Medicine and Health Sciences Commons^™

Mice With Deficient Bk Channel Function Show Impaired Prepulse Inhibition And Spatial Learning, But Normal Working And Spatial Reference Memory, Marei Typlt, Magdalena Mirkowski, Erin Azzopardi, Lukas Ruettiger, Peter Ruth, Susanne Schmid

Anatomy and Cell Biology Publications

Genetic variations in the large-conductance, voltage- and calcium activated potassium channels (BK channels) have been recently implicated in mental retardation, autism and schizophrenia which all come along with severe cognitive impairments. In the present study we investigate the effects of functional BK channel deletion on cognition using a genetic mouse model with a knock-out of the gene for the pore forming α-subunit of the channel. We tested the F1 generation of a hybrid SV129/C57BL6 mouse line in which the slo1 gene was deleted in both parent strains.

We first evaluated hearing and motor function to establish the suitability of this …

Reduced Expression Of The Vesicular Acetylcholine Transporter And Neurotransmitter Content Affects Synaptic Vesicle Distribution And Shape In Mouse Neuromuscular Junction, Hermann A. Rodrigues, Matheus De C. Fonseca, Wallace L. Camargo, Patricia M. A. Lima, Patricia M. Martinelli, Ligia A. Naves, Vania F. Prado, Marco A. M. Prado, Cristina Guatimosim

Anatomy and Cell Biology Publications

In vertebrates, nerve muscle communication is mediated by the release of the neurotransmitter acetylcholine packed inside synaptic vesicles by a specific vesicular acetylcholine transporter (VAChT). Here we used a mouse model (VAChT KDHOM) with 70% reduction in the expression of VAChT to investigate the morphological and functional consequences of a decreased acetylcholine uptake and release in neuromuscular synapses. Upon hypertonic stimulation, VAChT KDHOM mice presented a reduction in the amplitude and frequency of miniature endplate potentials, FM 1-43 staining intensity, total number of synaptic vesicles and altered distribution of vesicles within the synaptic terminal. In contrast, under electrical stimulation or …

Regulation Of Stress-Inducible Phosphoprotein 1 Nuclear Retention By Protein Inhibitor Of Activated Stat Pias1, Iaci N. Soares, Fabiana A. Caetano, Jordan Pinder, Bruna Roz Rodrigues, Flavio H. Beraldo, Valeriy G. Ostapchenko, Chantal Durette, Grace Schenatto Pereira, Marilene H. Lopes, Nicolle Queiroz-Hazarbassanov, Isabela W. Cunha, Paulo I. Sanematsu, Sergio Suzuki, Luiz F. Bleggi-Torres, Caroline Schild-Poulter, Pierre Thibault, Graham Dellaire, Vilma R. Martins, Vania F. Prado, Marco A. M. Prado

Anatomy and Cell Biology Publications

Stress-inducible phosphoprotein 1 (STI1), a cochaperone for Hsp90, has been shown to regulate multiple pathways in astrocytes, but its contributions to cellular stress responses are not fully understood. We show that in response to irradiation-mediated DNA damage stress STI1 accumulates in the nucleus of astrocytes. Also, STI1 haploinsufficiency decreases astrocyte survival after irradiation. Using yeast two-hybrid screenings we identified several nuclear proteins as STI1 interactors. Overexpression of one of these interactors, PIAS1, seems to be specifically involved in STI1 nuclear retention and in directing STI1 and Hsp90 to specific sub-nuclear regions. PIAS1 and STI1 co-immunoprecipitate and PIAS1 can function as …

The Prion Protein Ligand, Stress-Inducible Phosphoprotein 1, Regulates Amyloid-Beta Oligomer Toxicity, Valeriy G. Ostapchenko, Flavio H. Beraldo, Amro H. Mohammad, Yu-Feng Xie, Pedro H. F. Hirata, Ana C. Magalhaes, Guillaume Lamour, Hongbin Li, Andrzej Maciejewski, Jillian C. Belrose, Bianca L. Teixeira, Margaret Fahnestock, Sergio T. Ferreira, Neil R. Cashman, Glaucia N. M. Hajj, Michael F. Jackson, Wing-Yiu Choy, John F. Macdonald, Vilma R. Martins, Vania F. Prado, Marco A. M. Prado

Anatomy and Cell Biology Publications

In Alzheimer's disease (AD), soluble amyloid-beta oligomers (A beta Os) trigger neurotoxic signaling, at least partially, via the cellular prion protein (PrPC). However, it is unknown whether other ligands of PrPC can regulate this potentially toxic interaction. Stress-inducible phosphoprotein 1 (STI1), an Hsp90 cochaperone secreted by astrocytes, binds to PrPC in the vicinity of the A beta O binding site to protect neurons against toxic stimuli. Here, we investigated a potential role of STI1 in A beta O toxicity. We confirmed the specific binding of A beta Os and STI1 to the PrP and showed that STI1 efficiently inhibited A …

Forebrain Deletion Of The Vesicular Acetylcholine Transporter Results In Deficits In Executive Function, Metabolic, And Rna Splicing Abnormalities In The Prefrontal Cortex, Benjamin Kolisnyk, Mohammed A. Al-Onaizi, Pedro H. F. Hirata, Monica S. Guzman, Simona Nikolova, Shahar Barbash, Hermona Soreq, Robert Bartha, Marco A. M. Prado, Vania F. Prado

Anatomy and Cell Biology Publications

One of the key brain regions in cognitive processing and executive function is the prefrontal cortex (PFC), which receives cholinergic input from basal forebrain cholinergic neurons. We evaluated the contribution of synaptically released acetylcholine (ACh) to executive function by genetically targeting the vesicular acetylcholine transporter (VAChT) in the mouse forebrain. Executive function was assessed using a pairwise visual discrimination paradigm and the 5-choice serial reaction time task (5-CSRT). In the pairwise test, VAChT-deficient mice were able to learn, but were impaired in reversal learning, suggesting that these mice present cognitive inflexibility. Interestingly, VAChT-targeted mice took longer to reach criteria in …

Development And Assessment Of An Impact Apparatus And High-Speed Camera Motion Tracking System To Quantify The Effect Of Static Muscle Loads On Fracture Threshold Measures In The Distal Radius, Jacob M. Reeves

Electronic Thesis and Dissertation Repository

Distal radius fractures are prevalent, debilitating, and costly. This thesis conducts an in vitro investigation of these injuries, examining the role of static muscle loading on fracture threshold measures (i.e., force, impulse, energy). Initially, an impact apparatus and custom LabVIEW colour-thresholding program were designed and assessed for repeatability and accuracy in quantifying fracture measures and impact kinematics. These tools were then used to test six pairs of cadaveric forearms, with static muscle loads simulated in one specimen from each pair. Distal radius fractures were achieved in 5 pairs, with perilunate dislocations in the remaining pair. None of the …

Effects Of Prenatal Testosterone On The Reproductive And Metabolic Neurons Of The Sheep Hypothalamus, Maria Cernea

Electronic Thesis and Dissertation Repository

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting reproductively aged women. Women with PCOS and ewes prenatally exposed to testosterone (T) show similar reproductive and metabolic defects, including anovulatory dysfunctions stemming from abnormal gonadotropin releasing hormone (GnRH) secretion and insulin resistance. For this dissertation, I examined the effects of prenatal T treatment on androgen receptor (AR) and insulin receptor (IR) expression with the reproductive and metabolic neurons of the hypothalamus, the ARC KNDy (co-expressing kisspeptin, neurokinin B/dynorphin), AgRP (agouti-related peptide) and proopiomelanocortin (POMC) neurons, and the preoptic area (POA) kisspeptin neurons, and the GnRH neurons. …

Adverse Outcome Of Early Recurrent Ischemic Stroke Secondary To Atrial Fibrillation After Repeated Systemic Thrombolysis, Luciano A. Sposato, Valeria Salutto, Diego E. Beratti, Paula Monti, Patricia M. Riccio, Claudio Mazia

Anatomy and Cell Biology Publications

Background. Recurrent ischemic stroke is associated with adverse neurological outcome in patients with atrial fibrillation. There is very scarce information regarding the neurological outcome of atrial fibrillation patients undergoing repeated systemic thrombolysis after early recurrent ischemic stroke. Clinical Case and Discussion. We describe a case of a 76-year-old woman with known paroxysmal atrial fibrillation who was admitted because of an acute right middle cerebral artery ischemic stroke and who underwent repeated systemic thrombolysis within 110 hours. The patient underwent systemic thrombolysis after the first ischemic stroke with almost complete neurological recovery. On the fourth day after treatment, an …

The Role Of Kisspeptin And Kndy Cells In The Reproductive Neuroendocrine System, Christina M. Merkley

Electronic Thesis and Dissertation Repository

The gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus represent the final common output in the central control of reproduction. GnRH secretion is modulated indirectly by steroid feedback action of gonadal steroids on afferent interneurons. In recent years, the neuropeptide, kisspeptin, has emerged as a key mediator of steroid feedback onto GnRH neurons and the reproductive system. Kisspeptin neurons located in the preoptic area (POA) mediate estradiol (E2) positive feedback leading to the preovulatory surge, and kisspeptin cells in the arcuate nucleus (ARC) have been shown to mediate the negative feedback actions of E2 on pulsatile GnRH secretion. ARC kisspeptin neurons …

Defining The Efficacy Of Aortic Root Enlargement Procedures: A Comparative Analysis Of Surgical Techniques, Katie L. Losenno, Jill J. Gelinas, Marjorie Johnson, Michael W. A. Chu

Anatomy and Cell Biology Publications

Background: Aortic root enlargement (ARE) procedures are believed to allow implantation of larger valve prostheses; however, little evidence exists to support the specific efficacy of various techniques. Methods: Using a cadaveric model, 20 adult (72.4 +/- 15.3 years) hearts were stratified into 4 groups based on annular diameter: <20 mm, 20-22 mm, 22-24 mm, and >24 mm. Each heart underwent an aortic valve replacement following a Nicks, Manougian, aortoventriculoplasty and modified Bentall procedure, with appropriate reversals between procedures. Results: All 4 groups experienced similar increases in annular diameter (P = 0.43) and prosthesis size implanted (P = 0.51) with each enlargement technique. The Nicks, Manougian, modified Bentall …

Molecular Imaging To Target Transplanted Muscle Progenitor Cells, Kelly Gutpell, Rebecca Mcgirr, Lisa Hoffman

Anatomy and Cell Biology Publications

Duchenne muscular dystrophy (DMD) is a severe genetic neuromuscular disorder that affects 1 in 3,500 boys, and is characterized by progressive muscle degeneration(1, 2). In patients, the ability of resident muscle satellite cells (SCs) to regenerate damaged myofibers becomes increasingly inefficient(4). Therefore, transplantation of muscle progenitor cells (MPCs)/myoblasts from healthy subjects is a promising therapeutic approach to DMD. A major limitation to the use of stem cell therapy, however, is a lack of reliable imaging technologies for long-term monitoring of implanted cells, and for evaluating its effectiveness. Here, we describe a non-invasive, real-time approach to evaluate the success of myoblast …

Large Area Periodic, Systematically Changing, Multishape Nanostructures By Laser Interference Lithography And Cell Response To These Topographies, Erden Ertorer, Fartash Vasefi, Joel Keshwah, Mohamadreza Najiminaini, Christopher Halfpap, Uwe Langbein, Jeffrey J. L. Carson, Douglas W. Hamilton, Silvia Mittler

Anatomy and Cell Biology Publications

The fabrication details to form large area systematically changing multishape nanoscale structures on a chip by laser interference lithography (LIL) are described. The feasibility of fabricating different geometries including dots, ellipses, holes, and elliptical holes in both x- and y- directions on a single substrate is shown by implementing a Lloyd's interferometer. The fabricated structures at different substrate positions with respect to exposure time, exposure angle and associated light intensity profile are analyzed. Experimental details related to the fabrication of symmetric and biaxial periodic nanostructures on photoresist, silicon surfaces, and ion milled glass substrates are presented. Primary rat calvarial osteoblasts …

Development Of A 3d Ultrasound System To Investigate Post-Hemorrhagic Hydrocephalus In Pre-Term Neonates, J. Kishimoto, D. Lee, K. St. Lawrence, W. Romano, A. Fenster, S. De Ribaupierre

Anatomy and Cell Biology Publications

Clinical intracranial ultrasound (US) is performed as a standard of care on neonates at risk of intraventricular hemorrhaging (IVH) and is also used after a diagnosis to monitor for potential ventricular dilation. However, it is difficult to estimate the volume of ventricles with 2D US due to their irregular shape. We developed a 3D US system to be used as an adjunct to a clinical system to investigate volumetric changes in the ventricles of neonates with IVH. Our system has been found have an error of within 1% of actual distance measurements in all three directions and volume measurements of …

Assessing The Feasibility Of Time-Resolved Fnirs To Detect Brain Activity During Motor Imagery, Androu Abdalmalak, Daniel Milej, Mamdou Diop, Lorina Naci, Adrian M. Owen, Keith St. Lawrence

Anatomy and Cell Biology Publications

Functional near-infrared spectroscopy (fNIRS) is a non-invasive optical technique for detecting brain activity, which has been previously used during motor and motor executive tasks. There is an increasing interest in using fNIRS as a brain computer interface (BCI) for patients who lack the physical, but not the mental, ability to respond to commands. The goal of this study is to assess the feasibility of time-resolved fNIRS to detect brain activity during motor imagery. Stability tests were conducted to ensure the temporal stability of the signal, and motor imagery data were acquired on healthy subjects. The NIRS probes were placed on …

Assessing Tumor Physiology By Dynamic Contrast-Enhanced Near-Infrared Spectroscopy, Kyle Verdecchia, Jonathan Elliott, Mamadou Diop, Lisa Hoffman, Ting-Yim Lee, Keith St. Lawrence

Anatomy and Cell Biology Publications

The purpose of this study was to develop a dynamic contrast-enhanced (DCE) near-infrared spectroscopy (NIRS) technique to characterize tumor physiology. Dynamic data were acquired using two contrast agents of different molecular weights, indocyanine green (ICG) and IRDye 800CW carboxylate (IRDcxb). The DCE curves were analyzed using a kinetic model capable of extracting estimates of tumor blood flow (F), capillary transit time (t(c)) and the amount of dye that leaked into the extravascular space (EVS) - characterized by the extraction fraction (E). Data were acquired from five nude rats with tumor xenografts (>10mm) implanted in the neck. Four DCE-NIR datasets …

Assessing Residual Reasoning Ability In Overtly Non-Communicative Patients Using Fmri, Adam Hampshire, Beth L. Parkin, Rhodri Cusack, Davinia Fernandez Espejo, Judith Allanson, Evelyn Kamau, John D. Pickard, Adrian M. Owen

Anatomy and Cell Biology Publications

It is now well established that some patients who are diagnosed as being in a vegetative state or a minimally conscious state show reliable signs of volition that may only be detected by measuring neural responses. A pertinent question is whether these patients are also capable of logical thought. Here, we validate an fMRI paradigm that can detect the neural fingerprint of reasoning processes and moreover, can confirm whether a participant derives logical answers. We demonstrate the efficacy of this approach in a physically non-communicative patient who had been shown to engage in mental imagery in response to simple auditory …