Impacts of prenatal nanomaterial exposure on male adult Sprague-Dawley rat behavior and cognition

ABSTRACT It is generally accepted that gestational xenobiotic exposures result in systemic consequences in the adult F1 generation. However, data on detailed behavioral and cognitive consequences remain limited. Using our whole-body nanoparticle inhalation facility, pregnant Sprague-Dawley rats (gestational day [GD] 7) were exposed 4 d/wk to either filtered air (control) or nano-titanium dioxide aerosols (nano-TiO2; count median aerodynamic diameter of 170.9 ± 6.4 nm, 10.4 ± 0.4 mg/m3, 5 h/d) for 7.8 ± 0.5 d of the remaining gestational period. All rats received their final exposure on GD 20 prior to delivery. The calculated daily maternal deposition was 13.9 ± 0.5 µg. Subsequently, at 5 mo of age, behavior and cognitive functions of these pups were evaluated employing a standard battery of locomotion, learning, and anxiety tests. These assessments revealed significant working impairments, especially under maximal mnemonic challenge, and possible deficits in initial motivation in male F1 adults. Evidence indicates that maternal engineered nanomaterial exposure during gestation produces psychological deficits that persist into adulthood in male rats.

[1]  R. Morris Developments of a water-maze procedure for studying spatial learning in the rat , 1984, Journal of Neuroscience Methods.

[2]  O. Steward,et al.  On the role of hippocampal connections in the performance of place and cue tasks: comparisons with damage to hippocampus. , 1984, Behavioral neuroscience.

[3]  B. Pike,et al.  The rotarod test: an evaluation of its effectiveness in assessing motor deficits following traumatic brain injury. , 1994, Journal of neurotrauma.

[4]  R. D'Hooge,et al.  Applications of the Morris water maze in the study of learning and memory , 2001, Brain Research Reviews.

[5]  Athina Markou,et al.  Assessing antidepressant activity in rodents: recent developments and future needs. , 2002, Trends in pharmacological sciences.

[6]  T. Azar,et al.  Stress-like responses to common procedures in male rats housed alone or with other rats. , 2002, Contemporary topics in laboratory animal science.

[7]  W. Kreyling,et al.  Translocation of Inhaled Ultrafine Particles to the Brain , 2004, Inhalation toxicology.

[8]  John Balbus,et al.  CHILDREN's SUSCEPTIBILITY TO CHEMICALS: A REVIEW BY DEVELOPMENTAL STAGE , 2004, Journal of toxicology and environmental health. Part B, Critical reviews.

[9]  D. Frazer,et al.  Nanoparticle Inhalation Impairs Endothelium-Dependent Vasodilation in Subepicardial Arterioles , 2009, Journal of toxicology and environmental health. Part A.

[10]  Qing Huang,et al.  Systematic influence induced by 3 nm titanium dioxide following intratracheal instillation of mice. , 2010, Journal of nanoscience and nanotechnology.

[11]  Håkan Wallin,et al.  Effects of prenatal exposure to surface-coated nanosized titanium dioxide (UV-Titan). A study in mice , 2010, Particle and Fibre Toxicology.

[12]  Ken Takeda,et al.  Effects of fetal exposure to carbon nanoparticles on reproductive function in male offspring. , 2010, Fertility and sterility.

[13]  Vincent Castranova,et al.  Toxicology of Nanomaterials Used in Nanomedicine , 2011, Journal of toxicology and environmental health. Part B, Critical reviews.

[14]  C. Conrad,et al.  Sex differences and phase of light cycle modify chronic stress effects on anxiety and depressive-like behavior , 2011, Behavioural Brain Research.

[15]  Jason J. Corneveaux,et al.  Tonic Premarin dose-dependently enhances memory, affects neurotrophin protein levels and alters gene expression in middle-aged rats , 2011, Neurobiology of Aging.

[16]  Håkan Wallin,et al.  Prenatal exposure to carbon black (printex 90): effects on sexual development and neurofunction. , 2011, Basic & clinical pharmacology & toxicology.

[17]  Pei-Shan Liu,et al.  Demonstration of an Olfactory Bulb–Brain Translocation Pathway for ZnO Nanoparticles in Rodent Cells In Vitro and In Vivo , 2012, Journal of Molecular Neuroscience.

[18]  P. Westerhoff,et al.  Titanium dioxide nanoparticles in food and personal care products. , 2012, Environmental science & technology.

[19]  J. Talboom,et al.  Continuous estrone treatment impairs spatial memory and does not impact number of basal forebrain cholinergic neurons in the surgically menopausal middle-aged rat , 2012, Hormones and Behavior.

[20]  D. Frazer,et al.  Whole-body nanoparticle aerosol inhalation exposures. , 2013, Journal of visualized experiments : JoVE.

[21]  T. Nurkiewicz,et al.  Maternal engineered nanomaterial exposure and fetal microvascular function: does the Barker hypothesis apply? , 2013, American journal of obstetrics and gynecology.

[22]  F. Cupaioli,et al.  Engineered nanoparticles. How brain friendly is this new guest? , 2014, Progress in Neurobiology.

[23]  Mahmoud Hosseini,et al.  Maternal exposure to titanium dioxide nanoparticles during pregnancy; impaired memory and decreased hippocampal cell proliferation in rat offspring. , 2014, Environmental toxicology and pharmacology.

[24]  Cheryl S Rosenfeld,et al.  Barnes maze testing strategies with small and large rodent models. , 2014, Journal of visualized experiments : JoVE.

[25]  Manuela Semmler-Behnke,et al.  Supplementary information Size dependent translocation and fetal accumulation of gold nanoparticles from maternal blood in the rat , 2014 .

[26]  T. Nurkiewicz,et al.  Maternal nanomaterial exposure: a double threat to maternal uterine health and fetal development? , 2014, Nanomedicine.

[27]  Yonghua Cui,et al.  Prenatal exposure to nanoparticulate titanium dioxide enhances depressive-like behaviors in adult rats. , 2014, Chemosphere.

[28]  Aldert H Piersma,et al.  A perspective on the developmental toxicity of inhaled nanoparticles. , 2015, Reproductive toxicology.

[29]  K. Takeda,et al.  In utero exposure of mice to diesel exhaust particles affects spatial learning and memory with reduced N-methyl-D-aspartate receptor expression in the hippocampus of male offspring. , 2015, Neurotoxicology.

[30]  Vincent Castranova,et al.  INHALATION EXPOSURE TO CARBON NANOTUBES (CNT) AND CARBON NANOFIBERS (CNF): METHODOLOGY AND DOSIMETRY , 2015, Journal of toxicology and environmental health. Part B, Critical reviews.

[31]  T. Nurkiewicz,et al.  Microvascular and mitochondrial dysfunction in the female F1 generation after gestational TiO2 nanoparticle exposure , 2015, Nanotoxicology.

[32]  J. Zelikoff,et al.  Effects of Maternal Exposure to Cadmium Oxide Nanoparticles During Pregnancy on Maternal and Offspring Kidney Injury Markers Using a Murine Model , 2015, Journal of toxicology and environmental health. Part A.