Dr. Vega's Exam 1.pdf

Human critical periods of development Gastrulation (3rd week; day 15-16); Trilaminar germ layers development and cranio-caudal axis ○ Beginning of morphogenesis and primes for organogenesis ○ This process occur before the neurogenesis (neuralation) ○ 3 main cell la...

Human critical periods of development Gastrulation (3rd week; day 15-16); Trilaminar germ layers development and cranio-caudal axis ○ Beginning of morphogenesis and primes for organogenesis ○ This process occur before the neurogenesis (neuralation) ○ 3 main cell layers become differentiated from the primitive streak (from a bilaminar disk into a trilaminar disk) Ectoderm Mesoderm Endoderm ○ *bilaminar = epiblastic + hypoplastic cells When they migrate to become ectoderm, mesoderm and endoderm = trilaminar Neurulation (start 3rd week, completion at 4th week): Formation of neural tube and neural tissue development (CNS, PNS, and ANS) ○ The neuroectoderm receives signals from the notochord to invaginate and develops the neural tube- comes from neural plate ○ The neural folds (border between the neuroectoderm and surface ectoderm develops the neural crest cells) Eye development (4th week) ○ Development of eye structures are derived from ectoderm (neural and surface), mesoderm, and neural crest cells Epiblast and development of germ layers Detached epiblast cells replace the hypoblast cells = become the endoderm Epiblast cells continue to migrate → detach → invaginate → fill the space b/w the epiblast and endoderm → become the mesoderm Cells that remain in the epiblast layer = become the ectoderm Development of the CNS Start at 3rd week as the neural plate (dorsal surface of the embryo develops) A longitudinal neural groove develop in the center Two neural folds develop on each side of the groove Neural plate: origin and development The notochord and the paraxial mesoderm induced the overlying ectoderm to differentiate into the neural plate Induced by several factors, like chordin, noggin, follistatin, Xhr3, and Cerberus, but it is inhibited by the BMP The rostro-caudal pattern of the neural plate, is influenced by factors, like FGFs, homeobox genes, Wnt, and Retinoic acid (metabolism of Vitamin A)  The neural folds fuse in the midline and separate from the surface ectoderm to form the neural tube Neural crest develop between the surface ectoderm and the neural tube Neural tube lies b/w the neural crest and the notochord Neural plate becomes the neural tube which gives rise to the brain and spinal cord Cranio-caudal parts of the CNS ○ Cranial (rostral) → Brain ○ Caudal (anal) → Spinal cord ○ Cavities → Central canal (SC) and ventricles of brain Rostral (cranial) neuropore and caudal neuropore are located in the extremes of the neural tube Neural tube and neuropore closing The anterior neuropore closes first (25th day) 2 days later the posterior neuropore closes (27th day) Normally, the neural tube closure is completed within 28 days Meanwhile, the neural tube has sunk beneath the surface ectoderm Neural crest cells development Neural crest cells induction Neural crest development and differentiation are induced by several signaling molecules, that induce transcription factors and the genetic machinery of cells These inducing factors are: ○ BMP (intermediate levels) ○ Wnt ○ Notch ○ FGF Neural crest develop at the sides of the neural tube form by migrating ectodermal cells  Gives rise to ○ The posterior (dorsal) root ganglia (DRG in SC) ○ The sensory ganglia of the cranial nerves ○ Autonomic ganglia (CN V, VII, IX, X) ○ Cells of the suprarenal medulla ○ Melanocytes ○ Schwann cells (myelin in PNS) ○ Brain + SC meninges (arachnoid/pia matter) Primary embryologic division: The proliferation of cells at the cephalic end of the neural tube causes it to dilate and form 3 primary brain vesicles or “dilations” The caudal portion of the NT elongates and remains smaller in diameter (spinal cord) Forebrain vesicle (Prosencephalon) Midbrain vesicle (Mesencephalon) Hindbrain vesicle (Rhomboencephalon) These 3 vesicles develop 5 secondary vesicles Prosencephalon (forebrain) ○ Give rise to two subdivisions: telencephalon (endbrain) and diencephalon (between-brain) 1: Telencephalon develops Cerebral hemispheres Basal ganglia Hippocampus Lateral ventricles 2: Diencephalon develops Thalamus Hypothalamus Pineal gland Neurohypophysis Third ventricle Retina*** 3: Mesencephalon develops Midbrain Cerebral aqueduct Rhomboencephalon (hindbrain) ○ Give rise to 4: Metencephalon (afterbrain) Pons + cerebellum 4th ventricle (upper part) 5: Myelencephalon Medulla oblongata Stages of neural tube development Cephalic flexure (midbrain flexure) Pontine flexure (pons) ○ Delimit the development of the cerebellum and medulla oblongata Cervical flexure ○ Point of transition from brain to spinal cord Brain ventricles development Cerebral ventricles develop from the 5 secondary brain vesicles Telencephalon ○ Develop the lateral ventricles (2) Diencephalon ○ Develop the third ventricle Mesencephalon ○ Develop the cerebral aqueduct (aqueduct of Sylvius) Metencephalon and myelencephalon ○ Develop the fourth ventricle and central canal of SC Interventricular foramina (Monro) is developed by contributions from the telencephalon and diencephalon CSF = Cerebrospinal fluid, a fluid substance that maintains the electrochemical composition and transport nutrients and waste to and from the CNS (synthesized by choroid plexus (brain) and ependymal cells of SC) Neural tube layers Neuroepithelial cells of the neural tube give rise to ○ Neuroblast - neurons ○ Glioblast - supporting cells of the CNS (oligodendrocytes, astrocytes, and ependymal cells) ○ Microglia Comes from the mesenchyme (embryonic stem cells) that also forms the neuroepithelial cells Neural tube wall layers Neuroepithelial (ventricular) layer ○ Innermost layer ○ Lies the central canal and future brain ventricles Mantle (intermediate) layer ○ Middle layer ○ Contains developing Alar plate Becomes the dorsal horn of the spinal cord Basal plates Become the ventral horn of the spinal cord Marginal layer ○ Outermost layer ○ Produces the white matter of the spinal cord Development of sensory/motor neurons Brainstem and spinal cord have ○ Alar plate that gives rise to the sensory neurons ○ Basal plate that gives rise to the motor neurons Development of PNS Consists of spinal, cranial and visceral nerves, and spinal, cranial and autonomic ganglia Derived from 3 sources: ○ Neural crest cells Give rise to peripheral ganglia, Schwann cells, melanocytes, and adrenal medulla cells ○ Neural tube Gives rise to all preganglionic autonomic fibers and all fibers that innervate skeletal muscles ○ Mesoderm Gives rise to the dura mater and to the connective tissue investments of peripheral fibers Neural Tube Defects & Congenital Malformations Alpha-fetoprotein (AFP) is a glycoprotein produced in the yolk sac (embryo) and the liver (adult) Is also used as a tumoral marker of the liver AFP is done in the amniotic fluid by amniocentesis Detect prenatally by screening for high alpha-fetoprotein levels in the amniotic fluid Prevention/prescription: folic acid (600-800 ug/day) Rostral neuropore defects are related to brain and spinal cord Caudal neuropore defects are related to the end part of spinal cord (spina bifida) NTDs- 4th week  Spina bifida occulta ○ Defect in fusion of the vertebral arches (Lumbo-Sacral (L5-S1); 10% population) ○ Asymptomatic ○ Results from failure of the posterior neuropore to form ○ Hairy patch in the area ○ Associated w/ mutations in PAX-3 gene ○ Most common type ○ Intact meninges ○ Spina bifida variations ○ Spina bifida w/ meningocele Occurs when the meninges project through the vertebral defect, forming a sac filled w/ CSF ○ Spina bifida w/ meningomyelocele (myelomeningocele) Meninges & spinal cord project through a vertebral defect, forming a sac Associated to Arnold-Chiari malformation Arnold-Chiari Malformation ○ Symptoms: Hearing or balance problems, muscle weakness or numbness, dizziness, difficulty swallowing or speaking, vomiting, ringing or buzzing in the ears (tinnitus), curvature of the spine (scoliosis)  ○ Bone decompression by surgery ○ Congenital malformations (CNS) Anencephaly ○ Results from failure of the anterior neuropore closure ○ Brain and skull does not develop ○ High levels of AFP ○ Frequency 1:1000 ○ Fatal* ○ Hydrocephalus ○ Common cause: stenosis of the cerebral aqueduct during development ○ Excessive CSF accumulates in the ventricles and subarachnoid space ○ Can result from maternal infection (cytomegalovirus and toxoplasmosis) ○ Frequency 1:1000 ○ Alcohol (Teratogen): Fetal Alcohol Syndrome ○ Alcohol = toxic and teratogenic molecule ○ Pass directly and rapidly through the placenta into fetal organs including the developing brain ○ Most common cause of mental retardation  ○ Includes microcephaly ○ Congenital heart disease ○ Epicanthal folds ○ Small palpebral fissures ○ Low nasal bridge ○ Smooth philtrum ○ Thin upper lip ○ Holoprosencephaly is the most severe manifestation ○ Holoprosencephaly: cerebral and facial malformations due to incomplete division of the prosencephalon (forebrain) ○ Forebrain failing to cleave into 2 hemispheres, a process that is usually completed at 5th week of development ○ 1:8000 pregnancies second semester ○ ~40% due to chromosome abnormality of these 75% related to trisomy 13 ○ Associated w/ mutations in several genes, including: SHH, PTCH, SIX3, SK12, ZIC2, TGIF, TDGF1 and FAST1 ○ Disease associated w/ maternal diabetes (increase in 200-fold) Functions of the Nervous System Receiving sensory inputs ○ Receptors in PNS respond to both external and internal stimuli and send them to the CNS Performs input integration (brain as the boss) ○ CNS sums all the input and “decided” what to do about it ○ If a response is needed, the CNS “figures out” how to carry out that response Generate motor output responses ○ CNS sends signal through the PNS to the effectors ○ The signal is the “instruction set” to respond to the sensory input ○ Effectors are muscles and glands, that execute the planned response CNS: Brain Cerebrum ○ L/R cerebral hemispheres (Cerebral cortex) ○ Diencephalon Thalamus Hypothalamus Hypophysis (pituitary gland) (adenohypophysis and neurohypophysis) Epithalamus (pineal) Brainstem ○ Midbrain ○ Pons ○ Medulla Cerebellum ○ L/R cerebellar hemispheres Brain features Covered by 3 connective tissue membranes (meninges) ○ Dura mater (external) ○ Arachnoid Subarachnoid space (for spinal anesthesia; block sensory information) ○ Pia mater (internal; attached to the brain) Surrounded by CSF ○ Protection (cushioning the brain against the skull), nourishment and waste removal ○ CSF composition: 99% water + 1% (protein, glucose, ions (Na+, K+, Cl-, Ca2+, Mg 2+), urea, lactic acid, creatinine at a pH 7.3 Brainstem Controls functions of life, breathing, consciousness, blood pressure, heart rate, and sleep It is comprised of: ○ Midbrain (extensively related to the visual system)  ○ Pons ○ Medulla oblongata Midbrain Cerebral peduncles ○ Connects cerebellum w/ brainstem; bidirectional flow Tectum ○ Quadruplet bodies (corpora quadrigemina) Superior colliculi Receive visual inputs from the lateral geniculate nuclei (eye movements) Inferior colliculi Receive auditory inputs from the medial geniculate nuclei ○ Nuclei of CN III, IV Pons Prominent bulge of the anterior surface of the brainstem Is located ventral to the anterior part of the 4th ventricle (posteriorly have the cerebellum) Is attached to the cerebellum and relays information to the cerebellum and the forebrain, controls breathing Important areas of the Pons ○ Pneumotaxic Center: switches off respiration, and prevent *apneusis by modulating the respiratory rhythm Prevents apnea and inhibits apneusis ○ Apneustic Center: postpone the switch-off and regulates the rate of breathing by sending positive impulses to neurons responsible for inhalation in the medulla (promotes inspiration) Stimulates the development of apnea and apneusis ○ Nuclei of CN V, VI, VII, VIII Cerebellum Two hemispheres connected through a vermis Receive inputs and transmits output (Purkinje cells) Neurons: 69 billion compared to cerebral cortex (16 billions) Maintaining balance: special sensors that detects shift in balance and movement Coordination of Movement: coordination of multiple muscle groups Vision: coordinate eye movements Diencephalon Structures: ○ Thalamus  A relay station of all incoming motor (movement) and sensory information, including hearing, taste, sight and touch (but not smell) from your body to your brain. vLGN location that receives axons from the retina and send inputs to the superior colliculi (located in midbrain), pretectum, hypothalamus, and the PVC (V1). Glutamatergic (stimulation) and GABAergic (inhibition) neurons ○ Hypothalamus + hypophysis Hypothalamus: regulation of circadian rhythms Neuro-endocrine structure Helps to control body temperature, hunger, thirst, mood, sexual drive, blood pressure, breastfeeding, and sleep Releasing hormones (GnRH, GHRH) or inhibitory hormones (PIH) Hypophysis Divided into adenohypophysis (synthesized peptidic hormones) and neurohypophysis (storage hormones synthesized by the hypothalamus) ○ Epithalamus (pineal gland) Telencephalon Consist of ○ Cerebral hemispheres Comprise both cerebral cortex and white matter This contains the lateral ventricles Separated by the longitudinal cerebral fissure and the falx cerebri Interconnected by the corpus callosum Consist of six lobes and the olfactory structures ○ Basal Ganglia Caudate nucleus Head, body and tail Putamen, Globus Palidus Lentiform nucleus Putamen Globus pallidus ○ Lateral/external ○ Medial/internal Neostriatum = Caudate nucleus + Putamen Limbic system Hippocampus ○ Located in the medial aspect of the temporal lobe ○ Important in the information of short-term memory and transfer them to a long-term memory ○ Patients with Alzheimer's; hippocampus is responsible for this disease  Fornix Mamillary bodies Amygdala Functions ○ Establishment of emotional states and behavioral drives ○ Linking of conscious w/ unconscious functions Left Hemisphere Sensory stimulus from right side of body Motor control of right side of body Speech, language and comprehension Analysis and calculations Time and sequencing Recognitions of words, letters, and numbers Right Hemisphere Sensory stimulus from left side of body Motor control of left side of body Creativity Spatial ability Context/perception Recognition of faces, places, and object Cerebral cortex Outermost layer of brain cells Composed of 6 layers (neocortex) Areas w/ less than 6 layers (allocortex) Gyrus (bridges) Sulcus (grooves) Central Sulcus Lateral sulcus ○ Separate 4 lobes of the brain Frontal lobe (decision making, problem solving and planning) Parietal lobe (receives and process sensory information) Temporal lobe (Perception, memory, emotion, hearing, and language) Occipital lobe (vision) Brodmann Areas Regions of the cerebral cortex as determined by histological analysis. 47 Brodmann areas.