Light deprivation damages monoamine neurons and produces a depressive behavioral phenotype in rats

Abstract

Light is an important environmental factor for regulation of mood. There is a high frequency of seasonal affective disorder in high latitudes where light exposure is limited, and bright light therapy is a successful antidepressant treatment. We recently showed that rats kept for 6 weeks in constant darkness (DD) have anatomical and behavioral features similar to depressed patients, including dysregulation of circadian sleep-waking rhythms and impairment of the noradrenergic (NA)-locus coeruleus (LC) system. Here, we analyzed the cell viability of neural systems related to the pathophysiology of depression after DD, including NA-LC, serotoninergic-raphe nuclei and dopaminergicventral tegmental area neurons, and evaluated the depressive behavioral profile of light-deprived rats. We found increased apoptosis in the three aminergic systems analyzed when compared with animals maintained for 6 weeks in 12:12 light-dark conditions. The most apoptosis was observed in NA-LC neurons, associated with a significant decrease in the number of cortical NA boutons. Behaviorally, DD induced a depression-like condition as measured by increased immobility in a forced swim test (FST). DD did not appear to be stressful (no effect on adrenal or body weights) but may have sensitized responses to subsequent stressors (increased fecal number during the FST). We also found that the antidepressant desipramine decreases these neural and behavioral effects of light deprivation. These findings indicate that DD induces neural damage in monoamine brain systems and this damage is associated with a depressive behavioral phenotype. Our results suggest a mechanism whereby prolonged limited light intensity could negatively impact mood.epression is associated with decreased function in the noradrenergic (NA) locus coeruleus (LC), serotoninergic (5-HT) dorsal raphe (DR) and median raphe (MnR), and dopaminergic (DA) ventral tegmental area (VTA) systems (1-4). Behaviorally, depression is characterized by lethargy, feelings of helplessness, and profound alterations of sleep-wake rhythms (5). In at least some cases, depression is associated with decreased light availability (e.g., seasonal affective disorder) and a blunted amplitude and phase delay of circadian rhythms (5). Also, degeneration of NA fibers from LC has been associated with stress-induced depression in rats (6, 7). Recently, we showed that, as compared with animals on a 12:12 light-dark (LD) schedule, rats kept for 6 weeks in constant darkness (DD) exhibit decreased NA-LC fibers and boutons in the frontal cortex, a delayed onset of active/rest periods, and a decreased circadian amplitude of the sleep-waking rhythm (8). These results raise the possibility that the absence of light could contribute to depression, perhaps in part through effects on monoamine systems. Here, we evaluated the integrity of brain NA, 5-HT, and DA neurons, and depressive behavioral profiles, of animals kept in long-term DD to test the hypothesis that decreased function in one or more of these neural systems promotes...

The role of the circadian clock in animal models of mood disorders.

“…Kept in constant darkness (DD), mice show increases in depression-like behavior, based on increased immobility in the forced swim test (Gonzalez & Aston-Jones, 2008),…”

Dopamine and light: dissecting effects on mood and motivational states in women with subsyndromal seasonal affective disorder

“…27 Finally, in a preclinical model, rodents kept in constant darkness showed increased monoamine cell body apoptosis -changes that were associated with behavioural alterations indicative of a depressed state. 28 The purpose of the present study was to investigate the roles of DA and light on mood and motivational states using the acute phenylalanine/tyrosine depletion (APTD) method. 29,30 The APTD method has a number of advantages.…”

Is Sleep Disruption a Risk Factor for Alzheimer’s Disease?

“…Further studies are necessary to confirm the direct causal relationship between circadian rhythm disturbances and MCI/dementia and to establish if interventions that prevent circadian rhythm disturbances could delay the onset of MCI/dementia. Potential interventions include physical activity and light exposure [96][97][98][99][100][101][102], strengthen circadian activity rhythms, and improve sleep synchronization in older adults [102][103][104][105][106].…”