 400 ppm lead as acetate their drinking water for 4, 8 12 weeks. Control animals received distilled same exposure times after which blood, liver, kidney, brain, heart lungs removed from analyzed dynamics spectrophotometrically. Results accumulated organs following descending order: kidney > liver brain lungs. Lead-induced inhibition reverse cholesterol transport was both time-dependent well dose-dependent at 4 weeks evidenced by decrease HDL (17% 4-week ppm, 35, 43 49% doses respectively weeks). Free fatty acids (FFAs) plasma displayed a hormetic-like response with lowest dose instigating 51% FFA while 2-fold 1.5-fold increases respectively. Increases erythrocyte also observed 200 all Increased hepatic, renal cholesterogenesis generally highest occurring organs. Hepatic, renal, cardiac pulmonary phospholipidosis times. Cardiac decreased triacyglycerols increased Hepatic HMG-CoA reductase activities up-regulated most increase (35%) Positive correlations between (r = 0.476, p 0.01), 0.498, 0.01) negative correlation blood -0.523, 0.01). Conclusion These findings indicate that may be mediated through up-regulation activity, enhanced resulting availability FFA.

Language: Английский

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Neurotoxicology of Metals

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

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