title: Neural Androgen Receptor Deletion Impairs the Temporal Processing of Objects and Hippocampal CA1-Dependent Mechanisms.
abstract: We studied the role of testosterone, mediated by the androgen receptor (AR), in modulating temporal order memory for visual objects. For this purpose, we used male mice lacking AR specifically in the nervous system. Control and mutant males were gonadectomized at adulthood and supplemented with equivalent amounts of testosterone in order to normalize their hormonal levels. We found that neural AR deletion selectively impaired the processing of temporal information for visual objects, without affecting classical object recognition or anxiety-like behavior and circulating corticosterone levels, which remained similar to those in control males. Thus, mutant males were unable to discriminate between the most recently seen object and previously seen objects, whereas their control littermates showed more interest in exploring previously seen objects. Because the hippocampal CA1 area has been associated with temporal memory for visual objects, we investigated whether neural AR deletion altered the functionality of this region. Electrophysiological analysis showed that neural AR deletion affected basal glutamate synaptic transmission and decreased the magnitude of N-methyl-D-aspartate receptor (NMDAR) activation and high-frequency stimulation-induced long-term potentiation. The impairment of NMDAR function was not due to changes in protein levels of receptor. These results provide the first evidence for the modulation of temporal processing of information for visual objects by androgens, via AR activation, possibly through regulation of NMDAR signaling in the CA1 area in male mice.
authors: Neuroscience Paris Seine, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche (UMR) S1130, Université P. et M. Curie, Paris, France.|Centre National de la Recherche Scientifique, UMR 8246, Université P. et M. Curie, Paris, France.|Sorbonne Universités, Université P. et M. Curie UM CR18, Université Paris 06, France.
authors: Marie
authors: M
authors: Picot
authors: Centre de Psychiatrie et Neurosciences, Université Paris Descartes, Sorbonne Paris Cité, UMR 894, Paris, 75014 France.
authors: Jean-Marie
authors: JM
authors: Billard
authors: Neuroscience Paris Seine, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche (UMR) S1130, Université P. et M. Curie, Paris, France.|Centre National de la Recherche Scientifique, UMR 8246, Université P. et M. Curie, Paris, France.|Sorbonne Universités, Université P. et M. Curie UM CR18, Université Paris 06, France.
authors: Carlos
authors: C
authors: Dombret
authors: Neuroscience Paris Seine, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche (UMR) S1130, Université P. et M. Curie, Paris, France.|Centre National de la Recherche Scientifique, UMR 8246, Université P. et M. Curie, Paris, France.|Sorbonne Universités, Université P. et M. Curie UM CR18, Université Paris 06, France.
authors: Christelle
authors: C
authors: Albac
authors: Neuroscience Paris Seine, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche (UMR) S1130, Université P. et M. Curie, Paris, France.|Centre National de la Recherche Scientifique, UMR 8246, Université P. et M. Curie, Paris, France.|Sorbonne Universités, Université P. et M. Curie UM CR18, Université Paris 06, France.
authors: Nida
authors: N
authors: Karameh
authors: Neuroscience Paris Seine, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche (UMR) S1130, Université P. et M. Curie, Paris, France.|Centre National de la Recherche Scientifique, UMR 8246, Université P. et M. Curie, Paris, France.|Sorbonne Universités, Université P. et M. Curie UM CR18, Université Paris 06, France.
authors: Stéphanie
authors: S
authors: Daumas
authors: Neuroscience Paris Seine, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche (UMR) S1130, Université P. et M. Curie, Paris, France.|Centre National de la Recherche Scientifique, UMR 8246, Université P. et M. Curie, Paris, France.|Sorbonne Universités, Université P. et M. Curie UM CR18, Université Paris 06, France.
authors: Hélène
authors: H
authors: Hardin-Pouzet
authors: Neuroscience Paris Seine, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche (UMR) S1130, Université P. et M. Curie, Paris, France.|Centre National de la Recherche Scientifique, UMR 8246, Université P. et M. Curie, Paris, France.|Sorbonne Universités, Université P. et M. Curie UM CR18, Université Paris 06, France.
authors: Sakina
authors: S
authors: Mhaouty-Kodja
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics; D001522:Behavior, Animal; D003345:Corticosterone / Q000097:blood; D055724:Electrophysiological Phenomena; D017353:Gene Deletion; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D008570:Memory, Short-Term; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D065855:Spatial Processing / Q000502:physiology*; D009435:Synaptic Transmission
chemical_list: C000607144:AR protein, mouse; D011944:Receptors, Androgen; D016194:Receptors, N-Methyl-D-Aspartate; D003345:Corticosterone