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.
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.
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.
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.
These results suggest palm11-PrRP31 is a promising agent for the treatment of neurodegenerative disorders.
Prolactin-releasing peptide (PrRP), a natural ligand for the GPR10 receptor, is a neuropeptide with anorexigenic and antidiabetic properties. Due to its role in the regulation of food intake, PrRP is ...a potential drug for obesity treatment and associated type 2 diabetes mellitus (T2DM). Recently, the neuroprotective effects of lipidized PrRP analogs have been proven. In this study, we focused on the molecular mechanisms of action of natural PrRP31 and its lipidized analog palm
-PrRP31 in the human neuroblastoma cell line SH-SY5Y to describe their cellular signaling and possible anti-apoptotic properties. PrRP31 significantly upregulated the phosphoinositide-3 kinase-protein kinase B/Akt (PI3K-PKB/Akt) and extracellular signal-regulated kinase/cAMP response element-binding protein (ERK-CREB) signaling pathways that promote metabolic cell survival and growth. In addition, we proved via protein kinase inhibitors that activation of signaling pathways is mediated specifically by PrRP31 and its palmitoylated analog. Furthermore, the potential neuroprotective properties were studied through activation of anti-apoptotic pathways of PrRP31 and palm
-PrRP31 using the SH-SY5Y cell line and rat primary neuronal culture stressed with toxic methylglyoxal (MG). The results indicate increased viability of the cells treated with PrRP and palm
-PrRP31 and a reduced degree of apoptosis induced by MG, suggesting their potential use in the treatment of neurological disorders.
Abstract
When learning to discriminate between palatable and unpalatable prey, predators may encounter the prey either simultaneously or in a sequence. The two types of discrimination tasks, which ...are frequently used in experiments focused on aposematism and mimicry, may considerably differ in difficulty, as they differ in the information available to predators during individual encounters with prey. Surprisingly, there are very few studies directly comparing the performance of predators between sequential and simultaneous discrimination tasks using otherwise identical experimental design, the same predators and prey. We tested the effect of the type of discrimination task on the effectiveness of discrimination learning in adult and juvenile great tits (
Parus major
). Birds were trained to discriminate between palatable and unpalatable artificial prey items baited with mealworms soaked either in water or quinine. Prey shape, colours and patterns were derived from real shield bug species. We compared the performance of birds tested with two discriminative cues, colour and pattern, using three discrimination tasks: (1) sequential—alternating presentation of one palatable and one unpalatable prey item, (2) two‐choice—simultaneous presentation of one palatable and one unpalatable prey item and (3) multiple‐choice—simultaneous presentation of multiple palatable and unpalatable prey items. Colour was a more effective discriminative cue than pattern for both adult and juvenile birds. Adults performed better than juveniles regardless of task. The birds performed equally well in the sequential and two‐choice tasks, but their performance in the multiple‐choice task was worse than in the other two tasks. However, these differences were only present when the birds used the pattern as a discriminative cue. The birds tested with colour, a more salient cue, performed equally well in all three tasks. Type of discrimination task may therefore affect the learning performance of predators, but the effect also depends on the saliency of a particular discriminative cue.
The efficiency of defensive mechanisms in 11 European aposematic species of Heteroptera against various passerine predators was analysed. Bird species differed in their reactions to aposematic preys: ...small insectivorous birds generally avoided aposematic bugs, but granivorous birds as well as large insectivorous birds frequently attacked them. The ability to overcome heteropteran chemical defences appears to be connected with the larger body size of birds and with their food-storing behaviour. From the bird's point of view, various red-and-black aposematic species of Heteroptera form a mimetic complex. However, antipredatory defence properties of individual species differ substantially in their efficiency against bird predators, and the nature of the mimetic complex is rather quasi-Batesian than Muellerian.
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