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Öğe Functional neural networks stratify Parkinson's disease patients across the spectrum of cognitive impairment(Wiley, 2024) Hajebrahimi, Farzin; Budak, Miray; Sarıcaoğlu, Mevhibe; Temel, Zeynep; Kahraman Demir, Tuğçe; Hanoğlu, Lütfü; Yıldırım, Süleyman; Bayraktaroğlu, ZübeyirIntroduction Cognitive impairment (CI) is a significant non-motor symptoms in Parkinson's disease (PD) that often precedes the emergence of motor symptoms by several years. Patients with PD hypothetically progress from stages without CI (PD-normal cognition [NC]) to stages with Mild CI (PD-MCI) and PD dementia (PDD). CI symptoms in PD are linked to different brain regions and neural pathways, in addition to being the result of dysfunctional subcortical regions. However, it is still unknown how functional dysregulation correlates to progression during the CI. Neuroimaging techniques hold promise in discriminating CI stages of PD and further contribute to the biomarker formation of CI in PD. In this study, we explore disparities in the clinical assessments and resting-state functional connectivity (FC) among three CI stages of PD.Methods We enrolled 88 patients with PD and 26 healthy controls (HC) for a cross sectional clinical study and performed intra- and inter-network FC analysis in conjunction with comprehensive clinical cognitive assessment.Results Our findings underscore the significance of several neural networks, namely, the default mode network (DMN), frontoparietal network (FPN), dorsal attention network, and visual network (VN) and their inter-intra-network FC in differentiating between PD-MCI and PDD. Additionally, our results showed the importance of sensory motor network, VN, DMN, and salience network (SN) in the discriminating PD-NC from PDD. Finally, in comparison to HC, we found DMN, FPN, VN, and SN as pivotal networks for further differential diagnosis of CI stages of PD.Conclusion We propose that resting-state networks (RSN) can be a discriminating factor in distinguishing the CI stages of PD and progressing from PD-NC to MCI or PDD. The integration of clinical and neuroimaging data may enhance the early detection of PD in clinical settings and potentially prevent the disease from advancing to more severe stages.Öğe Intranasal levosimendan prevents cognitive dysfunction and apoptotic response induced by repeated isoflurane exposure in newborn rats(Springer, 2021) Demirgan, Serdar; Akyol, Onat; Temel, Zeynep; Şengelen, Aslıhan; Pekmez, Murat; Ulaş, Ozancan; Sevdi, Mehmet Salih; Erkalp, Kerem; Selcan, AyşinAnesthetic-induced toxicity in early life may lead to risk of cognitive decline at later ages. Notably, multiple exposures to isoflurane (ISO) cause acute apoptotic cell death in the developing brain and long-term cognitive dysfunction. This study is the first to investigate whether levosimendan (LVS), known for its protective myocardial properties, can prevent anesthesia-induced apoptotic response in brain cells and learning and memory impairment. Postnatal day (P)7 Wistar albino pups were randomly assigned to groups consisting of an equal number of males and females in this laboratory investigation. We treated rats with LVS (0.8 mg/kg/day) intranasally 30 min before each ISO exposure (1.5%, 3 h) at P7+9+11. We selected DMSO as the drug vehicle. Also, the control group at P7+9+11 received 50% O-2 for 3 h instead of ISO. Neuroprotective activity of LVS against ISO-induced cognitive dysfunction was evaluated by Morris water maze. Expression of apoptotic-related proteins was detected in the whole brain using western blot. LVS pretreatment significantly prevented anesthesia-induced deficit in spatial learning (at P28-32) and memory (at P33, P60, and P90). No sex-dependent difference occurred on any day of the training and probe trial. Intranasal LVS was also found to significantly prevent the ISO-induced apoptosis by reducing Bax and cleaved caspase-3, and by increasing Bcl-2 and Bcl-xL. Our findings support pretreatment with intranasal LVS application as a simple strategy in daily clinical practice in pediatric anesthesia to protect infants and children from the risk of general anesthesia-induced cell death and cognitive declines.Öğe İşaret dili ve konuşma dili kullanıcılarında düşünce ve emosyona ilişkin nörofizyolojik süreçlerin nırs ve elektrofizyolojik yöntemler yolu ile araştırılması(İstanbul Medipol Üniversitesi Sağlık Bilimleri Enstitüsü, 2017) Temel, Zeynep; Hanoğlu, Lütfüİşitme duyarlılığının azalması sonucu kişinin gelişim, uyum ve iletişim becerilerinin kısıtlanması işitme kaybı olarak tanımlanmaktadır. Bu çalışmada işitme kaybında ortaya çıkan duyusal modalite kaybının düşünce ve emosyona ilişkin nörofizyoljik süreçlerde yarattığı değişikliğin İşlevsel Yakın Kızılaltı Spektroskopisi (fNIRS)ve Elektroensefalografi (EEG) ile incelenmesi amaçlanmıştır. Çalışmanın ilk aşamasında doğuştan ileri derecede işitme kaybı olan ve işaret dili bilen 3 kişi deney grubunu, 3 sağlıklı katılımcı da kontrol grubunu oluşturmuştur. Katılımcılardan içten konuşma görevi esnasında fNIRS kaydı alınmış ve beyindeki fonksiyonel değişiklikleri değerlendirilmiştir. Araştırma sonucunda işitme kaybı olan katılımcılarda kontrol grubuna kıyasla daha lokalize ve sınırlı bir aktivite kaydedilirken; kontrol grubunda ön dil alanı odaklı yaygın bir hemodinamik yanıt izlenmiştir. Deneyin ikinci aşamasında doğuştan ya da dil ediniminden önce ileri derecede işitme kaybı olan ve işaret dili bilen 8 kişi deney grubunu, 8 sağlıklı katılımcı ise kontrol grubunu oluşturmaktadır. Emosyonal süreçlerin değerlendirilmesinde kızgın, mutlu ve nötral olmak üzere 3 farklı yüz ifadesi gösterilmiş ve uyaranlara verilen elektrofizyolojik yanıtlar EEG ile kaydedilmiştir. Beynin dinamik cevaplarının analizi, Olaya İlişkin Salınımlar (OİS) yaklaşımı kullanılarak yapılmıştır. Araştırma sonucunda, hedef uyaranlara karşı verilen delta, teta ve alfa yanıtlarının elektrot bölgesinin lokalizasyonuna göre farklılıklar gösterdiği bulunmuştur (p<0.05). Ayrıca sağ hemisferde izlenen alfa yanıtının sol hemisferden daha yüksek genlikte olduğu görülmüştür (p<0.05). Bu bulgular beynin çok boyutlu dinamik yapısına vurgu yaparak, modalite kaybında beynin farklı bilişsel ve emosyonel görevler için farklı stratejiler geliştirdiği yönünde yorumlanmıştı.Öğe Isoflurane exposure in infant rats acutely increases aquaporin 4 and does not cause neurocognitive impairment(Association of Basic Medical Sciences of FBIH, 2019) Demirgan, Serdar; Akyol, Onat; Temel, Zeynep; Şengelen, Aslıhan; Pekmez, Murat; Demirgan, Recep; Sevdi, Mehmet Salih; Erkalp, Kerem; Selcan, AyşinIsoflurane is commonly used in pediatric population, but its mechanism of action in cognition is unclear. Aquaporin 4 (AQP4) regulates water content in blood, brain, and cerebrospinal fluid. Various studies have provided evidence for the role of AQP4 in synaptic plasticity and neurocognition. In this study, we aimed to determine whether a prolonged exposure to isoflurane in infant rats is associated with cognition and what effect this exposure has on AQP4 expression. Ten-day-old [postnatal day (P) 10] Wistar albino rats were randomly allocated to isoflurane group (n = 32; 1.5% isoflurane in 50% oxygen for 6 hours) or control group (n = 32; only 50% oxygen for 6 hours). Acute (P11) and long-term (P33) effects of 6-hour anesthetic isoflurane exposure on AQP4 expression were analyzed in whole brains of P11 and P33 rats by RT-qPCR and Western blot. Spatial learning and memory were assessed on P28 to P33 days by Morris Water Maze (MWM) test. The analysis revealed that isoflurane increased acutely both mRNA (~4.5 fold) and protein (~90%) levels of AQP4 in P11 rats compared with control group. The increasing levels of AQP4 in P11 were not observed in P33 rats. Also, no statistically significant change between isoflurane and control groups was observed in the latency to find the platform during MWM training and probe trial. Our results indicate that a single exposure to isoflurane anesthesia does not influence cognition in infant rats. In this case, acutely increased AQP4 after isoflurane anesthesia may have a protective role in neurocognition.Öğe Optimization of morris water maze protocols: effects of water temperature and hypothermia on spatial learning and memory in aged female rats(2024) Oran, Duygu Sultan; Temel, Zeynep; Başer, İbrahim Gökşin; Temizyürek, Arzu; Selcan, AyşinIntroduction: Aging is a highly complex process driven by a multitude of factors. The use of humans in aging research is complicated by many factors (ethical issues; environmental and social factors; long natural life span). Therefore, rats are common models for the study of aging and age-related diseases. The Morris water maze test is one of the most common cognitive tests in studies investigating age-related learning and memory. However, standardized protocols are lacking, which could influence results. This study investigated the effects of water temperature and inter-trial interval on physiological parameters, hippocampus-dependent learning, and memory in aged female rats performing the Morris Water Maze. Materials and Methods: Thirty-two female Wistar Hannover rats, aged over 18 months, were divided into four groups based on water temperature (20 °C or 24 °C) and inter-trial interval (30 seconds or 13 minutes). Results: Rats exposed to 24 °C demonstrated better spatial learning and memory retention than those at 20 °C. The interaction between inter-trial interval and water temperature significantly affected memory, with higher temperatures improving memory, especially with shorter intervals. Inter-trial interval alone did not significantly affect learning, but longer durations were associated with more stable body temperatures. Neither water temperature nor inter-trial interval significantly influenced body weight. Conclusion: These findings emphasize the need to standardize environmental conditions in Morris water maze protocols to enhance research validity and reliability. Optimizing these protocols is crucial to upholding ethical standards and ensuring animal welfare, advancing more effective and scientifically sound practices in gerontological research, and fostering a better understanding of aging processes.
