Mice lacking integrin β3 expression exhibit altered response to chronic stress

Abstract

Recent studies indicate multiple roles for integrin αvβ3 in adult neurons, including response to pharmacological agents such as cocaine and selective serotonin reuptake inhibitors. In this study, we examined the role of the integrin β3 gene (Itgb3) in the response to environmental stimuli by subjecting Itgb3+/+ and Itgb3-/- mice to unpredictable chronic mild stressors. We found that genetic abrogation of integrin β3 expression elicits an exaggerated vulnerability to chronic unpredictable stress in the open field test. In this test, chronic stress elicited significant decreases in stereotypic behavior and horizontal locomotor activity, including increases in anxiety behaviors. Mild chronic stress led to reductions in dopamine turnover in midbrains of Itgb3+/+, but not Itgb3-/- mice, suggesting a disruption of stress-dependent regulation of DA homeostasis. Chronic stress elicited altered synaptic expression of syntaxin and synaptophysin in midbrains of Itgb3-/- mice, when compared to Itgb3+/+. Semi-quantitative Western blot studies revealed that the synaptic expression, but not total tissue expression, of multiple signaling proteins is correlated with integrin αv levels in the midbrain. Moreover, loss of integrin β3 expression modifies this correlation network. Together, these findings demonstrate that Itgb3-/- mice display a pattern of changes indicating disrupted regulation of midbrain synaptic systems involved in conferring resilience to mild stressors.

Integrin β3 organizes dendritic complexity of cerebral cortical pyramidal neurons along a tangential gradient

“…However, Itgb3 is also critical for platelet function, so knockout mice often hemorrhage during fetal development and adulthood, leading to low viability [ 7 , 30 ]. Other studies have pointed to an important role for Itgb3 in midbrain [ 15 , 50 , 59 , 75 , 81 ], hippocampus [ 10 , 37 , 63 ], and in cortical neurons in vitro [ 33 ]. Furthermore, various integrin subunits have been implicated in dendritic outgrowth [ 34 , 41 , 79 ] and Itgb3 specifically may be involved in Thy1 -mediated neurite retraction in vitro [ 29 ], but, to our knowledge, a putative role for Itgb3 in dendritic arborization has not been explored in vivo.…”

Differential biological effects in two pedigrees of clam Ruditapes philippinarum exposed to cadmium using iTRAQ-based proteomics

“…As it is known, focal adhesion cooperated with action cytoskeleton plays key roles in signal transduction, which contributes to the cell migration, growth, differentiation and other biological processes (Carragher and Frame, 2004;McKayed and Simpson, 2013;Pieri et al, 2014). As the key proteins involved in focal adhesion pathway, calcium-binding protein, guanine nucleotide exchange factor VAV2 and integrin have been commonly altered in Cd-treated White and Zebra clams samples in this work, which were also found in organisms in response to other stress factors like organic pollutant and changes of living environment (Liu et al, 2013a,b;Ji et al, 2014;Varney et al, 2015). In general, endocytosis plays key roles in nutrient uptaking, cell signaling and immune response (Miaczynska and Stenmark, 2008;Dannevig et al, 1994).…”

Prothymosin alpha‐deficiency enhances anxiety‐like behaviors and impairs learning/memory functions and neurogenesis

“…ProTα +/− mice showed down‐regulation of anxiety‐related Itgb3 gene (Varney et al . ) with 0.82‐fold and up‐regulation of Ntng1 gene (Zhang et al . ) with 1.36‐fold compared to ProTα +/+ mice (Table ).…”

“…Itgb3 protein functions as one of a modulator of serotonergic systems and Itgb3‐deficient mice displayed increased anxiety‐like behaviors with reduced locomotor activity (Varney et al . ), whereas anxiolytic behaviors with normal locomotor activity was observed Ntng1‐deficient mice (Zhang et al . ).…”