Palmitoylated Prolactin-releasing Peptide Reduced Aβ Plaques and Microgliosis in the Cerebellum: APP/PS1 Mice Study

0551939 - FGÚ 2022 RIV NL eng J - Článek v odborném periodiku
Mengr, A. - Hrubá, L. - Exnerová, A. - Holubová, M. - Popelová, A. - Železná, B. - Kuneš, Jaroslav - Maletínská, L.
Palmitoylated Prolactin-releasing Peptide Reduced Aβ Plaques and Microgliosis in the Cerebellum: APP/PS1 Mice Study.
Current Alzheimer Research. Roč. 18, č. 8 (2021), s. 607-622. ISSN 1567-2050. E-ISSN 1875-5828
Grant CEP: GA ČR(CZ) GA20-00546S
Institucionální podpora: RVO:67985823
Klíčová slova: APP/PS1 mice * Alzheimer´s disease * palm11-PrRP31 * hippocampus * cerebellum * amyloid-beta plaques * neuroinflammation * synaptogenesis
Obor OECD: Physiology (including cytology)
Impakt faktor: 3.040, rok: 2021
Způsob publikování: Omezený přístup
https://dx.doi.org/10.2174/1567205018666210922110652

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 palm(II)-PrRP31 was proven to exert beneficial effects in APP/PS1 mice, a model of Alzheimer's Disease (AD)-like amyloid-beta (A beta) pathology, reducing the A beta plaque load, microgliosis and astrocytosis in the hippocampus and cortex.
Objective: In this study, we focused on the neuroprotective and anti-inflammatory effects of palm(11)-PrRP31 and its possible impact on synaptogenesis in the cerebellum of APP/PS1 mice, be cause others have suggested that cerebellar A beta plaques contribute to cognitive deficits in AD.
Methods: APP/PS1 mice were treated subcutaneously with palm(11)-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 A beta 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. Palm(11)-PrRP31 treatment significantly reduced the A beta plaque load and microgliosis in the cerebellum. Furthermore, palm(11)-PrRP31 increased synaptogenesis and attenuated neuroinflammation and apoptosis in the hippocampus of APP/PS1 mice.
Conclusion: These results suggest palm(11)-PrRP31 is a promising agent for the treatment of neurodegenerative disorders.
Trvalý link: http://hdl.handle.net/11104/0327143