Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 3 de 3
Filter
Add more filters










Database
Language
Publication year range
1.
Sci Rep ; 7(1): 4934, 2017 07 10.
Article in English | MEDLINE | ID: mdl-28694481

ABSTRACT

Fetal alcohol spectrum disorders (FASD) constitute a wide range of disorders that arise from prenatal exposure to ethanol (EtOH). However, detailed reports regarding the adverse effects of prenatal EtOH exposure on neocortical morphology and its underlying pathogenic mechanisms are limited. In the present study, we aimed to characterize the anatomical abnormalities of neocortical development and their correlation with microglial properties and neuro-inflammation in a mouse model of FASD. We evaluated the development and maturation of the neocortex in ICR mice prenatally exposed to 25% (w/v) EtOH using histological and molecular analyses. Reduced proliferation and excessive cell death were observed in the dorsal telencephalon. Abnormal neuronal distribution, layer formation, and dopaminergic neuronal projections were observed in the neocortex. Disruption of microglial differentiation (M1/M2 microglial ratio) and abnormal expression of pro-inflammatory and neurotrophic factors were induced, and these abnormalities were ameliorated by co-treatment with an anti-inflammatory drug (pioglitazone). FASD model mice displayed histological abnormalities, microglial abnormalities, and neuro-inflammation in both the embryonic and newborn stages. Thus, anti-inflammatory therapeutics may provide a novel preventive approach for the treatment of FASD.


Subject(s)
Ethanol/adverse effects , Neocortex/drug effects , Neocortex/metabolism , Neurogenesis/drug effects , Prenatal Exposure Delayed Effects , Animals , Cell Proliferation/drug effects , Cell Survival/drug effects , Cytokines/metabolism , Dopaminergic Neurons/drug effects , Dopaminergic Neurons/metabolism , Female , Fetal Alcohol Spectrum Disorders/etiology , Fetal Alcohol Spectrum Disorders/metabolism , Fetal Alcohol Spectrum Disorders/pathology , Inflammation/etiology , Inflammation/metabolism , Inflammation/pathology , Inflammation Mediators/metabolism , Mice , Microglia/drug effects , Microglia/metabolism , Neocortex/pathology , Neurodevelopmental Disorders/etiology , Neurodevelopmental Disorders/metabolism , Neurodevelopmental Disorders/pathology , Neurons/drug effects , Neurons/metabolism , Pregnancy , Signal Transduction
2.
Toxicology ; 323: 51-60, 2014 Sep 02.
Article in English | MEDLINE | ID: mdl-24953688

ABSTRACT

The central nervous system is especially susceptible to toxic insults during development. Prenatal administration of bisphenol A (BPA) induces histologic anomalies in the dorsal telencephalon of the embryo. Whether these anomalies affect the morphogenesis and maturation of neuronal function of the newborn neocortex, however, is unknown. To evaluate the neurodevelopmental and behavioral effects of prenatal BPA exposure at 20 and 200µg/kg/day in newborn mice, we performed a detailed histologic analysis of the neocortex and tested for the presence of behavioral abnormalities in newborn mice prenatally exposed to BPA using our newly developed behavioral test. Observations of newborn mice prenatally exposed to BPA revealed abnormal neuronal distribution and layer formation, hypoplasia of layer 6b, and abnormal dopaminergic neuronal projections in the neocortex. Further, the newborn mice exhibited hyperactivity. These findings suggest that prenatal BPA exposure induces neurobehavioral toxicity associated with abnormal dopaminergic neuronal projections, and abnormal corticogenesis and lamination. Histologic and behavioral analyses of newborn mice are considered useful for assessing the neurodevelopmental and behavioral toxicity of chemicals.


Subject(s)
Benzhydryl Compounds/toxicity , Estrogens, Non-Steroidal/toxicity , Hyperkinesis/chemically induced , Neocortex/drug effects , Phenols/toxicity , Prenatal Exposure Delayed Effects , Animals , Animals, Newborn , Behavior, Animal/drug effects , Dopaminergic Neurons/drug effects , Female , Maternal-Fetal Exchange , Mice , Mice, Inbred ICR , Neocortex/abnormalities , Pregnancy
3.
J Toxicol Sci ; 39(2): 231-5, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24646703

ABSTRACT

There have been few neurobehavioral toxicology studies on newborn animals. Thus, we developed a mouse newborn behavioral testing method for evaluating the risk of neurotoxicity of environmental toxicants, by means of determining the newborn's motor activity applying the tare function of an analytical balance. Motor activities including crawling, pivoting, righting or tremors of mouse newborns were evaluated. Tremors of newborns of dams exposed to bisphenol A at 2, 20 or 200 µg/kg/day on days 5 through 18 of gestation were significantly increased when evaluated on postnatal day 1, as well as those of newborns exposed prenatally to diethylstilbestrol at 0.5 µg/kg/day. We suggest that our developed testing method may provide a useful addition to neurobehavioral assessment in very young rodents exposed to environmental hormone mimics.


Subject(s)
Behavior, Animal/drug effects , Benzhydryl Compounds/toxicity , Endocrine Disruptors/toxicity , Maternal Exposure/adverse effects , Maternal-Fetal Exchange , Motor Activity/drug effects , Phenols/toxicity , Prenatal Exposure Delayed Effects/chemically induced , Animals , Animals, Newborn , Benzhydryl Compounds/administration & dosage , Benzhydryl Compounds/metabolism , Endocrine Disruptors/administration & dosage , Endocrine Disruptors/metabolism , Female , Gestational Age , Male , Mice , Mice, Inbred ICR , Phenols/administration & dosage , Phenols/metabolism , Pregnancy , Tremor/chemically induced
SELECTION OF CITATIONS
SEARCH DETAIL
...