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Publication Metadata only Altered transcriptional profile of mitochondrial DNA-Encoded OXPHOS subunits, mitochondria quality control genes, and intracellular ATP levels in blood samples of patients with Parkinson's disease(Ios Press, 2020) Gezen-Ak, Duygu; Alaylioglu, Merve; Genc, Gencer; Sengul, Busra; Keskin, Ebru; Sordu, Pelin; Gulec, Zeynep Ece Kaya; Apaydin, Hulya; Bayram-Gurel, Cigdem; Ulutin, Turgut; Yilmazer, Selma; Dursun, Erdinc; N/A; Ertan, Fatoş Sibel; Faculty Member; School of Medicine; 112829Mitochondrial dysfunctions are significant contributors to neurodegeneration. One result or a cause of mitochondrial dysfunction might be the disruption of mtDNA transcription. Limited data indicated an altered expression of mtDNA encoded transcripts in Alzheimer's disease (AD) or Parkinson's disease (PD). The number of mitochondria is high in cells with a high energy demand, such as muscle or nerve cells. AD or PD involves increased risk of cardiomyopathy, suggesting that mitochondrial dysfunction might be systemic. If it is systemic, we should observe it in different cell types. Given that, we wanted to investigate any disruption in the regulation of mtDNA encoded gene expression in addition to PINK1, PARKIN, and ATP levels in peripheral blood samples of PD cases who are affected by a neurodegenerative disorder that is very well known by its mitochondrial aspects. Our results showed for the first time that: 1) age of onset > 50 PD sporadic (PDS) cases: mtDNA transcription and quality control genes were affected; 2) age of onset <50 PDS cases: only mtDNA transcription was affected; and 3) PD cases with familial background: only quality control genes were affected. mtDNA copy number was not a confounder. Intracellular ATP levels of PD case subgroups were significantly higher than those of healthy subjects. We suggest that a systemic dysregulation of transcription of mtDNA or mitochondrial quality control genes might result in the development of a sporadic form of the disease. Additionally, ATP elevation might be an independent compensatory and response mechanism. Hyperactive cells in AD and PD require further investigation.Publication Metadata only Extracellular vesicles derived from bone marrow mesenchymal stem cells enhance myelin maintenance after cortical injury in aged rhesus monkeys(Elsevier, 2021) Go, Veronica; Zhou, Yuxin; Bowley, Bethany G. E.; Pessina, Monica A.; Rosene, Douglas L.; Zhang, Zheng Gang; Chopp, Michael; Finklestein, Seth P.; Medalla, Maria; Buller, Benjamin; Moore, Tara L.; N/A; Sarıkaya, Deniz; Undergraduate Student; School of Medicine; N/ACortical injury, such as stroke, causes neurotoxic cascades that lead to rapid death and/or damage to neurons and glia. Axonal and myelin damage in particular, are critical factors that lead to neuronal dysfunction and impair recovery of function after injury. These factors can be exacerbated in the aged brain where white matter damage is prevalent. Therapies that can ameliorate myelin damage and promote repair by targeting oligodendroglia, the cells that produce and maintain myelin, may facilitate recovery after injury, especially in the aged brain where these processes are already compromised. We previously reported that a novel therapeutic, Mesenchymal Stem Cell derived extracellular vesicles (MSC-EVs), administered intravenously at both 24 h and 14 days after cortical injury, reduced microgliosis (Go et at, 2019), reduced neuronal pathology (Medalla et al. 2020), and improved motor recovery (Moore et al. 2019) in aged female rhesus monkeys. Here, we evaluated the effect of MSC-EV treatment on changes in oligodendrocyte maturation and associated myelin markers in the sublesional white matter using immunohistochemistry, confocal microscopy, stereology, qRT-PCR, and ELISA. Compared to vehicle control monkeys, EV-treated monkeys showed a reduction in the density of damaged oligodendrocytes. Further, EV-treatment was associated with enhanced myelin maintenance, evidenced by upregulation of myelin-related genes and increases in actively myelinating oligodendrocytes in sublesional white matter. These changes in myelination correlate with the rate of motor recovery, suggesting that improved myelin maintenance facilitates this recovery. Overall, our results suggest that EVs act on oligodendrocytes to support myelination and improves functional recovery after injury in the aged brain. Significance: We previously reported that EVs facilitate recovery of function after cortical injury in the aged monkey brain, while also reducing neuronal pathology (Medalla et al. 2020) and microgliosis (Go et al. 2019). However, the effect of injury and EVs on oligodendrocytes and myelination has not been characterized in the primate brain (Doewar et al. 1999; Sozem et al. 2013). In the present study, we assessed changes in myelination after cortical injury in aged monkeys. Our results show, for the first time, that MSC-EVs support recovery of function after cortical injury by enhancing myelin maintenance in the aged primate brain.Publication Metadata only A stimulus rate that is not influenced by homosynaptic post-activation depression in chronic stroke(Taylor & Francis Ltd, 2020) Yurttutmus, Zeynep; Ekici Zincirci, Dilara; Bardak, Ayşe Nur; Aydın, Tuğba; Karacan, İlhan; N/A; N/A; Topkara, Betilay; Türker, Kemal Sıtkı; PhD Student; Faculty Member; Graduate School of Health Sciences; School of Medicine; 353320; 6741Purpose: To determine a stimulus rate that is not influenced by homosynaptic post-activation depression for H-reflex studies in patients with chronic spasticity. Materials and Methods: A cohort of 15 chronic stroke patients with soleus spasticity who received inpatient treatment at our rehabilitation centre participated in this study. The effect of stimulus frequency related depression on H-reflex size was tested using four different stimulus rates (0.1, 0.2, 0.3 and 1 Hz). The affected sides stibial nerve was stimulated by a bipolar electrode. The H-reflex was recorded from the affected sideed sidee sidehe affected smine stimulus frequency related depression of H-reflex size, amplitude of the first H-reflex response (H-1) was used as control and amplitude of the second H-reflex response (H-2) as test. Results: H(2)amplitude for frequency of 1 Hz, 0.3 Hz, 0.2 Hz and 0.1 Hz were 74.3, 84.1, 85.5 and 92.7% of H-1, respectively. Depression of H(2)amplitude was statistically significant for 1 Hz, 0.3 Hz and 0.2 Hz (p < 0.001,p = 0.002,p = 0.024, respectively). Conclusions: Higher frequency stimulation of Ia afferents than 0.1 Hz induced a stimulus frequency-related depression of H-reflex size in patients with chronic spasticity. The optimal stimulus rate for H-reflex was found to be 0.1 Hz.Publication Metadata only Neurotrophin-3 provides neuroprotection via TrkC receptor dependent pErk5 activation in a rat surgical brain injury model(Academic Press Inc Elsevier Science, 2018) Akyol, Onat; Sherchan, Prativa; Yilmaz, Gokce; Reis, Cesar; Ho, Wingi Man; Wang, Yuechun; Huang, Lei; Zhang, John H.; N/A; Solaroğlu, İhsan; Faculty Member; School of Medicine; 102059Background: Surgical brain injury (SBI) which occurs due to the inadvertent injury inflicted to surrounding brain tissue during neurosurgical procedures can potentiate blood brain barrier (BBB) permeability, brain edema and neurological deficits. This study investigated the role of neurotrophin 3 (NT-3) and tropomyosin related kinase receptor C (TrkC) against brain edema and neurological deficits in a rat SBI model. Methods: SBI was induced in male Sprague Dawley rats by partial right frontal lobe resection. Temporal expression of endogenous NT-3 and TrkC was evaluated at 6, 12, 24 and 72 h after SBI. SBI rats received recombinant NT-3 which was directly applied to the brain surgical injury site using gelfoam. Brain edema and neurological function was evaluated at 24 and 72 h after SBI. Small interfering RNA (siRNA) for TrkC and Rap1 was administered via intracerebroventricular injection 24 h before SBI. BBB permeability assay and western blot was performed at 24 h after SBI. Results: Endogenous NT-3 was decreased and TrkC expression increased after SBI. Topical administration of recombinant NT-3 reduced brain edema, BBB permeability and improved neurological function after SIR Recombinant NT-3 administration increased the expression of phosphorylated Rap1 and Erk5. The protective effect of NT-3 was reversed with TrkC siRNA but not Rap1 siRNA. Conclusions: Topical application of NT-3 reduced brain edema, BBB permeability and improved neurological function after SBI. The protective effect of NT-3 was possibly mediated via TrkC dependent activation of Erk5.Publication Metadata only Sex differences in the timing behavior performance of 3xTg-AD and wild-type mice in the peak interval procedure(Elsevier, 2019) Fertan, Emre; Kosel, Filip; Wong, Aimee A.; Brown, Richard E.; N/A; Department of Psychology; Gür, Ezgi; Balcı, Fuat; PhD Student; Faculty Member; Department of Psychology; Graduate School of Social Sciences and Humanities; College of Social Sciences and Humanities; N/A; 51269We investigated interval timing behavior of 10-month-old male and female 3xTg-AD mice compared with their B6129F2/J wild type controls using the peak interval procedure with a 15 s target interval. Multiple parameters reflecting different aspects of timing performance were extracted from steady-state anticipatory nose-poking behavior using two different approaches: single trial analyses and average response curve analyses. These measures can dissociate the differences in performance due to distortions in the interval timing ability or to motivational decline (i.e. apathy); both of which have been reported in Alzheimer patients. We found that the interval timing ability of male and female 3xTg-AD mice did not differ from wild-type controls. However, in measures reflecting motivational state, we found significant sex differences regardless of genotype. Specifically, female mice initiated anticipatory responding later in the trial and had lower response amplitudes than males. Although our findings can also be interpreted in terms of differences in temporal control for response initiation, they more strongly suggest the effect of differential incentive motivation between sexes on timing behavior in these mice.Publication Metadata only The effect of cognitive tasks during electroencephalography recording in patients with reflex seizures(Sage Publications Inc, 2022) Abanoz, Yasin; Gülen Abanoz, Yeşim; Yeni, Seher Naz; N/A; Buluş, Eser; Doctor; School of Medicine; Koç University Hospital; N/AObjective We aimed to research the effect of cognitive tasks on interictal electroencephalographic (EEG) recordings in patients with epilepsy who had reported cognitive functions as a seizure trigger. We investigated the usefulness of cognitive function tasks as a method of activation in standard-awake EEG in daily practice. Methods Standard-awake EEG with cognitive activation tasks consisting of verbal and arithmetic tasks was administered to 35 (11.7%) of 299 patients with epilepsy who reported cognitive functions as a reflex seizure stimulus. During the background EEG, patients were divided into 2 groups: group 1 (17 patients) with interictal epileptiform discharges (IEDs), and group 2 (18 patients) without IEDs. Results IEDs were activated by a verbal task in 11.4% of patients and by an arithmetic task in 5.7%. All activated patients were in the genetic/idiopathic generalized epilepsy (IGE) group. In group 1, IEDs were activated in 17.6% of patients by a verbal task and in 5.9% by an arithmetic task. Both verbal and arithmetic tasks showed provocative effect in one patient in group 2. Hyperventilation was the most effective activation method, followed by cognitive activation tasks and photic stimulation. The provocative effects of verbal and arithmetic tasks were comparable to those of photic stimulation. Conclusion Cognitive tasks might activate the IEDs in patients reporting cognitive functions as a seizure trigger, particularly in IGE. Brief and standardized cognitive activation tasks should be developed and applied as a method of activation during standard-awake EEG recordings to increase the diagnostic yield of EEG.Publication Metadata only Jendrassik maneuver effect on spinal and brainstem reflexes(Springer, 2019) Kumru, Hatice; Opisso, Eloy; Valls-Sole, Josep; Cecen, Serpil; N/A; Ertuğlu, Lale Aslıhan; Aydın, Aslı; Türker, Kemal Sıtkı; Undergraduate Student; Undergraduate Student; Faculty Member; School of Medicine; School of Medicine; School of Medicine; Koç University Hospital; N/A; N/A; 6741The effect of Jendrassik Maneuver (JM) has been extensively studied on monosynaptic reflexes in numerous muscles below the level at which the maneuver was performed. Here we hypothesize that the effect of JM could be observed also on other reflexes, indicating a widespread influence of performing a motor act such as the JM. We examined polysynaptic reflexes caudal (i.e., the withdrawal reflex of the lower extremities) and rostral (i.e., the blink reflex to supraorbital nerve stimulation) to the level of JM contraction. We have assessed soleus tendon (T) reflex; withdrawal reflex in tibialis anterior and soleus muscle; blink reflex (BR), blink reflex excitability recovery curve (BR-ER) and prepulse inhibition of the blink reflex. Our results showed that (1) T-reflex amplitude increased during JM and decreased just after and 15 min after JM; (2) no change in the withdrawal reflex; (3) R2 area of BR reduced significantly just after or 15 min after JM; (4) Prepulse inhibition in BR reduced significantly during JM; (5) no change in BR-ER. Our results indicate that JM leads to generalized effects on neural excitability at both caudal and rostral levels. Furthermore, JM has a selective effect on excitability of reflex circuitries.Publication Metadata only A multicenter international study to evaluate different aspects of relationship between MS and pregnancy(Sage, 2019) Zakaria, M.; Alroughani, R.; Moghadasi, A. N.; Terzi, M.; Sen, S.; Koseoglu, M.; Efendi, H.; Soysal, A.; Gozubatik-Celik, G.; Ozturk, M.; Sahraian, M.; Akinci, Y.; Kaya, Z. E.; Saip, S.; Siva, A.; N/A; Department of Industrial Engineering; Altıntaş, Ayşe; Gönen, Mehmet; Faculty Member; Faculty Member; Department of Industrial Engineering; School of Medicine; College of Engineering; 11611; 237468N/APublication Metadata only Interval timing is disrupted in female 5xFAD mice: an indication of altered memory processes(Wiley, 2019) Fertan, Emre; Alkins, Kindree; Wong, Aimee A.; Brown, Richard E.; N/A; Department of Psychology; Gür, Ezgi; Balcı, Fuat; PhD Student; Faculty Member; Department of Psychology; Graduate School of Social Sciences and Humanities; College of Social Sciences and Humanities; N/A; 51269Temporal information processing in the seconds-to-minutes range is disrupted in patients with Alzheimer's disease (AD). In this study, we investigated the timing behavior of the 5xFAD mouse model of AD in the peak interval (PI) procedure. Nine-month-old female mice were trained with sucrose solution reinforcement for their first response after a fixed-interval (FI) and tested in the inter-mixed non-reinforced PI trials that lasted longer than FI. Timing performance indices were estimated from steady-state timed anticipatory nose-poking responses in the PI trials. We found that the time of maximal reward expectancy (peak time) of the 5xFAD mice was significantly earlier than that of the wild-type (WT) controls with no differences in other indices of timing performance. These behavioral differences corroborate the findings of previous studies on the disruption of temporal associative memory abilities of 5xFAD mice and can be accounted for by the scalar timing theory based on altered long-term memory consolidation of temporal information in the 5xFAD mice. This is the first study to directly show an interval timing phenotype in a genetic mouse model of AD.Publication Metadata only A multidisciplinary clinical approach to facioscapulohumeral muscular dystrophy orthopedic surgery in facioscapulohumeral dystrophy(Literatura Medica, 2018) N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; Çakmak, Özgür Öztop; Eren, İlker; Aslanger, Ayça Dilruba; Günerbüyük, Caner; Kayserili, Hülya; Oflazer, Piraye; Şar, Cüneyt; Demirhan, Mehmet; Özdemir, Yasemin Gürsoy; Faculty Member; Faculty Member; Doctor; Teaching Faculty; Faculty Member; Faculty Member; Doctor; Faculty Member; Faculty Member; School of Medicine; School of Medicine; N/A; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; Koc University Hospital; 107818; 168021; N/A; 380939; 7945; N/A; N/A; 9882; 170592Background - Impaired shoulder function is the most disabling problem for daily life of Fascioscapulohumeral muscular dystrophy (FSHD) patients. Scapulothoracic arthrodesis can give a high impact to the functionality of patients. Here we report our experience with scapulothoracic arthrodesis and spinal stenosis surgery in FSHD patients. Patients and methods - 32 FSHD patients were collected between 2015-2016. Demographical and clinical features were documented. All the patients were neurologically examined. The Medical Research Council (MRC) and the FSHD evaluation scale was used to assess muscle involvement(1). Scapulothoracic arthrodesis and spinal stenosis surgeries were performed in eligible patients. Results - There were 16 male and 16 female (mean age 34.4 years; range 12-73) patients. 6 shoulders of 4 patients aged between 2132 years underwent scapulothoracic arthrodesis (two bilateral, one left and one right sided). Only one 63 years old female patient with severe hyperlordosis had spinal fusion surgery. All of the patients undergoing these corrective surgeries have better functionality in daily life, as well as superior shoulder elevation. Conclusion - Until the emergence and clinical use of novel therapeutics, surgical interventions are indicated in carefully selected patients with FSHD to improve arm movements, the posture and the quality of life of patients in general. Scapulothorosic arthrodesis is a management with good clinical results and patient satisfaction. In selected cases other corrective orthopedic surgeries like spinal fusion may also be considered.