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The Effects of Biology Understanding the processes of normal brain development is a prerequisite for
understanding the influences of biological and environmental factors. At certain
stages in development, certain brain structures may be more vulnerable than
others to these factors. Research into these factors and their pathogenic mechanisms
is a crucial first step in designing interventions to prevent brain damage and
promote normal brain development. Genes play a major role in how the brain develops during the prenatal period and the first few months after birth. Scientists believe that one-half the entire human genome may be dedicated to the formation of the brain, which begins as a simple layer of cells and eventually includes as many as 10 billion brain cells called neurons, as well as billions of neuronal connections called synapses. Brain development occurs in overlapping phases. The first step is the formation of the primitive nervous system, the neural tube (NT). Closure of the NT takes place when the fetus is 21 to 26 days old. Neurons, which start to form before the neural tube closes and continue to form during the first year of life, differentiate according to structure and function. The large motor neurons form first, then the sensory neurons. Structures with complex layers of cells that are key to brain function, such as the cerebral cortex, hippocampus, and cerebellum, will add cells over a long period. The brain stem and diencephalon form early; the hippocampus, which serves memory function, is the only part of the brain in which neuron growth may continue into adulthood.
Other facets of early brain development include:
Interaction with the environment stimulates the creation of neural circuits -- the functional units of mental activity. In the newborn period, the brain also begins a pruning process to get rid of excess neurons and neuronal connections, and about half of the synapses present at age two years are eventually trimmed back. Usually this trimming removes unused neural connections..
Fragile X syndrome. Fragile X syndrome, the leading known cause of inherited mental retardation, occurs in approximately 1:1,200 males and 1:2,500 females. This syndrome is caused by a mutation in the FMR1 gene, located on the long arm of the X chromosome. The FMR1 gene codes for a protein whose exact function is an area of active investigation. Similar proteins often act on genes responsible for neuron function and migration. Individuals with fragile X syndrome, particularly males, show a significant degree of neuropsychological and communication dysfunction. Rett syndrome. Rett syndrome (RS), a genetically determined disorder, primarily affects brain growth in girls. Early development may be normal, followed by a period of regression with the loss of acquired hand use and speech by 3 years of age, precursors to severe mental retardation. Brain size and weight are markedly reduced from normal. Autism. We do not know the causes of autism; it appears to have multiple etiologies. The prevalence of autism is 4 to 5 per 10,000; its milder manifestation, pervasive developmental disorder (PDD), has a prevalence of about 8 to 10 per 10,000. MRI, CT, and PET imaging studies are being used to investigate anatomical and metabolic differences in autism; new research is looking at the immune system, embryology, and teratology. Primary brain malformations. A number of major malformations of the brain are seen in isolation, as well as with known genetic and chromosomal syndromes. The causes are probably multiple and overlapping. Recent research in molecular genetics has focused on looking for genetic markers associated with malformations. Environment and brain development Diabetes. Insulin-dependent diabetes mellitus poses a risk to the unborn child, and this risk may be increased if the diabetes is poorly controlled. The most common birth defects associated with diabetes include neural tube defects, other CNS defects, and congenital heart disease. Prevention is the best treatment; infants born to women whose diabetes is well-controlled during the first trimester appear to have a decreased risk of birth defects when compared to infants born to mothers whose diabetes is poorly controlled. Epilepsy. Maternal epilepsy is associated with a two- to threefold increase in birth defects. Fetal exposure to the anticonvulsants phenytoin and other hydantoins can cause fetal hydantoin syndrome (30% of exposed fetuses have anomalies; 10%,full syndrome). The anticonvulsant valproic acid has been associated with an increase in spina bifida; fetal carbamazepine exposure has also been implicated as a possible cause of increased rates of spina bifida. Hypoxia/ischemia. If a pregnant woman is oxygen-deprived for a significant time, or if the fetus is oxygen-starved for other reasons, damage to the brain of the unborn child can occur. Certain cells in the developing brain are more vulnerable to damage resulting from poor blood perfusion and low oxygen levels. Much of the damage appears to occur during the reoxygenation-reperfusion phase. Current research on the mechanisms of injury includes investigation of cell metabolism, enzyme activation, oxygen free radicals, and gene expression. Infection. The developing nervous system of the fetus is particularly sensitive to damage from a group of maternal infections known as TORCH infections: Toxoplasmosis, other (arbovirus, Coxsackie, mumps, HIV, mumps, parvovirus, varicella, syphilis), rubella (German measles), cytomegalovirus, and herpes. PKU. If a woman with PKU is not on a low phenylalanine diet during her pregnancy, there is a 90% chance that her child will be born with mental retardation due to fetal intrauterine exposure to high levels of phenylalanine. The best way to prevent this is for the mother to observe a strict, low phenylalanine diet prior to as well as during pregnancy. How environmental toxins affect the brain depends on developmental phase and the level of sensitivity in different regions of the brain. Ionizing radiation, such as x-rays or gamma rays, kill neurons that are being actively produced, but may have no impact on neurons made either before or after the exposure. Methylmercury, a toxic heavy metal, has the same effect. Because neurons usually are not replaced, cell loss is permanent. The loss of neurons can also interfere with normal neuronal cell migration. Toxins like lead, and conditions like malnutrition and hypothyroidism (low thyroid hormone levels), interfere with the development of synapses. Although new synapses can be made, interference with their development can block neurotransmitter signals at important stages in brain growth, and thus interfere with brain development. Pesticide and herbicide exposure are also thought to interfere with synapse formation and function. Medications. Current research reports that the average pregnant woman takes from 4 to 9 different medications during her pregnancy. While only a small number of medications have been identified as definitely teratogenic -- harmful to the fetus -- in humans, many drugs have never been tested. Some known teratogens are described below; for more information, see "Teratogens that Can Affect Brain Development." Alcohol. Alcohol is a known teratogen that has adverse effects on the development of multiple organ systems of the developing fetus, effects that persist throughout the individual's life. Autopsies of individuals with fetal alcohol syndrome (FAS) show such abnormalities as smaller than normal brain size and a deficit of neurons. The range of malformations suggests that alcohol may cause damage via multiple mechanisms. Cocaine. The recreational use of cocaine may also cause harm to the developing fetus. Infants born to women who abuse cocaine have had such brain abnormalities as cerebral infarction (stroke) and porencephaly. Toluene. Solvent abuse -- the "sniffing" of glue, paint, etc. -- is a practice followed by an estimated 3 to 4% of teenagers and young adults. Early research suggests that women who abuse solvents during pregnancy may bear children with abnormalities similar to those found in FAS. Promoting optimal development . Folic acid. Failure of neural tube closure produces neural tube defects (NTDs), most commonly anencephaly (absence of most of the brain) and spina bifida (a defect of the spine and spinal cord). Dietary supplementation with folic acid may prevent from 50% to 70% of this birth defect, but the mechanism is poorly understood. Because the neural tube closes by the 29th day after conception, folic acid is maximally effective if a woman begins taking it at least one month before conception occurs. The required dose, 0.4 mg per day, is found in many over-the-counter multivitamins. For women who have already had an affected pregnancy, the dose is higher: 4.0 mg per day. It is very important for women who take anticonvulsant medication to talk with their physicians about taking folic acid. Breast feeding. Recent studies show benefits in cognitive development when infants are breast fed, and a look at the structure of the brain helps to explain why. Approximately 60% of the material that makes up the brain is composed of lipids, a fatty material. Long-chain polyunsaturated fatty acids (LCPs) are an important component of lipids. Preliminary studies suggest that LCPs present in breast milk may play a critical role in the development of vision in newborns, and may contribute as well to cortical function and intellectual development. Certain fatty acids derived from LCPs may be absent or in short supply in certain formulas.
In conclusion, genetic influences play a substantial role in brain development. The high sensitivity of the brain to environmental influences during fetal and postnatal life is likewise a crucial factor. Every day, research into the molecular genetics, anatomy, and physiology of the brain adds to our understanding of how it functions; from this work will come new insights into how we, as health care providers, can best foster optimal brain development.
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