8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 1 Development of Complex Curricula for Molecular Bionics and InfobionicsPrograms within a consortial* framework** Consortium leader PETER PAZMANYCATHOLIC UNIVERSITY Consortium members SEMMELWEISUNIVERSITY, DIALOG CAMPUS PUBLISHER The Project has been realisedwith the support of the European Union and has been co-financed by the European Social Fund *** **Molekuláris bionika és Infobionika Szakok tananyagának komplex fejlesztése konzorciumi keretben ***A projekt az Európai Unió támogatásával, az Európai Szociális Alap társfinanszírozásával valósul meg. PETER PAZMANY CATHOLIC UNIVERSITY SEMMELWEIS UNIVERSITY sote_logo.jpg dk_fejlec.gif INFOBLOKK 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 2 Peter Pazmany Catholic University Faculty of Information Technology BASICS OF NEUROBIOLOGY NEUROGLIA www.itk.ppke.hu Neurobiológia alapjai (Neuroglia) ZSOLT LIPOSITS Basics of Neurobiology: Neuroglia 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 3 www.itk.ppke.hu CLASSIFICATION OF NEUROGLIA ASTORGLIA 1. PROTOPLASMIC ASTROCYTE 2. FIBROUS ASTROCYTE OLIGODENDROGLIA 1. INTRAFASCICULAR OLIGODENDROCYTE 2. SATELLITE OLIGODENDROCYTE MICROGLIA 1. RESTING 2. ACTIVATED EPENDYMA 1. EPENDYMOCYTE 2. TANYCYTE SCHWANNCELL Basics of Neurobiology: Neuroglia 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 4 www.itk.ppke.hu FUNCTIONS OF NEUROGLIA NEUROGLIA HAS BEEN CONSIDERED IN THE PAST AS THE SUPPORTING TISSUE OF NEURAL STRUCTURES THE CURRENTVIEWATTRIBUTESANEQUALLYIMPORTANTROLE TOGLIALAND NEURONALCELLS THE MAIN ROLES OF NEUROGLIA INCLUDE: GUIDANCE OF NEURON MIGRATION IN EARLY DEVELOPMENT ESTABLISHMENT OF THE BLOOD BRAIN BARRIER (BBB) FORMATION OF MYELIN PARTICIPATION IN BRAIN ENERGY METABOLISM PRODUCTION OF EXTRACELLULAR MATRIX NEUROTRANSMITTER UPTAKE, THE GLUTAMATE-GLUTAMINE SHUTTLE SYNTHESIS OF GROWTH FACTORS AND CYTOKINES PHAGOCYTOSIS, NEUROPROTECTION, AGING WITH THE EXCEPTION OF MICROGLIA, GLIAL CELLS DEVELOP FROM NEUROEPITHELCELLS Basics of Neurobiology: Neuroglia 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 5 www.itk.ppke.hu ASTROCYTES ASTROCYTES HAVE SEVERAL, THIN PROCESSES, CONTAIN GLIAL FIBRILLARY ACIDIC PROTEIN (GFAP) MADE FILAMENTS AND GLYCOGEN IN THE CNS, THE WHITE MATTER IS RICH IN FIBROUS, WHILE THE GREY MATTER CONTAINS PROTOPLASMIC ASTROCYTES SILVER IMPREGNATION TECHNIQUES ENABLE THEIR IDENTIFICATION THEIR PROCESSES FILL THE GAPS AMONG NEURONS, PROJECT TO BLOOD VESSELS TO FORM THE BLOOD-BRAIN BARRIER, SURROUND AND ISOLATE SYNAPSING NEURONAL ELEMENTS AND FORM THE INTERNAL AND EXTERNAL GLIAL LAMINAE ASTROCYTES ARE COUPLED BY GAP JUNCTIONS, THEY GENERATE SPREADINGCALCIUM WAVES THEYEXPRESS GLUTAMINE-SYNTHETASE, A KEY ENZYME PARTICIPATING IN AMMONIA DETOXIFICATION AND GABA, GLUTAMATE TRANSMITTER INACTIVATION Basics of Neurobiology: Neuroglia 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 6 www.itk.ppke.hu REGULATION OF EXTRACELLULAR POTASSIUM NA+/K+ATPase, K+/Cl-CO-TRANSPORT AND THE ACTIVATION OF K+ CHANNELS CONTROL OF CALCIUM HOMEOSTASIS. VOLTAGE-DEPENDENT CA+ +CHANNELS THE NA+ /Ca+ +EXCHANGER NEUROTRANSMITTER RECEPTORS REGULATION OF pH AND EXTRACELLULAR SPACE VOLUME PROLIFERATION OF ASTROCYTES, BRAIN TUMORS ASTROCYTES FLUORESCENT IMMUNOSTAINING OF AN ASTROCYTE IN VITRO SHOWS THE GFAP FILAMENTS THROUGHOUT THE CELL Basics of Neurobiology: Neuroglia 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 7 www.itk.ppke.hu BLOOD-BRAIN BARRIER THE POLARIZED ENDOTHELIUM MEMBRANE: LUMINAL AND ABLUMINAL PARTS TRANSPORTERS FOR SODIUM, AMINO ACIDS AND GLUCOSE OPENING AND MALFUNCTIONS OF THE BLOOD BRAIN BARRIER CAUSED BY: HYPERTENSIONHYPEROSMOLARITY MICROWAVESRADIATION INFECTIONTRAUMA ISCHEMIA INFLAMMATION CAPILLARY ENDOTHELIUMCELL TIGHT JUNCTIONS BASEMENT MEMBRANE END-FEET OF ASTROCYTES Basics of Neurobiology: Neuroglia 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 8 www.itk.ppke.hu OLIGODENDROGLIA OLIGODENDROCYTES ARE SMALL-SIZED CELLS WITH NUMEROUS BRANCHING PROCESSES AT THE ELECTRON MICROSCOPIC (EM) LEVEL, THEY DISPLAY HIGH ELECTRON DENSITY AND A LARGE QUANTITY OF RER AND POLYRIBOSOMES SATELLITE OLIGODENDROCYTES ARE JUXTAPOSED TO NEURONS AND SUPPORT THEM INTRAFASCICULAR OLIGODENDROCYTES OCCUR IN AXON BUNDLES OF THE CNS WHERE THEY INTERACT WITH AXONS AND FORM THE MYELIN SHEATH FOR THEM A SINGLE OLIGODENDROCYTE MAY WORK TOGETHER WITH DOZENS OF AXONS MYELIN BASIC PROTEIN (MBP) IS A SPECIFIC MARKER OF OLIGODENDROCYTES Basics of Neurobiology: Neuroglia 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 9 www.itk.ppke.hu MICROGLIA THEY DEVELOP FROMMESODERMAL, HAEMOPOETIC TISSUE OUTSIDE THE BRAIN THESE MONOCYTES MIGRATE TO THE BRAIN, SETTLE DOWN AND DIFFERENTIATE TO RESTING MICROGLIA CELLS THE RESTING MICROGLIA HAS SEVERAL RAMIFYING PROCESSES THAT MOVE CONSTANTLY AND SURVEY THE NEIGHBORING AREA THE TERM HORTEGA-GLIA IS A FREQUENTLY USED SYNONYM MICROGLIA CONSTITUTES A LARGE PERCENTAGE (5-20%) OF CELLS IN THEBRAIN THEY OPERATE AS RESIDENT IMMUNE CELLS OF THE CNS THEY ARE CAPABLE OF PHAGOCYTOSIS AND REMOVALOFDAMAGED NEURONS, DEGENERATIVE PLAQUES, AND INFECTIOUS AGENTS TOGETHER WITH ASTROCYTES, THEY FORM A POWERFUL DEFENSE SYSTEM FOR THE PROTECTION OF THE CENTRAL NERVOUS SYSTEM Basics of Neurobiology: Neuroglia 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 10 www.itk.ppke.hu ACTIVATED MICROGLIA THE PHENOTYPE OF THE REACTIVE MICROGLIA DIFFERS FROM THAT OF THERESTING TYPE. IT HAS A LARGER CELL BODY AND THICKER PROCESSES. IN CASE OF A SEVERE PATHOLOGICAL INSULT THE REACTIVE MICROGLIA CAN TRANSFORM INTO MACROPHAGES ACTIVATION OF THE CELLS ALSO RESULTS IN THE UP-REGULATION OF THEKNOWN MOLECULAR MARKERS OF MONOCYTE-MACROPHAGE CELLS THE TRIGGERS OF ACTIVATION: GLUTAMATE RECEPTOR ACTIVATION, CHANGES IN EXTRACELLULAR POTASSIUM LEVEL, LIPOPOLYSACCHARIDES, PRO-INFLAMMATORY CYTOKINES AND NECROSIS FACTORS THEIR SPECIAL FUNCTIONS INCLUDE: SCAVENGING: CLEANING UP DEBRIS PHAGOCYTOSIS: ENGULFING CELLULAR ELEMENTS CYTOTOXICITY: TO RELEASE PROTEASES, CYTOKINES, GLUTAMATE ANTIGEN PRESENTATION EXTRACELLULAR SIGNALING Basics of Neurobiology: Neuroglia 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 11 www.itk.ppke.hu EPENDYMA NEURAL TISSUE FACING THE CAVITIES OF THE BRAIN AND SPINAL CORD ARE ENLINED BY SPECIAL GLIAL CELLS CALLED EPENDYMA THEY ARE CUBOIDAL OR COLUMNAR IN NATURE CARRYING MICROVILLI ANDKINOCILIA ON THEIR VENTRICULAR, APICAL SURFACES THE KINOCILIA SUPPORT THE FLOW OF CSF, THE MICROVILLI ARE USED FOR ABSORPTION THEY ARE SITUATED AT THE BORDER OF THE CEREBROSPINAL FLUID AND THE EXTRACELLULAR SPACE LIQUID COMPARTMENTS TIGHT AND GAP JUNCTIONS OCCUR BETWEEN EPENDYMAL CELLS A SPECIALIZED FORM OF IT, THE CHOROIDAL EPITHEL COVERS THE SURFACE OF THE CHOROID PLEXUS, THE STRUCTURE PRODUCING THE CSF I CORONAL SECTION OF THE HYPOTHALAMUS SHOWING THE THIRD VENTRICLE AND ITS EPENDYMAL COVER (ARROWS) Basics of Neurobiology: Neuroglia 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 12 www.itk.ppke.hu TANYCYTES TANYCYTES ARE SPECIALIZED EPENDYMAL CELLS COVERING THE FLOOR REGION OF THE THIRD CEREBRAL VENTRICLE THEYHAVELONG PROCESSES THE ARCH THROUGH THE BASAL HYPOTHALAMUS AND TERMINATE ON BLOOD VESSEL ON THE VENTRAL BRAIN SURFACE THEY TRANSPORT SUBSTANCES FROM THE CSF TO THE CIRCU-LATION THEY CONTAIN TYPE 2 DEIODINASE ENZYME THATGENERATES THE ACTIVE THYROID HORMONE, TRIIODOTHYRONINE FROM ITS PRO- HORMONE THE FIGURE DEPICTS TANYCYTES (ARROWS) TRANSPORTING A HORMONE AFTER ITS INJECTION INTO THE VENTRICLE (ASTERISK)