Chemical nature of attention deficit hyperactivity disorder (ADHD) - related chemical subfamily.

Endocrine disruptors have been subjected to health risk assessments. Bioassays and chemoinformatics are very useful tools to characterize their chemical nature. By performing rat hyperactivity assays, we screened some endocrine disruptors, resulting in the classification of two groups: hyperactivity-associated and hyperactivity-negative chemicals.

Neonatal rotenone lesions cause onset of hyperactivity during juvenile and adulthood in the rat.

Attention deficit hyperactivity disorder (ADHD) is characterized by behavioral and cognitive symptoms. Longitudinal studies demonstrated that the symptoms remains clinically significant for the majority of ADHD children into adulthood. Furthermore, a population-based birth cohort provided the initial evidence of adult ADHD that lacks a history of childhood ADHD.

Repulsive Apoptosis During Exposure of Mesencephalic Neural Stem Cells to Silver Nanoparticles in a Neurosphere Assay In Vitro.

Neurodevelopmental toxicity of silver nanoparticles (AgNPs) remains largely unknown. In this study, we applied a neurosphere assay for neurodevelopmental effects of AgNPs. The neural stem cells were isolated from rat mesencephalon.

Classification of phthalates based on an in vitro neurosphere assay using rat mesencephalic neural stem cells.

Exposure to environmental neurotoxic chemicals both in utero and during the early postnatal period can cause neurodevelopmental disorders. To evaluate the disruption of neurodevelopmental programming, we previously established an in vitro neurosphere assay system using rat mesencephalic neural stem cells that can be used to evaluate. Here, we extended the assay system to examine the neurodevelopmental toxicity of the endocrine disruptors butyl benzyl phthalate, di-n-butyl phthalate, dicyclohexyl phthalate, diethyl phthalate, di(2-ethyl hexyl) phthalate, di-n-pentyl phthalate, and dihexyl phthalate at a range of concentrations (0-100 μM).

Rat hyperactivity by bisphenol A, but not by its derivatives, 3-hydroxybisphenol A or bisphenol A 3,4-quinone.

Detoxification in the central nervous system is largely unknown. The mechanism of neurotoxicity of bisphenol A, a toxic environmental chemical remains obscure. We examined the effects of bisphenol A, and its derivatives, 3-hydroxybisphenol A and bisphenol A 3,4-quinone on rat behavior as possible metabolites of bisphenol A.

Neurotoxicity of endocrine disruptors: possible involvement in brain development and neurodegeneration.

Environmental chemicals that act as endocrine disruptors do not appear to pose a risk to human reproduction; however, their effects on the central nervous systems are less well understood. Animal studies suggested that maternal exposure to endocrine-disrupting chemicals (EDC) produced changes in rearing behavior, locomotion, anxiety, and learning/memory in offspring, as well as neuronal abnormalities. Some investigations suggested that EDC exert effects on central monoaminergic neurons, especially dopaminergic neurons.

Transcriptome of tributyltin-induced apoptosis of the cultured rat mesencephalic neural stem cells.

Exposure to environmental neurotoxic chemicals both in utero and during the early postnatal period can cause neurodevelopmental disorders. To evaluate the disruption of neurodevelopmental programming, we previously established an in vitro neurosphere assay system, using rat mesencephalic neural stem cells (mNSC). Here, we examined the developmental neurotoxicity of tributyltin (TBT) in an in vitro neurosphere assay.

Activation of STAT3 by pituitary adenylate cyclase-activating polypeptide (PACAP) during PACAP-promoted neurite outgrowth of PC12 cells.

Addition of pituitary adenylate cyclase-activating polypeptide (PACAP) into the cultured PC12 cells promoted neurite outgrowth of the cells, indicating cell differentiation. Using DNA macroarray techniques, we have characterized the PC12 cell transcriptome, revealing that several genes were regulated by PACAP. Among many, we focused to investigate whether STAT3 molecule, whose message was up-regulated, might be involved in PACAP signaling.

Inhibition by rotenone of mesencephalic neural stem-cell migration in a neurosphere assay in vitro.

Parkinson disease is an age-related neurodegenerative disorder. Although the underlying pathophysiological mechanisms are incompletely understood, it has been suggested that environmental origins of sporadic Parkinson disease occur early in life. Here we examined the in vitro effects of the environmental dopaminergic toxin rotenone on neural stem cells, derived from the rat E16 mesencephalon.

Mesencephalic neurodegeneration in the orally administered bisphenol A-caused hyperactive rats.

Since an emerging body of evidence is accumulating that endocrine disruptors exert their effects on the central nervous system, their neuronal risk assessment is now required. A previous study showed that a single intracisternal administration of bisphenol A, an endocrine disruptor, into neonatal rats caused hyperactivity. To evaluate the neural risk assessment of bisphenol A, it is very important to test the potential of the chemical via an environmental exposure route.

Behavioural characteristics and gene expression in the hyperactive wiggling (Wig) rat.

Recently, congenic wiggling (Wig) rats were described as a good model for attention-deficit hyperactivity disorder; 12- to 14-week-old animals demonstrated hyperactivity, impulsive behaviour and an impaired working memory. Here, we show that 4- to 5-week-old Wig rats displayed significantly greater spontaneous motor activity than control rats during a period of darkness. Subcutaneous injection of 4 mg/kg methamphetamine exacerbated hyperactivity, the reverse of its effect in rats with neonatally induced 6-hydroxydopamine lesions.

Melatonin inhibits maneb-induced aggregation of alpha-synuclein in rat pheochromocytoma cells.

Melatonin, a secretory product of the pineal gland, is involved in the regulation of circadian and seasonal rhythms, in oncostasis, and in inducing osteoblast differentiation. Furthermore, melatonin is a scavenger of a number of reactive oxygen and reactive nitrogen species both in vitro and in vivo. In this study, the antioxidant nature of melatonin was shown to prevent cultured neural cells from apoptosis induced by endocrine-disrupting chemical, maneb.

Region-dependent differences and alterations of protective thiol compound levels in cultured astrocytes and brain tissues.

We examined region-dependent differences and alterations in the levels of protective thiol compounds, glutathione (GSH) and metallothionein (MT)-I and -II, in cultured rat astrocytes under several culture conditions and in brain tissues of rats at postnatal and weaning periods. Regardless of culture conditions, both protein concentrations and mRNA expressions of MT-I and -II were much higher in the cerebral hemisphere than in cerebellar astrocytes, whereas no difference was observed in GSH concentration. In both astrocytes, the GSH concentrations did not change within 12 h but significantly increased 24 h after being maintained in a serum-free defined medium.

Transient inhibition of synergistically insulin-like growth factor-1- and bisphenol A-induced poliferation of estrogen receptor alpha (ERalpha)-positive human breast cancer MCF-7 cells by melatonin.

There are many subclones of human breast cancer MCF-7 cells that respond to different levels of estrogen and that have been used for evaluating the estrogenic potential of environmental chemicals such as bisphenol A. In this study, I examined the effects of melatonin, an endogenous growth-inhibitory hormone, on the bisphenol A-induced proliferation of an MCF-7 subclone, designated as MCF-7-EMF cells. MCF-7-EMF cell growth was extremely slow in the presence of either estrogen at 10(-7) M or bisphenol A at 10(-7) M in a phenol-red-free medium and 10% charcoal-stripped fetal bovine serum.

Alteration of gene expression of G protein-coupled receptors in endocrine disruptors-caused hyperactive rats.

We examined the effects of endocrine disruptors on rat behavioral and cellular responses. Single intracisternal administration of bisphenol A, p-octylphenol, nonylphenol, dibutylphthalate (DBP), dicyclohexylphthalate (DCHP), or diethylhexylphthalate (DEHP) into 5-day-old male Wistar rats caused significant hyperactivity at 4-5 weeks of age. It was about 1.

Overexpression of Bcl-2 inhibits nuclear localization of annexin I during tumor necrosis factor-alpha-mediated apoptosis in porcine renal LLC-PK1 cells.

The addition of tumor necrosis factor (TNF)-alpha into the cultured porcine kidney LLC-PK1 cells caused apoptosis concomitantly with caspase-3 activation and the inductions of an endogenous Bcl-2 protein. An SDS-polyacrylamide electrophoretic analysis revealed that a 37-kDa protein in a nuclear fraction was increased during TNF-alpha-induced apoptosis. Partial amino acid sequence of the protein was A-L-T-G-H-L-E-E-V, perfectly matching that of annexin I.

Motor hyperactivity caused by a deficit in dopaminergic neurons and the effects of endocrine disruptors: a study inspired by the physiological roles of PACAP in the brain.

Recent studies have revealed that the pituitary adenylate cyclase-activating polypeptide (PACAP) might act as a psychostimulant. Here we investigated the mechanisms underlying motor hyperactivity in patients with pervasive developmental disorders, such as autism, and attention-deficit hyperactivity disorder (ADHD). We studied the effects of intracisternal administration of 6-hydroxydopamine (6-OHDA) or endocrine disruptors (EDs) on spontaneous motor activity (SMA) and multiple gene expression in neonatal rats.

Transcriptome of pituitary adenylate cyclase-activating polypeptide-differentiated PC12 cells.

Addition of pituitary adenylate cyclase-activating polypeptide (PACAP) into the cultured PC12 cells secreted dopamine and promoted neurite outgrowth of the cells, indicating cell differentiation. To characterize the PACAP-differentiated PC12 cell transcriptome, we applied DNA macroarray techniques, using Atlas Rat 1.2 Array membranes (BD Biosciences Clontech) that have 1176 cDNA.

Dicyclohexylphthalate causes hyperactivity in the rat concomitantly with impairment of tyrosine hydroxylase immunoreactivity.

Endocrine disruptors possibly exert effects on neuronal functions leading, in particular, to behavioural alterations. In this study, we examined the effects of dicyclohexylphthalate (DCHP), an endocrine disruptor, on rat behavioural and cellular responses. Single intracisternal administration of DCHP (0.

Motor activity and gene expression in rats with neonatal 6-hydroxydopamine lesions.

A rat model of a hyperkinetic disorder was used to investigate the mechanisms underlying motor hyperactivity. Rats received an intracisternal injection of 6-hydroxydopamine on post-natal day 5. At 4 weeks of age, the animals showed significant motor hyperactivity during the dark phase, which was attenuated by methamphetamine injection.

Effects of neonatal treatment with 6-hydroxydopamine and endocrine disruptors on motor activity and gene expression in rats.

To investigate the mechanisms underlying motor hyperactivity, we performed intracisternal injection of 6-hydroxydopamine or endocrine disruptors in rats on postnatal day 5. 6-Hydroxydopamine (100 microg, 488 nmol) caused a significant increase in spontaneous motor activities at 4 weeks of age. Gene-expression profiling using a cDNA membrane array revealed alterations in several classes of gene at 8 weeks of age.

p-Nitrotoluene causes hyperactivity in the rat.

It has not been known which endocrine disruptors exert their effects on neuronal functions, particularly leading to behavioral alterations. To address this, we examined the effects of p-nitrotoluene, an endocrine disruptor, on rat behavior and gene expression. Single intracisternal administration of p-nitrotoluene (ca.

Bisphenol A causes hyperactivity in the rat concomitantly with impairment of tyrosine hydroxylase immunoreactivity.

We examined the effects of bisphenol A, an endocrine disruptor, on rat behavioral and cellular responses. Single intracisternal administration of bisphenol A (0.2-20 microg) into 5-day-old male Wistar rats caused significant hyperactivity at 4-5 weeks of age.

Effects of neonatal 6-hydroxydopamine lesion on the gene expression profile in young adult rats.

Patients with pervasive developmental disorders, including autism, and attention-deficit hyperactivity disorder show behavioral hyperactivity during childhood. We investigated the effects of a neonatal 6-hydroxydopamine lesion on multiple gene expression in the rat striatum and midbrain. Spontaneous motor activity was significantly increased at 4-5 weeks of age.