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Detection of Abnormal Prion Protein by Immunohistochemistry
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An ancient conserved role for prion protein in learning and memory
Patricia L A Leighton1,2, Nathan J Nadolski3, Adam Morrill3
1Centre for Prions and Protein Folding Disease, University of Alberta, Edmonton, AB T6G 2M8, Canada.
Biology Open
|January 24, 2018
Summary
Cellular prion protein (PrPC) plays a vital role in memory. Zebrafish lacking PrPC show age-dependent memory decline, suggesting a conserved function in cognition relevant to neurodegenerative diseases.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Cellular prion protein (PrPC) misfolding causes neurodegeneration in prion diseases.
- Understanding normal PrPC function is crucial for comprehending disease mechanisms.
- Previous studies in mice suggest controversial roles for PrPC in memory and learning.
Purpose of the Study:
- To investigate the role of PrPC in memory using zebrafish as a model organism.
- To determine if PrPC deficiency leads to memory impairment in an age-dependent manner.
- To explore the potential link between PrPC function and cognitive decline relevant to Alzheimer's and prion diseases.
Main Methods:
- Utilized zebrafish (prp2 mutant) to study prion protein function.
- Assessed memory performance using an object recognition task in aged (3-year-old) and young (1-year-old) fish.
- Employed a novel object approach (NOA) test and a novel tank diving test to evaluate cognitive appraisal and anxiety levels.
Main Results:
- Aged prp2 zebrafish exhibited significant memory decline in the object recognition task compared to younger counterparts.
- In the NOA test, aged prp2 fish showed altered interaction with novel objects, approaching them more frequently.
- Anxiety levels, assessed via the novel tank diving test, were not significantly different between aged prp2 fish and controls.
Conclusions:
- PrPC plays a conserved and ancient role in memory, with its absence leading to age-dependent cognitive deficits.
- The findings suggest that PrPC deficiency impacts cognitive appraisal of novelty, rather than general anxiety.
- This study establishes a zebrafish model for investigating PrPC-related cognitive dysfunction and for screening potential therapeutics for prion and Alzheimer's diseases.
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