Full metadata
Title
Validation of Early Synapse Loss in a Mouse Model of Frontotemporal Dementia
Description
Frontotemporal dementia (FTD) is a neurodegenerative disease that causes deterioration of the frontal and temporal lobe. Detection is pivotal in preventative care, but current screening methods are not sensitive enough to detect early-stage disease. Synapse loss has been implicated as an early contributor to neurodegeneration and subsequent atrophy. Fluorine-18 fluorodeoxy-glucose (18[F]-FDG) positron emission tomography (PET) is a noninvasive imaging biomarker method frequently used as a surrogate measure for synaptic activity in the brain. PET scans using 18[F]-FDG tracers were performed on progranulin (GRN) knockout mice (Grn-/-), a commonly used mouse model of FTD. Interestingly, 18[F]-FDG PET at both, 9 months and 11 months, two time points considered early symptomatic in the Grn-/- mouse model, did not detect significant changes in synaptic activity, suggesting that no synapse loss has occurred yet at these early stages of FTD in this model. After the last PET scan, the imaging data were validated via fluorescent immunostaining for pre- and post-synaptic marker proteins SV2 and PSD95, respectively. Quantifications in several brain regions, including the frontal cortex, did not reveal any significant differences in protein expression, supporting the lack of aberrant 18[F]-FDG tracer uptake measured via PET. Additional examinations for activated microglia, a known aspect of FTD pathology recently observed in end Grn-/- mice, did not reveal microglia activation as measured via CD68 immunostaining. These data suggest that Grn-/- mice at 9 and 11 months do not exhibit synaptic dysfunction in the frontal cortex when measured via 18[F]-FDG PET or immunostaining of pre- and postsynaptic marker proteins SV2 and PSD95.
Date Created
2022
Contributors
- Weisman, Hannah (Author)
- Sattler, Rita G (Thesis advisor)
- Mastroeni, Diego (Committee member)
- Velazquez, Ramon (Committee member)
- Arizona State University (Publisher)
Topical Subject
Resource Type
Extent
47 pages
Language
eng
Copyright Statement
In Copyright
Primary Member of
Peer-reviewed
No
Open Access
No
Handle
https://hdl.handle.net/2286/R.2.N.171855
Level of coding
minimal
Cataloging Standards
Note
Partial requirement for: M.S., Arizona State University, 2022
Field of study: Biology
System Created
- 2022-12-20 06:19:18
System Modified
- 2022-12-20 06:19:18
- 1 year 11 months ago
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