Browsing by Subject "Neurons"
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Item Open Access 4,5-dianilinophtalimide protects neuroendocrine cells against serum deprivation-induced stress and apoptosis(2013) Ergin V.; Erdogan, M.; Karasu Ç.; Menevşe, A.OBJECTIVE: The aim of this study was to reveal the effects of 4,5-dianilinophthalimide (DAPH), which inhibits amyloid β fibrillization, against serum deprivation (SD)-induced apoptosis and the possible mechanisms in differentiated PC12 neuron cells. METHODS: Firstly, we evaluated whether DAPH protects cell viability exposed to SD by MTT assay. Next, we examined the changes of phospho-p38 MAPK (Thr180/Tyr182), phospho-HSP27 (Ser82), phospho-c-JUN (Ser73) and cleaved-CASP3 (Asp175) profiles by immunoblotting, in PC12 cells exposed to SD. Intracellular reactive oxygen species (ROS) level was also measured. RESULTS: SD induced apoptosis accompanied by up-regulation of phospho-p38 MAPK (Thr180/Tyr182), phospho-HSP27 (Ser82), phospho-c-JUN (Ser73), cleaved-CASP3 (Asp175) and intracellular ROS content. Co-treatment with nontoxic doses of DAPH prevented apoptosis by the attenuation of activated proteins and reduction of ROS level. These results suggest that serum deprivation-induced apoptosis inhibited by DAPH administration. CONCLUSION: We have provided for the first evidence that DAPH has a neuroprotective effect on SD-caused stress, probably via contributing the reestablishment of redox homeostasis. © 2013 Neuroendocrinology Letters.Item Open Access Baseline regularized sparse spatial filters(IEEE, 2013) Onaran, İbrahim; Ince, N.F.; Cetin, A. EnisThe common spatial pattern (CSP) method has large number of applications in brain machine interfaces (BMI) to extract features from the multichannel neural activity through a set of linear spatial projections. These spatial projections minimize the Rayleigh quotient (RQ) as the objective function, which is the variance ratio of the classes. The CSP method easily overfits the data when the number of training trials is not sufficiently large and it is sensitive to daily variation of multichannel electrode placement, which limits its applicability for everyday use in BMI systems. To overcome these problems, the amount of channels that is used in projections, should be limited to some adequate number. We introduce a spatially sparse projection (SSP) method that renders unconstrained minimization possible via a new objective function with an approximated ℓ1 penalty. We apply our new algorithm with a baseline regularization to the ECoG data involving finger movements to gain stability with respect to the number of sparse channels. © 2013 IEEE.Item Open Access Beyond Bouma's window: how to explain global aspects of crowding?(Public Library of Science, 2019-05) Doerig, A.; Bornet, A.; Rosenholtz, R.; Francis, G.; Clarke, Aaron M.; Herzog, M. H.In crowding, perception of an object deteriorates in the presence of nearby elements. Although crowding is a ubiquitous phenomenon, since elements are rarely seen in isolation, to date there exists no consensus on how to model it. Previous experiments showed that the global configuration of the entire stimulus must be taken into account. These findings rule out simple pooling or substitution models and favor models sensitive to global spatial aspects. In order to investigate how to incorporate global aspects into models, we tested a large number of models with a database of forty stimuli tailored for the global aspects of crowding. Our results show that incorporating grouping like components strongly improves model performance. Author summary Visual crowding highlights interactions between elements in the visual field. For example, an object is more difficult to recognize if it is presented in clutter. Crowding is one of the most fundamental aspects of vision, playing crucial roles in object recognition, reading and visual perception in general, and is therefore an essential tool to understand how the visual system encodes information based on its retinal input. Hence, classic models of crowding have focused only on local interactions between neighboring visual elements. However, abundant experimental evidence argues against local processing, suggesting that the global configuration of visual elements strongly modulates crowding. Here, we tested all available models of crowding that are able to capture global processing across the entire visual field. We tested 12 models including the Texture Tiling Model, a Deep Convolutional Neural Network and the LAMINART neural network with large scale computer simulations. We found that models incorporating a grouping component are best suited to explain the data. Our results suggest that in order to understand vision in general, mid-level, contextual processing is inevitable.Item Open Access Bioactive peptide functionalized aligned cyclodextrin nanofibers for neurite outgrowth(Royal Society of Chemistry, 2017) Hamsici, S.; Cinar, G.; Celebioglu A.; Uyar, Tamer; Tekinay, A. B.; Güler, Mustafa O.Guidance of neurite extension and establishment of neural connectivity hold great importance for neural tissue regeneration and neural conduit implants. Although bioactive-epitope functionalized synthetic or natural polymeric materials have been proposed for the induction of neural regeneration, chemical modifications of these materials for neural differentiation still remain a challenge due to the harsh conditions of chemical reactions, along with non-homogeneous surface modifications. In this study, a facile noncovalent functionalization method is proposed by exploiting host-guest interactions between an adamantane-conjugated laminin derived bioactive IKVAV epitope and electrospun cyclodextrin nanofibers (CDNFs) to fabricate implantable scaffolds for peripheral nerve regeneration. While electrospun CDNFs introduce a three-dimensional biocompatible microenvironment to promote cellular viability and adhesion, the bioactive epitopes presented on the surface of electrospun CDNFs guide the cellular differentiation of PC-12 cells. In addition to materials synthesis and smart functionalization, physical alignment of the electrospun nanofibers guides the cells for enhanced differentiation. Cells cultured on aligned and IKVAV functionalized electrospun CDNFs had significantly higher expression of neuron-specific βIII-tubulin and synaptophysin. The neurite extension is also higher on the bioactive aligned scaffolds compared to random and non-functionalized electrospun CDNFs. Both chemical and physical cues were utilized for an effective neuronal differentiation process. © The Royal Society of Chemistry.Item Open Access Effects of aging on gene expression levels of inflammatory, cytoskeletal and microglial markers in the brain using the zebrafish (Danio Rerio) model organism(Bilkent University, 2021-01) Aydoğan, Hande ÖzgeAge-related cognitive decline burdens the elderly population, limiting their abil-ity to socialize and be independent. To be able to develop proper treatments, healthy aging should be examined. Previous studies focusing on healthy brain aging revealed that abnormal microglial activation was observed. Aging microglia exhibits 0partial loss of motility due to cytoskeletal changes, leading to decreases in their ability to respond to environmental cues. Thus, a more inflammatory phe-notype was observed in microglia. These disruptions of the previously established homeostasis in the brain could be the underlying reason for cognitive decline ex-perienced during aging. To understand these changes during aging in the brain, cytoskeletal, microglial, and inflammation-related markers were investigated by using both in silico and in vivo approaches. In silico analyses were performed on mice hippocampus and the whole brain revealed that the genes involved in the actin cytoskeleton reorganization (Arpc1b), neurogenesis (Erbb4), and proinflam-matory related pathways (Il1b, P2x7r, Elf2b) showed differential gene expression levels among different age groups, genders, and tissue of origin. On the other hand, no differential expression was observed in microglial (Coro1a and Aif1) and anti-inflammatory markers (Tgfb1 and Il10). To further validate these re-sults in vivo, quantitative polymerase chain reaction (qPCR) was performed on young and old zebrafish brains. According to the results, only two genes showed marginally significant differences among young and old brains: arpc1b and p2x7r. These results collectively could mean 1) the overall microglia population does not change during aging, 2) the brain does not exhibit imbalances in terms of pro-and anti-inflammatory cytokines, and 3) neurogenesis. Furthermore, the signifi-cant changes observed in arpc1b and p2x7r indicated the iii iv importance of the cytoskeleton and inflammation-related pathways in the correct functioning of the cells. Therefore, this study showed that in silico analysis are the reliable indica-tors of in vivo experiments, zebrafish can be used as a gerontological model, and the importance of cytoskeleton in motile cells. However, to understand these de-scribed relations, further investigation on the protein level of these genes should be done.Item Open Access İki durumlu bir beyin bilgisayar arayüzünde özellik çıkarımı ve sınıflandırma(IEEE, 2017-10) Altındiş, Fatih; Yılmaz, B.Beyin bilgisayar arayüzü (BBA) teknolojisi motor nöronlarının özelliğini kaybeden ve hareket kabiliyeti kısıtlanmış ALS ve felçli hastalar gibi birçok kişinin dış dünya ile iletişimini sağlamaya yönelik kullanılmaktadır. Bu çalışmada, Avusturya’daki Graz Üniversitesi’nde alınmış EEG veri seti kullanılarak gerçek zamanlı EEG işleme simülasyonu ile motor hayal etme sınıflandırılması amaçlanmıştır. Bu veri setinde sağ el ya da sol elin hareket ettirilme hayali esnasında 8 kişiden alınmış iki kanallı EEG sinyalleri bulunmaktadır. Her katılımcıdan 60 sağ ve 60 sol olmak üzere toplamda 120 adet yaklaşık 9 saniyelik motor hayal etme deneme sinyali kayıt edilmiştir. Bu sinyaller filtrelemeye tabi tutulmuştur. Yirmi dört, 32 ve 40 elemanlı özellik vektörü bant geçiren filtreler kullanarak elde edilen göreceli güç değişim değerleridir (GGDD). Bu çalışmada, lineer diskriminant analizi (LDA), k en yakın komşular (KNN) ve destek vektör makinaları (SVM) ile sınıflandırma yapılmış, en iyi sınıflandırma performansının 24 değerli özellik vektörüyle ve LDA sınıflandırma yöntemiyle elde edildiği gösterilmiştir.Item Open Access A novel objective function minimization for sparse spatial filters(IEEE, 2014) Onaran, İ.; İnce, N. F.; Çetin, A. EnisCommon spatial pattern (CSP) method is widely used in brain machine interface (BMI) applications to extract features from the multichannel neural activity through a set of spatial projections. The CSP method easily overfits the data when the number of training trials is not sufficiently large and it is sensitive to daily variation of multichannel electrode placement, which limits its applicability for everyday use in BMI systems. To overcome these problems, the amount of channels that is used in projections, should be limited. We introduce a spatially sparse projection (SSP) method that exploits the unconstrained minimization of a new objective function with approximated l\ penalty. The SSP method is employed to classify the two class EEG data set. Our method outperforms the standard CSP method and provides comparable results to £o norm based solution and it is associated with less computational complexity.Item Open Access Prostate stem cell antigen is an endogenous lynx1-like prototoxin that antagonizes α7-containing nicotinic receptors and prevents programmed cell death of parasympathetic neurons(2009) Hruska, M.; Keefe J.; Wert, D.; Tekinay, A.B.; Hulce J.J.; Ibañez-Tallon I.; Nishi, R.Vertebrate α-bungarotoxin-like molecules of the Ly-6 superfamily have been implicated as balancers of activity and survival in the adult nervous system. To determine whether a member of this family could be involved in the development of the avian ciliary ganglion, we identified 6 Gallus genes by their homology in structure to mouse lynx1 and lynx2. One of these genes, an ortholog of prostate stem cell antigen (psca), is barely detectable at embryonic day (E) 8, before neuronal cell loss in the ciliary ganglion, but increases > 100-fold as the number of neurons begins to decline between E9 and E14. PSCA is highly expressed in chicken and mouse telencephalon and peripheral ganglia and correlates with expression of α7-containing nicotinic acetylcholine receptors (α7-nAChRs). Misexpressing PSCA before cell death in the ciliary ganglion blocks α7-nAChR activation by nicotine and rescues the choroid subpopulation from dying. Thus, PSCA, a molecule previously identified as a marker of prostate cancer, is a member of the Ly-6 neurotoxin-like family in the nervous system, and is likely to play a role as a modulator of α7 signaling-induced cell death during development. Copyright © 2009 Society for Neuroscience.Item Open Access Protein-releasing conductive anodized alumina membranes for nerve-interface materials(Elsevier Ltd, 2016) Altuntas, S.; Buyukserin, F.; Haider, A.; Altinok, B.; Bıyıklı, Necmi; Aslim, B.Nanoporous anodized alumina membranes (AAMs) have numerous biomedical applications spanning from biosensors to controlled drug delivery and implant coatings. Although the use of AAM as an alternative bone implant surface has been successful, its potential as a neural implant coating remains unclear. Here, we introduce conductive and nerve growth factor-releasing AAM substrates that not only provide the native nanoporous morphology for cell adhesion, but also induce neural differentiation. We recently reported the fabrication of such conductive membranes by coating AAMs with a thin C layer. In this study, we investigated the influence of electrical stimulus, surface topography, and chemistry on cell adhesion, neurite extension, and density by using PC 12 pheochromocytoma cells in a custom-made glass microwell setup. The conductive AAMs showed enhanced neurite extension and generation with the electrical stimulus, but cell adhesion on these substrates was poorer compared to the naked AAMs. The latter nanoporous material presents chemical and topographical features for superior neuronal cell adhesion, but, more importantly, when loaded with nerve growth factor, it can provide neurite extension similar to an electrically stimulated CAAM counterpart.Item Open Access Sciatic nerve regeneration induced by glycosaminoglycan and laminin mimetic peptide nanofiber gels(Royal Society of Chemistry, 2016) Mammadov, B.; Sever, M.; Gecer, M.; Zor, F.; Ozturk, S.; Akgun, H.; Ulas, U. H.; Orhan, Z.; Güler, Mustafa O.; Tekinay, A. B.In the USA, 20 million patients suffer from neuropathy caused by peripheral nerve injuries, which costs approximately 150 billion annually. For longer nerve gaps and multiple injury sites, it is essential to use nerve guidance conduits for healthy pathfinding of regenerating axons. Here, extracellular matrix mimetic peptide nanofiber hydrogels were used for functionalizing guidance conduits to enhance neuronal regeneration in the distal stump of full transaction sciatic nerve injury in rats with functional repair. Conduits filled with heparan sulfate and laminin mimetic peptide nanofibers significantly improved electromyography response and promoted neuronal regeneration in a rat model of sciatic nerve defect. In addition, Schwann cells cultured on these nanofibers showed increased viability and significantly enhanced nerve growth factor (NGF) release. Overall, these results suggest that extracellular matrix mimetic peptide nanofibers present a promising treatment option for peripheral nerve injuries.Item Open Access Strain-and region-specific gene expression profiles in mouse brain in response to chronic nicotine treatment(Wiley-Blackwell Publishing, 2008) Wang, J.; Gutala, R.; Hwang, Y. Y.; Kim J. -M.; Konu, O.; Ma, J. Z.; Li, M. D.A pathway-focused complementary DNA microarray and gene ontology analysis were used to investigate gene expression profiles in the amygdala, hippocampus, nucleus accumbens, prefrontal cortex (PFC) and ventral tegmental area of C3H/HeJ and C57BL/6J mice receiving nicotine in drinking water (100 μg/ml in 2% saccharin for 2 weeks). A balanced experimental design and rigorous statistical analysis have led to the identification of 3.5-22.1% and 4.1-14.3% of the 638 sequence-verified genes as significantly modulated in the aforementioned brain regions of the C3H/HeJ and C57BL/6J strains, respectively. Comparisons of differential expression among brain tissues showed that only a small number of genes were altered in multiple brain regions, suggesting presence of a brain region-specific transcriptional response to nicotine. Subsequent principal component analysis and Expression Analysis Systematic Explorer analysis showed significant enrichment of biological processes both in C3H/HeJ and C57BL/6J mice, i.e. cell cycle/proliferation, organogenesis and transmission of nerve impulse. Finally, we verified the observed changes in expression using real-time reverse transcriptase polymerase chain reaction for six representative genes in the PFC region, providing an independent replication of our microarray results. Together, this report represents the first comprehensive gene expression profiling investigation of the changes caused by nicotine in brain tissues of the two mouse strains known to exhibit differential behavioral and physiological responses to nicotine.Item Open Access Systematic discovery of Rab GTPases with synaptic functions in Drosophila(2011) Chan, C.-C.; Scoggin, S.; Wang, D.; Cherry, S.; Dembo, T.; Greenberg, B.; Jin, E.J.; Kuey, C.; Lopez, A.; Mehta, S.Q.; Perkins, T.J.; Brankatschk, M.; Rothenfluh, A.; Buszczak, M.; Hiesinger P.R.Background: Neurons require highly specialized intracellular membrane trafficking, especially at synapses. Rab GTPases are considered master regulators of membrane trafficking in all cells, and only very few Rabs have known neuron-specific functions. Here, we present the first systematic characterization of neuronal expression, subcellular localization, and function of Rab GTPases in an organism with a brain. Results: We report the surprising discovery that half of all Drosophila Rabs function specifically or predominantly in distinct subsets of neurons in the brain. Furthermore, functional profiling of the GTP/GDP-bound states reveals that these neuronal Rabs are almost exclusively active at synapses and the majority of these synaptic Rabs specifically mark synaptic recycling endosomal compartments. Our profiling strategy is based on Gal4 knockins in large genomic fragments that are additionally designed to generate mutants by ends-out homologous recombination. We generated 36 large genomic targeting vectors and transgenic rab-Gal4 fly strains for 25 rab genes. Proof-of-principle knockout of the synaptic rab27 reveals a sleep phenotype that matches its cell-specific expression. Conclusions: Our findings suggest that up to half of all Drosophila Rabs exert specialized synaptic functions. The tools presented here allow systematic functional studies of these Rabs and provide a method that is applicable to any large gene family in Drosophila. © 2011 Elsevier Ltd. All rights reserved.