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Lecture 11

LMP410H1 Lecture 11: Lecture 11 - Regenerative Strategies

3 Pages
Fall 2016

Laboratory Medicine and Pathobiology
Course Code
Mc Laurin

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Lecture 11 – Regenerative Strategies for
Neurodegenerative Diseases
CNS Regeneration – Basic Knowledge
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Lecture 11 – Regenerative Strategies for Neurodegenerative Diseases CNS Regeneration – Basic Knowledge  CNS and PNS – neurons are incredibly complex so regeneration is pretty complex… how are you going to grow those axons to a specific area of the brain? Which stem cell is going to talk to which cell? How are you going to recreate new memories or restore functions that are quite complex… YELLOW STARS ARE FOR THE EXAM!!! BLUE ARE FOR THE QUIZ!!!  Brain is harder to repair but is majorly protected with the skull… the peripheral neurons are able to repair more easily as they are more prone to injury  Both oligodendrocytes and Schwann cells make myelin though they are very different in the CNS and PNS – ones in the PNS make nerve growth factor (NGF) via Schwann cells…  Axonal Growth – can happen in the hippocampus via mossy fibers… this is axonal elongation – in the damaged brain, axonal growth occurs in 2 different forms: axonal regeneration is essentially the REGROWTH of injured or degenerating axons vs that of sprouting when neurons that are not injured takes advantage of the neural chemotaxis and growth factors to elongate an axon and attach to that synapse… this sprouting my not innervate the proper target and it may not work properly o Challenges – Permissive environment… includes cell survival, axonal growth of the injured axons, adequate target innervation and a functional outcome  Permissive Environment – have reactive gliosis and inflammation… can cause lesions… even during surgery, this can cause gliosis and can cause the glial scar around the inflammatory side… this can stop the axonal growth and elongation to that area… astrocytes have both a bright and dark side… a little astrogliosis is good but a lot is not causing inhibition of regeneration  Discovery of Regeneration… Cajal’s student provided a nourishing trophic environment of peripheral nerves (with Schwann cells) and grafted into the brain of the rabbit and a lot of axons from the brain went into the graft and innervated the graft… o Discovery of Epidermal growth factor (EGF), nerve growth factor (NGF), brain derived nerve factor (BDNF)  Neurogenesis is the birth of new neurons… occurs in the hippocampus (dentate gyrus) and the subventricular zone lining the lateral ventricles (migrate to the olfactory bulb via the rostral migratory stream) o Discovery of Adult Neurogenesis – Peter Eriksson used BrdU which incorporates into the cells that divides then extract the brain and do antibody treatment against BrdU… he was able to see in the dentate gyrus of the hippocampus that those cells were dividing… In the human brain, can pulse BrdU and stain with NeuN… o Enjoyable exercise… shown that in the mouse brain that if exercising, the mouse has more BrdU cells in the hippocampus… when the mouse is swimming (stressful) there is not much neurogenesis which is different from that of running rodents… o Exercise in AD patients has been shown to be much better than that o
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