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

Mengr, Anna; Hrubá, Lucie; Exnerová, Aneta; Holubová, Martina; Popelová, Andrea; Železná, Blanka; Kuneš, Jaroslav; Maletínská, Lenka

doi:https://dx.doi.org/10.2174/1567205018666210922110652

Number of the records: 1

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

1.

SYSNO ASEP	0549436
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Palmitoylated Prolactin-releasing Peptide Reduced Aβ Plaques and Microgliosis in the Cerebellum: APP/PS1 Mice Study
Author(s)	Mengr, Anna (UOCHB-X) Hrubá, Lucie (UOCHB-X) Exnerová, Aneta (UOCHB-X) Holubová, Martina (UOCHB-X)_{RID, ORCID} Popelová, Andrea (UOCHB-X)_{RID, ORCID} Železná, Blanka (UOCHB-X)_{RID, ORCID} Kuneš, Jaroslav (UOCHB-X)_{ORCID, RID} Maletínská, Lenka (UOCHB-X)_{RID, ORCID}
Source Title	Current Alzheimer Research. - : Bentham Science Publishers - ISSN 1567-2050 Roč. 18, č. 8 (2021), s. 607-622
Number of pages	16 s.
Language	eng - English
Country	NL - Netherlands
Keywords	APP/PS1 mice ; Alzheimer´s disease ; palm11-PrRP31 ; hippocampus ; cerebellum ; amyloid-β plaques ; neuroinflammation ; synaptogenesis
OECD category	Physiology (including cytology)
R&D Projects	GA20-00546S GA ČR - Czech Science Foundation (CSF)
Method of publishing	Limited access
Institutional support	UOCHB-X - RVO:61388963
UT WOS	000723717100001
EID SCOPUS	85125720272
DOI	10.2174/1567205018666210922110652
Annotation	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.
Workplace	Institute of Organic Chemistry and Biochemistry
Contact	asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418
Year of Publishing	2022
Electronic address	https://doi.org/10.2174/1567205018666210922110652

Number of the records: 1