Browsing by Subject "Brain aging"
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Item Open Access Effects of varying levels and differing durations of calorie restriction on cellular and synaptic proteins, as well as the inflammatory state of the female mouse brain(2020-09) Macaroğlu, DuyguAging is an inevitable and complicated process leading to functional decline. Regarding brain aging, cognitive decline takes place in multiple domains, including learning, memory, executive functions, motor coordination, and language. At the cellular and molecular level, age-related cognitive decline is elucidated with certain hallmarks, including aberrant neuronal network, stem cell exhaustion, glial cell activation, and inflammation. Calorie restriction (CR) is a widely-utilized approach for coping with aging’s detrimental effects even though there is no one agreed way for the application of CR. In this study, varying levels of CRs were applied for differing durations to MMTV-TGF-alpha female mice. The study initiated when mice were 10-weeks of age (Baseline) and carried out until 49/50 weeks of age and 81/82 weeks of age. There were four dietary groups named Adlibitum (AL; control), Chronic Calorie Restriction (CCR), Intermittent Calorie Restriction - Restriction (ICR-R), and Intermittent Calorie Restriction -Refeed (ICR-RF). The study’s first aim was to show age-related changes in the cellular and synaptic proteins and the inflammatory state of the female mice’s brains. The second aim of the study is to demonstrate the effects of varying levels of CR implemented for the short-term and the long-term manner on the same hallmarks. Our findings showed both chronic- or intermittent- CR altered the synaptic integrity proteins against brain aging at the long-term period (81/82 weeks) compared to the short-term (49/50 weeks) period except for PSD-95. Similarly, both chronic- or intermittent- CR showed an attenuative impact on the pro-inflammatory markers, but IL-6 was affected only by CCR at the same periods. Furthermore, an age-related imbalance between neurogenesis and astrogliogenesis was shown based on DCX and GFAP. Both chronic- or intermittent- CR showed a compensatory effect on it acting through astrogliogenesis, even though it was not statistically significant.Item Open Access Expression of key synaptic proteins in Zebrafish (Danio Rerio) brain following caloric restriction and its mimetic and their relationship with gender(2017-01) Dede, AyşegülAging is a progressive decline of physiological functioning and metabolic processes. Among all the organs, the brain seems to be the most vulnerable part of the body to the age-related changes because of the relatively high consumption of oxygen and glucose as compared to other organs. Both structural and cognitive changes occur during the aging process. A great effort has been spent to ameliorate the outcomes occurring within the brain as a result of aging. Caloric restriction (CR) is considered to be the only non-genetic intervention which decreases age-related cognitive decline. Rapamycin (RAP) has become a candidate drug which was shown to mimic the effects of CR by blocking the nutrient-sensing pathway, the mammalian target of Rapamycin, (mTOR) pathway. The first aim of this study was to investigate the expressions of key synaptic proteins; gephyrin, PSD-95 and synaptophysin, which are involved in the synaptic plasticity, after short-term (4 weeks) CR and RAP interventions in young and old, male and female zebrafish. The second aim was to investigate whether the expression of glutamate receptor subunits, NR2B and GluR2/3, display a sexually dimorphic pattern in middle age zebrafish. It was found that there was no significant difference in the expression of key synaptic proteins between the CR and RAP animal groups as compared to the ad libitium (AL) fed group and also no significance was found in the expression of NR2B and GluR2/3 in middle-aged male and female zebrafish. Highlighted studies in this thesis demonstrate that short-term (4 weeks) of CR and RAP treatments were too short to observe an effect in the expression level of gephyrin, synaptophysin, and PSD-95, and in the middle age, expression of NR2B and GluR2/3 did not display sexually dimorphic pattern. Our initial results of key synaptic protein levels indicate that they are stable throughout aging with respect to gender and CR interventions.Item Open Access Zebrafish brain RNA sequencing reveals that cell adhesion molecules are critical in brain aging(Elsevier, 2020) Erbaba, Begün; Burhan, Özge Pelin; Şerifoğlu, Naz; Muratoğlu, B.; Kahveci, Fatma; Adams, Michelle M.; Arslan-Ergül, A.Brain aging is a complex process, which involves multiple pathways including various components from cellular to molecular. This study aimed to investigate the gene expression changes in zebrafish brains through young-adult to adult, and adult to old age. RNA sequencing was performed on isolated neuronal cells from zebrafish brains. The cells were enriched in progenitor cell markers, which are known to diminish throughout the aging process. We found 176 statistically significant, differentially expressed genes among the groups, and identified a group of genes based on gene ontology descriptions, which were classified as cell adhesion molecules. The relevance of these genes was further tested in another set of zebrafish brains, human healthy, and Alzheimer’s disease brain samples, as well as in Allen Brain Atlas data. We observed that the expression change of 2 genes, GJC2 and ALCAM, during the aging process was consistent in all experimental sets. Our findings provide a new set of markers for healthy brain aging and suggest new targets for therapeutic approaches to neurodegenerative diseases.