DOCSLIB.ORG

Epilepsy-Associated Reelin Dysfunction Induces Granule Cell Dispersion in the Dentate Gyrus&Z.Star;

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Epilepsy-Associated Reelin Dysfunction Induces Granule Cell Dispersion in the Dentate Gyrus&Z.Star; Epilepsy-Associated Reelin Dysfunction Induces Granule Cell Dispersion in the Dentate Gyrusq M Frotscher, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany CA Haas, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Germany Ó 2017 Elsevier Inc. All rights reserved. Introduction 1 BackgrounddGranule Cell Dispersion in Epilepsyda Migration Defect? 1 Methods 2 Recent Results 3 Unilateral Injection of Kainate, an Agonist of the Excitatory Transmitter Glutamate, Results in the Development of GCD in Mice 3 Reelin’s Role in the Development of GCD 4 Reelin Keeps Adult Granule Cells in Register 5 Summary and Conclusions 5 Future Directions 5 Further Reading 7 Introduction Ammon’s horn sclerosis (AHS) is a hallmark of temporal lobe epilepsy. AHS is characterized by neuronal loss in hippocampal regions CA3 and CA1 and in the hilus of the dentate gyrus, and by granule cell dispersion (GCD). The term sclerosis describes a glial hypertrophy accompanying the neuronal loss. The neuron loss is likely to represent excitotoxic cell death associated with increased calcium entry into the cells. This mechanism of cell death is supported by studies showing that intracellular application of calcium buffers prevents excitotoxic cell death of hilar neurons. Neurons in hippocampal region CA2, which is located in between CA1 and CA3, are less vulnerable and are particularly rich in calcium-binding proteins. The factors that induce a broadening of the granule cell layerdie, granule cell dispersiondare less clear. Does increased neuronal activity force the granule cells to leave their normally tightly packed layer? Does seizure activity stimulate neurogenesis in the den- tate gyrus, leading to an increase in neuron number and thus to a broadening of the granule cell layer? Does glial hypertrophy in AHS play a role in the development of granule cell dispersion? In this article, we summarize our recent studies which addressed these questions. In these studies, we used tissue samples from temporal lobe epilepsy (TLE) patients subjected to hippocampal resection for therapeutical reasons. In addition, we used tissue from mice that had received a unilateral hippocampal injection of kainate. By comparing our results in human tissue and in exper- imental animals, we obtained new insights into the processes leading to the development of granule cell dispersion in epilepsy. BackgrounddGranule Cell Dispersion in Epilepsyda Migration Defect? Granule cell dispersion is best described as an abnormal broadening of the granule cell layer, with many granule cells migrating far into the molecular layer (Fig. 1). GCD is regularly associated with Ammon’s horn sclerosis, but there are also cases of Ammon’s horn sclerosis lacking a prominent GCD. There is strong evidence that Ammon’s horn sclerosis, the degeneration of neurons in hippo- campal regions CA1 and CA3 and in the hilus of the dentate gyrus, represents excitotoxic changes resulting from increased neuronal activity. Does this also hold true for GCD? The neurons that migrate out into the molecular layer do not show signs of neuronal degeneration. Alternatively, is GCD a migration defect of the granule cells during development that eventually leads to epilepsy? It would not be too far-fetched to assume a developmental migration defect, as there are mouse mutants that show a structural phenotype reminiscent of GCD and a functional phenotype of seizures/epilepsy. A more scattered distribution of the granule cells leads to an overlap of the normally segregated input and output sides of the granule cells. In a densely packed granule cell layer, the input side (ie, the granule cell dendritic arbors in the molecular layer) is normally separated from the output side (the mossy fiber axons invading the hilus). A loss of this clear-cut lamination will allow more superficially located granule cells to contact dendrites of deeply located neurons, resulting in an increased granule cell-to-granule cell connectivity. Would this aberrant circuitry contribute to increased excitability of the granule cells, resulting in epileptic activity? q Change history: December 2015. Author Carola Haas and author Michael Frotscher made minor corrections to the text with a major change to the paragraph “Future directions” (the changes are on page 12). In addition, a few references were added. They were not cited in the text since all other references of the original manuscript were also not cited in the text but added as “Further Reading”. Reference Module in Neuroscience and Biobehavioral Psychology http://dx.doi.org/10.1016/B978-0-12-809324-5.00032-8 1 2 Epilepsy-Associated Reelin Dysfunction Induces Granule Cell Dispersion in the Dentate Gyrus (A) (C) (B) (D) Figure 1 Morphology of normal and epileptic human hippocampus stained with cresyl violet. (A) Human control hippocampus with normal distri- bution of neurons in hippocampal subfields and in the dentate gyrus, where the granule cells are located in a dense layer. (B) Epileptic human hippo- campus with characteristic features of Ammon’s horn sclerosis. Selective cell loss is obvious in hippocampal subfields CA1 and CA3. The granule cell layer is dispersed. (C) Granule cell layer of a normal human dentate gyrus. The granule cells are arranged in a densely packed layer. (D) Loss of dense granule cell packing (granule cell dispersion) in temporal lobe epilepsy. Scale bars A, B: 600 mm; C, D: 75 mm. CA1, CA2, CA3, hippocampal subfields; GCL, granule cell layer. Reproduced from Haas, A., Frotscher, M., 2004. Migration disorders and epilepsy. In: Herdegen, T., Delgado- García, J.M. (Eds.), Brain. Damage and Repair. Kluwer Academic Publishers, Dordrecht, pp. 391–402; copyright Kluwer Academic Publishers. One mutant that shows a migration defect similar to GCD is the reeler mouse lacking the extracellular matrix protein reelin. Reelin is known to be synthesized and secreted by Cajal-Retzius cells in the marginal zones of cortex and hippocampus, and there are severe migration defects in these regions in the reeler mutant. Could it be that GCD in epileptic patients is associated with an altered reelin expression? As a first step towards a better understanding of GCD, we looked at reelin expression in tissue samples from epileptic patients with GCD and in samples from autopsy controls. These control patients did not suffer from epileptic seizures and did not show Ammon’s horn sclerosis and GCD. We measured reelin expression by real-time PCR and quantified reelin-expressing cells using in situ hybridization for reelin mRNA. We found a significant decrease in reelin expression in patients with granule cell dispersion with both methods. Moreover, there was an inverse correlation between the number of reelin mRNA-expressing cells in the dentate gyrus and the extent of granule cell dispersion, quantified by measuring the width of the granule cell layer. While these findings pointed to a role of reelin in the development of granule cell dispersion, they could not clarify whether decreased reelin expression during development had caused granule cell dispersion which in turn led to epilepsy or, alternatively, epileptic seizures interfered with reelin expression, leading to GCD. For obvious reasons, these questions could not be addressed in studies of tissue samples from patients. Methods We used tissue samples from TLE patients and a mouse epilepsy model that recapitulates the main histopathological and electro- physiological features of human TLE. A single unilateral injection of the glutamate agonist kainate (KA) into the hippocampus of adult mice induced spontaneous, focal epileptic seizures and Ammon’s horn sclerosis, including GCD. We used cresyl violet stain- ing, immunohistochemistry, in situ hybridization and real-time PCR analysis to monitor cell death, GCD development, neurogen- esis, glial cell proliferation, and reelin expression in human tissue and tissue obtained from kainate-injected mice. Epilepsy-Associated Reelin Dysfunction Induces Granule Cell Dispersion in the Dentate Gyrus 3 Recent Results Unilateral Injection of Kainate, an Agonist of the Excitatory Transmitter Glutamate, Results in the Development of GCD in Mice Increased neuronal activity is associated with an increased release of the excitatory neurotransmitter, glutamate. Thus, glutamate receptor agonists, such as kainate, are often injected into animals to induce epileptic activity. Unilateral injection of kainate into one hippocampus (in mice) was not only found to induce seizure activity but also to lead to Ammon’s horn sclerosis with neuronal degeneration in CA1 and CA3 and granule cell dispersion in the dentate gyrus. Interestingly, these degenerative changes are not found on the contralateral, non-injected side. After a latency period of 2 weeks, the animals developed seizure activity as monitored by EEG recordings. They also developed a prominent granule cell dispersion on the side of kainate injection but not on the contralateral side, indicating that GCD resulted from the injection of the excitotoxin. The broadening of the granule cell layer developed progressively; GCD was evident as early as 1 week post injection and was fully expressed after 6 weeks (Fig. 2). What is the nature of kainate-induced GCD? Is it a migration of fully differentiated granule cells, or does seizure activity increase neurogenesis and aberrant migration of the newly generated granule cells? It is generally accepted that post-migratory neuroblasts that are about to
Load more

Recommended publications
  • Cortical Layer V Neurons in the Auditory and Visual Cortices of Normal, Reeler, and Yotari Mice
    Kobe J. Med. Sci., Vol. 56, No. 2, pp. E50-E59, 2010 Cortical Layer V Neurons in the Auditory and Visual Cortices of Normal, reeler, and yotari Mice YASUO YOSHIHARA1, 2, TOMIYOSHI SETSU2, YU KATSUYAMA2, SATOSHI KIKKAWA2, TOSHIO TERASHIMA2*, and KIYOSHI MAEDA1 1Division of Psychiatry, 2Division of Anatomy and Developmental Neurobiology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan Received 19 January 2010/ Accepted 19 January 2010 Key Words: reeler, yotari, cortex, superior colliculus, inferior colliculus ABSTRACT Both in the Reelin-deficient reeler and Dab1-deficient yotari mice, layer V corticospinal tract neurons in the sensory-motor cortex are radially spread instead of being confined to a single cortical layer. In the present study, we examined distribution pattern of cortical layer V neurons in the visual and auditory cortices of reeler and yotari mice with the injection of HRP into the superior and inferior colliculi of the adult animals, respectively. After the injection of HRP into the superior colliculus of the normal mouse, retrogradely labeled cells were distributed in layer V of the visual cortex, while the similar injection of HRP in the reeler and yotari mice produced radial dispersion of retrograde labeling through all of the depths of the visual cortex of these mutant mice. Next, we injected HRP into the inferior colliculus of the normal, reeler and yotari mice. Retrogradely labeled neurons were distributed in layer V of the normal auditory cortex, whereas they were again radially scattered in the auditory cortex of the reeler and yotari mice. Taken together with the previous and present findings, layer V cortical efferent neurons are radially scattered in the sensory-motor, visual and auditory cortices of the reeler and yotari mice.
    [Show full text]
  • Case Study: Right Temporal Lobe Epilepsy
    Case Study: Right temporal lobe epilepsy Group Members • Rudolf Cymorr Kirby P. Martinez • Yet dalen • Rachel Joy Alcalde • Siriwimon Luanglue • Mary Antonette Pineda • Khayay Hlaing • Luch Bunrattana • Keo Sereymonica • Sikanal Chum • Pyone Khant khant • Men Puthik • Chheun Chhorvy Advisers: Sudasawan Jiamsakul Janyarak Supat 2 Overview of Epilepsy 3 Overview of Epilepsy 4 Risk Factor of Epilepsy 5 Goal of Epilepsy Care 6 Case of Patient X Patient Information & Hx • Sex: Female (single) • Age: 22 years old • Date of admission: 15 June 2017 • Chief Complaint: Jerking movement of all 4 limbs • Past Diagnosis: Temporal lobe epilepsy • No allergies, family history & Operation Complete Vaccination. (+) Developmental Delay Now she can take care herself. Income: Helps in family store (can do basic calculation) History Workup Admission Operation ICU Female Surgery D/C 7 • Sex: Female Case of Patient X • Age: 22 years old • CC: Jerking movement of all 4 limbs History Past Present History Workup Admission Operation ICU Female Surgery D/C 8 • Sex: Female Case of Patient X • Age: 22 years old • CC: Jerking movement of all 4 limbs Past Present (11 mos) (+) high fever. Prescribed AED for 2-3 Treatment at Songkranakarin Hosp. mos. After AED stops, no further episode Prescribe AED but still with 4-5 ep/mos 21 yrs 6 yrs Present PTA PTA (15 y/o) (+) jerking movement (15 y/o) (+) aura as jerking Now 2-3 ep/ mos both arms and legs with LOC movement at chin & headache Last attack 2 mos for 5 mins. Drowsy after attack ago thus consult with no memory of attack 15-17 episode/ mos History Workup Admission Operation ICU Female Surgery D/C 9 • Sex: Female Case of Patient X • Age: 22 years old • CC: Jerking movement of all 4 limbs Past Present 2 months prior to admission, she had jerking movement both arms and legs, blinking both eyes, corner of the mouth twitch, and drool.
    [Show full text]
  • Reelin Is Preferentially Expressed in Neurons Synthesizing ␥-Aminobutyric Acid in Cortex and Hippocampus of Adult Rats
    Proc. Natl. Acad. Sci. USA Vol. 95, pp. 3221–3226, March 1998 Neurobiology Reelin is preferentially expressed in neurons synthesizing g-aminobutyric acid in cortex and hippocampus of adult rats C. PESOLD*†,F.IMPAGNATIELLO*, M. G. PISU*, D. P. UZUNOV*, E. COSTA*, A. GUIDOTTI*, AND H. J. CARUNCHO*‡ *Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612; and ‡Department of Morphological Sciences, University of Santiango de Compostela School of Medicine, 15705 Santiago de Compostela, Spain Contributed by Erminio Costa, December 24,1997 ABSTRACT During embryonic development of brain lam- sion, prevent Reelin transcription or secretion (4, 12, 14). In inated structures, the protein Reelin, secreted into the extracel- the cortex and hippocampus of rat embryos, Reelin begins to lular matrix of the cortex and hippocampus by Cajal–Retzius be synthesized in Cajal–Retzius (CR) cells from embryonic day (CR) cells located in the marginal zone, contributes to the 13 to the second postnatal week, and in the cerebellum Reelin regulation of migration and positioning of cortical and hip- is expressed first in the external granule cell layer (EGL) pocampal neurons that do not synthesize Reelin. Soon after before the granule cell migration to the internal granule cell birth, the CR cells decrease, and they virtually disappear during layer (IGL) (2, 15–17). When the CR50 antibody is added to the following 3 weeks. Despite their disappearance, we can embryonic preparations expressing normal histogenetic pat- quantify Reelin mRNA (approximately 200 amolymg of total terns of lamination, it induces typical histogenetic abnormal- RNA) and visualize it by in situ hybridization, and we detect the ities of the Relnrl phenotype (7, 9, 10, 17).
    [Show full text]
  • Reelin Supplementation Into the Hippocampus Rescues Abnormal Behavior in a Mouse Model of Neurodevelopmental Disorders
    fncel-14-00285 August 31, 2020 Time: 14:32 # 1 ORIGINAL RESEARCH published: 02 September 2020 doi: 10.3389/fncel.2020.00285 Reelin Supplementation Into the Hippocampus Rescues Abnormal Behavior in a Mouse Model of Neurodevelopmental Disorders Daisuke Ibi1*†, Genki Nakasai1†, Nayu Koide1†, Masahito Sawahata2, Takao Kohno3, Rika Takaba1, Taku Nagai2,4, Mitsuharu Hattori3, Toshitaka Nabeshima5, Kiyofumi Yamada2* and Masayuki Hiramatsu1 1 Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan, 2 Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan, 3 Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan, 4 Project Office for Neuropsychological Research Center, Fujita Health University, Toyoake, Japan, 5 Advanced Diagnostic System Research Laboratory, Fujita Health University, Graduate School of Health Sciences, Toyoake, Japan Edited by: Marie-Eve Tremblay, In the majority of schizophrenia patients, chronic atypical antipsychotic administration University of Victoria, Canada produces a significant reduction in or even complete remission of psychotic symptoms Reviewed by: such as hallucinations and delusions. However, these drugs are not effective in Dilja Krueger-Burg, improving cognitive and emotional deficits in patients with schizophrenia. Atypical University Medical Center Göttingen, Germany antipsychotic drugs have a high affinity for the dopamine D2 receptor, and a José M. Delgado-García,
    [Show full text]
  • Long-Term Results of Vagal Nerve Stimulation for Adults with Medication-Resistant
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Seizure 22 (2013) 9–13 Contents lists available at SciVerse ScienceDirect Seizure jou rnal homepage: www.elsevier.com/locate/yseiz Long-term results of vagal nerve stimulation for adults with medication-resistant epilepsy who have been on unchanged antiepileptic medication a a, b a c a Eduardo Garcı´a-Navarrete , Cristina V. Torres *, Isabel Gallego , Marta Navas , Jesu´ s Pastor , R.G. Sola a Division of Neurosurgery, Department of Surgery, University Hospital La Princesa, Universidad Auto´noma, Madrid, Spain b Division of Neurosurgery, Hospital Nin˜o Jesu´s, Madrid, Spain c Department of Physiology, University Hospital La Princesa, Madrid, Spain A R T I C L E I N F O A B S T R A C T Article history: Purpose: Several studies suggest that vagal nerve stimulation (VNS) is an effective treatment for Received 15 July 2012 medication-resistant epileptic patients, although patients’ medication was usually modified during the Received in revised form 10 September 2012 assessment period. The purpose of this prospective study was to evaluate the long-term effects of VNS, at Accepted 14 September 2012 18 months of follow-up, on epileptic patients who have been on unchanged antiepileptic medication. Methods: Forty-three patients underwent a complete epilepsy preoperative evaluation protocol, and Keywords: were selected for VNS implantation. After surgery, patients were evaluated on a monthly basis, Vagus nerve increasing stimulation 0.25 mA at each visit, up to 2.5 mA. Medication was unchanged for at least 18 Epilepsy months since the stimulation was started.
    [Show full text]
  • The Reeler Mouse: a Translational Model of Human 3 Neurological Conditions Or Simply a Good Tool for 4 Better Understanding Neurodevelopment?
    Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 10 October 2019 doi:10.20944/preprints201910.0120.v1 Peer-reviewed version available at J. Clin. Med. 2019, 8, 2088; doi:10.3390/jcm8122088 1 Review 2 The Reeler Mouse: A Translational Model of Human 3 Neurological Conditions or Simply a Good Tool for 4 Better Understanding Neurodevelopment? 5 6 7 Laura Lossi 1, Claudia Castagna2, Alberto Granato3*, and Adalberto Merighi4* 8 1 Department of Veterinary Sciences, University of Turin, Grugliasco (TO) I-10095, Italy. [email protected] 9 2 Department of Veterinary Sciences, University of Turin, Grugliasco (TO) I-10095, Italy. 10 [email protected] 11 3 Department of Psychology, Catholic University of the Sacred Heart, Milano (MI) I-20123, Italy. 12 [email protected] 13 4 Department of Veterinary Sciences, University of Turin, Grugliasco (TO) I-10095, Italy. 14 [email protected] 15 16 * Correspondence: [email protected], Tel ++39. 02.7234.8588; [email protected] , Tel.: 17 ++39.011.670.9118 18 19 Abstract: 20 The Reeler mutation was described in mouse more than fifty years ago. Later, its causative gene 21 (reln) was discovered in mouse, and its human orthologue (RELN) was demonstrated to be 22 causative of lissencephaly 2 (LIS2) and about 20% of the cases of autosomal-dominant lateral 23 temporal epilepsy (ADLTE). In both human and mice the gene encodes for a glycoprotein referred 24 to as Reelin (Reln) that plays a primary role in neuronal migration during development and 25 synaptic stabilization in adulthood. Besides LIS2 and ADLTE, RELN and/or other genes coding for 26 the proteins of the Reln intracellular cascade have been associated more or less substantially to 27 other conditions such as spinocerebellar ataxia type 7 and 37, VLDLR-associated cerebellar 28 hypoplasia, PAFAH1B1-associated lissencephaly, autism and schizophrenia.
    [Show full text]
  • Clinical Study High Complement Factor I Activity in the Plasma of Children with Autism Spectrum Disorders
    Hindawi Publishing Corporation Autism Research and Treatment Volume 2012, Article ID 868576, 6 pages doi:10.1155/2012/868576 Clinical Study High Complement Factor I Activity in the Plasma of Children with Autism Spectrum Disorders Naghi Momeni,1 Lars Brudin,2 Fatemeh Behnia,3 Berit Nordstrom,¨ 4 Ali Yosefi-Oudarji,5 Bengt Sivberg,4 Mohammad T. Joghataei,5 and Bengt L. Persson1 1 School of Natural Sciences, Linnaeus University, 39182 Kalmar, Sweden 2 Department of Clinical Physiology, Kalmar County Hospital, 39185 Kalmar, Sweden 3 Department of Occupational Therapy, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran 4 Department of Health Sciences, Autism Research, Faculty of Medicine, Lund University, Box 157, 22100 Lund, Sweden 5 Cellular and Molecular Research Centre, Tehran University of Medical Sciences (TUMS), Tehran, Iran Correspondence should be addressed to Bengt Sivberg, [email protected] Received 17 June 2011; Revised 22 August 2011; Accepted 22 August 2011 Academic Editor: Judy Van de Water Copyright © 2012 Naghi Momeni et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Autism spectrum disorders (ASDs) are neurodevelopmental and behavioural syndromes affecting social orientation, behaviour, and communication that can be classified as developmental disorders. ASD is also associated with immune system abnormality. Im- mune system abnormalities may be caused partly by complement system factor I deficiency. Complement factor I is a serine pro- tease present in human plasma that is involved in the degradation of complement protein C3b, which is a major opsonin of the complement system.
    [Show full text]
  • God and the Limbic System from Phantoms in the Brain, by V.S
    Imagine you had a machine, a helmet of sorts that you could ... http://www.historyhaven.com/TOK/God and the Limbic Syst... God and the Limbic System From Phantoms in the Brain, by V.S. Ramachandran Imagine you had a machine, a helmet of sorts that you could simply put on your head and stimulate any small region of your brain without causing permanent damage. What would you use the device for? This is not science fiction. Such a device, called a transcranial magnetic stimulator, already exists and is relatively easy to construct. When applied to the scalp, it shoots a rapidly fluctuating and extremely powerful magnetic field onto a small patch of brain tissue, thereby activating it and providing hints about its function. For example, if you were to stimulate certain parts of your motor cortex, different muscles would contract. Your finger might twitch or you'd feel a sudden involuntary, puppetlike shrugging of one shoulder. So, if you had access to this device, what part of your brain would you stimulate? If you happened to be familiar with reports from the early days of neurosurgery about the septum-a cluster of cells located near the front of the thalamus in the middle of your brain-you might be tempted to apply the magnet there. Patients "zapped" in this region claim to experience intense pleasure, "like a thousand orgasms rolled into one." If you were blind from birth and the visual areas in your brain had not degenerated, you might stimulate bits of your own visual cortex to find out what people mean by color or "seeing." Or, given the well-known clinical observation that the left frontal lobe seems to be involved in feeling "good," maybe you'd want to stimulate a region over your left eye to see whether you could induce a natural high.
    [Show full text]
  • Thalamocortical Development: How Are We Going to Get There?
    REVIEWS THALAMOCORTICAL DEVELOPMENT: HOW ARE WE GOING TO GET THERE? Guillermina López-Bendito and Zoltán Molnár The arealization of the mammalian cortex is believed to be controlled by a combination of intrinsic factors that are expressed in the cortex, and external signals, some of which are mediated through thalamic input. Recent studies on transgenic mice have identified families of molecules that are involved in thalamic axon growth, pathfinding and cortical target selection, and we are beginning to understand how thalamic projections impose cytoarchitectonic differentiation on the developing cortex. By unravelling these mechanisms further, we should be able to increase our understanding of the principles of cortical organization. EPIGENETIC The mechanisms that control neocortical regionaliza- each area send corticofugal projections back to the Describes a change in tion — or arealization — have been the subject of much corresponding thalamic nucleus, and layer V sends phenotype that is brought about debate. Intrinsic mechanisms, such as differential gene projections to additional nuclei4 (FIG. 1c). by changes in the regulation of expression that is autonomous to the neocortex, and This article provides an overview of the exciting gene expression or changes in the function of gene products, extrinsic influences, such as input from thalamocortical recent progress that has been made in the field of thala- rather than by a change in afferents, have both gained support from recent mocortical development. The transgenic mouse has genotype. studies1. Although some components of local special- proved to be a very powerful tool to increase our under- ization are determined by differential patterns of com- standing of the principal developmental mechanisms, VENTRICULAR ZONE The proliferative inner layer mitment at an early stage of development (perhaps and it has helped us to dissect the causal relationships of the developing brain and even during mitosis), there is considerable evidence that between thalamocortical fibre targeting and areal spinal cord.
    [Show full text]
  • Title: Comparison of the Structural Organization of Reeler Hippocampal
    bioRxiv preprint doi: https://doi.org/10.1101/508648; this version posted December 31, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Title: Comparison of the structural organization of reeler hippocampal CA1 region with wild type CA1. Malikmohamed Yousuf 1, 2, 3, Shanting Zhao 4, 5 and Michael Frotscher 4 1Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Albert-Ludwigs- University Freiburg, 79104 Freiburg, Germany; 2Faculty of Biology, Albert-Ludwigs-University Freiburg, Germany; 3 Centre for Clinical Brain Sciences, Chancellor’s Building, 49 Little France Crescent, University of Edinburgh, EH16 4SB, UK; 4Institute for Structural Neurobiology, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; 5 College of Veterinary Medicine, Northwest A&F University, Yangling 712100 Shaanxi, China Correspondence to: Malikmohamed Yousuf, PhD Centre for Clinical Brain Sciences Chancellors Building, 49 Little France Crescent Edinburgh University, EH16 4SB, UK Phone: ++44 – (0) 131242 9491 E-Mail: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/508648; this version posted December 31, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract The dendritic pattern defines the input capacity of a neuron. Existing methods such as Golgi impregnation or intracellular staining only label a small number of neurons.
    [Show full text]
  • Surgical Alternatives for Epilepsy (SAFE) Offers Counseling, Choices for Patients by R
    UNIVERSITY of PITTSBURGH NEUROSURGERY NEWS Surgical alternatives for epilepsy (SAFE) offers counseling, choices for patients by R. Mark Richardson, MD, PhD Myths Facts pilepsy is often called the most common • There are always ‘serious complications’ from Epilepsy surgery is relatively safe: serious neurological disorder because at epilepsy surgery. Eany given time 1% of the world’s popula- • the rate of permanent neurologic deficits is tion has active epilepsy. The only potential about 3% cure for a patient’s epilepsy is the surgical • the rate of cognitive deficits is about 6%, removal of the seizure focus, if it can be although half of these resolve in two months identified. Chances for seizure freedom can be as high as 90% in some cases of seizures • complications are well below the danger of that originate in the temporal lobe. continued seizures. In 2003, the American Association of Neurology (AAN) recognized that the ben- • All approved anti-seizure medications should • Some forms of temporal lobe epilepsy are fail, or progressive and seizure outcome is better when efits of temporal lobe resection for disabling surgical intervention is early. seizures is greater than continued treatment • a vagal nerve stimulator (VNS) should be at- with antiepileptic drugs, and issued a practice tempted and fail, before surgery is considered. • Early surgery helps to avoid the adverse conse- parameter recommending that patients with quences of continued seizures (increased risk of temporal lobe epilepsy be referred to a surgi- death, physical injuries, cognitive problems and cal epilepsy center. In addition, patients with lower quality of life. extra-temporal epilepsy who are experiencing • Resection surgery should be considered before difficult seizures or troubling medication side vagal nerve stimulator placement.
    [Show full text]
  • Temporal Lobe Epilepsy: Clinical Semiology and Age at Onset
    Original article Epileptic Disord 2005; 7 (2): 83-90 Temporal lobe epilepsy: clinical semiology and age at onset Vicente Villanueva, José Maria Serratosa Neurology Department, Fundacion Jimenez Diaz, Madrid, Spain Received April 23, 2003; Accepted January 20, 2005 ABSTRACT – The objective of this study was to define the clinical semiology of seizures in temporal lobe epilepsy according to the age at onset. We analyzed 180 seizures from 50 patients with medial or neocortical temporal lobe epilepsy who underwent epilepsy surgery between 1997-2002, and achieved an Engel class I or II outcome. We classified the patients into two groups according to the age at the first seizure: at or before 17 years of age and 18 years of age or older. All patients underwent intensive video-EEG monitoring. We reviewed at least three seizures from each patient and analyzed the following clinical data: presence of aura, duration of aura, ictal and post-ictal period, clinical semiology of aura, ictal and post-ictal period. We also analyzed the following data from the clinical history prior to surgery: presence of isolated auras, frequency of secondary generalized seizures, and frequency of complex partial seizures. Non-parametric, chi-square tests and odds ratios were used for the statistical analysis. There were 41 patients in the “early onset” group and 9 patients in the “later onset” group. A relationship was found between early onset and mesial tempo- ral lobe epilepsy and between later onset and neocortical temporal lobe epilepsy (p = 0.04). The later onset group presented a higher incidence of blinking during seizures (p = 0.03), a longer duration of the post-ictal period (p = 0.07) and a lower number of presurgical complex partial seizures (p = 0.03).
    [Show full text]