title: Prothymosin alpha-deficiency enhances anxiety-like behaviors and impairs learning/memory functions and neurogenesis.
abstract: Prothymosin alpha (ProTα) is expressed in various mammalian organs including the neuronal nuclei in the brain, and is involved in multiple functions, such as chromatin remodeling, transcriptional regulation, cell proliferation, and survival. ProTα has beneficial actions against ischemia-induced necrosis and apoptosis in the brain and retina. However, characterizing the physiological roles of endogenous ProTα in the brain without stress remains elusive. Here, we generated ProTα-deficiency mice to explore whether endogenous ProTα is involved in normal brain functions. We successfully generated heterozygous ProTα knockout (ProTα+/-) mice, while all homozygous ProTα knockout (ProTα-/-) offspring died at early embryonic stage, suggesting that ProTα has crucial roles in embryonic development. In the evaluation of different behavioral tests, ProTα+/-mice exhibited hypolocomotor activity in the open-field test and enhanced anxiety-like behaviors in the light/dark transition test and the novelty induced hypophagia test. ProTα+/-mice also showed impaired learning and memory in the step-through passive avoidance test and the KUROBOX test. Depression-like behaviors in ProTα+/-mice in the forced swim and tail suspension tests were comparable with that of wild-type mice. Furthermore, adult hippocampal neurogenesis was significantly decreased in ProTα+/-mice. ProTα+/-mice showed an impaired long-term potentiation induction in the evaluation of electrophysiological recordings from acute hippocampal slices. Microarray analysis revealed that the candidate genes related to anxiety, learning/memory-functions, and neurogenesis were down-regulated in ProTα+/-mice. Thus, this study suggests that ProTα has crucial physiological roles in the robustness of brain.
authors.affiliation: Department of Pharmacology and Therapeutic Innovation, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueda
authors.affiliation: Department of Pharmacology and Therapeutic Innovation, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Pharmacology and Therapeutic Innovation, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Sebok Kumar
authors.initials: SK
authors.lastname: Halder
authors.affiliation: Department of Pharmacology and Therapeutic Innovation, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Deguchi
authors.affiliation: Section of Behavior Patterns, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, NINS, Okazaki, Aichi, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Takao
authors.affiliation: Section of Behavior Patterns, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, NINS, Okazaki, Aichi, Japan.|Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyakawa
authors.affiliation: Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Ishikawa, Japan.
authors.forename: Atsushi
authors.identifier: 0000-0001-6808-5491
authors.initials: A
authors.lastname: Tajima
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007858:Learning / Q000502:physiology*; D008297:Male; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055495:Neurogenesis / Q000502:physiology*; D011498:Protein Precursors / Q000172:deficiency* / Q000235:genetics; D013947:Thymosin / Q000031:analogs & derivatives* / Q000172:deficiency / Q000235:genetics
chemical_list: D011498:Protein Precursors; C040782:prothymosin alpha; D013947:Thymosin
keywords: 
  LTP
  ; adult neurogenesis; anxiety; learning and memory; prothymosin alpha