Impaired emotional response to stress in mice lacking galectin-1 or galectin-3

Abstract

Galectin-1 (Gal-1) and galectin-3 (Gal-3) are multifunctional glycan-binding proteins, expressed in the brain and in its limbic structures that are involved in behavioral control. Gal-1 induces the expression of the brain-derived neurotrophic factor (BDNF) and promotes adult neural stem cells proliferation, biological events impaired in stress-related psychiatric disorders, such as depression and anxiety. Despite that, there is no evidence regarding galectin involvement in emotional control during stressful situations. Thus, we analyzed the behavioral phenotype of Gal-1 or Gal-3 knock-out mice (Gal-1 KO or Gal-3 KO) in different experimental models predictive of depressive and compulsive-like behaviors.

Methods: C57BL-6 Gal-1 KO, Gal-3 KO, and wild-type mice (WT) were analyzed under the open field test (OFT) and, 6 h later, under the forced swim test (FST). Additionally, independent groups of male mice, lacking galectins or not, were exposed to the tail suspension test (TST) or to the marble burying test (MBT). The hippocampus and prefrontal cortex (PFC) of the mice submitted to MBT were dissected to access BDNF levels.

Results: Both Gal-1 and Gal-3 KO mice showed increased time of immobility in the FST and in the TST compared to WT animals, thus reflecting an impaired stress-coping behavior. Additionally, Gal-1 and Gal-3 KO female mice presented increased compulsive-like behavior in the MBT, without significant changes in the locomotor activity. BDNF levels were found to be decreased in the PFC of Gal-1 KO mice.

Discussion: Our results demonstrate that the absence of either endogenous Gal-1 and Gal-3 impairs stress-coping and increases compulsive-like behavior, suggesting that Gal-1 and Gal-3 are involved in the neurobiology of depression and obsessive-compulsive-like disorder.

Keywords: Brain-derived neurotrophic factor; Depression; Forced swim test; Galectin-1; Galectin-3; Hippocampus; Marble-burying test; Obsessive-compulsive disorder; Prefrontal cortex; Stress.