Scholarly Publications - UMRAM

Permanent URI for this collectionhttps://hdl.handle.net/11693/115674

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Browsing Scholarly Publications - UMRAM by Author "Adams, Michelle M."

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    Dietary and pharmacological interventions that inhibit mammalian target of rapamycin activity alter the brain expression levels of neurogenic and glial markers in an age-and treatment-dependent manner
    (Mary Ann Liebert, 2020) Çelebi-Birand, Dilan; Ardıç, Narin İlgim; Karoğlu-Eravşar, Elif Tuğçe; Şengül, Göksemin Fatma; Kafalıgönül, Hulusi; Adams, Michelle M.
    Intermittent fasting (IF) and its mimetic, rapamycin extend lifespan and healthspan through mechanisms that are not fully understood. We investigated different short-term durations of IF and rapamycin on cellular and molecular changes in the brains of young (6–10 months) and old (26–31 months) zebrafish. Interestingly, our results showed that IF significantly lowered glucose levels while increasing DCAMKL1 in both young and old animals. This proliferative effect of IF was supported by the upregulation of foxm1 transcript in old animals. Rapamycin did not change glucose levels in young and old animals but had differential effects depending on age. In young zebrafish, proliferating cell nuclear antigen and the LC3-II/LC3-I ratio was decreased, whereas glial fibrillary acidic protein and gephyrin were decreased in old animals. The changes in proliferative markers and a marker of autophagic flux suggest an age-dependent interplay between autophagy and cell proliferation. Additionally, changes in glia and inhibitory tone suggest a suppressive effect on neuroinflammation but may push the brain toward a more excitable state. Mammalian target of rapamycin (mTOR) activity in the brain following the IF and rapamycin treatment was differentially regulated by age. Interestingly, rapamycin inhibited mTOR more potently in young animals than IF. Principal component analysis supported our conclusion that the regulatory effects of IF and rapamycin were age-specific, since we observed different patterns in the expression levels and clustering of young and old animals. Taken together, our results suggest that even a short-term duration of IF and rapamycin have significant effects in the brain at young and old ages, and that these are age and treatment dependent.
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    Long-term acetylcholinesterase depletion alters the levels of key synaptic proteins while maintaining neuronal markers in the aging zebrafish (Danio rerio) Brain
    (S. Karger AG, 2023-10-04) Karoğlu-Eravsar, Elif Tuğçe; Tüz-Şaşik, Melek Umay; Karaduman, Ayşenur; Keşküş, Ayse Gökçe; Arslan-Ergul, Ayça; Konu, Özlen; Kafalıgönül, Hulusi; Adams, Michelle M.
    Introduction: Interventions targeting cholinergic neurotransmission like acetylcholinesterase (AChE) inhibition distinguish potential mechanisms to delay age-related impairments and attenuate deficits related to neurodegenerative diseases. However, the chronic effects of these interventions are not well described. Methods: In the current study, global levels of cholinergic, cellular, synaptic, and inflammation-mediating proteins were assessed within the context of aging and chronic reduction of AChE activity. Long-term depletion of AChE activity was induced by using a mutant zebrafish line, and they were compared with the wildtype group at young and old ages. Results: Results demonstrated that AChE activity was lower in both young and old mutants, and this decrease coincided with a reduction in ACh content. Additionally, an overall age-related reduction in AChE activity and the AChE/ACh ratio was observed, and this decline was more prominent in wildtype groups. The levels of an immature neuronal marker were upregulated in mutants, while a glial marker showed an overall reduction. Mutants had preserved levels of inhibitory and presynaptic elements with aging, whereas glutamate receptor subunit levels declined. Conclusion: Long-term AChE activity depletion induces synaptic and cellular alterations. These data provide further insights into molecular targets and adaptive responses following the long-term reduction of AChE activity that was also targeted pharmacologically to treat neurodegenerative diseases in human subjects.
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    Passive exposure to visual motion leads to short-term changes in the optomotor response of aging zebrafish
    (Cambridge University Press, 2024-03) Karaduman, Ayşenur; Karaoğlu-Eravşar, Elif Tuğçe; Adams, Michelle M.; Kafalıgönül, Hulusi
    Numerous studies have shown that prior visual experiences play an important role in sensory processing and adapting behavior in a dynamic environment. A repeated and passive presentation of visual stimulus is one of the simplest procedures to manipulate acquired experiences. Using this approach, we aimed to investigate exposure- based visual learning of aging zebrafish and how cholinergic intervention is involved in exposure-induced changes. Our measurements included younger and older wild-type zebrafish and achesb55/+mutants with decreased acetylcholinesterase activity. We examined both within-session and across-day changes in the zebrafish optomotor responses to repeated and passive exposure to visual motion. Our findings revealed short- term (within-session) changes in the magnitude of optomotor response (i.e., the amount of position shift by fish as a response to visual motion) rather than long-term and persistent effects across days. Moreover, the observed short-term changes were age- and genotype-dependent. Compared to the initial presentations of motion within a session, the magnitude of optomotor response to terminal presentations decreased in the older zebrafish. There was a similar robust decrease specific to achesb55/+mutants. Taken together, these results point to short- term (within-session) alterations in the motion detection of adult zebrafish and suggest differential effects of neural aging and cholinergic system on the observed changes. These findings further provide important insights into adult zebrafish optomotor response to visual motion and contribute to understanding this reflexive behavior in the short- and long-term stimulation profiles.
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    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.