Лекция 15 Развитие головного мозга
Спецификация клеток зародышевых листков у млекопитающих
Гаструляция зародыша млекопитающего (Gilbert, 2003).
Эмбриональное развитие головного мозга
Образование мозговых пузырей In the chick embryo brain volume expands 30-fold between days 3 and 5 development. It appears, as the neurula folds close in the region between presumptive brain and presumptive spinal cord, the surrounding dorsal tissues push in to constrict the neural tube at the base of the brain and cause its swelling (Gilbert, 2000)
Ранний морфогенез головного мозга (замыкание нервной трубки) (Gilbert, 2003)
Сравнение структур головного мозга позвоночных Forebrain Midbrain Hindbrain Embryonic Shark Goose Human
Эмбрион человека
Similar across species is due to phyletic constraints on the evolution on new structures. Similarity is expanding on basic nervous developmental modules.
Regional specification of anteror (rostral) part of neural tube (Gilbert, 2003)
Gilbert, 2003
Рост нервной трубки (птицы) (Gilbert, 2003)
«Дни рождения» нейронов и их последующая миграция определяют слои коры головного мозга (Gilbert, 2003)
Миграция нефронов вдоль отростков радиальной глии в развитии мозжечка, гиппокампа и коры (Gilbert, 2003) In vitro migration of hippocampal neurons along the process of astroglia cells from the cerebellum. Neurons can migrate along a variety of radial glia fibers. Migrating neurons are apposed to glia cells, which guide them from the ventri- cular zone to their final destination.
(Gilbert, 2003)
Коммитирование нейронов при образовании слоев в мозжечке (Gilbert, 2003)
Кора головного мозга The lobes of the cerebral cortex include the frontal (blue), temporal (green), occipital (red), and parietal lobes (yellow). The cerebellum (unlabeled) is not part of the telencephalon.
Гиппокамп The hippocampus is a part of the forebrain, located in the medial temporal lobe. It belongs to the limbic system and plays major roles in short term memory and spatial navigation. Humans and other mammals have two hippocampi, one in each side of the brain. In rodents, where it has been studied most extensively, the hippocampus is shaped something like a banana. In humans it has a curved and convoluted shape that reminded early anatomists of a seahorse. The name, in fact, derives from the Greek word for deahorde (Greek: ιππος, hippos = horse, καμπος, kampos = sea monster).
Локализация гиппокампа в коре головного мозга Гиппокампы локализованы в пересечении осей (зелёным) Гиппокампы локализованы в срединной части височной доли коры (красным)
Функции Hyppocampal olfactory responses Role in General Memory Role in spatial memory and navigation
The limbic system (or Paleomammalian brain) is a set of brain structures including the hippocampus, amygdala, anterior thalamic nuclei, and limbic cortex, which support a variety of functions including emotion, behavior, long term memory, and jlfaction. The term "limbic" comes from Latin limbus, meaning "border" or "belt".
The limbic system includes many structures in the cerebral cortex and sub- cortex of the brain. The term has been used within psychiatry and neurology, although its exact role and definition has been revised considerably since the term was introduced. The limbic system is embryologically older than other parts of the brain. It developed to manage 'fight' or 'flight' chemicals and is an evolutionary necessity for reptilies as well as humans. Recent studies of the limbic system of tetrapods have challenged some long-held tenets of forebrain evolution. The common ancestors of reptiles and mammals had a well-developed limbic system in which the basic subdivisions and connections of the amygdalar nuclei were established.
Промежуточный мозг (Diencephalon) The diencephalon is the part of the forebrain that contains such important structures as the thalamus,hypothalamus and the posterior portion of the pituitary gland. The hypothalamus performs numerous vital functions, most of which relate directly or indirectly to the regulation of visceral activities by way of other brain regions and the autonomic nervous system.
Diencephalon The diencephalon (or interbrain) is the region of the brain that includes the thalamus, hypothalamus, epithalamus, prethalamus or subthalamus and pretectum. The diencephalon is located at the midline of the brain, above the mesencephalon of the brain stem. The diencephalon contains the zona limitans intrathalamica as morphological boundary and signalling center between the prethalamus and the thalamus.
Средний мозг -Mesencephalon (Midbrain) In biological anatomy, the mesencephalon (or midbrain) comprises the tectum (or corpora quadrigemini), tegmentum, the ventricular mesocoelia (or "iter"), and the cerebral peduncles, as well as several nuclei and fasciculi. Caudally the mesencephalon adjoins the pons (metencephalon) and rostrally it adjoins the diencephalon (Thalamus, hypothalamus, et al). The human mesencephalon is archipallian in origin, meaning its general architecture is shared with the most ancient of vertebrates. Dopamine produced in the substantia nigra plays a role in motivation and habituation of species from humans to the most elementary animals such as insects.
Mesencephalon During development, the mesencephalon forms from the middle of three vesicles that arise from the neural tube to generate the brain. In mature human brains, the mesencephalon becomes the least differentiated, from both its developmental form and within its own structure, among the three vesicles. The mesencephalon is considered part of the brain stem. Its substantia nigra is closely associated with motor system pathways of the basal ganglia.
Средний мозг The optic tectum or simply tectum is a paired structure that forms a major component of the vertebrate midbrain. In mammals this structure is more commonly called the superior colliculus (Latin, higher hill), but even in mammals, the adjective tectal is commonly used. The tectum is a layered structure, with a number of layers that varies by species. The superficial layers are sensory-related, and receive input from the eyes as well as other sensory systems.The deep layers are motor-related, capable of activating eye movements as well as other responses. There are also intermediate layers, with mixed sensory and motor properties
Tectum Section through superior colliculus (unlabeled) showing path of oculomotor nerve
Средний мозг In some non-mammal species, including fish and birds, the tectum is one of the largest components of the brain. In mammals, and especially primates, the massive expansion of the cerebral cortex reduces the tectum ("superior colliculus") to a much smaller fraction of the whole brain. Even there, though, it remains functionally very important as the primary integrating center for eye movements.
Задний мозг The rhombencephalon (or hindbrain) is a developmental categorization of portions of the central nervous system in vertebrates. The rhombencephalon can be subdivided in a variable number of transversal swellings called rhombomeres. In the human embryo we can distinguish eight rhombomeres, from caudal to rostral: Rh7-Rh1 and the isthmus (the most rostral rhombomere). A rare disease of the rhombencephalon, "rhombencephalosynapsis" is characterized by a missing vermis resulting in a fused cerebellum. Patients generally present with cerebellar ataxia. The caudal rhombencephalon has been generally considered as the initiation site for neural tube closure
В заднем мозге (rhombencephalon) первые нейроны появляются в чётных ромбомерах (Gilbert, 2003).
Задний мозг (Metencephalon) Rhombomeres Rh3-Rh1 form the metencephalon. The metencephalon is composed of the pons and the cerebellum; it contains: a portion of the fourth ventricle, the trigeminal nerve (CN V), abducens nerve (CN VI), facial nerve (CN VII), and a portion of the vestibulocochlear nerve (CN VIII).
Мозжечок The cerebellum (Latin for little brain) is a region of the brain that plays an important role in the integration of sensory perception, coordination and motor control. In order to coordinate motor control, there are many neural pathways linking the cerebellum with the cerebral motor cortex (which sends information to the muscles causing them to move) and the spinocerebellar tract (which provides proprioceptive feedback on the position of the body in space). The cerebellum integrates these pathways, like a train conductor, using the constant feedback on body position to fine-tune motor movements.
Мозжечок Human brain, with the cerebellum in purple
Мозжечок The cerebellum is of archipalliar phylogenetic origin. The pallium is a term for gray matter that forms the cortex. The archipallium is one of the most evolutionarily primitive brain regions. The circuits in the cerebellar cortex look similar across all classes of vertebrates, including fish, reptiles, birds, and mammals. This has been taken as evidence that the cerebellum performs functions important to all vertebrate species.
Мозжечок During the early stages of embryonic development, the brain starts to form in three distinct segments: the prosoencephalon, mesencephalon, and rhomboencephalon. The rhombencephalon is the most caudal (toward the tail) segment of the embryonic brain; it is from this segment that the cerebellum develops. Along the embryonic rhombencephalic segment develop eight swellings, called rhombomeres. The cerebellum arises from two rhombomeres located in the alar plate of the neural tube, a structure that eventually forms the brain and spinal cord. The specific rhombomeres from which the cerebellum forms are rhombomere 1 (Rh.1) caudally (near the tail) and the "isthmus" rostrally (near the front).
Мозжечок Two primary regions are thought to give rise to the neurons that make up the cerebellum. The first region is the ventricular zone in the roof of the fourth ventricle. This area produces Purkinje cells and deep cerebellar nuclear neurons. These cells are the primary output neurons of the cerebellar cortex and cerebellum. The second germinal zone (cellular birthplace) is known as the Rhombic lip, neurons then move by embryonic week 27 to the external granular layer. This layer of cellsfound on the exterior the cerebellumproduces the granule neurons. The granule neurons migrate from this exterior layer to form an inner layer known as the internal granule layer. The external granular layer ceases to exist in the mature cerebellum, leaving only granule cells in the internal granule layer. The cerebellar white matter may be a third germinal zone in the cerebellum; however, its function as a germinal zone is controversial.
Изменения паттернов экспрессии Hox-генов изменяют спецификацию клеток нервного гребня (Gilbert, 2003)
Gilbert, 2000
Дефекты мозга зародышей с разрушенным геном Sonic hedgehog (Gilbert, 2000)
Индукция передних районов мозга прехордальной пластинкой The forebrain and midbrain regions are defined by the underlying prechordal mesoderm and anterior notochord. Two genes that are expressed in these anterior mesodermal tissues are Lim1 and Otx2. If either one is missing, the embryo does not form a forebrain or midbrain
Schematic representation of the alterations in the Pax2/5 compound mutant mouse. In the wild-type neural plate, expression of Pax6 (red) and Pax2 and 5 (blue) delimit three domains - the prosencephalon (PROS), mesencephalon/myelencephalon (MSE/MET) and hindbrain (MY). In the Pax2/5 double mutant, the middle subdivison is absent, its only remnant being a small ventral region (light blue) that expresses engrailed-2 and corresponds to the basal region of the metencephalon. (After Schwarz et al; 1999.)
Rubenstein and Puelles (1994) have proposed that the forebrain is composed of six neuromeric regions called prosomeres. Prosomeres p1-p3 comprise the diencephalon, whereas prosomeres p4-p6 comprise the hypothalamus (ventrally) and the telencephalon (dorsally). The prosomeric boundaries coincide with the expression boundaries of several genes that are thought to be important in neural specification. They are also seen to be the boundaries that limit the responses to certain external stimuli. The p2/p3 boundary may be critical in patterning the forebrain region. This boundary corresponds to the zona limitans. It is also a source of Sonic hedgehog, a diffusible protein known to induce patterning during gastrulation and limb formation
Neuromeric structure of the brain with the hypothetical inductive events superpositioned on them. (A) The mesencephalon/metencephalon boundary is positive for both Fgf8 and Wnt1 gene expression. The p2/p3 border is thought to be the source of sonic hedgehog protein. (B) In situ hybridization of a 3-day chick embryo for Fgf8 expression. One of the major areas of expression can be seen at what will become the boundary between the midbrain and hindbrain. (A- After Bally-Cuif and Wassef, 1995; B - After E. Laufer, C-Y. Yeo, and C. Tabin.
У человека 1. Сохранение скорости роста нейронов плода после рождения. 2. Миграция клеток из переднего мозга в промежуточный. 3. Активность транскрипции. 4. Специфическая форма гена FOXP2. 5. Продолжение процесса созревания мозга во взрослом состоянии
Сохранение нейронами младенца человека скорости роста, характерной для плода (до 12 месяцев) (Gilbert, 2003)
У человека миграция клеток конечного мозга в промежуточный мозг (Gilbert, 2003)
Нейральные стволовые клетки у взрослого человека (Gilbert, 2003)
Особенности развития среднего мозга One of the critical regions for midbrain development is the metencephalon/mesencephalon border that will normally give rise to the tissues of the isthmus. No morphological boundary can be seen here, but it is marked by the most posterior portion of Otx2 gene expression. When mid-to-anterior mesencephalon tissue is transplanted to the diencephalon or rhombencephalon, it induces the cells surrounding it to develop mesencephalonic fates (in the diencephalon) or cerebellar fates (in the rhombencephalon) (Bally-Cuif and Wassef, 1994; Marin and Puelles, 1994). When rotated, a "triplication" can ensue, since tissues on both sides of the graft are induced
Присутствие клеток среднего мозга в мозжечке. The presence of mesencephalon cells in the cerebellum was shown by replacing chick mesencephalon with the corresponding region from the quail. (A) Summary drawing of the distribution of quail (red triangle) and chick (green triangle) Purkinje cells and quail (red circles) and chick (green circles) ventricular epithelial cells. The Purkinje cells overlie a ventricular epithelium of the same species type. III and IV indicate the third and fourth ventricles, respectively. Is is the isthmus. (B) Derivatives of the brain vesicles, seen schematically from the dorsal surface (A from Hallonet et al., 1990; B after Hallonet and Le Douarin, 1993)
The mesencephalon/metencephalon ("mes/met") junction region can act as an inducer of midbrain development and engrailed expression when rotated or transplanted to other regions of the brain. (A) Transplantation of the mes/met junction results in the induction of engrailed gene expression and midbrain and cerebellar structures in ectopic positions. (B) Rotation of the mes/met junction causes "triplications" of certain structures, such as the optic tectum. Abbreviations: gt, griseum tectale; TS, torus semicircularis; P1, pretectal segment; P2, dorsal thalamic segment; cb, cerebellum; ot, optic tectum; ist, isthmus; III, third cranial, or oculomotor, nerve; IV, fourth cranial, or trochlear, nerve. The postulated polarity is represented by arrows. (B after Rubenstein and Puelles, 1994.
Индуцирующие свойства пограничных отделов головного мозга This mes/met-inducing region appears to be controlled by fibroblast growth factor 8 (FGF8). Crossley and colleagues (1996) found that this isthmus-forming tissue secreted FGF8. Moreover, when they transplanted FGF8-containing beads into the diencephalon or rhombencephalon, they obtained the same duplicated midbrain structures. Control beads soaked in saline did not show any such duplications. The FGF8 beads also induced the expression of three genes in the surrounding tissues–Wnt1, Engrailed-2, and Fgf8 itself. These three genes are normally expressed in the isthmus region. Wnt1 and Engrailed are known to be important in the formation of the cerebellum. Even though the cerebellum does not express Wnt1 genes, mice deficient in Wnt1 lack their midbrain regions as well as the cerebellum (McMahon and Bradley, 1990; Thomas and Cappecchi, 1990). Wnt1 appears to maintain Engrailed gene expression in the cerebellar precursor cells, enabling the cells to proliferate (Dickinson et al., 1994; Danielian and McMahon, 1996).
Гематоэнцефалический барьер В представлениях о гематоэнцефалическом барьере в качестве основных положений подчеркивается следующее: 1) проникновение веществ в мозг осуществляется главным образом не через ликворные пути, а через кровеносную систему на уровне капилляр нервная клетка; 2) гематоэнцефалический барьер является в большей степени не анатомическим образованием, а функциональным понятием, характеризующим определенный физиологический механизм. Как лю бой существующий в организме физиологический механизм, гематоэнцефалический барьер находится под регулирующим влиянием нервной и гуморальной систем; 3) среди управляющих гематоэнцефалическим барьером факторов ведущим является уровень деятельности и метаболизма нервной ткани
Гематоэнцефалический барьер
Нейроны, глия, внеклеточное пространство и кровь
ЦНС защищена от резких изменений внешней среды гематоэнцефалическим барьером. Гематоэнцефалический барьер - полупроницаемый барьер между кровью и нервной тканью, препятствующий проникновению в мозг крупных или полярных молекул, а также клеток крови, в том числе иммунной системы. Плотные контакты между клетками эндотелия капилляров ЦНС препятствуют выходу лейкоцитов, микроорганизмов и даже макромолекул в субарахноидальное пространство. У некоторых микробов выработались высокоспециализированные механизмы (пока малоизученные) преодоления этого барьера. Известно, что вирусы бешенства и ыирцсы простого герпеса (у человека) и реовирус (у экспериментальных животных) попадают в ЦНС, передвигаясь по нервам, а инкапсулированные бактерии и грибы обладают поверхностными компонентами, позволяющими им проходить через гематоэнцефалический барьер. Таким образом, механизмы преодоления гематоэнцефалического барьера высокоспециализированы. Так, они имеются лишь у определенных серотипов возбудителей, способных вызывать менингит. Менингит новорожденных, например, вызывают только те Streptococcus agalactiae, которые относятся к серотипу III. Другие серотипы тоже патогенны, но вызывают инфекционные процессы вне ЦНС. Такая избирательность, видимо, определяется пространственной структурой капсульного полисахарида серотипа III, так как капсульные полисахариды других серотипов содержат те же компоненты, но имеют иную пространственную структуру. Астроциты - единственные клетки, располагающиеся между капиллярами и телами нейронов и участвующие в транспорте веществ из крови к нейронам и транспорте продуктов метаболизма нейронов обратно в кровь, - формируют гематоэнцефалический барьер. Он обеспечивает избирательное прохождение из крови в ткань мозга различных веществ. Благодаря гематоэнцефалическому барьеру в экспериментах многие продукты обмена, токсины, вирусы, яды при введении в кровь почти не обнаруживаются в спинномозговой жидкости.
Гематоэнцефалический барьер Ведущим компонентом морфологического субстрата гематоэнцефалического барьера, обеспечивающим его функции, является стенка капилляра мозга. Существуют два механизма проникновения вещества в клетки мозга: через цереброспинальную жидкость, которая служит промежуточным звеном между кровью и нервной или глиальной клеткой, которая выполняет питательную функцию (так называемый ликворный путь), и через стенку капилляра. У взрослого организма основным путем движения вещества в нервные клетки является гематогенный (через стенки капилляров); ликворный путь становится вспомогательным, дополнительным.
Глиальные клетки ЦНС позвоночных можно разделить на несколько групп Astrоcytes make contacts with cappilaries and neurons (fibrous astrocytes, which contain filamenta and are prevalent among bundles of myelinated nerve fibers in the white matter of the brain; protoplasmic astrocytes, which contain less fibrous material and are abundant in the gray matter around nerve cell bodies, dendrites and synapses Oligodednrocytes are predominant in the white matter, where they form myelin around large axones Radial glial cells play essential role in the developing mammalian central nervous system. In adult CNS resembling radial glia are the Bergman cells in the Cerebellum and Müller cells in the retina. Ependymal cells that line the inner surfaces of the brain, in the ventricles, are usially classified as glial cells Microglial cells are distinct from neuroglial cells in structure, properties, and lineage. They resemble marophages in the blood and probably arise from them.
Глиальные клетки мозга млекопитающих: олигодендроциты и астроциты