Publications by authors named "Melek Umay Tuz-Sasik"

3 Publications

  • Page 1 of 1

Short-term dietary restriction maintains synaptic plasticity whereas short-term overfeeding alters cellular dynamics in the aged brain: evidence from the zebrafish model organism.

Neurobiol Aging 2021 10 19;106:169-182. Epub 2021 Jun 19.

Interdisciplinary Program in Neuroscience, Aysel Sabuncu Brain Research Center, Bilkent University, Ankara, Turkey; National Nanotechnology Research Center (UNAM), Bilkent University, Ankara, Turkey; Department of Molecular Biology and Genetics, Zebrafish Facility, Bilkent University, Ankara, Turkey; Department of Psychology, Bilkent University, Ankara, Turkey. Electronic address:

Increased caloric intake (OF) impairs quality of life causing comorbidities with other diseases and cognitive deficits, whereas dietary restriction (DR) increases healthspan by preventing age-related deteriorations. To understand the effects of these opposing dietary regimens on the cellular and synaptic dynamics during brain aging, the zebrafish model, which shows gradual aging like mammals, was utilized. Global changes in cellular and synaptic markers with respect to age and a 12 week dietary regimen of OF and DR demonstrated that aging reduces the levels of the glutamate receptor subunits, GLUR2/3, inhibitory synaptic clustering protein, GEP, synaptic vesicle protein, SYP, and early-differentiated neuronal marker, HuC. DR significantly elevates levels of glutamate receptor subunits, GLUR2/3, and NMDA clustering protein, PSD95, levels, while OF subtly increases the level of the neuronal protein, DCAMKL1. These data suggest that decreased caloric intake within the context of aging has more robust effects on synapses than cellular proteins, whereas OF alters cellular dynamics. Thus, patterns like these should be taken into account for possible translation to human subjects.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.06.010DOI Listing
October 2021

Environmental enrichment applied with sensory components prevents age-related decline in synaptic dynamics: Evidence from the zebrafish model organism.

Exp Gerontol 2021 07 8;149:111346. Epub 2021 Apr 8.

Interdisciplinary Program in Neuroscience, Aysel Sabuncu Brain Research Center, Bilkent University, Ankara, Turkey; National Nanotechnology Research Center (UNAM), Bilkent University, Ankara, Turkey; Department of Molecular Biology and Genetics, Zebrafish Facility, Bilkent University, Ankara, Turkey; Department of Psychology, Bilkent University, Ankara, Turkey. Electronic address:

Progression of cognitive decline with or without neurodegeneration varies among elderly subjects. The main aim of the current study was to illuminate the molecular mechanisms that promote and retain successful aging in the context of factors such as environment and gender, both of which alter the resilience of the aging brain. Environmental enrichment (EE) is one intervention that may lead to the maintenance of cognitive processing at older ages in both humans and animal subjects. EE is easily applied to different model organisms, including zebrafish, which show similar age-related molecular and behavioral changes as humans. Global changes in cellular and synaptic markers with respect to age, gender and 4-weeks of EE applied with sensory stimulation were investigated using the zebrafish model organism. Results indicated that EE increases brain weight in an age-dependent manner without affecting general body parameters like body mass index (BMI). Age-related declines in the presynaptic protein synaptophysin, AMPA-type glutamate receptor subunits and a post-mitotic neuronal marker were observed and short-term EE prevents these changes in aged animals, as well as elevates levels of the inhibitory scaffolding protein, gephyrin. Gender-driven alterations were observed in the levels of the glutamate receptor subunits. Oxidative stress markers were significantly increased in the old animals, while exposure to EE did not alter this pattern. These data suggest that EE with sensory stimulation exerts its effects mainly on age-related changes in synaptic dynamics, which likely increase brain resilience through specific cellular mechanisms.
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http://dx.doi.org/10.1016/j.exger.2021.111346DOI Listing
July 2021

Expression Levels of SMAD Specific E3 Ubiquitin Protein Ligase 2 (Smurf2) and its Interacting Partners Show Region-specific Alterations During Brain Aging.

Neuroscience 2020 06 8;436:46-73. Epub 2020 Apr 8.

Interdisciplinary Program in Neuroscience, Aysel Sabuncu Brain Research Center, Bilkent University, Ankara, Turkey; National Nanotechnology Research Center (UNAM), Bilkent University, Ankara, Turkey; Department of Molecular Biology and Genetics, Zebrafish Facility, Bilkent University, Ankara, Turkey; Department of Psychology, Bilkent University, Ankara, Turkey. Electronic address:

Aging occurs due to a combination of several factors, such as telomere attrition, cellular senescence, and stem cell exhaustion. The telomere attrition-dependent cellular senescence is regulated by increased levels of SMAD specific E3 ubiquitin protein ligase 2 (smurf2). With age smurf2 expression increases and Smurf2 protein interacts with several regulatory proteins including, Smad7, Ep300, Yy1, Sirt1, Mdm2, and Tp53, likely affecting its function related to cellular aging. The current study aimed at analyzing smurf2 expression in the aged brain because of its potential regulatory roles in the cellular aging process. Zebrafish were used because like humans they age gradually and their genome has 70% similarity. In the current study, we demonstrated that smurf2 gene and protein expression levels altered in a region-specific manner during the aging process. Also, in both young and old brains, Smurf2 protein was enriched in the cytosol. These results imply that during aging Smurf2 is regulated by several mechanisms including post-translational modifications (PTMs) and complex formation. Also, the expression levels of its interacting partners defined by the STRING database, tp53, mdm2, ep300a, yy1a, smad7, and sirt1, were analyzed. Multivariate analysis indicated that smurf2, ep300a, and sirt1, whose proteins regulate ubiquitination, acetylation, and deacetylation of target proteins including Smad7 and Tp53, showed age- and brain region-dependent patterns. Our data suggest a likely balance between Smurf2- and Mdm2-mediated ubiquitination, and Ep300a-mediated acetylation/Sirt1-mediated deacetylation, which most possibly affects the functionality of other interacting partners in regulating cellular and synaptic aging and ultimately cognitive dysfunction.
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http://dx.doi.org/10.1016/j.neuroscience.2020.04.003DOI Listing
June 2020
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