L02 - Development and Anomalies of Development in the CNS

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BAB Mind Map on L02 - Development and Anomalies of Development in the CNS, created by chris.brees on 16/01/2014.
chris.brees
Mind Map by chris.brees, updated more than 1 year ago
chris.brees
Created by chris.brees about 10 years ago
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L02 - Development and Anomalies of Development in the CNS
  1. Brain development
    1. Understanding pathology with age comes from understanding the development
      1. Key points in development
        1. Development continues throughout life - not complete at birth
          1. First neurones are created at 3 weeks - early start to development
            1. Damage easily caused by toxic substances
            2. By 3 months there is an early brain plan
              1. 6-9 months white matter develops
                1. After being born for 12 months - no neuronal proliferation, but slight ability to regenerate
                  1. Myelination is 50% complete by 18 months (not complete until teens)
                    1. By 20, the brain is mature in structure and it looks like this for the rest of your life
                      1. Dynamic processes of the brain (formation & destruction of synapses) continues throughout life
                    2. Issues
                      1. How do some cells end up as neurones?
                        1. In the embryo, Gastrulation occurs
                          1. Ball of cells polarised
                            1. Head and tail discernible
                              1. Layers
                                1. Endoderm
                                  1. Viscera
                                  2. Ectoderm
                                    1. Musculoskeletal system
                                    2. Ectoderm
                                      1. Nervous system (+skin)
                                        1. Neurulation
                                          1. Occurs 3 weeks after conception
                                            1. Therefore can be dysrupted by toxic agents
                                            2. Formation of the neural plate
                                              1. Due to interactions between cell surface proteins of the ectoderm, notochord and mesoderm
                                                1. Cells near the notochord form the neural plate
                                                  1. Neural plate formation due to conc. gradient of secreted molecules by the notochord
                                                    1. Neural folds form, with a neural groove in between
                                                      1. Involves; (i) changes in cell shape, (ii) movement of cells, (iii) interactions with surrounding tissues
                                                        1. Neural folds fuse, forming:
                                                          1. Neural Tube
                                                            1. Spinal Cord
                                                              1. Brain Cells
                                                                1. Clinical relevance
                                                                  1. Defective closure of neural tube
                                                                    1. Anteriorly
                                                                      1. Anencephaly
                                                                      2. Posteriorly
                                                                        1. Spina Bifida
                                                                      3. Massive cell division
                                                                        1. Dependent on folic acid
                                                                        2. Gene Defects
                                                                          1. Defects in protein expression
                                                                            1. Affect Cell-Cell interactions
                                                                              1. Often results in embryo death
                                                                      4. Neural crest
                                                                        1. Neurones with cells body in Peripheral NS
                                                                          1. e.g. Dorsal Root Ganglia, Sympathetic chain, Schwann cells
                                                  2. How do they become organised in the developing brain?
                                                    1. Anterior-Posterior patterning
                                                      1. Anterior end
                                                        1. 3 Vesicles
                                                          1. All brain derived from walls
                                                        2. Signals for polarity; secreted and cell-surface
                                                          1. Dickkopf ('fat brain' in German)
                                                            1. Anteriorising, over-expression = large forehead
                                                            2. Noggin
                                                              1. Vit. A
                                                                1. Used in organisation pathway
                                                                  1. Excess intake can interrupt anterior brain formation in the embryo
                                                            3. Dorsal-Ventral (Top-Bottom) patterning
                                                              1. Sonic Hedgehog (Shh)
                                                                1. (Mutation causes spikey effect)
                                                                  1. Causes ventral formation
                                                                    1. Motor neurones of cranial nerves
                                                                      1. Dopaminergic neurones
                                                                        1. Impact in Parkinsons Disease
                                                                        2. Serotonergic neurones
                                                                          1. Impact in psychiatric issues (depression) - therapy?
                                                                    2. Organisation into regions/nuclei
                                                                      1. Cortical Layering
                                                                        1. Migration of neuroblasts (created weeks 5-20) from the Ventricular Zone into the Cortical Plate
                                                                          1. Along Radial Glia
                                                                            1. Migration Abnormalities
                                                                              1. Cortical Dysgenesis
                                                                                1. Many syndromes with differing degrees of migration issues and differing degrees of impact
                                                                                2. Lissencephaly
                                                                                  1. Significant cortical dysgenesis
                                                                                    1. Smooth cortex
                                                                                      1. Large functional issues
                                                                                      2. Other disorders
                                                                                        1. Autism
                                                                                          1. Schizophrenia
                                                                                            1. Epilepsy
                                                                                              1. Dyslexia
                                                                                                1. Cerebral palsy
                                                                                                  1. Specific disorders due to cortical dysgenesis in particular areas
                                                                                                2. Differentiation
                                                                                                  1. Cell maturation and differentiation
                                                                                                    1. Inputs - Dendritic Processes form
                                                                                                      1. Outputs - Axons form
                                                                                                        1. No further division (after processes formed)
                                                                                                          1. This is why damage is such a problem
                                                                                                        2. Differential gene activation
                                                                                                          1. Transmitters/Receptors
                                                                                                3. How do they make appropriate connections with each other?
                                                                                                  1. Axons Need to...
                                                                                                    1. Extend
                                                                                                      1. Lamellipodia
                                                                                                        1. Receptors on the axon which attach to the extracellular environment (proteins such as laminin) and promote growth
                                                                                                        2. Grow in groups
                                                                                                          1. Form white matter tracts (bundles)
                                                                                                            1. Fasciculation into fascicles
                                                                                                              1. Cell adhesive molecules allow this - surface receptors
                                                                                                            2. Grow towards correct targets
                                                                                                              1. Chemoattractants
                                                                                                                1. Attract axon
                                                                                                                  1. e.g. netrin
                                                                                                                  2. Chemorepellants
                                                                                                                    1. Repel axon
                                                                                                                      1. e.g. ephrin
                                                                                                                      2. This occurs due to axon receptor expression - creating a specific chemical environment
                                                                                                                    2. Synaptogenesis
                                                                                                                      1. Two-way signalling
                                                                                                                        1. Presynaptic sends an invitation
                                                                                                                          1. Postsynaptic must accept/reject signal
                                                                                                                            1. Signalling via trophic factors such as NGF
                                                                                                                            2. Synaptic loss important in degeneration of brain function
                                                                                                                            3. Refinement
                                                                                                                              1. Organised apoptosis of neuronal cells
                                                                                                                                1. Removing sub-standard/incorrect signalling cells
                                                                                                                                  1. Controlled by gene expression
                                                                                                                                  2. Also occurs pathologically
                                                                                                                                    1. Alzheimer's Dementia
                                                                                                                                      1. Parkinsons Disease
                                                                                                                                  3. Neurodevelopmental disorders
                                                                                                                                    1. Autism
                                                                                                                                      1. Schizophrenia
                                                                                                                                        1. Cerebral palsy
                                                                                                                                          1. Epilepsy
                                                                                                                                            1. Dyslexia
                                                                                                                                              1. Gene expression vital in development
                                                                                                                                          2. Therapeutic Revevance
                                                                                                                                            1. Hijack processes
                                                                                                                                              1. Stem cells
                                                                                                                                                1. Activating stem cells in adults
                                                                                                                                                  1. CNS repair?
                                                                                                                                                  2. Spinal cord damage
                                                                                                                                                    1. Stem cell transplant in neurodegenerative disorders?
                                                                                                                                                      1. SC must develop in neurone in developing brain - problem
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