title: Social isolation stress-induced fear memory deficit is mediated by down-regulated neuro-signaling system and Egr-1 expression in the brain.
abstract: We previously reported that social isolation (SI) rearing of rodents not only elicits a variety of behavioral abnormalities including attention deficit hyperactivity disorder-like behaviors, but also impairs fear memory in mice. This study aimed to clarify a putative mechanism underlying SI-induced conditioned fear memory deficit. Mice were group-housed (GH) or socially isolated for 2 weeks or more before the experiments. SI animals acquired contextual and auditory fear memory elucidated at 90 min and 4 h after training, respectively; however, they showed significantly impaired contextual and auditory memory performance at 24 h and 4 days after the training, respectively, indicating SI-induced deficit of the consolidation process of fear memory. Neurochemical studies conducted after behavioral tests revealed that SI mice had a significantly down-regulated level of Egr-1 but not Egr-2 in the hippocampal and cortical cytosolic fractions compared with those levels in the GH control animals. Moreover, in the SI group, phosphorylated levels of synaptic plasticity-related signaling proteins in the hippocampus, NR1 subunit of N-methyl-D-aspartate receptor, glutamate receptor 1, and calmodulin-dependent kinase II but not cyclic AMP-responsive element binding protein were significantly down-regulated compared with those levels in GH animals, whereas non-phosphorylated levels of these proteins were not affected by SI. These findings suggest that dysfunctions of Egr-1 and neuro-signaling systems are involved in SI-induced deficits of fear memory consolidation in mice.
authors.affiliation: Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Okada
authors.forename: Kinzo
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Ryohei
authors.initials: R
authors.lastname: Tsushima
authors.forename: Hironori
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsuneyama
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002540:Cerebral Cortex / Q000378:metabolism; D003214:Conditioning, Classical; D015536:Down-Regulation; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis*; D051767:Early Growth Response Protein 2 / Q000096:biosynthesis; D005239:Fear; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000503:physiopathology*; D008813:Mice, Inbred ICR; D009473:Neuronal Plasticity; D015398:Signal Transduction; D012934:Social Isolation; D013315:Stress, Psychological
chemical_list: D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; C486109:Egr1 protein, mouse; C497327:Egr2 protein, mouse