title: 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 subjectingItgb3+/+andItgb3-/-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 ofItgb3+/+, but notItgb3-/-mice, suggesting a disruption of stress-dependent regulation of DA homeostasis. Chronic stress elicited altered synaptic expression of syntaxin and synaptophysin in midbrains ofItgb3-/-mice, when compared toItgb3+/+. 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 thatItgb3-/-mice display a pattern of changes indicating disrupted regulation of midbrain synaptic systems involved in conferring resilience to mild stressors.
authors.affiliation: Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232-6600, USA.
authors.forename: Seth
authors.initials: S
authors.lastname: Varney
authors.affiliation: Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232-6600, USA.
authors.forename: Keith F
authors.initials: KF
authors.lastname: Polston
authors.affiliation: Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232-6600, USA.
authors.forename: Tammy
authors.initials: T
authors.lastname: Jessen
authors.affiliation: Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232-6600, USA.
authors.forename: Ana M D
authors.initials: AM
authors.lastname: Carneiro
keywords: Chronic stress; Depression; Glutamate; ITGB3; Integrin; Serotonin