Perfluorooctane sulfonate (PFOS) exposure could modify the dopaminergic system in several limbic brain regions

Environmental contextPerfluoroalkyl acids are persistent environmental contaminants that are also found in soils. We use a metabolomics approach based on nuclear magnetic resonance analyses to investigate the responses of earthworms to exposure to sub-lethal levels of two perfluoroalkyl acids. The results indicate that this metabolomics approach is able to delineate the toxic mode of action of contaminants present at sub-lethal levels. AbstractMetabolomics entails the analysis of endogenous metabolites within organisms exposed to an external stressor such as an environmental contaminant. We utilised 1H NMR-based metabolomics to elucidate sub-lethal toxic mechanisms of Eisenia fetida earthworms after exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Earthworms were exposed to a range of concentrations of PFOA (6.25 to 50 μg cm–2) and PFOS (3.125 to 25 μg cm–2) by contact tests for 2 days. Earthworm tissues were extracted using a mixture of chloroform, methanol and water, and the polar fraction was analysed by 1H NMR spectroscopy. NMR-based metabolomic analysis revealed heightened E. fetida toxic responses with higher PFOA and PFOS exposure concentrations. Principal component analysis (PCA) exhibited significant separation between control and exposed earthworms along PC1 for all PFOA and PFOS exposure concentrations. Leucine, arginine, glutamate, maltose and adenosine triphosphate (ATP) are potential indicators of PFOA and PFOS exposure as these metabolite concentrations fluctuated with exposure. Our data also indicate that PFOA and PFOS exposure may increase fatty acid oxidation and interrupt ATP synthesis due to a disruption in the inner mitochondrial membrane structure. NMR-based metabolomics has promise as an insightful tool for elucidating the environmental toxicology of sub-lethal contaminant exposure.

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Perfluorooctane Sulfonate (PFOS) and Related Perfluorinated Compounds in Human Maternal and Cord Blood Samples: Assessment of PFOS Exposure in a Susceptible Population during Pregnancy

Environmental Health Perspectives ◽

10.1289/ehp.6864 ◽

2004 ◽

Vol 112 (11) ◽

pp. 1204-1207 ◽

Cited By ~ 303

Author(s):

Koichi Inoue ◽

Fumio Okada ◽

Rie Ito ◽

Shizue Kato ◽

Seiko Sasaki ◽

...

Keyword(s):

Cord Blood ◽

Perfluorooctane Sulfonate ◽

Perfluorinated Compounds ◽

Susceptible Population ◽

Blood Samples ◽

Pfos Exposure

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Long-term effects of cariprazine exposure on dopamine receptor subtypes

CNS Spectrums ◽

10.1017/s1092852913000680 ◽

2013 ◽

Vol 19 (3) ◽

pp. 268-277 ◽

Cited By ~ 9

Author(s):

Yong Kee Choi ◽

Nika Adham ◽

Béla Kiss ◽

István Gyertyán ◽

Frank I. Tarazi

Keyword(s):

Dopamine Receptor ◽

Dopaminergic System ◽

Partial Agonist ◽

Brain Regions ◽

Repeated Treatment ◽

Receptor Subtypes ◽

Long Term Effects ◽

Tissue Sections ◽

Preferential Binding

IntroductionAll clinically effective antipsychotics are known to act on the dopaminergic system, and previous studies have demonstrated that repeated treatment with antipsychotics produced region-specific changes in dopamine receptor levels. Cariprazine is a dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors. We examined the effects of chronic cariprazine administration on dopamine receptor levels.MethodsRats were administered either vehicle or cariprazine (0.06, 0.2, or 0.6 mg/kg) for 28 days. Dopamine receptor levels were quantitated using autoradiographic assays on brain tissue sections from the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), caudate putamen (CPu), hippocampus (HIPP), olfactory tubercle (OT), and islands of Calleja (ICj).ResultsChronic treatment with cariprazine did not alter D1 receptor levels in any brain region tested. Cariprazine increased D2 receptor levels in mPFC (27%–43%), NAc (40%–45%), medial (41%–53%) and lateral (52%–63%) CPu, and HIPP (38%). Cariprazine dose-dependently upregulated D3 receptor levels in ICj (32%–57%), OT (27%–67%), and NAc shell (31%–48%). Repeated cariprazine treatment increased D4 receptor in NAc (53%–82%), medial (54%–98%) and lateral (58%–74%) CPu, and HIPP (38%–98%).ConclusionSimilar to other antipsychotics, cariprazine upregulated D2 and D4 receptor levels in various brain regions. Cariprazine was unique among antipsychotics in increasing D3 receptor levels, which may support its unique psychopharmacologic properties.

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