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    Altered gut microbiota in patients with idiopathic Parkinson’s disease: an age–sex matched case–control study
    (Springer, 2023) Babacan Yıldız, Gülşen; Kayacan, Zeynep Çiğdem; Karacan, İlker; Sümbül, Bilge; Elibol, Birsen; Gelisin, Özlem; Akgül, Özer
    Objective: The investigations related to how gut microbiota changes the brain-gut axis in idiopathic Parkinson's disease (PD) attract growing interest. We aimed to determine whether gut microbiota is altered in PD patients and whether non-motor symptoms of PD and disease duration had any relation with alterations of microbiota profiles among patients. Methods: Microbial taxa in stool samples obtained from 84 subjects (42-PD patients and 42-healthy spouses) were analyzed using 16S rRNA amplicon-sequencing. Results: We observed a significant decrease of Firmicutes and a significant increase of Verrucomicrobiota at the phylum level. At the family level, Lactobacillaceae and Akkermansiaceae were significantly increased and Coriobacteriales Incertae Sedis were significantly decreased in the PD patients compared to their healthy spouses. Genus level comparison inferred significant increase in abundance only in Lactobacillus while the abundance of Lachnospiraceae ND3007 group, Tyzzerella, Fusicatenibacter, Eubacterium hallii group and Ruminococcus gauvreauii group were all decreased. We determined that the abundance of Prevotella genus decreased, but not significantly in PD patients. In addition, we found differences in microbiota composition between patients with and without non-motor symptoms. Conclusion: We observed differences in gut microbiota composition between PD patients and their healthy spouses. Our findings suggest that disease duration influenced microbiota composition, which in turn influenced development of non-motor symptoms in PD. This study is the first in terms of both gut microbiota research in Turkish PD patients and the probable effect of microbiota on non-motor symptoms of PD.
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    Chronic pantoprazole exposure induces behavioral deficits and region‑specific molecular changes in the rat motor cortex and cerebellum
    (Nencki Institute of Experimental Biology, 2026) Çaglar, Emine; Elibol, Birsen; Polat, Nurhayat; Dursun, İlknur
    Proton pump inhibitors are widely used, but their long‑term effects on the central nervous system are not well understood. In this study, we investigated whether chronic pantoprazole use alters sensorimotor function, oxidative stress, inflammatory response, and apoptosis in the motor cortex and cerebellum. Twenty‑one female Wistar rats were randomized to control (C), gavage control (GC), or pantoprazole (P; 20 mg/kg/day for 12 weeks) groups. Sensorimotor coordination (rotarod), water‑maze swim velocity, and open‑field locomotion were assessed as behavioral parameters. The cortical and cerebellar tissues were analyzed by Enzyme‑Linked Immunosorbent Assay (ELISA) for apoptosis, inflammation, and oxidative stress. Pantoprazole impaired sensorimotor coordination compared to both control groups. However, its effects on swim velocity and locomotor activity were primarily significant when compared to the naive control group, suggesting that gavage‑related stress may have contributed to these behavioral outcomes. Bcl‑2‑associated X protein (BAX) and Bcl‑2 associated agonist of cell death (BAD) protein levels and the BAX/Bcl‑2 ratio increased with pantoprazole, particularly in the motor cortex, indicating enhanced pro‑apoptotic activity. While tumor necrosis factor levels did not change, interleukin (IL)‑6 and IL‑1β levels were significantly higher in the cerebellum, suggesting neuroinflammatory activation associated with both pantoprazole and gavage‑induced stress. Furthermore, oxidative stress analyses revealed elevated malondialdehyde and oxidative stress index levels, as well as increased total antioxidant status, in specific regions, suggesting an imbalance between oxidative and antioxidant responses. Chronic pantoprazole administration resulted in modest motor deficits and region‑specific molecular alterations, including a pro‑apoptotic shift in the motor cortex. In addition, an inflammatory/compensatory antioxidant response in the cerebellum was observed due to both gavage‑induced stress and pantoprazole administration. These findings highlight the need for further studies on dose‑response, reversibility, and synaptic consequences, and suggest the importance of considering the risks of prolonged proton pump inhibitors exposure.
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    Strain-dependent differences in neuroplasticity markers related to memory
    (İnönü University Faculty of Medicine, 2026) Dursun, İlknur; Kılıç, Ertuğrul; Elibol, Birsen
    Aim: Spatial learning and memory both rely critically on hippocampal plasticity which are a core feature of several neurological and psychiatric disorders; but commonly used different rat strains might exhibit differences in these processes which may influence the translational relevance of preclinical findings Herein, we examined the long-term spatial memory of adult Wistar (n=5), Sprague Dawley (n=6), and Long Evans (n=5) rats, and their hippocampalexpressionoftwo plasticity markers: brain-derivedneurotrophicfactor (BDNF) and doublecortin (DCX). Materials and Methods: TheanimalsweretrainedintheMorriswatermazeforfourdays, followed by a probe trial with no platform. Hippocampal BDNF and DCX protein levels were quantified by Western blotting. Results: All strains learned the task, as indicated by a decrease in escape latency and swim distance over time. Sprague Dawley rats swam faster than the other strains, sug gesting that swim distance evaluates learning independently of speed. On the first train ing day, Wistar rats swam the shortest distances, whereas by the final day Long Evans rats did. In the probe trial, Sprague Dawley rats spent a greater proportion of time in the target quadrant than Wistar rats did. Long Evans rats displayed an intermediate pattern. At the molecular level, Sprague--Dawley rats had higher hippocampal BDNF levels than Wistar and Long-Evans rats. DCX levels were higher in Sprague Dawley and Long Evans rats than in Wistar rats. Conclusion: These findings suggest that although all three strains can acquire and retain spatial memory under identical conditions, they differ in behavioral strategies and hip pocampal plasticity. Therefore, strain background should be carefully considered when designing and interpreting rodent studies of learning and memory.
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    The effects of early postnatal alcohol exposure on bone molecular composition in a mouse model
    (Wiley, 2026) Dursun, İlknur; Elibol, Birsen; Garip Ustaoğlu, Şebnem
    Background: Perinatal exposure to alcohol is a critical risk factor for long- term skeletal health in humans and has been demon strated in rodent models. Early postnatal alcohol gavage exposure in mice is used to study third trimester toxicity in humans. However, further research is required to fully characterize the effects of alcohol on bone molecular composition and distinguish them from the alterations associated with gavage- related stress in mouse models. Methods: Female mouse pups were assigned to untreated control (C), gavage control (GC), and alcohol- treated (A) groups. Between postnatal days 3 and 20, the A group received ethanol (3.0 g/kg/day) by intragastric gavage, while the GC group under went the same gavage procedure without any solution (neither milk nor ethanol). At postnatal day 90, femoral bone molecular composition and bone metabolism were evaluated by attenuated total reflection Fourier- transform infrared (ATR- FTIR) spec troscopy and biochemical studies. Results: Several ATR- FTIR- derived matrix and mineral- related alterations, including reduced total protein- related indices, lower collagen cross- link ratio, reduced mineral- to- matrix ratio, and increased crystallinity, were observed in both GC and A groups rel ative to untreated controls, indicating a substantial long- term influence of the gavage procedure itself. Compared with the GC, the A group showed additional selective differences, most notably reduced relative carbonate content and increased CTX- I levels. In the C group, serum 25(OH)D, PTH, and calcitonin levels differed from both GC and A groups, whereas osteocalcin was increased in the GC group relative to the C group, and no significant difference was observed between the GC and A groups. Conclusion: Prolonged neonatal gavage was associated with substantial long- term changes in bone molecular composition and several circulating bone- related hormonal markers. Against this background, postnatal alcohol exposure was associated with additional selective differences, particularly in CTX- I and relative carbonate content. These findings highlight the importance of discriminating between the effect of the procedure and the effect of alcohol in developmental models based on repeated neonatal gavage.

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