Prenatal brain development

The neurodevelopmental hypothesis of schizophrenia posits that the disorder is due to a subtle defect in prenatal brain development but is not clinically manifest until many years later (Murray and Lewis, 1987 Weinberger, 1987). This theory has two essential components a presumption of developmental neuropathology and an expectation that this developmental neuropathology results in a pattern of brain malfunction which ultimately produces the symptoms of schizophrenia. 

Neurodevelopmental models of schizophrenia have for the most part emphasized prenatal brain development, focusing on effects that may alter gene expression.15 For example, according to one idea, individuals with schizophrenia inherit genes that cause structural brain deviations that may be compounded by early environmental impact.16 Much of the focus of this hypothesis has been on postnatal impact, such as stress, that changes brain chemistry, but the idea can also accommodate a focus on prenatal impact. 

It is well known that the timing of brain development differs between species. In the human, maximum growth occurs at the time of parturition which is also the time of maximum growth of the pig brain (hence termed "perinatal brain developer"). In the rat and rabbit the maximum growth period is postnatal (termed "postnatal brain developer"). In the sheep and the monkey the maximum growth period is prenatal (termed "prenatal brain developer"). 

Brain development occurs in a complex series of events regulated by cellular and environmental interactions (Levitt, 1998). Most abused substances readily cross the placenta. Many are concentrated in the amniotic fluid and metabolized less efficiently by the fetus, exacerbating the teratogenic consequences of exposure. The effects of prenatal exposure to drugs of abuse... 

Levitt, P. (1998) Prenatal effects of drugs of abuse on brain development. Drug Alcohol Depend 51 109-125. 

FAS is now considered to be a leading cause of mental retardation in the general population. Figure 7.13 shows the comparison between brain growth spurt in humans and rats. It should be noted that brain development characterized by accelerated synaptogenesis, neuronal proliferation, and myelination commences prenatally during the third trimester in humans and continues into early postnatal life. 

It is also unclear what role the predicted DNA-PK site in dysbindin-1 may have in enabling or mediating its anti-apoptotic effect. As explained earlier (see Section 2.2.3.3.1), DNA-PK, which phosphorylates dysbindin-1 (Oyama et al., 2009), helps repair double-strand DNA breaks and suppresses apoptosis in developing and adult neurons (cf., Chechlacz et al., 2001, Culmsee et al., 2001, Vermuri et al., 2001, and Neema et al., 2005). Anti-apoptotic effects of DNA-PK on prenatal neurons (Vermuri et al., 2001) presumably have a major impact on brain development, especially given that the highest levels of DNA-PK are found in fetal tissue (Oka et al., 2000). It will thus be important to test if DNA-PK phosphorylation of nuclear dysbindin-1 in developing neurons contributes to the survival of those cells. 

Whitaker-Azmitia PM (2005) Behavioral and cellular consequences of increasing serotonergic activity during brain development a role in autism Int J Dev Neurosd 23 75-83 Whitaker-Azmitia PM, Lauder JM, Shemmer A, Azmitia EC (1987) Postnatal changes in serotonin receptors following prenatal alterations in serotonin levels further evidence for functional fetal serotonin receptors. Brain Res 430 285-289... 

Neural rosette formation and neural gene expression as endpoints for early brain development were studied in 9 days retinoic acid (RA) treated hESC-HUES-1-derived Neural Rosettes. RA regulated a variety of gene products involved in early brain development indicating that this in vitro test might be well suited for assessing prenatal developmental neural teratogenicity [110]. 

Most of these neurobehavioral effects presumably stemmed from changes in the development of several neurotransmitter systems caused by exposure to cannabinoids during critical prenatal and early postnatal periods of brain development. A large number of studies have demonstrated effects of cannabinoids on the maturation of dopamine (DA) (Fernandez-Ruiz et al. 1992, 1994, 1996 Walters and Carr 1988 Garcfa-Gil et al. 1998), serotonin (5-HT) (Molina-Holgado et al. 1997),... 

Altman J. and Bayer S. A. (1994) Atlas of Prenatal Rat Brain Development. CRC Press. 

Meanwhile, the plasticity of the cerebral cortex, its ability to have its connections shaped by experience, is one of its outstanding properties, and understanding its mechanisms makes possible an understanding of what governs the wiring of the brain. It also raises the implication that any prenatal impact that affects plasticity in the fetal brain can seriously wreck the brain development that occurs both before and after birth. 

We know that in the mature brain, neurotransmitters are released by nerve cell endings and act at synapses to mediate the interaction between nerve cells. There s now evidence that during the development of the prenatal brain, neurons can release transmitters before any connections are made, and that such released transmitters, acting as trophic factors, guide the formation of connections.17 Any environmental impact or mutation that affects the synthesis or release of neurotransmitters can be expected to have an effect on the development of the fetal brain. For example, during fetal development in Down syndrome, reductions apparently occur in the levels of various neurotransmitters. This may be one mechanism for the impaired brain development characteristic of this syndrome.18... 

Researchers argue about the effects of prenatal exposure to PCBs on brain development and later childhood cognitive performance. Some studies find effects and some don t. Some studies do not involve direct measurements of PCBs in blood but rely on surrogate (proxy) measurements, such as consumption of fish from contaminated waters. It s also difficult to locate a population in which fetuses have been exposed to PCBs but not to other toxins. It may be that cognitive effects are limited to certain kinds of brain-work not revealed by current tests. We don t know yet. But given all the evidence that exists about serious effects in animals and human adults, and given the general axiom that the human fetus is about a hundred times more vulnerable than adults to toxins, it s reasonable to say that the question of the effects of prenatal exposure to PCBs is not yet resolved. 

Each year in America, the national consumption of alcohol by women of child-bearing age adds approximately 100,000 more mentally retarded children to the population. How many more children not diagnosed as mentally retarded are affected by prenatal exposure to alcohol We know only that this exposure is related to atypical brain development, neuropsychological deficits, academic difficulties, emotional dysfunction, and social dysfunction.39 Is this constellation of problems acceptable collateral damage of the alcoholic beverages industry ... 

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