Book 2 Listening (1108796), страница 11
Текст из файла (страница 11)
They might beused to study, in ways that would be unethical in a living human being or impossible even ina mouse, the crucial early stages of brain development, and how they can go wrong. Theycould be employed to test drugs in ways that mere cell cultures cannot be. And because they46can be made, if needed, from the cells of living people, they might even illuminate theparticular problems of individual patients.To make an organoid, Dr Lancaster’s team start, as they describe in an article inNature, with what is known as an embryoid body. Just as an organoid has some features ofan organ without truly being one, so an embryoid body has some features of an embryowithout actually being one. Embryoid bodies can be grown either from natural stem cells themselves derived ultimately from real embryos - or from what are known as inducedpluripotent cells, which are made from adult cells (usually skin cells) that have been treatedwith four crucial biochemical factors which cause them to forget their identity and behave likeembryonic cells.Embryos have three layers: endoderm, mesoderm and ectoderm.
Each turns into aneclectic mixture of body parts in the complete organism. Nervous systems grow from theectoderm (which also contributes dental enamel and the skin’s epidermis, among otherthings), so the team put ectodermal cells into droplets of gel and then floated the droplets in anutrient broth in a gently rotating bioreactor (which allowed the cells to grow without beingshaped by the constraint of a vessel such as a Petri dish) to see what would happen.Though the result may not look much like a brain to a layman, to an expert theresemblance is remarkable. After ten days the organoid has developed neurons. After 30days it has regions recognizably similar to some of those in a real brain. And though,because they lack the blood supply of a real brain, organoids never grow much bigger than4mm across, they live a long time.
Some are now a year old and still going strong.Real brains consist in large measure of layers of neurons called the cortex. Thissurrounds fluid-filled spaces known as ventricles. That is more or less the anatomy of anorganoid. Many of them also contain areas which look like choroid plexuses. These areplaces that absorb nutrients from the bloodstream and dump waste into it. They alsogenerate the cerebrospinal fluid that fills ventricles. Signs of other structures turn up too.The various lobes of a real brain sport different mixtures of neurons. The team seesigns of this in the organoids. They found evidence of retinas (the back of the eye is anoutgrowth of the brain), of meninges (the membranes that surround the brain) and ofhippocampal cells (the hippocampus is a part of the brain which is crucial for memoryformation).
The organoids, then, look as though they are making a fair _st of trying to becomereal brains.Script 13.2 Growing model brains. Part II.So the method clearly works. The next question was whether the team could doanything useful with it. And they could. They were able to realise one of the desiderata ofstem-cell science and investigate the condition of a particular individual who hasmicrocephaly.Microcephaly, as its name suggests, is a developmental condition in which someone’sbrain fails to grow as much as it should.
The consequence is that his head is small and hesuffers a range of debilitating symptoms. Microcephaly is hard to study in a laboratorybecause tinkering in mice with the genes that cause it in people does not replicate theseverity of the condition. The team therefore wondered if they would have more luck bygrowing an organoid derived from their patient’s skin.
And they did.First, the organoid actually grew, proving the method works with induced cells as well asnatural ones. Second, it showed that what seems to be going wrong in microcephaly is thatthe process of development is running too fast. Neurons differentiate more rapidly than theyshould. And once that has happened, the brain’s growth slows down.This is no help to the patient.
No one thinks microcephaly can be reversed. But if it werebetter understood, it might be prevented _as might a host of other neurological problemswhose roots lie in the brain’s early development. Schizophrenia and autism, for example, areboth suspected of being caused by mistakes in the migration of developing nerve cellsthrough the early embryonic brain. Dr Lancaster hopes the group will be able to model theseprocesses in the future.47Dr Lancaster’s organoids, then, would seem to have a bright future, helping scientistsunderstand both how the brain works and what has gone wrong when it doesn’t.
Smallthough they are, they could be the start of something very big indeed. (From The Economist,August 31, 2013)Script 14.1 Genes and intelligence. Part I.The 3% solutionA potent source of genetic variation in cognitive ability has just been discovered.People are living longer, which is good. But old age often brings a decline in mentalfaculties and many researchers are looking for ways to slow or halt such decline. One groupdoing so is led by Dena Dubal of the University of California, San Francisco, and LennartMucke of the Gladstone Institutes, also in San Francisco.
Dr Dubal and Dr Mucke have beenstudying the role in ageing of klotho, a protein encoded by a gene called KL. A particularversion of this gene, KL-VS, promotes longevity. One way it does so is by reducing agerelated heart disease. Dr Dubal and Dr Mucke wondered if it might have similar powers overage-related cognitive decline.What they found was startling. KL-VS did not curb decline, but it did boost cognitivefaculties regardless of a person’s age by the equivalent of about six IQ points.
If this result,just published in Cell Reports, is confirmed, KL-VS will be the most important genetic agentof non-pathological variation in intelligence yet discovered.Dr Dubal and Dr Mucke made their discovery when they looked at 220 volunteers aged52 to 85, to study the effects of KL-VS on ageing. They assessed their volunteers’ faculties ofmemory, attention, visuo-spatial awareness and language. From these, they constructed acomposite measure of cognition.That measure suggested people with a VS version of the KL gene in their chromosomeshad better cognition than those without one.
When they analysed data collected by two othergroups who work independently on KL-VS they discovered these researchers had found thesame thing. That comparison brought the number of people examined to 718, a fifth of whomwere possessors of KL-VS.
The six-point IQ gap is an extrapolation, since the cognitive testsdid not measure general intelligence directly. But if it is correct, variation in the KL gene couldaccount for as much as 3% of the variation of IQ in the general population (or, rather, in thepopulation from which the researchers’ sampleswere drawn, namely white Americans).In comparison, the previous record holders, HMGA2 and NPTN, each account for onlyhalf a percent of that variation.Script 14.2 Genes and intelligence.
Part II.This sort of result, it must be cautioned, has a tendency to come and go. The genomehas so many genes in it that flukey correlations between one of them and some human traitare common. But there are two reasons to believe this is not a fluke. One is that these threeindependent studies have found it. The second is that Dr Dubal and Dr Mucke did not rest ontheir laurels, but did some experiments on mice to investigate KL-VS’s actions.To do this they added the murine equivalent of KL-VS to the genomes of some mice.Doing this increases klotho levels in mice (an effect also seen in KL-VS-positive people).
Thegenetically engineered animals did much better than regular mice at learning how to navigatemazes and other memory tests which psychologists like to inflict on their subjects. Andanalysis of their brain tissue revealed differences from regular mice in the structure of theirsynapses, the junctions between nerve cells that act as neural switches.Signals cross synapses in chemical form. The most common messenger chemical,known as glutamate, is picked up by the receiving cell using molecules called NMDAreceptors. It is known from previous work that glutamate stimulation of NMDA, or the lack ofit, can strengthen or weaken synaptic connections.
This is believed to be the basis ofmemory.The team’s genetic engineering changed the nature of the NMDA receptors in themice’s hippocampuses and frontal cortices—two regions of the brain particularly involved in48memory formation—by doubling in them the number of a particular sort of molecular subunit,GluN2B. Previous research has found links between GluN2B levels and cognitiveperformance.Dr Dubal and Dr Mucke discovered that blocking GluN2B with a drug called ifenprodilabolished the genetically engineered mice’s advantage.
That suggests klotho works itsmagic, at least in part, by increasing the number of GluN2B subunits in the NMDA receptorsof the brain’s memory and learning circuits.Dr Dubal and Dr Mucke hope, despite their failure to show any protective effect of KLVS on age-related cognitive decline, that this knowledge may be put to use. A drug thatelevates klotho levels, or mimics that protein’s function, might indeed enhance cognition, andthere is no obvious reason why such a drug should be restricted to the elderly. If it could bedeveloped everyone—except, maybe, those already in possession of a copy of KL-VS in theirgenes—might be able to take pills to make themselves a little brighter.
(From The Economist,May 10, 2014)49Unit 7. SleepScript 15. Children's intellectual developmentBedtime storiesRegular sleeping hours really are good for children-if they are girlsIn that mythical era when children were seen and not heard, and did as they were toldwithout argument, everyone knew that regular bedtimes were important. "Dream on!" mostmodern parents might reply. But research by Yvonne Kelly of University College, London,shows that the ancient wisdom is right - half the time. Daughters, it seems, do benefit fromregular bedtimes. Sons do not.Dr Kelly knew of many studies that had looked at the connection between sleep habitsand cognitive ability in adults and adolescents.
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