Week 4 Flashcards
1
Q
Points of Toxicity: how LRRK2, DJ1, Parkin and PINK1 affect cells
- how rotenone, iron and manganse affect cells
A
- LRRK2 and DJ1 affects cells through oxidative stress
- Parkin and pink1 affect mitochondria depolarization. Parkin through substrate accumulation
- Rotenone affects mitochondria depolarization
- Iron= Asyn accumulation and aggregation
- Manganese = Er stress and UPr activation
2
Q
- what is evidence that cells are under stress (oxidative)
- indication of ER stress
- what is PDI
A
stress granuales are evidence of oxidative stress and PDI dysfucntion (protein disulfide isomerase) = ER stress (Er stress is protein agregation stress)
PDI allows for normal protein folding
3
Q
- origin of AD
- what is the normal transmembrane protein and how does it change with AD
- what is a marker of this biofilm, what does the biofilm activate and does what
A
- Borrelia (Lyme disease) bacteria found in pathological specimens of Alzheimer’s
disease and suggested to be the origin of AD - normal transmembrane protein is amyloid beta, but in AD, it interacts with a biofilm that tries to destroy it
- marker of this biofilm is alginate
- biofilms actibate TLR2 on microgilial cells which lead to proinflammatory cytokines which leads to neuronal loss
4
Q
Brain and Gut
- what underlies PD and mood disorder
- what does gut microbiota interact with
- what interacts with the vagus nerve
- what is the vagus nerve
- What is the microbiota
- what is the microbiome
A
- brain inflammation underlines PD and mood disorder
- gut microbiota interactions with the immune cells that make cytokines to travel between blood and brain which can cause inflammation
- Microbiota also interacts with enteroendocrine cells that produce neuroactive molecules that interact with the vagus nerve
- the vagus nerve is dominant nerve
- microbiota: assemblage of living microorganisms present in a defined location. Affected by many factors such as diet, hygiene, drugs, and personal genetics
- microbiome consists of all genes the microbiota encodes for.
5
Q
Dysbiosis
What kind of bacteria is gut bacteria
most abundant phyla
Colonisation of the gut begins at
A
- dysbiosis: imbalance in the normal microbial community
- occurs when changes are made to diets and a deviation from healthy lifestyle
- Gut virome is mostly stable (>95%) in health individuals
- gut bacteria is mainly anaerobic
- the most abundant phyla:
- Bacteriodetes (gram -) and Firmicutes (gram +)
- Proteobacteria, Verrumicrobia, and Actinobacteria
- olonisation of the gut begins at birth and continues during development
6
Q
Microbiota and PD
- connection between dysbiosis and neurological diseases.
- Braak’s hypothesis
A
- dysbiosis has been reported in subjects with neurological diseases
- Braak’s hypothesis: Syn accumulation can propagate via the vagus nerve in a prion-like fashion= Asyn inclsuions appear in gut first
7
Q
Gut and Motor Dysfunction
- Role of Thy1-aSyn
- how motor functions are analyzed (four tests)
- Abbreviations for Mice Lines: SPF, GF, ASO
- Strains Used: Neurotrace, Phospho-Ser129-asyn antibody, Phsohp-aSyn
- what was stained and what was seen
A
- Thy1aSyn (ASO) = motor deficits and gut motility deficits
- Four motor tests: beam traversal, pole descent, nasal adhesive, hindlimb clamping
- Abbreviations: SPF : pathogen free; normal gut bacteria that do not cause disease
GF: no gut bacteria
ASO: overexpression of a-Syn
Stains used: - Neurotrace: stains all neurons blue
- Phospho-Ser129-aSyn antibody: stains a-syn aggregates pink
- Phospho-aSyn: stains phosphorylated a-syn green
- Stained the caudoputamen and SN
- SPF-ASO mice had a lot more phosphorylated aSyn and aSyn aggregates compared to GF-ASO. This suggests that the gut microbiota had something to do with this increase.
- In Diagram C, both SPF and GF mice had monomeric (soluble) a-syn, but it
becomes clear in the SPF-ASO mice that levels of insoluble aggregates of a-syn will
sharply increase
8
Q
A
