Brain Aging

• Why is it important to study normal aging ?

  In order to distinguish normal vs pathological aging
• How does aging impact cognition ?

  Aging starts affecting processes during middle ages but this decline in cognition is not the same for everybody
• What are the main changes in network and connectivity ?

  • Hyperexcitability of hippocampus
  • Reorganization of networks aka compensation
• What elements cause hyperexcitability in hippocampus ?

  • Impairment in GABA inhibtion
  • E/I ration in granule cell increased
• What is the compensation phenomenon ?

  It is the recruitment of additional brain regions in order to perform a task
• What are the 2 forms of reorganization in compensation ?

  • HAROLD
  • PASA
• What is Harold ?

  Model stating that aging causes reduced hemispheric asymetry
• What is PASA ?


  Model stating that aged individuals use more their anterior regions : posterior anterior activity shift
• What are the 6 changes at the cellular level ?

  • Mitochondrial dysfunction
  • Disruption of homeostasis
  • Disruption of inflamation
  • Changes in glial cells
  • Changes in neuronal cells
  • Gene modification
• What are the 4 gene modification you can observe in aging ?

  • NT receptors and vesicles
  • Synaptic calcium systems : calmodulin and PKC
  • Vesicle, protein transport and cytoskeleton modulation : MT, dyneine, GTPase and clathrine
  • base-excision pair = increased oxidative DNA damage
• More DNA damages in downregulated genes than upregulated genes
• Where are located most activated cells in aged mice ?

  • for astro and oligo in the subcortical white matter = corpus callosum
  • for microglia in the superficial white matter
• What do you see in oligodendrocytes ?

  • INCREASE of : myelin decompaction, ribosome biogenesis, immune genes
  • DECREASE of : OPC, myelin genes, cholesterol synthesis
• What do you see in astrocytes ?

  • INCREASE of : inflamation and reactivity of astrocytes
  • DECREASE of : trophic support, reduced density and upregulation of reactive genes
• What do you see in microglia ?

  • INCREASE of : activated morphology
  • DECREASE of : phagocytosis, total nb of microglia and those that are reactive, upregulation of immune response
• What are the 3 elements important about neuronal + synaptic loss ?

  • you don't loose neurons but you have abnormal synaptic connection
  • downregulation of most synaptic function genes
  • reduced adult neurogenesis in hippocampus and olfactory bulb
• What did they prove in terms of synaptic loss in rats vs monkeys ?

  • rats : loss of spines not uniform
  • monkeys : loss of spine + less axospinal synapses BUT ONLY in thin synapses
• What do you see in neurons ?

  • Biophysical changes
  • Modification of dendritic dynamics
  • Loss of spines
  • Synaptic function changes
• Modification of dendritic dynamics in neurons involve ?

  • increased turnover
  • longer spines
  • voluminous spines
  • less elimination of the spines
• Biophysical changes in neurons involve...?

  Increased AHP
• Synaptic function changes in neurons involve...?

  Harder to produce an LTP response
• What techniques can you use to improve aging ? (6 elements)

  • Parabiosis
  • Target NT signalling
  • Decrease inflamation
  • Epigenetics
  • Bone marrow transplant
  • Change lifestyle
• What is cognitive reserve ?

  Ressources available to preserve normal cognition despite brain damage
• What are the challenges met in brain aging ?

  Brain aging is heterogenous both inter and intra individuals