Effects of lactational exposure to benzo[α]pyrene (B[α]P) on postnatal neurodevelopment, neuronal receptor gene expression and behaviour in mice

Bouayed, Jaouad; Desor, Frédéric; Rammal, Hassan; Kiemer, Alexandra K.; Tybl, Elisabeth; Schroeder, Henri; Rychen, Guido; Soulimani, Rachid

doi:10.1016/j.tox.2009.02.010

Cited by 74 publications

(56 citation statements)

References 47 publications

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“…These indicators suggested sub-chronic exposure to B(a)P also induced significant impairment on the function of LM. Our results were in agreement with previous studies (Bouayed et al 2009;Grova et al, 2007).…”

Section: Discussionsupporting

confidence: 94%

New candidate proteins for Benzo(a)pyrene-induced spatial learning and memory deficits

et al. 2011

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-Spatial learning and memory (LM) is a property of central importance in the nervous system, yet many of the molecular mechanisms for benzo(a)pyrene[B(a)P]-induced LM deficits remain enshrouded in mystery. In this study, influence of exposure to B(a)P on LM deficits in adult male SpragueDawley rats was evaluated by Morris water maze. Then morphological changes in the ultramicrostructure of hippocampal neurons were observed by transmission electron microscopy. Furthermore, to better understand the molecular changes that occur in B(a)P induced LM deficits, antibody-based protein microarrays was used to analyze protein expression changes in rats submitted to sub-chronic oral gavage of B(a)P (2 mg/kg for 90 days). Results suggested that rats in the B(a)P-treated groups have significantly impaired Morris water maze performance when compared to controls. Meanwhile, the B(a)P-induced neuronal damage was also found in the hippocampus under transmission electron microscopy. Our results demonstrate that LM deficits associated protein expression signatures could be identified from tissue proteomes, as well as potential biomarkers such as retinoic acid receptor b (RARb), synaptotagmin iosfomrs 1 (Syt1) and Brain-derived neurotrophic factor (BDNF), previously not found. This study, therefore, identifies, for the first time, multiple novel proteins that are dysregulated by B(a)P, which both enhance our understanding of B(a)P induced LM deficits and represent targets of novel therapeutics.

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Section: Discussionsupporting

confidence: 94%

New candidate proteins for Benzo(a)pyrene-induced spatial learning and memory deficits

et al. 2011

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“…The MWM is a classical method for studying the learning, memory, spatial orientation and cognitive ability of mice. Our findings have revealed that the escape latency increases while the number of crossing platform and time spent in target quadrant is decreased by B(a)P as compared to control groups, indicating that the spatial memory is impaired in the rats exposed to B(a)P. These results are in agreement with Bouayed [26] who has reported that B(a)P exposure induces the impairments in the behavioral function of neonatal rats. Our data also reflects that the neurotoxic effects of B(a)P are restricted to 0.2 mg/kg and 2 mg/kg of B(a)P. Adenosine triphosphatase, a protease on the biofilm, exists in the histiocyte and organelle membranes and plays an important role in the substance transportation, energy conversion and information transmission [27].…”

Section: Atpase Activitysupporting

confidence: 92%

Effects of benzo(a)pyrene exposure on the atpase activity and calcium concentration in the hippocampus of neonatal rats

Yang

Chen

Cheng

et al. 2017

Int J Occup Med Environ Health

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Objectives: To investigate whether postnatal benzo(a)pyrene (B(a)P) exposure caused the impairments on the process of neurodevelopment and the alteration in the calcium medium in the neonatal rats. Material and Methods: Eighty neonatal Sprague Dawley (SD) rats were randomly divided into 5 groups (untreated control group, vehicle group, 0.02 mg/kg, 0.2 mg/kg and 2 mg/kg B(a)P-exposed group). Rats were treated with B(a)P by the intragastric administration from postnatal day (PND) 4 to 25. Morris water maze (MWM) was employed to observe the spatial memory of rats. The activity of calcium adenosine triphosphatase (Ca 2+ -ATPase), sodium-potassium adenosine triphosphatase (Na + -K + -ATPase) and calcium-magnesium adenosine triphosphatase (Ca 2+ -Mg 2+ -ATPase) in the hippocampus were detected by commercial kits. Fura-2 pentakis(acetoxymethyl) (Fura-2/AM) probe and reactive oxygen species (ROS) reagent kit were used for measuring the concentration of Ca 2+ and ROS in the hippocampus synapse, respectively. Results: Rats exposed to B(a)P resulted in the deficits in the spatial memory manifested by the increased escape latency and decreased number of crossing platform and time spent in target quadrant in comparison with the control groups. Benzo(a)pyrene exposure caused the significant decrease in the ATPase activity in the hippocampus and caused Ca 2+ overload in the synaptic, besides, the ROS concentration increased significantly which may further induce neurobehavioral impairment of the neonatal rats. Conclusions: Our findings suggest that postnatal B(a)P exposure may cause the neurobehavioral impairments in the neonatal rats, which were mediated by the decreased ATPase activity and elevated Ca 2+ concentration. Int J Occup Med Environ Health 2017;30(2):203-211

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“…Experiments and quantification were performed as previously described [22] . Primer sequences are listed in Table 2.…”

Section: Real-time Reverse Transcription-polymerase Chain Reactionmentioning

confidence: 99%

Elevated free cholesterol in a p62 overexpression model of non-alcoholic steatohepatitis

Simon

Kessler

Gemperlein

et al. 2014

WJG

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AIM:To characterize how insulin-like growth factor 2 (IGF2 ) mRNA binding protein p62/IMP2-2 promotes steatohepatitis in the absence of dietary cholesterol. METHODS:Non-alcoholic steatohepatitis (NASH) was induced in wild-type mice and in mice overexpressing p62 specifically in the liver by feeding the mice a methionine and choline deficient (MCD) diet for either two or four weeks. As a control, animals were fed a methionine and choline supplemented diet. Serum triglycerides, cholesterol, glucose, aspartate aminotransferase and alanine transaminase were determined by standard analytical techniques. Hepatic gene expression was determined by real-time reverse transcription-polymerase chain reaction. Generation of reactive oxygen species in liver tissue was quantified as thiobarbituric acid reactive substances using a photometric assay and malondialdehyde as a standard. Tissue fatty acid profiles and cholesterol levels were analyzed by gas chromatographymass spectrometry after hydrolysis. Hepatocellular iron accumulation was determined by Prussian blue staining in paraffin-embedded formalin-fixed tissue. Filipin staining on frozen liver tissue was used to quantify hepatic free cholesterol levels. Additionally, nuclear localization of the nuclear factor kappa B (NF-κB) subunit p65 was examined in frozen tissues. RESULTS:Liver-specific overexpression of the insulin-like growth factor 2 mRNA binding protein 2-2 (IGF2BP2-2/IMP2-2/p62) induces steatosis with regular chow and amplifies NASH-induced fibrosis in the MCD mouse model. Activation of NF-κB and expression of NF-κB target genes suggested an increased inflammatory response in p62 transgenic animals. Analysis of hepatic lipid composition revealed an elevation of monounsaturated fatty acids as well as increased hepatic cholesterol. Moreover, serum cholesterol was significantly elevated in p62 transgenic mice. Dietary cholesterol represents a critical factor for the development of NASH from hepatic steatosis. Filipin staining revealed increased free cholesterol in p62 transgenic livers, which were not diet-derived. The mRNA levels of the rate-limiting enzyme for cholesterol synthesis 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase or HMGCR) were not significantly upregulated, potentially due to increased cholesterol biosynthesis via elevated sterol regulatory element binding transcription factor 2 (SREBF2 ) gene expression and increased iron deposition in transgenic animals. CONCLUSION:This study provides evidence that p62/IGF2BP2-2 drives the progression of NASH through elevation of hepatic iron deposition and increased production of hepatic free cholesterol.

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Effects of lactational exposure to benzo[α]pyrene (B[α]P) on postnatal neurodevelopment, neuronal receptor gene expression and behaviour in mice

Cited by 74 publications

References 47 publications

New candidate proteins for Benzo(a)pyrene-induced spatial learning and memory deficits

New candidate proteins for Benzo(a)pyrene-induced spatial learning and memory deficits

Effects of benzo(a)pyrene exposure on the atpase activity and calcium concentration in the hippocampus of neonatal rats

Elevated free cholesterol in a p62 overexpression model of non-alcoholic steatohepatitis

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