Assessment of Depression in a Rodent Model of Spinal Cord Injury

Abstract

Despite an increased incidence of depression in patients after spinal cord injury (SCI), there is no animal model of depression after SCI. To address this, we used a battery of established tests to assess depression after a rodent contusion injury. Subjects were acclimated to the tasks, and baseline scores were collected before SCI. Testing was conducted on days 9-10 (acute) and 19-20 (chronic) postinjury. To categorize depression, subjects' scores on each behavioral measure were averaged across the acute and chronic stages of injury and subjected to a principal component analysis. This analysis revealed a two-component structure, which explained 72.2% of between-subjects variance. The data were then analyzed with a hierarchical cluster analysis, identifying two clusters that differed significantly on the sucrose preference, open field, social exploration, and burrowing tasks. One cluster (9 of 26 subjects) displayed characteristics of depression. Using these data, a discriminant function analysis was conducted to derive an equation that could classify subjects as ''depressed'' on days 9-10. The discriminant function was used in a second experiment examining whether the depression-like symptoms could be reversed with the antidepressant, fluoxetine. Fluoxetine significantly decreased immobility in the forced swim test (FST) in depressed subjects identified with the equation. Subjects that were depressed and treated with saline displayed significantly increased immobility on the FST, relative to not depressed, saline-treated controls. These initial experiments validate our tests of depression, generating a powerful model system for further understanding the relationships between molecular changes induced by SCI and the development of depression.

Endoplasmic Reticulum Stress and Disrupted Neurogenesis in the Brain Are Associated with Cognitive Impairment and Depressive-Like Behavior after Spinal Cord Injury

“…[17][18][19][20] However, a direct relationship between injury severity and associated cognitive deficits or depression has not been established. Importantly, for an SCI model, the characterization of behaviors for cognition and depression should not depend on motor function.…”

“…In SCI model, Leudtke and colleagues determined that approximately 35-39% of rats with a moderate contusion display characteristics of depression, including decreased anhedonia and social exploration, as well as increased immobility. 20 The latter symptom on the FS test can be reversed by an antidepressant fluoxetine with a dose that has been shown to be subthreshold for increasing motor activity. In the present study, moderately-or severely-injured mice displayed depressive-like behavior, with no significant differences observed between these groups.…”

“…This is in agreement with prior reports in rat SCI. 20,21 Whereas the SDPA was independent of motor activity, pain sensation changes in injured mice may affect this test. SCImediated chronic pain could potentially contribute to depression.…”

IL-4 Knock Out Mice Display Anxiety-Like Behavior

“…While best known as a sensitive indication of sickness symptoms (Bluthe et al 1994), disturbances in social exploration are also seen after generalized hypoxia (Johnson et al 2008) and starvation (Joesting et al 2014). Burrowing and social exploration generally parallel each other and are reduced (Luedtke et al 2014) in conditions tied to reduced motivation like sickness and depression. However, reductions in burrowing and social exploration are also seen in conditions that provoke anxiety (Crawley 1985).…”

Brain-derived neurotrophic factor-TrkB signaling in the medial prefrontal cortex plays a role in the anhedonia-like phenotype after spared nerve injury

“…A recent longitudinal analysis demonstrated that chronic pain strongly predicts the development of more depressive symptoms in patients with pain compared with those without pain [6]. These epidemiological studies suggest that individual differences exist in the development of pain and depression comorbidities [1,2,[7][8][9]. Although pain and depression share biological pathways, the precise mechanisms underlying the comorbidity of pain and depression remain unknown.…”