Neuroanatomy 4 Flashcards
Do you remember what did they find to be the risk factors and protective factors of/against Parkinson’s disease?
Note: milk is likely connected due to pesticides that the cow may have eaten
What would we expect in
- Braak 1-2 stages
- Braak 3-4 stages
- Braak 5-6 stages?
What is the possible cause of typical Parkinsonism (or atypical)?
So far the precise cause is unknown (leading to neurodegeneration of dopaminergic cells)
- but we have few theories:
- accumulation of alpha Synuclein from the gut (comes from the pesticides)
- Telencephalisation = excessive development of telencephalon with which the basal ganglia cannot keep up
- Toxines, pesticides, heavy metals
- Viral infections
- other e.g. damage to the brain, drugs
What is probably to most important message Tonny was trying to rise during the lecture?
- Avoid pesticides!!!
How can we create Model of Parkinson’s to study?
One study used mice that were injected with alfa-synuclein into their substantia nigra -> over few days the cell died
=> mice exhibited motor problems, specifically with walking distance, jump and speed of movement
How did they demonstrate how alfa-synuclein gets to the brain?
They had 2 groups of mice, both injected with a substance into their digestive system
- one group received alfa synuclein
- second group just a sham treatment
-> waiting to be taken up by the vagus nerve and transported to the brain
=> the first group showed degradation of dopaminergic neurons as opposed to the second group
How did they study this in humans - what were their conclusions?
They created human dopaminergic neurons in petri dish -> tested them on all kinds of different pesticides
=> Results showed that every type of pesticides could lead to neurodegeneration
=> They established a clear amount of pesticide type that could cause this
=> BUT the issue is they did so separately (which is the data farms are working with) => BUT actually even at small amounts, if we combine all these we get even worse prognosis
What was found in a study about pesticide exposure and cognitive functions?
They measured cognitive functions e.g. memory, executive, language, in people living n close vecinity of pesticide fields and those without exposure => close to pesticides was connected to higher cognitive decline in all categories
Why do we use Ldopa (precursor) instead of dopamine? What else do we need to add to ensure its effectiveness?
Because dopamine doesn’t cross the blood-brain barrier (and would be digested by the enzymes outside) while L-dopa does
But in order for L-dopa to NOT convert into dopamine before it crosses we need to add Benzerazide carbidopa (prevents decarboxylation of L-dopa)
- also cannot cross BBB
Plus also Entacapone - slows metabolism of L-Dopa by blocking cathechol-O-methyltransferase (COMT)
What is BBB made up of?
What can and cannot pass through?
Yes:
- O2, CO2, lipid substances (membrane is also lipid)
- via carriers: aminoacids, glucose
No:
- charged molecules
- large molecules
Where do we get synthesis of acetylcholine (except for neuromascular junctions)?
Basal forebrain
- Medial septum
- vertical and horizontal limb of diagonal band of Broca
What was the poison they used on Alexei Navalny? What’s the mechanism?
Name: Novichok
- organophosphate, not much known
Mechanism:
- blocks acetylcholine esterase -> at first acetylcholine will keep getting released as normal -> it won’t get broken down so there will be too much of it => muscle spasms -> once choline is depleted => paralysis (death comes once this happens at the heart or lungs)
Just briefly - what was the aim of Tonny’s PHD?
It drew upon the findings of his predecessor (i.e. retrograde tracing of neurons in the medial/lateral nucleus accumbens)
-> based on that they wanted to visualize which cells in the nucleus accumbens are responding to hippocampus, amygdala or both (then they could also stimulate the structures and see how would NC respond)
