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The effects of perinatal exposure to low, intermediate, or highly polluted eels on neonatal, postnatal, adult and middle-aged brain inflammation, and on cognitive performances of middle-aged offspring mice were compared to those of offspring controls. Inflammatory markers in microglia were assessed in offspring on the postnatal days-PNDs 1, 21, 100 and 330. Activated p38MAPK, ERK-1/2 and p65, and acetylcholine levels were assessed in the middle-aged hippocampus. Plasma myeloperoxidase and corticosterone levels were evaluated at PND 330. Learning and its retention, and working memory in middle-aged offspring were assessed using the Morris water maze, and Y-maze. Our results showed enhanced microglia production of inflammatory markers across the lifespan of male as well as female exposed offspring. Inflammation and increased p38 MAPK activation were detected in the exposed middle-aged hippocampus of both exposed sexes. Significant levels of MPO, but not corticosterone, were found in middle-aged males and females perinatally exposed to eels. However, decreases in ERK1/2 and p65 activation, and acetylcholine levels were only detected in female hippocampus exposed to either intermediately or highly polluted eels. Sex selective effects were also detected with regard to memory, the only altered cognitive function. Thus, middle-aged females, but not males, perinatally exposed to either intermediately or highly polluted eels take longer to locate the escape platform, spend considerably less time in the platform and perform less visit to the platform in the retention test. Our results suggest perinatal programming of hippocampal-dependent memory deficit by inflammation in middle-aged offspring, in sex and dose dependent manner., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Several lines of evidence indicate that early-life inflammation may predispose to mental illness, including depression, in later-life. We investigated the impact of perinatal exposure to polluted eels on neonatal, postnatal, and adult brain inflammation, and on the resignation behavior of male and female adult offspring mice. The effects of maternal standard diet (laboratory food) were compared to the same diet enriched with low, intermediate, or highly polluted eels. Brain inflammatory markers including cytokines were assessed in offspring mice on the day of birth (i.e., on the postnatal day-PND 1), upon weaning (PND 21) and at adulthood (PND 100). Plasma myeloperoxidase and corticosterone levels were evaluated at PND 100. Immobility behavior of offspring was assessed in adulthood (i.e., at PNDs 95-100), using the tail suspension and forced swimming tests. Chronic brain inflammation was found in male and female offspring mice compared to controls, as assessed at PNDs 1, 21, and 100. The level of myeloperoxidase was found to be significantly higher in both adult males and females vs. control offspring. However, high corticosterone levels were only found in male offspring mice that were perinatally exposed to eels, suggesting a gender-selective dysregulation of the adult hypothalamic-pituitaryadrenal (HPA) axis. Gender-specific differences were also detected in adulthood in regard to offspring resignation behavior. Thus, compared to controls, males, but not females, whose mothers were fed eels during pregnancy and lactation exhibited a depressive-like behavior in adult age in both behavioral models of depression. Depressive symptoms were more pronounced in male mice perinatally exposed to either intermediate or highly polluted eels than those exposed to only lowly polluted eels. Our results indicate that early-life inflammatory insult is a plausible causative factor that induces the depressive phenotype exhibited by male adult offspring mice, most likely through a gender-specific HPA axis enhanced activation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In this study, the neurobehavioral toxicity of lactational exposure to a representative mixture of the six indicator non-dioxin-like-polychlorinated biphenyls (∑6 NDL-PCBs 28, 52, 101, 138, 153 and 180) found in contaminated fish matrices were assessed in neonatal (postnatal day 0) to adult (postnatal day 275) mice. Thus, a battery of developmental, behavioral and cognitive tests was performed. The performance of mice whose mothers were orally exposed to ∑6 NDL-PCBs at environmental doses of 1 ng/kg, 10 ng/kg or 100 ng/kg was compared to that of mice whose mothers were orally exposed to vehicle. Our results showed that neonatal offspring mice exposed to ∑6 NDL-PCBs through lactation exhibited significantly longer turning reflexes on postnatal days 7 and 9 (p=0.001, p=0.002, respectively) at 100 ng/kg and showed a reduction in their general activity at 1 ng/kg (p=0.002) and 10 ng/kg (p=0.001) compared to controls. However, these developmental alterations were sex-dependent; only the female reflexes and male locomotor activity were affected. These disturbances were transient, and they disappeared with age. In addition, the males' visuomotor integration was also altered at the doses of 1 ng/kg (p=0.02) and 100 ng/kg (p=0.004), as revealed by the WESPOC test. Nevertheless, lactational exposure to ∑6 NDL-PCBs (1-100 ng/kg) resulted in persistent disturbances despite a long post-weaning period; the exposed mice exhibited anxious behavior that was detected at more progressive life stages, i.e., at postnatal days 40 and 160, using an elevated plus maze and the light/dark choice test, respectively. This persistent anxious behavior could be related to the overexpression of RyR₃ in the cerebellum via the disruption of calcium signaling in the neurons. We found no differences in the offspring mice with regard to their cognitive function and mood or mRNA neurotransmitter receptor gene expression in several brain areas, including 5-HT(1A), MOR₁ and GABA(Aα1), suggesting the absence of adverse effects of postnatal exposure to ∑6 NDL-PCBs under these conditions. Therefore, our results suggest that regular consumption of contaminated fish matrices by lactating women could be detrimental to the neurodevelopment of their newborns., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Benzo[alpha]pyrene (B[alpha]P) is a neurotoxic pollutant which is also able to affect some behaviour and cognitive function. Here we report that a subacute oral exposure to B[alpha]P increases aggressiveness and affects copulatory behaviour in male mice. Indeed, after 3 weeks of exposure to B[alpha]P at 0.02 and 0.2mg/kg, we have observed that B[alpha]P 0.02 mg/kg-treated male mice are more aggressive than control mice in resident-intruder test because a significant decrease in the latency time of the first attack and a significant increase in the number of attacks in B[alpha]P 0.02 mg/kg-treated mice were found. On the other hand, we have found that subacute exposure (4 weeks) to B[alpha]P, does not affect the appetitive aspects and sexual motivation in copulatory behaviour because the latency to the first mount between control and B[alpha]P-treated male mice was not significantly different. We have nevertheless, surprisingly found that B[alpha]P (0.02-0.2)mg/kg-treated mice have performed significantly more sexual behavioural acts including mounting, intromission latency and intromission frequency than control mice. Although these last results suggest that B[alpha]P improves the consummatory aspects of sexual behaviour, we cannot conclude that this neurotoxic pollutant has advantage of sexual function because B[alpha]P has been shown to alter the monoaminergic neurotransmitter system and causes endocrine dysregulation via toxic effect.

The harmful effects of exposure to benzo[alpha]pyrene (B[alpha]P), which is a neurotoxic pollutant, on mammalian neurodevelopment and/or behaviour as yet remain widely unclear. In the present investigation, we evaluated the impact of the lactational exposure to B[alpha]P on postnatal development of pups and behaviour of young mice. The neurobiological effects of B[alpha]P during lactation were also evaluated on pups' brain. Here, we found that lactational exposure to B[alpha]P at 2 and 20mg/kg affects the neuromaturation of pups by significantly decreasing their reflex as highlighted in surface righting reflex and negative geotaxis tests. However, we noted a significant increase in muscular strength of lactationally B[alpha]P mg/kg-exposed pups, which was probably due to the impact of the exposure to this toxic compound on body weight gain. At the pup stage, lactational exposure to B[alpha]P also provoked a neurobiological change, which was assessed by determination of neuronal receptor gene expression. Indeed, a significant reduction in gene expression of 5HT(1A) receptors in pups exposed to B[alpha]P through lactation was found in comparison to controls. Additionally, attenuation in the expression of MOR(1) mRNA was observed, but statistically significant only in animals receiving the higher dose. Neither the expression levels of ADRA(1D) nor GABA(A) mRNA were altered. Interestingly, the harmful effects of lactational exposure to B[alpha]P on behaviour and cognitive function were still found despite a long post-weaning period. Young mice whose mothers were exposed to B[alpha]P displayed a disinhibition behaviour towards the aversive spaces of the elevated plus maze. Furthermore, a significant increase of spontaneous alternation in the Y-maze was observed, but only in young mice whose mothers were orally exposed to the lower dose of B[alpha]P. Our results suggest a close link between the neurobiological change highlighted in pups' brain and the different behavioural disturbances observed during postnatal development period until young adult stage.

Oxidative stress in central and peripheral systems is involved in many diseases, including cancer, cardiovascular diseases, neurodegenerative diseases and several psychiatric disorders. In the present study, the brain and peripheral oxidative status of non-anxious and anxious mice was evaluated using 2',7'-dichlorofluorescin diacetate (DCFH-DA), a sensor of reactive oxygen species (ROS). Here we report that anxiety levels are linked to the oxidative status in both neuronal and glial cells in the cerebellum and hippocampus, in neurons of the cerebral cortex and in peripheral leucocytes (monocytes, granulocytes and lymphocytes), revealing the presence of oxidative stress in the central and peripheral systems of anxious mice. These findings suggest the redox system in anxious mice may play a role in neuroinflammation and neurodegeneration, predisposing them to recurrent infections and chronic inflammation.

Background: Oxidative stress is linked to neurodegenerative diseases, cancer, cardiovascular diseases and to some behaviors, such as anxiety and depression. In particular, recent research observed a close relationship between oxidative stress and anxiety., Methods: We investigated the anxiolytic effect of chlorogenic acid, a dietary antioxidant present in fruits, in mouse models of anxiety including the light/dark test, the elevated plus maze and the free exploratory test. Moreover, the antioxidative effect of chlorogenic acid on peripheral blood granulocytes was investigated., Results: Chlorogenic acid (20 mg/kg) induced a decrease in anxiety-related behaviors suggesting an anxiolytic-like effect of this polyphenol. The anti-anxiety effect was blocked by flumazenil suggesting that anxiety is reduced by activation of the benzodiazepine receptor. In vitro, chlorogenic acid protected granulocytes from oxidative stress., Conclusions: Chlorogenic acid is one of the most abundant polyphenols in fruits. We demonstrated in vivo and in vitro for the first time, that chlorogenic acid has anxiolytic effects coupled with antioxidant activity. Thus, fruits such as plums (Mirabelle), apples and cherries may provide health-promoting advantages to consumers.