Lipidized analogues of the anorexigenic CART (cocaine- and amphetamine-regulated transcript) neuropeptide show anorexigenic and neuroprotective potential in mouse model of monosodium-glutamate induced obesity.

AIMS: This study investigates the neuroprotective effects of lipidized analogues of 2-SS-CART(61-102) derived from anorexigenic neuropeptide cocaine- and amphetamine-regulated transcript peptide (CARTp) in light of the link between obesity, its comorbidities, and the development of Alzheimer's disease. METHODS: We introduce novel lipidized analogues derived from 2-SS-CART(61-102), a specific analogue of natural CART(61-102), with two disulfide bridges. Using hypothermic PC12 cells, we tested the effect of the most potent analogues on Tau phosphorylation. We further described the anorexigenic and neuroprotective potential of subcutaneously (SC) injected lipidized CARTp analogue in a mouse model with prediabetes and obesity induced by neonatal monosodium glutamate (MSG) administration. RESULTS: Compared to the non-lipidized 2-SS-CART(61-102), all lipidized analogues exhibited a potent binding affinity to PC12 cells and enhanced in vitro stability in rat plasma. Two most potent lipidized analogues attenuated hypothermia-induced Tau hyperphosphorylation at multiple epitopes. Subsequently, chronic SC treatment with palm-2-SS-CART(61-102) significantly decreased body weight and food intake, improved metabolic parameters, decreased level of pTau and increased neurogenesis in hippocampi of obese MSG mice. CONCLUSION: Our unique CARTp analogue palm-2-SS-CART(61-102) shows promise as a potent anti-obesity and neuroprotective agent.

Pupils' Attitudes toward Inclusive Education.

The presented research is a study of the attitudes of adolescents toward individuals with disabilities and a description of the level of knowledge about this issue among a selected group of adolescents. The study is focused on the school social environment, specifically on pupils without disabilities and their attitudes toward pupils with disabilities, which is one of the factors influencing their school success. The target group was 1806 pupils between the ages of 11 and 16 from the entire Czech Republic, approached by random selection. The research tool for the quantitative approach was a questionnaire developed by the authors of this article. The questionnaire section with open questions served for the qualitative part of the research. The results show that 70% of the respondents have basic knowledge about people with disabilities. Furthermore, it was shown that these adolescents have an overall positive attitude toward people with disabilities. This attitude is statistically significantly better among the girls than the boys, and the girls are also more open to discussing individuals with disabilities. At the same time, even if attitudes are positive, they still depend on the type of disability. The greatest uncertainty or discomfort is manifested when interacting with individuals with intellectual disabilities.