Medicine and Health Sciences Commons^™

Multiple Subject Barycentric Discriminant Analysis (Musubada): How To Assign Scans To Categories Without Using Spatial Normalization, Hervé Abdi, Lynne J. Williams, Andrew C. Connolly, M. Ida Gobbini

Dartmouth Scholarship

We present a new discriminant analysis (DA) method called Multiple Subject Barycentric Discriminant Analysis (MUSUBADA) suited for analyzing fMRI data because it handles datasets with multiple participants that each provides different number of variables (i.e., voxels) that are themselves grouped into regions of interest (ROIs). Like DA, MUSUBADA (1) assigns observations to predefined categories, (2) gives factorial maps displaying observations and categories, and (3) optimally assigns observations to categories. MUSUBADA handles cases with more variables than observations and can project portions of the data table (e.g., subtables, which can represent participants or ROIs) on the factorial maps. Therefore MUSUBADA can …

Degeneration Of Phrenic Motor Neurons Induces Long-Term Diaphragm Deficits Following Mid-Cervical Spinal Contusion In Mice., Charles Nicaise, Rajarshi Putatunda, Tamara J Hala, Kathleen A Regan, David M Frank, Jean-Pierre Brion, Karelle Leroy, Roland Pochet, Megan C Wright, Angelo C Lepore

Department of Neuroscience Faculty Papers

A primary cause of morbidity and mortality following cervical spinal cord injury (SCI) is respiratory compromise, regardless of the level of trauma. In particular, SCI at mid-cervical regions targets degeneration of both descending bulbospinal respiratory axons and cell bodies of phrenic motor neurons, resulting in deficits in the function of the diaphragm, the primary muscle of inspiration. Contusion-type trauma to the cervical spinal cord is one of the most common forms of human SCI; however, few studies have evaluated mid-cervical contusion in animal models or characterized consequent histopathological and functional effects of degeneration of phrenic motor neuron-diaphragm circuitry. We have …

Rat Brain Pro-Oxidant Effects Of Peripherally Administered 5 Nm Ceria 30 Days After Exposure, Sarita S. Hardas, Rukhsana Sultana, Govind Warrier, Mo Dan, Rebecca L. Florence, Peng Wu, Eric A. Grulke, Michael T. Tseng, Jason M. Unrine, Uschi M. Graham, Robert A. Yokel, D. Allan Butterfield

Chemistry Faculty Publications

The objective of this study was to determine the residual pro-or anti-oxidant effects in rat brain 30 days after systemic administration of a 5 nm citrate-stabilized ceria dispersion. A ∼4% aqueous ceria dispersion was iv-infused (0 or 85 mg/kg) into rats which were terminated 30 days later. Ceria concentration, localization, and chemical speciation in the brain was assessed by inductively coupled plasma mass spectrometry (ICP-MS), light and electron microscopy (EM), and electron energy loss spectroscopy (EELS), respectively. Pro- or anti-oxidant effects were evaluated by measuring levels of protein carbonyls (PC), 3-nitrotyrosine (3NT), and protein-bound-4-hydroxy-2-trans-nonenal (HNE) in the hippocampus, cortex, and …

Effect Of Chronic Treatment With Clozapine And Haloperidol On 5- Ht2a And 2c Receptor Mrna Expression In The Rat Brain, Xu-Feng Huang, Qing Wang, Yean Yeow Tan

Xu-Feng Huang

No abstract provided.

Chronic Treatment With Simvastatin Upregulates Muscarinic M1/4 Receptor Binding In The Rat Brain, Kelly Newell, P Wong, Xu-Feng Huang, Qing Wang, Wilfred Yeo, P Wang, Weihai Ying, Midori Yenari, Ayse Zengin

Xu-Feng Huang

Statins are increasingly being used for the treatment of a variety of conditions beyond their original indication for cholesterol lowering. We previously reported that simvastatin affected the dopaminergic system in the rat brain. This study aims to investigate regional changes of muscarinic M1/4 receptors in the rat brain after 4-week administration of simvastatin (1 or 10 mg/kg/day). M1/4 receptor distribution and alterations in the post-mortem rat brain were detected by [3H]pirenzepine binding autoradiography. Simvastatin (1 mg/kg/day) increased [3H]pirenzepine binding, predominantly in the prefrontal cortex (171%, P<0.001), primary motor cortex (153%, P=0.001), cingulate cortex (109%, P<0.001), hippocampus (138%, P …

Short And Long Term Changes In Nmda Receptor Binding In Mouse Brain Following Chronic Phencyclidine Treatment, Kelly Newell, Xu-Feng Huang, Katerina Zavitsanou

Xu-Feng Huang

No abstract provided.

Effects Of Chronic Treatment Of Olanzapine And Haloperidol On Peptide Yy Binding Densities In The Rat Brain, Xu-Feng Huang, Qing Wang

Xu-Feng Huang

This study examined regional changes of peptide YY (PYY) binding densities in the rat brain after chronic administration of olanzapine (1.2 mg/kg/day and haloperidol (2.0 mg/kg/day)for 36 days. PYY binding densities and distributions were detected by [125I] binding autoradiography after ratswere sacrificed either 2 h or 48 h after the last drug administration to examine both immediate and delayed effects following the drugwithdrawal. Following 2 h of drug administration, it showed that olanzapine administration significantly decreased PYY binding densities, predominantly in the posterodorsal part of medial amygdaloid nucleus (52 percent, pb0.05), dorsal part of medial geniculate nucleus (56 percent, pb0.05), …

Effects Of Antipsychotic Medication On Muscarinic M1 Receptor Mrna Expression In The Rat Brain, Kelly Newell, Xu-Feng Huang, Katerina Zavitsanou, Chao Deng, Mei Han

Xu-Feng Huang

Alterations in muscarinic M1 receptor protein and mRNA expression have been revealed in post-mortem brains of schizophrenia patients. Most patients had been treated with antipsychotics, so medication effects cannot be excluded as a possible explanation for these results. With in situ hybridization, this study investigated M1 receptor mRNA expression in rats treated with the typical antipsychotic haloperidol (0.3 mg/kg/day) and the atypical antipsychotics olanzapine (1.5 mg/kg/day) and aripiprazole (2.25 mg/kg/day) for 1 or 12 weeks. Compared with the control group, haloperidol significantly increased (13-21%, P < 0.05) M1 mRNA expression in the CA1, CA2, and CA3 regions of the hippocampus after both 1 and 12 weeks of treatment, and it also increased (17%, P < 0.01) M1 mRNA expression in the substantia nigra compacta after 1 week of treatment. Olanzapine significantly increased (14-22%, P < 0.05) M1 mRNA expression in the hippocampus (CA1, CA2, and CA3) and substantia nigra compacta after 12 weeks of treatment, but not after 1 week. Aripiprazole significantly increased (17%, P < 0.01) M1 mRNA expression in the hippocampus (CA1) after both 1 and 12 week treatments and increased (12%, P < 0.05) M1 mRNA expression in the nucleus accumbens after 1 week of treatment. Despite their different affinities for muscarinic M1 receptors, all three antipsychotic medications induced a similar trend of change in M1 mRNA expression in selected brain regions. These data suggest that the decreased M1 receptor protein and mRNA expression observed in schizophrenia patients is unlikely to be a consequence of drug treatments and implicates muscarinic M1 receptors in the pharmacotherapy of the disease. © 2007 Wiley-Liss, Inc.

Fatty Acids Differentially Affect 5-Ht2 Receptor And Transporter Binding In The Rat Brain, Xu-Feng Huang, Chao Deng, Warren Bell, Teresa Du Bois

Xu-Feng Huang

No abstract provided.

Temporal And Site-Specific Brain Alterations In Cb1 Receptor Binding In High Fat Diet-Induced Obesity In C57bl/6 Mice, Xu-Feng Huang, Timothy South

Xu-Feng Huang

The cannabinoid CB1 receptor has been implicated in the regulation of appetite and the consumption of palatable foods. This experiment aimed to explore the involvement of the CB1 receptor in the early and late stages of high fat diet-induced obesity in C57BL/6 mice. The C57Bl/6 mice were placed on a high fat (HF) or low fat/high carbohydrate (LF) diet for 3 or 20 weeks. Quantitative autoradiography revealed that binding of [3H] CP-55,940 (CB1 receptor ligand) was elevated following 3 weeks of HF feeding in areas including the medial/ventral anterior olfactory nucleus (22.1%), agranular insular cortex (24.0%) and the hypothalamus (31.5%) …

High Dose Of Simvastatin Induces Hyperlocomotive And Anxiolytic-Like Activities: The Association With The Up-Regulation Of Nmda Receptor Binding In The Rat Brain, Kelly Newell, Xu-Feng Huang, Chao Deng, Qing Wang, Einar Wilder-Smith, Yun Li, Ying Lu, Ayse Zengin, Guo-Yuan Yang, Heng Zhao

Xu-Feng Huang

Statins are widely being used for the treatment of a variety of conditions beyond their original indication for lowering cholesterol. We have previously reported that simvastatin affected the dopaminergic system in the rat brain. This study aims to investigate locomotor and anxiety effects along with the regional changes of N-methyl-d-aspartate (NMDA) receptors in the rat brain after 4-week administration of simvastatin. Hyperlocomotive and anxiolytic-like activities in the rat were observed after chronic administration of high dose simvastatin (10 mg/kg/day). Distributions and alterations of NMDA receptors in the post-mortem rat brain were detected by [3H] MK-801 binding autoradiography. Simvastatin increased [3H] …

Olanzapine Differentially Affects 5-Ht2a And 2c Receptor Mrna Expression In The Rat Brain, Xinyi Huang, Xu-Feng Huang, Katerina Zavitsanou, Chao Deng, Mei Han

Xu-Feng Huang

No abstract provided.

A High N-6 Polyunsaturated Fatty Acid Diet Reduces Muscarinic M2/M4 Receptor Binding In The Rat Brain, Xu-Feng Huang, Chao Deng, Warren Bell, Teresa Du Bois

Xu-Feng Huang

No abstract provided.

Energy-Restricted Pair-Feeding Normalizes Low Levels Of Brain-Derived Neurotrophic Factor/Tyrosine Kinase B Mrna Expression In The Hippocampus, But Not Ventromedial Hypothalamic Nucleus, In Diet-Induced Obese Mice, Xu-Feng Huang, Qing Wang, Yinghua Yu

Xu-Feng Huang

Brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) are closely associated with the regulation of energy homeostasis, but their roles in diet-induced obesity have not been explored. Using dietary interventions, this study examined regional changes of BDNF and TrkB mRNA expression in different brain regions of diet-induced obese (DIO) and resistant (DR) mice in response to high-fat (HF), energy-restricted pair-feeding and low fat (LF) diets. Using in situ hybridization, DIO mice had significantly decreased levels of BDNF mRNA expression (¿32% to ¿37%) and TrkB (¿21% to ¿23%) in the hippocampus compared to DR mice on an HF …

Effects Of Typical And Atypical Antipsychotic Drugs On Rat Brain Muscarinic Receptors, Van Nguyen, Xu-Feng Huang, Katerina Zavitsanou, Mei Han

Xu-Feng Huang

No abstract provided.

Perlecan Domain V Induces Vegf Secretion In Brain Endothelial Cells Through Integrin Α5Β1 And Erk-Dependent Signaling Pathways, Douglas N. Clarke, Abraham Al Ahmad, Boyeon Lee, Christi Parham, Lisa Auckland, Andrezj Fertala, Michael Kahle, Courtney S. Shaw, Jill Roberts, Gregory J. Bix

Sanders-Brown Center on Aging Faculty Publications

Perlecan Domain V (DV) promotes brain angiogenesis by inducing VEGF release from brain endothelial cells (BECs) following stroke. In this study, we define the specific mechanism of DV interaction with the α(5)β(1) integrin, identify the downstream signal transduction pathway, and further investigate the functional significance of resultant VEGF release. Interestingly, we found that the LG3 portion of DV, which has been suggested to possess most of DV's angio-modulatory activity outside of the brain, binds poorly to α(5)β(1) and induces less BEC proliferation compared to full length DV. Additionally, we implicate DV's DGR sequence as an important element for the interaction …

Perlecan Domain V Induces Vegf Secretion In Brain Endothelial Cells Through Integrin Α5Β1 And Erk-Dependent Signaling Pathways., Douglas N Clarke, Abraham Al Ahmad, Boyeon Lee, Christi Parham, Lisa Auckland, Andrezj Fertala, Michael Kahle, Courtney S Shaw, Jill Roberts, Gregory J Bix

Department of Dermatology and Cutaneous Biology Faculty Papers

Perlecan Domain V (DV) promotes brain angiogenesis by inducing VEGF release from brain endothelial cells (BECs) following stroke. In this study, we define the specific mechanism of DV interaction with the α(5)β(1) integrin, identify the downstream signal transduction pathway, and further investigate the functional significance of resultant VEGF release. Interestingly, we found that the LG3 portion of DV, which has been suggested to possess most of DV's angio-modulatory activity outside of the brain, binds poorly to α(5)β(1) and induces less BEC proliferation compared to full length DV. Additionally, we implicate DV's DGR sequence as an important element for the interaction …

Brain Microvascular Endothelial Cell Association And Distribution Of A 5 Nm Ceria Engineered Nanomaterial, Mo Dan, Michael T. Tseng, Peng Wu, Jason M. Unrine, Eric A. Grulke, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

PURPOSE: Ceria engineered nanomaterials (ENMs) have current commercial applications and both neuroprotective and toxic effects. Our hypothesis is that ceria ENMs can associate with brain capillary cells and/or cross the blood-brain barrier.

METHODS: An aqueous dispersion of ∼5 nm ceria ENM was synthesized and characterized in house. Its uptake space in the Sprague Dawley rat brain was determined using the in situ brain perfusion technique at 15 and 20 mL/minute flow rates; 30, 100, and 500 μg/mL ceria perfused for 120 seconds at 20 mL/minute; and 30 μg/mL perfused for 20, 60, and 120 seconds at 20 mL/minute. The capillary …

Diffusion Weighted Mr Imaging Of Ring Enhancing Brain Lesions, Muhammad Shahbaz Alam, Zafar Sajjad, Muhammad Azeemuddin, Zahid Anwar Khan, Fatima Mubarak, Waseem Akhtar

Department of Radiology

Objective: To evaluate the role of diffusion weighted imaging in differentiating the cause of ring enhancing brain lesions.

Study Design: Analytical, descriptive study.

Place and Duration of Study: Department of Radiology, The Aga Khan University Hospital, Karachi, from March 2007 to July 2011. Methodology: Diffusion weighted imaging (DWI) was performed on 37 patients having ring enhancing lesions on their post-contrast brain MRI scans. These lesions were characterized into neoplastic and abscess cavity on the basis of diffusion restriction. Correlation of all these findings was done with histopathology obtained in all these patients. Sensitivity, specificity, positive and negative predictive values and …

Isolation Of Phosphatidylethanolamine As A Solitary Cofactor For Prion Formation In The Absence Of Nucleic Acids, Nathan R. Deleault, Justin R. Piro, Daniel J. Walsh, Fei Wang, Jiyan Ma, James C. Geoghegan, Surachai Supattapone

Dartmouth Scholarship

Infectious prions containing the pathogenic conformer of the mammalian prion protein (PrP(Sc)) can be produced de novo from a mixture of the normal conformer (PrP(C)) with RNA and lipid molecules. Recent reconstitution studies indicate that nucleic acids are not required for the propagation of mouse prions in vitro, suggesting the existence of an alternative prion propagation cofactor in brain tissue. However, the identity and functional properties of this unique cofactor are unknown. Here, we show by purification and reconstitution that the molecule responsible for the nuclease-resistant cofactor activity in brain is endogenous phosphatidylethanolamine (PE). Synthetic PE alone facilitates conversion of …

Multi-Scale Modeling Of Angiotensin Ii Induced Neuronal Regulatory Mechanisms In The Brain, Rajanikanth Vadigepalli

Rajanikanth Vadigepalli

Poster Presentation.

Genetics Of Clusterin Isoform Expression And Alzheimer's Disease Risk, I-Fang Ling, Jiraganya Bhongsatiern, James F. Simpson, David W. Fardo, Steven Estus

Sanders-Brown Center on Aging Faculty Publications

The minor allele of rs11136000 within CLU is strongly associated with reduced Alzheimer's disease (AD) risk. The mechanism underlying this association is unclear. Here, we report that CLU1 and CLU2 are the two primary CLU isoforms in human brain; CLU1 and CLU2 share exons 2-9 but differ in exon 1 and proximal promoters. The expression of both CLU1 and CLU2 was increased in individuals with significant AD neuropathology. However, only CLU1 was associated with the rs11136000 genotype, with the minor "protective" rs11136000T allele being associated with increased CLU1 expression. Since CLU1 and CLU2 are predicted to encode intracellular and secreted …

Dyschronic, A Drosophila Homolog Of A Deaf-Blindness Gene, Regulates Circadian Output And Slowpoke Channels., James E C Jepson, Mohammad Shahidullah, Angelique Lamaze, Drew Peterson, Huihui Pan, Kyunghee Koh

Farber Institute for Neuroscience Faculty Papers

Many aspects of behavior and physiology are under circadian control. In Drosophila, the molecular clock that regulates rhythmic patterns of behavior has been extensively characterized. In contrast, genetic loci involved in linking the clock to alterations in motor activity have remained elusive. In a forward-genetic screen, we uncovered a new component of the circadian output pathway, which we have termed dyschronic (dysc). dysc mutants exhibit arrhythmic locomotor behavior, yet their eclosion rhythms are normal and clock protein cycling remains intact. Intriguingly, dysc is the closest Drosophila homolog of whirlin, a gene linked to type II Usher syndrome, the leading cause …

Independent Evolution Of Macrophage-Tropism And Increased Charge Between Hiv-1 R5 Envelopes Present In Brain And Immune Tissue, Maria Paz Gonzalez-Perez, Olivia O’Connell, Rongheng Lin, W Matthew Sullivan, Jeanne Bell, Peter Simmonds, Paul R. Clapham

Rongheng Lin

Background: Transmitted HIV-1 clade B or C R5 viruses have been reported to infect macrophages inefficiently, while other studies have described R5 viruses in late disease with either an enhanced macrophage-tropism or carrying envelopes with an increased positive charge and fitness. In contrast, our previous data suggested that viruses carrying non-macrophage-tropic R5 envelopes were still predominant in immune tissue of AIDS patients. To further investigate the tropism and charge of HIV-1 viruses in late disease, we evaluated the properties of HIV-1 envelopes amplified from immune and brain tissues of AIDS patients with neurological complications. Results: Almost all envelopes amplified were …

Bmi-1 Absence Causes Premature Brain Degeneration, Guangliang Cao, Minxia Gu, Min Zhu, Junying Gao, Ying Yin, Charles Marshall, Ming Xiao, Jiong Ding, Dengshun Miao

Physical Therapy Faculty Publications

Bmi-1, a polycomb transcriptional repressor, is implicated in cell cycle regulation and cell senescence. Its absence results in generalized astrogliosis and epilepsy during the postnatal development, but the underlying mechanisms are poorly understood. Here, we demonstrate the occurrence of oxidative stress in the brain of four-week-old Bmi-1 null mice. The mice showed various hallmarks of neurodegeneration including synaptic loss, axonal demyelination, reactive gliosis and brain mitochondrial damage. Moreover, astroglial glutamate transporters and glutamine synthetase decreased in the Bmi-1 null hippocampus, which might contribute to the sporadic epileptic-like seizures in these mice. These results indicate that Bmi-1 is required for maintaining …

Graft Versus Host Disease Of The Brain Following Allogeneic Stem Cell Transplant For Myelodysplastic Syndrome, Janet Yoo, Lindsay Simon, Zi-Xuan Wang, Phd, Lawrence C. Kenyon

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Graft-versus-host disease (GVHD) is a frequent cause of morbidity and mortality following bone marrow transplantation (BMT). GVHD occurs when immune cells transplanted from a non-identical donor (the graft) recognize the transplant recipient (the host) as foreign, thereby initiating an immune reaction that causes disease in the transplant recipient. GVHD, which can present either acutely or chronically, typically involves the skin, gastrointestinal tract, and liver. In contrast, GVHD involving other organs such as the heart and kidney is highly uncommon and involvement of the central nervous system has only very rarely been described in the literature. We report an unusual case …

Asperger Syndrome And Blogging; Theory Of Mind And The Extreme Male Brain Theory In Self-Identified Women With Asperger Syndrome, Vanesa Morgan

Dissertations and Theses

No abstract provided.

Interferon-Α Regulates Glutaminase 1 Promoter Through Stat1 Phosphorylation: Relevance To Hiv-1 Associated Neurocognitive Disorders., Lixia Zhao, Yunlong Huang, Changhai Tian, Lynn Taylor, Norman Curthoys, Yi Wang, Hamilton Vernon, Jialin C. Zheng

Journal Articles: Pharmacology & Experimental Neuroscience

HIV-1 associated neurocognitive disorders (HAND) develop during progressive HIV-1 infection and affect up to 50% of infected individuals. Activated microglia and macrophages are critical cell populations that are involved in the pathogenesis of HAND, which is specifically related to the production and release of various soluble neurotoxic factors including glutamate. In the central nervous system (CNS), glutamate is typically derived from glutamine by mitochondrial enzyme glutaminase. Our previous study has shown that glutaminase is upregulated in HIV-1 infected monocyte-derived-macrophages (MDM) and microglia. However, how HIV-1 leads to glutaminase upregulation, or how glutaminase expression is regulated in general, remains unclear. In …

Support And Services For People With Alcohol-Related Brain Injury, Renee Brighton, Lorna Moxham, Victoria Traynor

Faculty of Health and Behavioural Sciences - Papers (Archive)

Integrated treatment and support from both mental health services and drug and alcohol treatment services is needed for those living with alcohol-related brain injury. This is because alcohol-related brain injury (ARBI) remains a forgotten disorder.

Evaluation Of Age-Related Changes In Translocator Protein (Tspo) In Human Brain Using 11C-[R]-Pk11195 Pet, Ajay Kumar, Otto Muzik, Varun Shandal, Diane Chugani, Pulak Chakraborty, Harry T. Chugani

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

We studied the distribution and expression of translocator protein in the human brain using ¹¹C-[R]-PK-11195 positron emission tomography (PK11195 PET) and evaluated age-related changes.

Methods

A dynamic PK11195 PET scan was performed in 15 normal healthy adults (mean age: 29 ±8.5 years (range: 20 to 49); 7 males) and 10 children (mean age: 8.8 ±5.2 years (range: 1.2 to 17); 5 males), who were studied for potential neuroinflammation but showed no focally increased PK11195 binding. The PET images were evaluated by calculating standard uptake values and regional binding potential, based on a simplified reference region model, as …