scholarly journals Rere-dependent Retinoic Acid signaling controls brain asymmetry and handedness

2019 ◽  
Author(s):  
Michael Rebagliati ◽  
Gonçalo C. Vilhais-Neto ◽  
Alexandra Petiet ◽  
Merlin Lange ◽  
Arthur Michaut ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Motor Cortex ◽  
Neuronal Differentiation ◽  
Bilateral Symmetry ◽  
Brain Asymmetry ◽  
Retinoic Acid Signaling ◽  
Vertebrate Brain ◽  
And Function ◽  
And Behavior ◽  
The Brain

While the vertebrate brain appears largely bilaterally symmetrical in humans, it presents local morphological Left-Right (LR) asymmetries as, for instance, in the petalia. Moreover, higher functions such as speech or handedness are asymmetrically localized in the cortex. How these brain asymmetries are generated remains unknown. Here, we reveal a striking parallel between the control of bilateral symmetry in the brain and in the precursors of vertebrae called somites, where a “default” asymmetry is buffered by Retinoic Acid (RA) signaling. This mechanism is evident in zebrafish and mouse and, when perturbed in both species, it translates in the brain into lateralized alterations of patterning, neuronal differentiation and behavior. We demonstrate that altering levels of the mouse RA coactivator Rere results in subtle cortex asymmetry and profoundly altered handedness, linking patterning and function in the motor cortex. Together our data uncover a novel mechanism that could underlie the establishment of brain asymmetries and handedness in vertebrates.

Steroids and Plasticity

2017 ◽  
Author(s):  
Alyssa L. Pedersen ◽  
Colin J. Saldanha
Keyword(s):  
End Points ◽  
Cellular Processes ◽  
Vertebrate Brain ◽  
Synaptic Neurotransmission ◽  
And Function ◽  
And Behavior ◽  
The Brain ◽  
Vertebrate Central Nervous System ◽  
Made In

Given the profound influence of steroids on the organization and activation of the vertebrate central nervous system (CNS), it is perhaps not surprising that these molecules are involved in processes that restructure the cytoarchitecture of the brain. This includes processes such as neurogenesis and the connectivity of neural circuits. In the last 30 years or so, we have learned that the adult vertebrate brain is far from static; it responds to changes in androgens and estrogens, with dramatic alterations in structure and function. Some of these changes have been directly linked to behavior, including sex, social dominance, communication, and memory. Perhaps the most dramatic levels of neuroplasticity are observed in teleosts, where circulating and centrally derived steroids can affect several end points, including cell proliferation, migration, and behavior. Similarly, in passerine songbirds and mammals, testosterone and estradiol are important modulators of adult neuroplasticity, with documented effects on areas of the brain necessary for complex behaviors, including social communication, reproduction, and learning. Given that many of the cellular processes that underlie neuroplasticity are often energetically demanding and temporally protracted, it is somewhat surprising that steroids can affect physiological and behavioral end points quite rapidly. This includes recent demonstrations of extremely rapid effects of estradiol on synaptic neurotransmission and behavior in songbirds and mammals. Indeed, we are only beginning to appreciate the role of temporally and spatially constrained neurosteroidogenesis, like estradiol and testosterone being made in the brain, on the rapid regulation of complex behaviors.

scholarly journals Brain Plasticity and Behavior

2003 ◽  
Vol 12 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Bryan Kolb ◽  
Robbin Gibb ◽  
Terry E. Robinson
Keyword(s):  
Brain Plasticity ◽  
Recovery Of Function ◽  
Psychological Disorders ◽  
Abnormal Behavior ◽  
Brain Organization ◽  
Functional Changes ◽  
Brain Circuitry ◽  
And Function ◽  
And Behavior ◽  
The Brain

Although the brain was once seen as a rather static organ, it is now clear that the organization of brain circuitry is constantly changing as a function of experience. These changes are referred to as brain plasticity, and they are associated with functional changes that include phenomena such as memory, addiction, and recovery of function. Recent research has shown that brain plasticity and behavior can be influenced by a myriad of factors, including both pre- and postnatal experience, drugs, hormones, maturation, aging, diet, disease, and stress. Understanding how these factors influence brain organization and function is important not only for understanding both normal and abnormal behavior, but also for designing treatments for behavioral and psychological disorders ranging from addiction to stroke.

scholarly journals Retinoic acid signaling and neuronal differentiation

2015 ◽  
Vol 72 (8) ◽  
pp. 1559-1576 ◽  
Author(s):  
Amanda Janesick ◽  
Stephanie Cherie Wu ◽  
Bruce Blumberg
Keyword(s):  
Retinoic Acid ◽  
Neuronal Differentiation ◽  
Retinoic Acid Signaling

Developmental psychopathology in an era of molecular genetics and neuroimaging: A developmental neurogenetics approach

2015 ◽  
Vol 27 (2) ◽  
pp. 587-613 ◽  
Author(s):  
Luke W. Hyde
Keyword(s):  
Molecular Genetics ◽  
Developmental Psychopathology ◽  
Imaging Genetics ◽  
Gene Environment ◽  
Brain Structure And Function ◽  
Brain And Behavior ◽  
And Function ◽  
And Behavior ◽  
The Brain

AbstractThe emerging field of neurogenetics seeks to model the complex pathways from gene to brain to behavior. This field has focused on imaging genetics techniques that examine how variability in common genetic polymorphisms predict differences in brain structure and function. These studies are informed by other complimentary techniques (e.g., animal models and multimodal imaging) and have recently begun to incorporate the environment through examination of Imaging Gene × Environment interactions. Though neurogenetics has the potential to inform our understanding of the development of psychopathology, there has been little integration between principles of neurogenetics and developmental psychopathology. The paper describes a neurogenetics and Imaging Gene × Environment approach and how these approaches have been usefully applied to the study of psychopathology. Six tenets of developmental psychopathology (the structure of phenotypes, the importance of exploring mechanisms, the conditional nature of risk, the complexity of multilevel pathways, the role of development, and the importance of who is studied) are identified, and how these principles can further neurogenetics applications to understanding the development of psychopathology is discussed. A major issue of this piece is how neurogenetics and current imaging and molecular genetics approaches can be incorporated into developmental psychopathology perspectives with a goal of providing models for better understanding pathways from among genes, environments, the brain, and behavior.

scholarly journals Inhibiting retinoic acid signaling ameliorates graft-versus-host disease by modifying T-cell differentiation and intestinal migration

Blood ◽  
2013 ◽  
Vol 122 (12) ◽  
pp. 2125-2134 ◽  
Author(s):  
Kazutoshi Aoyama ◽  
Asim Saha ◽  
Jakub Tolar ◽  
Megan J. Riddle ◽  
Rachelle G. Veenstra ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
T Cell ◽  
T Cell Differentiation ◽  
Retinoic Acid Signaling ◽  
Mesenteric Lymph Nodes ◽  
Metabolizing Enzymes ◽  
Graft Versus Host ◽  
Mesenteric Lymph ◽  
Key Points ◽  
And Function

Key Points Expression and function of vitamin A metabolizing enzymes are increased in the intestine and mesenteric lymph nodes during GVHD. Inhibiting donor T-cell RAR signaling reduces Th1 differentiation, gut homing, and GVHD while preserving graft-versus-lymphoma effects.

scholarly journals 13-P031 Rere (Atrophin2) controls retinoic acid signaling and somite bilateral symmetry

2009 ◽  
Vol 126 ◽  
pp. S203-S204
Author(s):  
Gonçalo C. Vilhais-Neto ◽  
Karen Smith ◽  
Andrew Peterson ◽  
Jerry Workman ◽  
Olivier Pourquié
Keyword(s):  
Retinoic Acid ◽  
Bilateral Symmetry ◽  
Retinoic Acid Signaling

scholarly journals The Brain of the Planarian as the Ancestor of the Human Brain

1985 ◽  
Vol 12 (4) ◽  
pp. 296-302 ◽  
Author(s):  
Harvey B. Sarnat ◽  
Martin G. Netsky
Keyword(s):  
Nervous System ◽  
Human Brain ◽  
Photoreceptor Cells ◽  
Bilateral Symmetry ◽  
Entire Body ◽  
Synaptic Organization ◽  
Vertebrate Brain ◽  
Neurotransmitter Substances ◽  
The Brain ◽  
Human Nervous System

ABSTRACT:The planarian is the simplest living animal having a body plan of bilateral symmetry and cephalization. The brain of these free-living flatworms is a biiobed structure with a cortex of nerve cells and a core of nerve fibres including some that decussate to form commissures. Special sensory input from chemoreceptors, photoreceptor cells of primitive eyes, and tactile receptors are integrated to provide motor responses of the entire body, and local reflexes. Many morphological, electrophysiological, and pharmacological features of planarian neurons, as well as synaptic organization, are reminiscent of the vertebrate brain. Multipolar neurons and dendritic spines are rare in higher invertebrates, but are found in the planarian. Several neurotransmitter substances identified in the human brain also occur in the planarian nervous system. The planarian evolved before the divergence of the phylogenetic line leading to vertebrates. This simple worm therefore is suggested as a living example of the early evolution of the vertebrate brain. An extraordinary plasticity and regenerative capacity, and sensitivity to neurotoxins, provide unique opportunities for studying the reorganization of the nervous system after injury. Study of this simple organism may also contribute to a better understanding of the evolution of the human nervous system.

scholarly journals Retinoic acid signaling is dispensable for somatic development and function in the mammalian ovary

2017 ◽  
Vol 424 (2) ◽  
pp. 208-220 ◽  
Author(s):  
Anna Minkina ◽  
Robin E. Lindeman ◽  
Micah D. Gearhart ◽  
Anne-Amandine Chassot ◽  
Marie-Christine Chaboissier ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Signaling ◽  
Somatic Development ◽  
And Function

scholarly journals Retinoic acid is detected at relatively high levels in the CNS of adult rats

2002 ◽  
Vol 282 (3) ◽  
pp. E672-E678 ◽  
Author(s):  
Elizabeth A. Werner ◽  
Hector F. Deluca
Keyword(s):  
Spinal Cord ◽  
Retinoic Acid ◽  
Organic Phase ◽  
Adult Brain ◽  
Cellular Growth ◽  
Adult Rats ◽  
Developmental Defects ◽  
All Trans Retinoic Acid ◽  
And Function ◽  
The Brain

Retinoic acid (RA) is essential for cellular growth and differentiation in developing and adult animals. The central nervous system (CNS) suffers developmental defects if embryonic levels of RA are too high or too low. The production and function of RA in adult brain are unclear. We report that RA is present throughout the brain and spinal cord of adult, vitamin A-deficient (VAD) rats treated with a physiological amount of all- trans-retinol. The hippocampus/cortex contained the highest proportion of RA in the brain (27.2 ± 2.9% of the organic phase radioactivity, and 23.5 ± 0.8% of the organic phase radioactivity extracted from spinal cord was RA). RA comprises a higher proportion of the retinoid pool in the CNS compared with amounts reported in other target tissues (E Werner and HF DeLuca. Arch Biochem Biophys 393: 262–270, 2001). However, RA is not preferentially transported from the blood to the brain. There were 2.90 ± 0.20 fmol RA/g tissue transported to the brain of VAD rats treated with 2.00 nmol [20-3H]all- trans-retinoic acid, but higher amounts of RA were delivered to the liver, testis, and spleen. Because RA is not transported preferentially to brain, this tissue likely synthesizes RA more efficiently than other target tissues.

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