Vulnerability of synapses in the frontal cortex of mice developmentally exposed to an insecticide: Potential contribution to neuropsychiatric disease. - PubMed - NCBI

Increasingly, exposure to various chemicals found in our environment has
been found to be a significant contributor to the risk of developing
neurological disease, such as Parkinson disease, autism spectrum
disorder, as well as other deficits in thought and function. Exposure to
these compounds during critical periods of neurodevelopment,
encompassing exposures that occur in utero, during infancy,
childhood, and adolescence, represents a time period of nervous system
growth that is uniquely vulnerable to disruption by environmental
chemicals. Indeed, a contemporary hypothesis suggests that the
pathological cascade associated with many common neurological disorders
has its origin in disturbances of normal neurodevelopment. Moreover,
alterations to the ontogeny of the synapse and neurotransmitter
signaling during neurodevelopment may be a premier pathological event
that underlies neuropsychiatric and neurodegenerative disease. To
interrogate the impact of exposure to a ubiquitous environmental
chemical, the pesticide, endosulfan, on development of neurotransmitter
circuits, we coupled in vitro and in vivo platforms to
evaluate its effect on the formation of GABAergic, glutamatergic, and
dopaminergic pathways in the frontal cortex. With this approach we found
exposure of cortical neurons, in vitro, exhibited a marked
reduction in the length of their neurite process as well as the number
of synaptic connections. Further investigation using an in vivo
model of developmental exposure identified significant alterations to
pre and postsynaptic proteins involved in neurotransmitter handling and
signaling in each of the neurotransmitter systems investigated. These
findings suggest that exposure to endosulfan during vulnerable periods
of neurodevelopment can alter the normal development and potential
function of neurotransmission in the frontal cortex. Interestingly, the
alterations identified in our study closely mimic the pathological
markers associated with schizophrenia, which shows disturbances in
synaptic proteins important for GABAergic, glutamatergic, and
dopaminergic signaling in the frontal cortex. These findings provide
important support for the impact of exposure to environmental chemicals
during neurodevelopment and risk for neurological disease.

Opinion: Toxicants and the Brain | The Scientist Magazine®

The recent US and European BRAIN initiative do not  identify brain development as a key area of research, nor the possible effects of environmental toxicants on brain health.

This is a shame. A wealth of research shows that metals, pesticides, solvents, and other chemicals can seriously impede brain development in children. So far, we have identified about a dozen chemicals that can harm brain development in children and result in lasting deficits and disease, and there are more than 200 additional substances, the majority commonly present in the environment, that are known to be neurotoxic in adults, but for which we have little or no evidence for the effects on brain development. Furthermore, animal models suggest that brain toxicity during early development may lead to degenerative brain disease, such as Parkinson’s and autism, later in life. We need to understand better the causation and emergence of brain diseases as a result of toxic chemicals.

Molecular Psychiatry - : The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner

Bacterial colonisation of the intestine has a major role in the post-natal development and maturation of the immune and endocrine systems. These processes are key factors underpinning central nervous system (CNS) signalling. Regulation of the microbiome–gut–brain axis is essential for maintaining homeostasis, including that of the CNS. However, there is a paucity of data pertaining to the influence of microbiome on the serotonergic system. Germ-free (GF) animals represent an effective preclinical tool to investigate such phenomena. Here we show that male GF animals have a significant elevation in the hippocampal concentration of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid, its main metabolite, compared with conventionally colonised control animals. Moreover, this alteration is sex specific in contrast with the immunological and neuroendocrine effects which are evident in both sexes. Concentrations of tryptophan, the precursor of serotonin, are increased in the plasma of male GF animals, suggesting a humoral route through which the microbiota can influence CNS serotonergic neurotransmission. Interestingly, colonisation of the GF animals post weaning is insufficient to reverse the CNS neurochemical consequences in adulthood of an absent microbiota in early life despite the peripheral availability of tryptophan being restored to baseline values. In addition, reduced anxiety in GF animals is also normalised following restoration of the intestinal microbiota. These results demonstrate that CNS neurotransmission can be profoundly disturbed by the absence of a normal gut microbiota and that this aberrant neurochemical, but not behavioural, profile is resistant to restoration of a normal gut flora in later life.

Cognitive Deficits and Behavior Problems in Children with Prenatal Polybrominated diphenyl ethers Exposure

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are persistent chemicals that were widely used as flame retardants in furniture, carpet padding, car seats and other consumer products during the past three decades. Little is known about the impact of prenatal PBDE exposures on children's intellectual abilities or behavioral problems.
OBJECTIVE: To investigate the association between prenatal exposure to PBDEs and child neurodevelopment.
DESIGN/METHODS: We measured maternal serum concentrations of BDE-47 and the sum of 4 PBDE chemicals (-47, -99, -100, -153) in 301 women at 16 weeks of gestation and followed their children annually until 5 years of age in the HOME Study in Cincinnati, OH. We examined the associations with children's cognitive and motor abilities using the Bayley Scales of Infant Development-II at ages 1, 2, 3 years, and intelligence using the Wechsler Preschool and Primary Scale of Intelligence-III at age 5 years. We also investigated the association with children's behaviors using the Behavioral Assessment System for Children-2 at ages 2, 3, 4, and 5 years. We used linear mixed models with adjustment for maternal age, race, education, marital status, serum cotinine, IQ, blood lead, depression score, household income, child sex, and the HOME Inventory, a measure of the nurturing environment of the home. 
RESULTS: Prenatal exposure to BDE-47 and sum₄BDEs was associated with cognitive deficits at 2, 3, and 5 years; the deficits were larger in older children. The geometric mean of sum₄BDEs was 37 ng/g lipid, with BDE-47 at 20 ng/g lipid, comparable to US national average in the 2003-2004. For a 10-fold increase in BDE-47 there was a -4.6 decrement in Bayley Mental Development Index (95% CI=-8.4, -0.8) at age 3 and a -7.5 decrement in Wechsler Full Scale IQ (95% CI=-11.9, -3.1) at 5 years. Prenatal BDE-47 and sum₄BDEs exposure was also associated with an increase in hyperactivity symptoms. A ten-fold increase in BDE-47 was associated with 2.4 increment (95% CI=0.1, 4.6) in hyperactivity score.
CONCLUSIONS: Prenatal exposure to PBDEs, a group of flame retardants that are detectable in virtually all US children, was strongly associated with cognitive deficits and hyperactivity behaviors in children.

Effect of Intestinal Microbial Ecology on the Developing Brain

The mammalian gastrointestinal tract harbors a highly diverse microbial population that plays a major role in nutrition, metabolism, protection against pathogens, and development of the immune system. It is estimated that at least 1000 different bacterial species cohabit the human intestinal tract. Most recently, the Human Microbiome Project, using new genomic technologies, has started a catalog of specific microbiome composition and its correlation with health and specific diseases. Herein we provide a brief review of the intestinal microbiome, with a focus on new studies showing that there is an important link between the microbes that inhabit the intestinal tract and the developing brain. With future research, an understanding of this link may help us to treat various neurobehavioral problems such as autism, schizophrenia, and anxiety.

Genes for autism and schizophrenia only active in developing brains

"Genes linked to autism and schizophrenia are only switched on during the early stages of brain development, according to a study in mice led by researchers at the University of Oxford."

Low Levels Of Common Flame-Retardant Chemical Damages Brain Cells

Finding may have implications for autism

A common ingredient in flame retardants, BDE-49 accumulates in human blood, fat and breast milk. Despite these concentrations, little research has been done on the chemical's potential health risks. However, a study by scientists at the UC Davis MIND Institute is shedding new light on BDE-49's potential danger to brain health. The study showed that even tiny amounts of the compound damage neural mitochondria, the energy plants that power our cells. The chemical, quite literally, reduces brain power. 

BPA's real threat may be after it has metabolized: Chemical found in many plastics linked to multiple health threats

 "In recent years, numerous studies have reported alarming associations between BPA exposure and myriad adverse health and development effects, from cancer and neurological disorders to physiological defects and, perhaps, a cause of childhood obesity."

NIH-supported study shows how immune cells change wiring of the developing mouse brain, May 23, 2012 News Release - National Institutes of Health (NIH)

Researchers have shown in mice how immune cells in the brain target and remove unused connections between brain cells during normal development. This research, supported by the National Institutes of Health, sheds light on how brain activity influences brain development, and highlights the newly found importance of the immune system in how the brain is wired, as well as how the brain forms new connections throughout life in response to change.
Disease-fighting cells in the brain, known as microglia, can prune the billions of tiny connections (or synapses) between neurons, the brain cells that transmit information through electric and chemical signals.