Gender-dependent and genotype-sensitive monoaminergic changes induced by polychlorinated biphenyl 153 in the rat brain

Dervola, Kine S.N.; Johansen, Espen Borgå; Walaas, S. Ivar; Fonnum, Frode

doi:10.1016/j.neuro.2015.07.004

Cited by 13 publications

(13 citation statements)

References 49 publications

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“…Rodent models have revealed sex-dependent effects of developmental PCB exposure on brain neurochemistry (Dervola et al, 2015) and behavior (Bell et al, 2016;Gillette et al, 2017;Tian et al, 2011). Here, we extend these in vivo observations to demonstrate sex-dependent PCB effects on neurodevelopment in vitro.…”

Section: Discussionsupporting

confidence: 56%

Sex-Dependent Effects of 2,2′,3,5′,6-Pentachlorobiphenyl on Dendritic Arborization of Primary Mouse Neurons

Keil

Sethi

Lein

2018

Toxicological Sciences

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Early life exposures to environmental contaminants are implicated in the pathogenesis of many neurodevelopmental disorders (NDDs). These disorders often display sex biases, but whether environmental neurotoxicants act in a sex-dependent manner to modify neurodevelopment is largely unknown. Since altered dendritic morphology is associated with many NDDs, we tested the hypothesis that male and female primary mouse neurons are differentially susceptible to the dendrite-promoting activity of 2,2′,3,5′,6-pentachlorobiphenyl (PCB 95). Hippocampal and cortical neuron-glia co-cultures were exposed to vehicle (0.1% dimethylsulfoxide) or PCB 95 (100 fM–1 μM) from day in vitro 7–9. As determined by Sholl analysis, PCB 95-enhanced dendritic growth in female but not male hippocampal and cortical neurons. In contrast, both male and female neurons responded to bicuculline with increased dendritic complexity. Detailed morphometric analyses confirmed that PCB 95 effects on the number and length of primary and nonprimary dendrites varied depending on sex, brain region and PCB concentration, and that female neurons responded more consistently with increased dendritic growth and at lower concentrations of PCB 95 than their male counterparts. Exposure to PCB 95 did not alter cell viability or the ratio of neurons to glia in cultures of either sex. These results demonstrate that cultured female mouse hippocampal and cortical neurons are more sensitive than male neurons to the dendrite-promoting activity of PCB 95, and suggest that mechanisms underlying PCB 95-induced dendritic growth are sex-dependent. These data highlight the importance of sex in neuronal responses to environmental neurotoxicants.

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Section: Discussionsupporting

confidence: 56%

Sex-Dependent Effects of 2,2′,3,5′,6-Pentachlorobiphenyl on Dendritic Arborization of Primary Mouse Neurons

Keil

Sethi

Lein

2018

Toxicological Sciences

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“…However, looking at the same PCB (PCB 153) as Chu et al (1996b), Dervola et al (2015) studied gender-dependent monoaminergic changes induced by PCB153 in the rat brain and found changes in both the female and male brain with slightly more changes in the male brain. PCB-exposure led to increases in monoamine transmitter turnover in both male and female animals.…”

Section: Polychlorinated Biphenyls (Pcbs)mentioning

confidence: 99%

Developmental neurotoxicants and the vulnerable male brain: a systematic review of suspected neurotoxicants that disproportionally affect males

Kern¹,

Homme

King³

et al. 2017

Acta Neurobiologiae Experimentalis

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The prevalence of neurodevelopmental disorders (NDs), including autism spectrum disorder, attention-deficit/hyperactivity disorder, tic disorder, obsessive-compulsive disorder, and emotional disturbances, has increased notably in the past few decades.To date, debate continues as to the origins of NDs. Increases in widespread exposure to and bioaccumulation of chemical neurotoxicants have paralleled the upsurge in NDs, and are suggested to be causal agents for NDs. One consistent aspect of NDs is the male preponderance. This review considers the issue of male preponderance by reviewing the gender-specific neurotoxic effects of recognized neurotoxicant chemicals to assess their possible etiology in NDs. This investigation consisted of a systematic literature review of original studies published from 1970-2016 on suspected neurotoxicants, to examine whether they have a disproportionate adverse effect based on gender. Based on that review, the neurotoxicants exhibiting consistent gender-specific effects, with exposed males being more affected (than similarly exposed females), were: lead, Thimerosal/ethylmercury, some organochlorine pesticides (e.g., dieldrin, endosulfan, and heptachlor), and air pollution. The next group identified were neurotoxicants exhibiting gender-specific neurotoxic effects, with males being somewhat (but not consistently) more affected than females: mercury vapor, polychlorinated biphenyls (PCBs), and organophosphate pesticides. Finally, there was a group of studies in which the neurotoxicants exhibited apparent gender-related neurotoxic effects but failed to show whether exposed males were consistently more affected than females: inorganic mercury salts, methylmercury species, and certain endocrine disruptors (e.g., phthalates and BPA). The overall conclusion from the studies reviewed was that the brain in males is more vulnerable to many toxic exposures than it is in females. Evidence suggests that the reasons for the male brain being more vulnerable include:(1) greater glutathione availability in females; (2) greater sulfate-based detoxification capacity in females; (3) potentiating effects of co-exposure to neurotoxicants and testosterone; (4) greater neuroinflammatory response in males; (5) reduced vulnerability to oxidative stress in females; and (6) neuroprotective effects of female hormones (estrogen and progesterone), especially in the reduction of inflammation and oxidative stress.

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“…Experimental studies also have implicated multiple ortho-substituted PCB congeners in developmental neurotoxicity 48 . PCB153 induced neostriatal toxicity in adult WKY and SHR rats through changes in the monoaminergic but not amino acidergic neurotransmitter systems 49 . The effect of exposure of zebrafish larvae to a PCB mixture and Aroclor 1254 on neurodevelopment was also observed 50 .…”

Section: Discussionmentioning

confidence: 95%

Chiral PCB 91 and 149 Toxicity Testing in Embryo and Larvae (Danio rerio): Application of Targeted Metabolomics via UPLC-MS/MS

Chai

Cui

Yin

et al. 2016

Sci Rep

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In this study, we aimed to investigate the dysfunction of zebrafish embryos and larvae induced by rac-/(+)-/(−)- PCB91 and rac-/(−)-/(+)- PCB149. UPLC-MS/MS (Ultra-performance liquid chromatography coupled with mass spectrometry) was employed to perform targeted metabolomics analysis, including the quantification of 22 amino acids and the semi-quantitation of 22 other metabolites. Stereoselective changes in target metabolites were observed in embryos and larvae after exposure to chiral PCB91 and PCB149, respectively. In addition, statistical analyses, including PCA and PLS-DA, combined with targeted metabolomics were conducted to identify the characteristic metabolites and the affected pathways. Most of the unique metabolites in embryos and larvae after PCB91/149 exposure were amino acids, and the affected pathways for zebrafish in the developmental stage were metabolic pathways. The stereoselective effects of PCB91/149 on the metabolic pathways of zebrafish embryos and larvae suggest that chiral PCB91/149 exposure has stereoselective toxicity on the developmental stages of zebrafish.

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Gender-dependent and genotype-sensitive monoaminergic changes induced by polychlorinated biphenyl 153 in the rat brain

Cited by 13 publications

References 49 publications

Sex-Dependent Effects of 2,2′,3,5′,6-Pentachlorobiphenyl on Dendritic Arborization of Primary Mouse Neurons

Sex-Dependent Effects of 2,2′,3,5′,6-Pentachlorobiphenyl on Dendritic Arborization of Primary Mouse Neurons

Developmental neurotoxicants and the vulnerable male brain: a systematic review of suspected neurotoxicants that disproportionally affect males

Chiral PCB 91 and 149 Toxicity Testing in Embryo and Larvae (Danio rerio): Application of Targeted Metabolomics via UPLC-MS/MS

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