Genetic Perturbation of TIA1 Reveals a Physiological Role in Fear Memory.

Autor:	Rayman JB; Department of Neuroscience, Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA., Hijazi J; Department of Neuroscience, Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA., Li X; Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China., Kedersha N; Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA., Anderson PJ; Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA., Kandel ER; Department of Neuroscience, Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA; Howard Hughes Medical Institute at Columbia University, New York, NY 10032, USA; Kavli Institute for Brain Science, Columbia University, New York, NY 10032, USA. Electronic address: erk5@columbia.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2019 Mar 12; Vol. 26 (11), pp. 2970-2983.e4.
DOI:	10.1016/j.celrep.2019.02.048
Abstrakt:	TIA1 is a prion-related RNA-binding protein whose capacity to form various types of intracellular aggregates has been implicated in neurodegenerative disease. However, its role in normal brain function is poorly understood. Here, we show that TIA1 bidirectionally modulates stress-dependent synaptic plasticity in the hippocampus, a brain region involved in fear memory and olfactory discrimination learning. At the behavioral level, conditioned odor avoidance is potentiated by TIA1 deletion, whereas overexpression of TIA1 in the ventral hippocampus inhibits both contextual fear memory and avoidance. However, the latter genetic manipulations have little impact on other hippocampus-dependent tasks. Transcriptional profiling indicates that TIA1 presides over a large network of immune system genes with modulatory roles in synaptic plasticity and long-term memory. Our results uncover a physiological and partly sex-dependent function for TIA1 in fear memory and may provide molecular insight into stress-related psychiatric conditions, such as post-traumatic stress disorder (PTSD) and anxiety. (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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