Prenatal Exposure to Paint Thinner Alters Postnatal Development and Behavior in Mice

Occupational exposure and sniffing of volatile organic solvents continue to be a worldwide health problem, raising the risk for teratogenic sequelae of maternal inhalant abuse. Real life exposures usually involve simultaneous exposures to multiple solvents, and almost all the abused solvents contain a mixture of two or more different volatile compounds. However, several studies examined the teratogenicity due to industrial exposure to a single volatile solvent but investigating the teratogenic potential of complex chemical mixture such as thinner remains unexplored. This study was undertaken to evaluate developmental neurotoxicity of paint thinner using a mouse model. Mated female mice (N = 21) were, therefore, exposed to repeated and brief inhalation episodes of 0, 300 or 600 ppm of thinner during the entire period of pregnancy. Females weigh was recorded and their standard fertility and reproductive parameters were assessed. After birth postnatal day 1 (PND1), offspring (N = 88) length and body weight were measured in a daily basis. At PND5, the pups were assessed for their postnatal growth, physical maturation, reflex development, neuromotor abilities, sensory function, activity level, anxiety, depression, learning and memory functions. At adulthood, structural changes of the hippocampus were examined by estimating the total volume of the dentate gyrus. Except one case of thinner induced abortion at the higher dose, our results showed that the prenatal exposure to the solvent did not cause any maternal toxicity or decrease in the viability of the offspring. Therefore, a lower birth weight, decrease in the litter size and delayed reflexes ontogeny were registered in prenatally exposed offspring to both 300 ppm and 600 ppm of thinner. In addition, prenatally exposure to thinner resulted in increased anxiolytic- and depression-like behaviors. In contrast, impaired learning and memory functions and decreased hippocampal dentate gyrus volume were revealed only in the prenatally treated offspring by 600 ppm of thinner. Based on these results, we can conclude that prenatally exposure to paint thinner causes a long-lasting developmental neurotoxicity and alters a wide range of behavioral functions in mice. This shows the risk that mothers who abuse thinner paint expose their offspring

Anti-inflammatory, Antinociceptive, and Antioxidant Activities of Methanol and Aqueous Extracts of Anacyclus pyrethrum Roots

Anacyclus pyrethrum (L.) is a plant widely used in Moroccan traditional medicine to treat inflammatory and painful diseases. The objective of the present study was to evaluate the antinociceptive, anti-inflammatory and antioxidant activities of aqueous and methanol extracts of Anacyclus pyrethrum roots (AEAPR and MEAPR). The anti-inflammatory effect of AEAPR and MEAPR was determined in xylene–induced ear edema and Complete Freund’s Adjuvant (CFA)-induced paw edema. The antinociceptive activity of AEAPR and MEAPR (125, 250, and 500 mg/kg) administered by gavage was examined in mice by using acetic acid-induced writhing, hot plate, and formalin tests, and the mechanical allodynia were assessed in CFA-induced paw edema. In addition, the in vitro antioxidant activities of the extracts were determined by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method, ferric reducing power and β-carotene-linoleic acid assay systems. AEAPR and MEAPR produced significant reductions in CFA-induced paw edema and xylene-induced ear edema. A single oral administration of these extracts at 250 and 500 mg/kg significantly reduced mechanical hypersensitivity induced by CFA, which had begun 1 h 30 after the treatment, and was maintained till 7 h. Chronic treatment with both extracts significantly reduced mechanical hypersensitivity in persistent pain conditions induced by CFA. Acute pretreatment with AEAPR or MEAPR at high dose caused a significant decrease in the number of abdominal writhes induced by acetic acid injection (52.2 and 56.7%, respectively), a marked increase of the paw withdrawal latency in the hot plate test, and also a significant inhibition of both phases of the formalin test. This antinociceptive effect was partially reversed by naloxone pretreatment in the hot plate and formalin tests. Additionally, a significant scavenging activity in DPPH, reducing power and protection capacity of β-carotene was observed in testing antioxidant assays. The present study suggests that AEAPR and MEAPR possess potent anti-inflammatory, antinociceptive and antioxidant effects which could be related to the presence of alkaloids and phenols in the plant. In addition, the antinociceptive effect of APR extracts seems to partly involve the opioid system. Taken together, these results suggest that Anacylcus pyrethrum may indeed be useful in the treatment of pain and inflammatory disorders in humans

Repeated cocaine exposure prior to fear conditioning induces persistency of PTSD-like symptoms and enhancement of hippocampal and amygdala cell density in male rats

International audiencePre- and post-trauma drug use can interfere with recovery from post-traumatic stress disorder (PTSD). However, the biological underpinnings of this interference are poorly understood. Here we examined the effect of pre-fear conditioning cocaine self-administration on PTSD-like symptoms in male rats, and defined impairment of fear extinction as difficulty to recover from PTSD. We also examined cell density changes in brain regions suspected of being involved in resistance to PTSD recovery. Before footshock stress testing, rats were trained to self-administer cocaine during 20 consecutive days, after which they were exposed to footshocks, while other rats continued to self-administer cocaine until the end of the experiment. Upon assessment of three PTSD-like symptoms (fear during situational reminders, anxiety-like behavior, and impairment of recognition memory) and fear extinction learning and memory, changes in cell density were measured in the medial prefrontal cortex, hippocampus, and amygdala. Results show that pre-footshock cocaine exposure did not affect fear during situational reminders. Fear conditioning did not lead to an increase in cocaine consumption. However, in footshock stressed rats, cocaine induced a reduction of anxiety-like behavior, an aggravation of recognition memory decline, and an impairment of extinction memory. These behavioral alterations were associated with increased cell density in the hippocampal CA1, CA2, and CA3 regions and basolateral amygdala, but not in the medial prefrontal cortex. Our findings suggest that enhancement of cell density in the hippocampus and amygdala may be changes associated with drug use, interfering with PTSD recovery

Anxiety and Gene Expression Enhancement in Mice Exposed to Glyphosate-Based Herbicide

Growing evidence demonstrates that serotonin (5-HT) depletion increases activity in the amygdala and medial prefrontal cortex (mPFC), ultimately leading to anxiety behavior. Previously, we showed that glyphosate-based herbicides (GBHs) increased anxiety levels and reduced the number of serotoninergic fibers within the mPFCs and amygdalas of exposed mice. However, the impact of this 5-HT depletion following GBH exposure on neuronal activity in these structures is still unknown. In this study, we investigated the effects of GBH on immediate early gene (IEG) activation within the mPFCs and amygdalas of treated mice from juvenile age to adulthood and its subsequent effects on anxiety levels. Mice were treated for subchronic (6 weeks) and chronic (12 weeks) periods with 250 or 500 mg/kg/day of GBH and subjected to behavioral testing using the open field and elevated plus maze paradigms. Then, we analyzed the expression levels of c-Fos and pCREB and established the molecular proxies of neuronal activation within the mPFC and the amygdala. Our data revealed that repeated exposure to GBH triggers anxiogenic behavior in exposed mice. Confocal microscopy investigations into the prelimbic/infralimbic regions of the mPFC and in basolateral/central nuclei of the amygdala disclosed that the behavioral alterations are paralleled by a robust increase in the density and labelling intensity of c-Fos- and pCREB-positive cells. Taken together, these data show that mice exposed to GBH display the hyperactivation of the mPFC–amygdala areas, suggesting that this is a potential mechanism underlying the anxiety-like phenotype

Fenugreek exposure decreased the frequency and the alternations of the locomotor like activity.

<p>(A) NMA ⁄ 5-HT induced locomotor like activity in control. The top and bottom traces represent the row and the integrated signals, respectively. Traces on the right represent the enlargement of the grey rectangle, the trace shows the alternation of motor bursts 10 minutes after the drugs application. (B) Fictive locomotion induced in control and treated mice. An alternating pattern was observed in both groups. (C) The graph shows the evolution of the left-right alternation during the 30 min of the NMA/5-HT exposure. Triangles and circles represent the evolution of the cross-correlation coefficient for treated and control mice, respectively. When this coefficient is positive the traces are in phase and when the coefficient is negative the traces are out of phase and the pattern is alternating. (D) The cross-correlation coefficient calculated for the opposite ventral roots (L2) calculated between the 20-30 minutes time window was more negative in control than in treated mice (Control: n = 7; treated: n = 7). (E) There was a non-significant trend towards less negative values for the cross-correlation coefficient calculated from the L2 (extensor) and L5 (flexor) ventral roots in prenatally treated mice compared with controls (Control: n = 4; treated: n = 3). (F) The period of locomotor-like activity is shorter in control compared with prenatally treated mice. Periods were compared during the 20-30 minutes time window. *P < 0.05.</p

Fenugreek exposure affected swimming performances.

<p>We scored the direction of swimming in A. (0; floating, 1; circling, 2; swimming straight or nearly straight, 3), the angle of the head in B (head submerged, 0; nose at the surface, 1; nose and top of head at or above the surface but ears still below the surface, 2; ears half way above the surface, 3; ears completely above the surface,4) and the use of paws in C (0; paddling with all four limbs, 1; paddling with only the hind limbs and the forelimbs remaining motionless, 2). Control mice had a higher performance compared with treated mice, (n = 6). *P < 0.05, **P < 0.01. </p