Behavioural phenotyping of knockout mice for the sigma-1 (σ1) chaperone protein revealed gender-related anxiety, depressive-like and memory alterations

Abstract

The sigma-1 (σ1) protein regulates calcium homeostasis and acts as an endoplasmic reticulum chaperone. It can be activated by ligands which impact memory, depression, anxiety or addiction processes. We here characterized the behavioural phenotype of knockout (KO) mice for the σ1 protein. Two-month old male σ1-/- mice showed signs of anxiety in the open-field, passive avoidance or elevated plus-maze test, but other activity or memory responses were unchanged. Female σ1-/- mice showed deficits in spontaneous alternation or water-maze learning. Twelve-month old σ1+/- female mice showed deficits in alternation and σ1-/- mice in avoidance escape latency. Two- and 14-month old female σ1-/- mice showed decreased plasma 17β-estradiol levels. Treatment with 17β-estradiol (0.1, 0.2 mg/kg i.p.) reversed the spatial memory deficits in young and aged mice. Male σ1 KO mice showed enhanced response in the forced swimming test. Igmesine, a σ1 agonist, failed to decrease immobility in σ1 KO mice. Fluoxetine and sertraline were more efficient in σ1 KO mice, an effect likely related to their σ1 antagonist activity. Imipramine, desipramine and amitriptyline were equally active. σ1 Protein invalidation therefore affected stress or anxiety response but not memory in males. Changes in steroid tonus in female animals led, however, to memory impairments that increased with age. © The Author(s) 2011 Reprints and permissions: sagepub.co.uk/ journalsPermissions.nav.