Sartim A G, Sartim M A, Cummings R D, Dias-Baruffi M, Joca S R
Department of Biomolecular Sciences, School of Pharmaceutical Science of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Basic and Applied Immunology Graduate Program, Institute of Biological Sciences, Federal University of Amazonas, Manaus, AM, Brazil.
Physiol Behav. 2020 Jun 1;220:112862. doi: 10.1016/j.physbeh.2020.112862. Epub 2020 Mar 7.
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.
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.
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.
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.
半乳糖凝集素-1(Gal-1)和半乳糖凝集素-3(Gal-3)是多功能聚糖结合蛋白,在大脑及其参与行为控制的边缘结构中表达。Gal-1诱导脑源性神经营养因子(BDNF)的表达并促进成年神经干细胞增殖,而这些生物学事件在与压力相关的精神疾病(如抑郁症和焦虑症)中受损。尽管如此,尚无证据表明半乳糖凝集素在应激情况下参与情绪控制。因此,我们在预测抑郁和强迫样行为的不同实验模型中分析了Gal-1或Gal-3基因敲除小鼠(Gal-1 KO或Gal-3 KO)的行为表型。
对C57BL-6 Gal-1 KO、Gal-3 KO和野生型小鼠(WT)进行旷场试验(OFT)分析,并在6小时后进行强迫游泳试验(FST)。此外,独立的雄性小鼠组,无论是否缺乏半乳糖凝集素,均接受悬尾试验(TST)或埋大理石试验(MBT)。对接受MBT试验的小鼠的海马体和前额叶皮质(PFC)进行解剖以检测BDNF水平。
与WT动物相比,Gal-1和Gal-3 KO小鼠在FST和TST中的不动时间均增加,从而反映出应激应对行为受损。此外,Gal-1和Gal-3 KO雌性小鼠在MBT中表现出增加的强迫样行为,运动活动无明显变化。发现Gal-1 KO小鼠的PFC中BDNF水平降低。
我们的结果表明,内源性Gal-1和Gal-3的缺失会损害应激应对并增加强迫样行为,表明Gal-1和Gal-3参与抑郁症和强迫样障碍的神经生物学过程。