Lecture 27 Stem Cells Study Guide 1. Know the different kinds of stem cells and their characteristics 2. Compare and contrast the two techniques for measuring neurogenesis 3. Identify two areas in the adult brain that support neurogenesis. Describe neurogenesis in these two areas. Stem Cells Fertilized egg totipotent stem cell self-renewing give rise to all cells Embryonic stem cells (ES) – derived from pre-gastrula self-renewing give rise to most tissue and cell types through organism (pluripotent) Somatic stem cells – committed stem cell broad class of stem cells self-renewing differentiate into full range of cell classes within a tissue Neural Stem Cells Neural stem cells somatic stem cells self-renewing differentiate into main cell classes found in CNS and PNS (neurons and glia) Neuroblasts non-dividing cells that develop into neurons Differentiated neuron cannot divide Embryonic Stem Cells From a Blastocyte Gastrulation Neurulation Neurogenesis from Neural Stem Cells in Neural Tube Cloned Neuronal Stem Cells A. Neurosphere: from adult forebrain i.. GABAergic neurons ii. Astrocytes iii. Oligodendrocytes Induction of Neurons from Stem Cells Pretreatment of embryonic stem cells with retinoic acid: differentiate into mature motor neurons when introduced into embryo Middle – cells extending axons Bottom – motor neuron-like morphology Activation of neuronal development by retinoic acid Retinoic acid is inductive signal for neuron differentiation Left – blue areas indicate gene activation Right – retinoic acid increases gene activation Retinoic Acid as a nervous system teratogen Teratogen – birth defects induced by exogenous agents Left – normal brain Right – Retinoic acid delivered at mid-gestation as Accutane drug to treat severe acne Neuronal Stem Cells in the Adult Brain History 1950’s: 3H-thymidine incorporation of DNA into dividing cells autoradiography 1960’s: 3H-thymidine method applied to adult brain showing neurogenesis in neocortex, dentate gyrus and olfactory bulb (Joseph Altman) ignored for two decades as an artifact (difficult to distinguish developing neuron from glia) 1980’s: Fernando Nottebohm (Rockefeller University) adult song birds make new neurons in brain region associated with song process accelerates during season birds acquire songs process accelerates during season when memory is very important to remember dispersed food storage sites canary makes 20,000 neurons per day 1984: Pasko Rakic: leading researcher on primate brain development found no 3H-thymidine accumulation in monkey brain Neuronal Stem Cells in the Adult Brain History 1990’s: BrdU (5-bromo-3’-deoxyuridine) like thymidine, taken up by cells during S-phase of mitosis visualized by immunocytochemistry (combine with other cell markers New evidence for neurogenesis in adult nonhuman, primate brain by Elizabeth Gould and Bruce McEwen (Rockefeller) and Eberhard Fuchs (German Primate Center) 1997, neurogenesis in hippocampus of primate-like tree shrew 1998, neurogenesis in marmoset, distant primate relative of human 1998, Gould and Rakic found neurogenesis in hippocampus of rhesus monkeys 1999, Princeton researches found neurogenesis in cerebral cortex Evidence for neurogenesis in adult human BrdU used in cancer patients (tongue or larynx) to monitor growth 1998, Fred Gage (Salk Institute) and Peter Eriksson (Sweden) examined brains on autopsy found neurogenesis in hippocampus patients aged from 57 to 72 Labeling Neurogenesis a. 3H – thymidine in rat b. BrdU in rat c. BrdU in mitotic anaphase d. BrdU in dying (pyknotic) cell Labeling Neurogenesis and Cell Markers a. BrdU (red) and oligodendrocyte marker (CNP, green) b. BrdU (red) and neuronal marker (MAP-2, green) c. BrdU (red) and neuronal marker (TuJ1, green) d. BrdU (red) and retrograde tracer to mark cell body (Blue) e. BrdU (red) and neuronal marker (NeuN, green) Neurogenesis in the Olfactory Bulb Stem cells found in anterior subventricular zone (epithelial lining of ventricles) Postmitotic neuroblasts migrate to olfactory bulb through rostral migratory stream Neurogenesis in the hippocampus Stem cells in basal aspect of granule cell layer in dentate gyrus Postmitotic neuroblasts translocate to granule cell layer in apical levels Control of Neurogenesis Stress Exercise Intellectual Activity i.e., live right!!!!
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