Lecture 4- Brain disorders involving deficits of learning and memory Flashcards
What are the seven common disorders involving learning and memory deficits?
•Mental retardation/learning disorders •Alzheimer’s disease, dementia •Huntington’s disease •Post-traumatic stress disorder (PTSD) •Depression •Schizophrenia •Addiction
What is Huntington’s disease?
-Progressive neurodegenerative disorder affecting the cerebral cortex and striatum -HD is the most common polyglutamine neurodegenerative disease (the others are mainly spinocerebellar ataxias)
What are the symptoms of Huntington’s?
-Motor (e.g.chorea), cognitive (e.g.learning and memory deficits) and psychiatric (e.g. depression) symptoms -involves neurdegeneration -leads to form of dementia -depression even in mice so it is not just situational
When is the onset of Huntington’s?
-Onset usually in fourth or fifth decade of life (5% of cases have juvenile onset)
How long does it take for a Huntington’s patient to die after symptoms start to show?
-progresses for 10-20 years before death
What are the brain regions affected by Huntington’s?
-striatum and cerebral cortex are the most affected areas in the brain
What is Huntington’s caused by?
- Caused by a CAG repeat expansion encoding an expanded polyglutamine tract in the huntingtin protein
- the repeats are dynamic= can change within cells of the same body and between generation
- caused by a dynamic mutation
What does the age of onset depend on?
-Age of onset inversely proportional to CAG repeat length, and often occurs earlier in subsequent generations (genetic anticipation)
How does Huntington’s disease happen (DNA picture)?
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What are the Huntington’s disease transgenic mice?
• R6/1 mice expressing human HD transgene (~115 CAG repeats) encoding expanded polyglutamine • Progressive neurodegenerative phenotype similar to human HD, including motor, learning and memory deficits • Shrinkage of cortex and striatum,etc.
How is mice behaviour analysed? (5)
- Locomotor habituation (e.g. photobeam arenas) 2. Motor learning (e.g. repeated accelerating rotarod): motor learning, implicit learning, mice can learn ti improve their motor behaviour in tasks, realise over time what is happening 3.Discrimination learning (e.g. somatosensory or visual) 4. Short-term spatial memory (e.g. T-maze, Y-maze) 5. Long-term spatial memory (e.g. Morris water maze, Barnes circular maze)
What happens when you put a mouse in a photobeam arena?
-Data analysis of upper (vertical movements) and lower (horizontal movements) 8 x 8 arrays of photobeams over 30 minutes -explore a lot at first few tries, later it habituates= explores less
How are motor abilities and learning on the accelerating rotarod affected in the Huntington’s mice?
-motor sign= when holding them by tail they put paws together only if Huntington’s -the rotor= of you repeat it, wild type will improve its performance, but huntington’s won’t
How is short term memory tested in mice?
-spatial working memory -Y maze –one arm blocked off, -then put back in, arm not blocked off -if it spends more time in unexplored= remembers -Huntington’s don’t remember
How is somatosensory discrimination tested in mice?
-put in a box with platforms, shape of a y maze–they can’t see anything in this light, practically blind -different tactile surface -behind one is a reward -they remember behind which one, Huntington’s don’t
What effect do HD and fluoxentine on the adult neurogenesis?
–Flx= prozac
-if given prozac it reccued the deficit in the dentate gyrus in huntigton mice -on right= can specify adult born cells, neurogenesis decreases in huntington mice, but when given prozac it made the effects smaller
What causes Alzheimer’s?
- dystrophite neurites and plaques the two major differences in an alzheimer brain
- they cause cognitive deficits, even before the neuronal death
How does environmental enrichment affect dementia?
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