title: IL-13-Mediated Regulation of Learning and Memory.
abstract: The role of proinflammatory cytokines in cognitive function has been investigated with both beneficial and possible detrimental effects, depending on the cytokine. More recently, the type 2 IL-4 has been demonstrated to play a role in cognition. In this study, using the Morris water maze task, we demonstrate that IL-13-deficient mice are significantly impaired in working memory as well as attenuated reference memory, both functions essential for effective complex learning. During the learning process, wild-type mice increased the number of CD4+T cells in the meninges and production of IL-13, whereas neither Morris water maze-trained IL-4 nor trained IL-13-deficient mice were able to increase CD4+T cells in the meninges. Mechanistically, we showed that IL-13 is able to stimulate primary astrocytes to produce brain-derived neurotrophic factor, which does foster cognitive functions. Moreover, Morris water maze-trained wild-type mice were able to increase astrocyte-produced glial fibrillary acidic protein in the hippocampus, which was impaired in Morris water maze-trained IL-4- and IL-13-deficient mice. Collectively, this study strongly suggests that the Th2 cytokines, not only IL-4 but also IL-13, are involved in cognitive functions by stimulating astrocytes from the meninges and hippocampus. These results may be important for future development of therapeutic approaches associated with neurologic disorders such as Parkinson disease-associated dementia and HIV-associated dementia among others.
authors.affiliation: Cape Town Component, International Centre for Genetic Engineering and Biotechnology, Cape Town 7925, South Africa.|Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Health Science Faculty, University of Cape Town, Cape Town 7925, South Africa.|South African Medical Research Council, Cape Town 7501, South Africa.
authors.forename: Tiroyaone Masego H
authors.initials: TMH
authors.lastname: Bogale
authors.affiliation: Cape Town Component, International Centre for Genetic Engineering and Biotechnology, Cape Town 7925, South Africa.|Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Health Science Faculty, University of Cape Town, Cape Town 7925, South Africa.|South African Medical Research Council, Cape Town 7501, South Africa.|Medical Research Centre, Institute of Medical Research and Medicinal Plant Studies, Ministry of Scientific Research and Innovation, Yaoundé, Cameroon; and.
authors.forename: Justin K
authors.identifier: 0000-0001-6153-9729
authors.initials: JK
authors.lastname: Nono
authors.affiliation: Cape Town Component, International Centre for Genetic Engineering and Biotechnology, Cape Town 7925, South Africa.|Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Health Science Faculty, University of Cape Town, Cape Town 7925, South Africa.|South African Medical Research Council, Cape Town 7501, South Africa.
authors.forename: Keisha S
authors.identifier: 0000-0003-3816-082X
authors.initials: KS
authors.lastname: De Gouveia
authors.affiliation: Department of Human Biology, University of Cape Town, Cape Town 7925, South Africa.
authors.forename: Nokuthula
authors.initials: N
authors.lastname: Makena
authors.affiliation: Cape Town Component, International Centre for Genetic Engineering and Biotechnology, Cape Town 7925, South Africa.|Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Health Science Faculty, University of Cape Town, Cape Town 7925, South Africa.|South African Medical Research Council, Cape Town 7501, South Africa.
authors.forename: Matthew
authors.identifier: 0000-0002-3701-0056
authors.initials: M
authors.lastname: Darby
authors.affiliation: Department of Human Biology, University of Cape Town, Cape Town 7925, South Africa.
authors.forename: Jacqueline
authors.identifier: 0000-0001-9731-4505
authors.initials: J
authors.lastname: Womersley
authors.affiliation: Cape Town Component, International Centre for Genetic Engineering and Biotechnology, Cape Town 7925, South Africa.|Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Health Science Faculty, University of Cape Town, Cape Town 7925, South Africa.|South African Medical Research Council, Cape Town 7501, South Africa.
authors.forename: Ousman
authors.identifier: 0000-0001-6991-8088
authors.initials: O
authors.lastname: Tamgue
authors.affiliation: Cape Town Component, International Centre for Genetic Engineering and Biotechnology, Cape Town 7925, South Africa; frank.brombacher@icgeb.org.|Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Health Science Faculty, University of Cape Town, Cape Town 7925, South Africa.|South African Medical Research Council, Cape Town 7501, South Africa.
authors.forename: Frank
authors.initials: F
authors.lastname: Brombacher
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D008578:Meninges / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D015213:Neuroimmunomodulation / Q000276:immunology*
chemical_list: D018793:Interleukin-13; D015847:Interleukin-4