Behavioral changes following PCB 153 exposure in the Spontaneously Hypertensive rat – an animal model of Attention-Deficit/Hyperactivity disorder

Johansen, Espen Borgå; Fonnum, Frode; Lausund, Per Leines; Walaas, S. Ivar; Bærland, Nora Elise; Wøien, Grete; Sagvolden, Terje

doi:10.1186/1744-9081-10-1

Cited by 43 publications

(23 citation statements)

References 95 publications

(124 reference statements)

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“…Therefore, despite other recorded sex differences in SHR behavior (Berger and Sagvolden, 1998;Ferguson et al, 2003;Dervola et al, 2012;Johansen et al, 2014), increased responsiveness on an orienting task appears common to both sexes. It noteworthy that SHRs have been found to show reduced habituation (Hendley et al, 1985) and increased locomotor activity at some ages (Bayless et al, 2015) when compared to WKY and alterations in either of these could have confounded our results.…”

Section: Discussionmentioning

confidence: 76%

Altered visual processing in a rodent model of Attention-Deficit Hyperactivity Disorder

et al. 2015

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A central component of Attention-Deficit Hyperactivity Disorder (ADHD) is increased distractibility, which is linked to the superior colliculus (SC) in a range of species, including humans. Furthermore, there is now mounting evidence of altered collicular functioning in ADHD and it is proposed that a hyper-responsive SC could mediate the main symptoms of ADHD, including distractibility. In the present study we have provided a systematic characterization of the SC in the most commonly used and well-validated animal model of ADHD, the spontaneously hypertensive rat (SHR). We examined collicular-dependent orienting behavior, local field potential (LFP) and multiunit responses to visual stimuli in the anesthetized rat and morphological measures in the SHR in comparison to the Wistar Kyoto (WKY) and Wistar (WIS). We found that SHRs remain responsive to a repeated visual stimulus for more presentations than control strains and have a longer response duration. In addition, LFP and multiunit activity within the visually responsive superficial layers of the SC showed the SHR to have a hyper-responsive SC relative to control strains, which could not be explained by altered functioning of the retinocollicular pathway. Finally, examination of collicular volume, neuron and glia densities and glia:neuron ratio revealed that the SHR had a reduced ratio relative to the WKY which could explain the increased responsiveness. In conclusion, this study demonstrates strain-specific changes in the functioning and structure of the SC in the SHR, providing convergent evidence that the SC might be dysfunctional in ADHD.

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Section: Discussionmentioning

confidence: 76%

Altered visual processing in a rodent model of Attention-Deficit Hyperactivity Disorder

et al. 2015

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“…In a study by Johansen (2006), rats were exposed to PCB 153 three times between postnatal day (PND) 8 and 20, which is a period of major brain development. In rats, the growth spurt of the brain peaks around PND 7 and is largely completed by PND 20.…”

Section: Nervous Systemmentioning

confidence: 99%

The effect of maternal exposure to endocrine disrupting chemicals on fetal and neonatal development: A review on the major concerns

Mallozzi¹,

Bordi²,

Garo³

et al. 2016

Birth Defects Research Pt C

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There is a widespread exposure of general population, including pregnant women and developing fetuses, to the endocrine disrupting chemicals (EDCs). These chemicals have been reported to be present in urine, blood serum, breast milk, and amniotic fluid. Endocrine disruptions induced by environmental toxicants have placed a heavy burden on society, since environmental exposures during critical periods of development can permanently reprogram normal physiological responses, thereby increasing susceptibility to disease later in life-a process known as developmental reprogramming. During development, organogenesis and tissue differentiation occur through a continuous series of tightly-regulated and precisely-timed molecular, biochemical, and cellular events. Humans may encounter EDCs daily and during all stages of life, from conception and fetal development through adulthood and senescence. Nevertheless, prenatal and early postnatal windows are the most critical for proper development, due to rapid changes in system growth. Although there are still gaps in our knowledge, currently available data support the urgent need for health and environmental policies aimed at protecting the public and, in particular, the developing fetus and women of reproductive age. Birth Defects Research (Part C) 108:224-242, 2016. © 2016 Wiley Periodicals, Inc.

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“…Recent studies have reported effects of PCB 153 on the behavior of spontaneously hypertensive rats (SHRs) obtained from Charles River and the Wistar Kyoto (WKY) strain obtained from Harlan, UK, which are genetically related (DasBanerjee et al, 2008;Johansen et al, 2011Johansen et al, , 2014. At the present time, the SHRs appear to constitute the best validated animal model of ADHD, combined subtype .…”

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confidence: 96%

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

et al. 2015

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Polychlorinated biphenyls (PCBs) are present as ortho- and non-ortho-substituted PCBs, with most of the ortho-substituted congeners being neurotoxic. The present study examined effects of the ortho-substituted PCB 153 on dopamine, serotonin and amino acid neurotransmitters in the neostriatum of both male and female Wistar Kyoto (WKY) and spontaneously hypertensive rat (SHR) genotypes. PCB 153 exposure at p8, p14 and p20 had no effects on levels of these transmitters when examined at p55, but led to increased levels of both homovanillic acid and 5-hydroxyindoleacetic acid, the degradation products of dopamine and serotonin, respectively, in all groups except the female SHR. Immunoblotting showed that PCB exposure induced gender-specific decreases in dopaminergic synaptic proteins. These included a novel finding of decreased levels of the dopamine D5 receptor in both genders and genotypes, whereas male-specific changes included decreases in the postsynaptic density (PSD)-95 protein in the WKY and SHRs and a decrease in the presynaptic dopamine transporter in both the WKY and, less clearly in the male SHR. A female-specific tendency of increased vesicular monoamine transporter-2 was observed in the SHRs after PCB exposure. No changes were seen in tyrosine hydroxylase, the cytoskeletal neurotubulin or the plasma membrane marker Na(+)/K(+)-ATPase in any strain. Hence, PCB-exposure led to increases in monoamine transmitter turnover in both male and female animals, whereas decreases in both pre- and postsynaptic dopaminergic proteins were predominantly seen in male animals. PCB 153 may therefore induce neostriatal toxicity through both presynaptic and postsynaptic mechanisms in both genotypes and genders, including effects on the aspiny interneurons, which employ the D5 receptor to mediate dopamine effects on interneurons in the basal ganglia.

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Behavioral changes following PCB 153 exposure in the Spontaneously Hypertensive rat – an animal model of Attention-Deficit/Hyperactivity disorder

Cited by 43 publications

References 95 publications

Altered visual processing in a rodent model of Attention-Deficit Hyperactivity Disorder

Altered visual processing in a rodent model of Attention-Deficit Hyperactivity Disorder

The effect of maternal exposure to endocrine disrupting chemicals on fetal and neonatal development: A review on the major concerns

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

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