Palmitoylated Prolactin-releasing Peptide Reduced Aβ Plaques and Microgliosis in the Cerebellum: APP/PS1 Mice Study
Language English Country United Arab Emirates Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
20-00546S, RVO:61388963, RVO:67958523
Czech Science Foundation
PubMed
34551697
DOI
10.2174/1567205018666210922110652
PII: CAR-EPUB-118110
Knihovny.cz E-resources
- Keywords
- APP/PS1 mice, Alzheimer's disease, amyloid-β plaques, cerebellum, hippocampus, neuroinflammation, palm11-PrRP31, synaptogenesis.,
- MeSH
- Alzheimer Disease * metabolism MeSH
- Amyloid beta-Peptides metabolism MeSH
- Plaque, Amyloid pathology MeSH
- Amyloid beta-Protein Precursor genetics metabolism MeSH
- Diabetes Mellitus, Type 2 * MeSH
- Prolactin-Releasing Hormone metabolism pharmacology MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Cerebellum MeSH
- Mice, Transgenic MeSH
- Mice MeSH
- Presenilin-1 genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Amyloid beta-Peptides MeSH
- Amyloid beta-Protein Precursor MeSH
- Prolactin-Releasing Hormone MeSH
- Presenilin-1 MeSH
BACKGROUND: Prolactin-releasing peptide (PrRP) is a potential drug for the treatment of obesity and associated Type 2 Diabetes Mellitus (T2DM) due to its strong anorexigenic and antidiabetic properties. In our recent study, the lipidized PrRP analog palm11-PrRP31 was proven to exert beneficial effects in APP/PS1 mice, a model of Alzheimer´s Disease (AD)-like amyloid-β (Aβ) pathology, reducing the Aβ plaque load, microgliosis and astrocytosis in the hippocampus and cortex. OBJECTIVE: In this study, we focused on the neuroprotective and anti-inflammatory effects of palm11-PrRP31 and its possible impact on synaptogenesis in the cerebellum of APP/PS1 mice, because others have suggested that cerebellar Aβ plaques contribute to cognitive deficits in AD. METHODS: APP/PS1 mice were treated subcutaneously with palm11-PrRP31 for 2 months, then immunoblotting and immunohistochemistry were used to quantify pathological markers connected to AD, compared to control mice. RESULTS: In the cerebella of 8 months old APP/PS1 mice, we found widespread Aβ plaques surrounded by activated microglia detected by ionized calcium-binding adapter molecule (Iba1), but no increase in astrocytic marker Glial Fibrillary Acidic Protein (GFAP) compared to controls. Interestingly, no difference in both presynaptic markers syntaxin1A and postsynaptic marker spinophilin was registered between APP/PS1 and control mice. Palm11-PrRP31 treatment significantly reduced the Aβ plaque load and microgliosis in the cerebellum. Furthermore, palm11-PrRP31 increased synaptogenesis and attenuated neuroinflammation and apoptosis in the hippocampus of APP/PS1 mice. CONCLUSION: These results suggest palm11-PrRP31 is a promising agent for the treatment of neurodegenerative disorders.
References provided by Crossref.org
An analogue of the Prolactin Releasing Peptide reduces obesity and promotes adult neurogenesis
Age-related metabolic and neurodegenerative changes in SAMP8 mice
