Development and aging

Development and aging

1. Prinicpals of development

   • Neurulation
   • cell birth
     • neurogenesis, gliogenesis
   • cell migration
   • cell differentiation
   • cell maturation
     • denritic and axonal growth
   • Synaptogenesis
   • Cell death and synaptic pruning
   • Myelogenesis

2. The early brain

   • Neurodevelopment begins 18 days post fertilization
     • neural plate to neural tube = neurulation
   • Neural tube
     • becomes brain and spinal cord
     • Grows in 3 ways
       • Thickening and elongation
       • Folding
       • Convergence
         • Dorso lateral hinge points form a tube
     • Tube fuses in the middle then towards the edges
       • Spina bifida
         • Neural tube fails to close at ends
           • Spinal cord protrudes from unclosed sections of spinal cord
             • Can cause cerebellum to misposition

3. Neurogenesis

   • Cells born then move
     • Move due to concentration gradients
       • Concentration gradients
         • Attrative gradient
           • Diffuse across area and attracts more cells to higher gradients
         • Repulsive gradient
           • Diffuse across area and repulses cells to lower gradients
         • Supports growth and patterning of neurons
         • Within neural tube
           • Double gradient
           • Shh
             • Sonia Hedge hog
             • Controls cell differenciation on ventral half of neural tube
             • Holoprosencephaly
               • Mutation of Shh can cause unified hemispheres
                 • Cyclopia
   • First symmetrical cells then asymmetric neurons
   • Adult neurogenesis
     • Dentate gyrus in the hippocampus
     • Subventricular zone (lines the ventricles)
     • Olfactory bulbs
   • Proliferate areas
     • centre of neural tube
     • Neurons and glial cells are created,

4. Neural Migration

   • Leading and a trailing process
     • Based on chemical cues
       • Neural cells migrate along glial cells
   • Ectopic
     • Neurons = wrong place or layer
     • Linked to Neurodevelopmental disorder
   • Inside-out proliferation
     • New neurons push past old to pial surface of the tube
       • Some sit below old ones
   • In adults
     • Progenitor cells lay in white and grey matter

5. Cell differenciation

   • Axonal growth
     • Tip of axon = growth cone
       • Finger like processes = filopodia
         • Search for chemical signals
         • Allow neuron to move to final place
         • Sensitive to whole brain and nearby cells
           • Attracted or repulsed by them
             • Layering of the cortex / neural architecture explained by this
   • Retinotopy
     • Controlled by chemical gradients
       • Cells = map what eye sees
         • Cells that react same way = move and communicate
   • Hemisphere commisure
     • Attracts commisure cells
       • Repels others
     • Acallosal Syndrome
       • Corpus callosum starts with a few cells
         • Those cells attract other callosum cells
           • If this is disrupted early on, no corpus callosum forms
       • Not 100% penetrant
         • Not call children with gene will get Acallosal syndrome
   • Dendritic changes
     • Axons = no move, dentrites = move
     • Synaptogenesis and pruning
       • Many cells present at birth
         • This decreases over time
       • Nurotropic factors
         • Cell used = release NF
         • Not used = no NF, no cell survival
         • Only cells that are used / connections strengthened survive
       • Regressive growth
         • 50% of neurons die prenatally
           • About getting most efficient amount
         • Exuberant or transient connections
           • Extra uncessary connections
           • Common for exuberant connections then pruning
         • Synaptic pruning
           • Most synaptic pruning is due to learning and experiencing
           • Chosen cell death through apoptosis
             • Getting rid of unused cells
             • Cancer cells do not die through apoptosis, which is why they are dangerous

6. Pruning

   • Experience dependent cells
     • Learning a skill
       • Kicking a ball
     • Easier to fom connections young
       • Harder as we age
   • Experience independent cells
     • Sensory systems
       • Visual system ready and waiting for input

7. Glial cells

   • Astrocytes, microglia, oligodendroglia, satellite cells, schwann cells.
   • Myelination
     • Insulates the axon, increases velocity of electric signals
     • Oligodendroglia - in the CNS, schwann are in the PNS
     • Post-natal as most cells aren't developed yet
     • Changes across time but it peaks generally at adulthood

8. Physical changes with age

   • White matter loss
   • Grey mater loss
   • Loss of neuronal plasticity
     • Ability to alter neurons related to memory
       • Memory declines with age
   • Dendrite loss
   • Causes of physical changes
     • Accumulation of proteins
     • Oxidative stress
     • Toxins
     • Cell death
       • Cell breaks down into organelles
         • Phagocytes clean this us
       • Necrosis
         • non-programmed cell death
           • Cells bursts contents and harm other cells

9. Pruning in aging

   • Under-pruning and over-pruning
     • Associated with disorder
     • Not 1:1 link as pruning is normal
       • Could be many protective factors that stop it becoming disordered

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