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...

Noradrenergic LC neurons provide a circadian regulation of the sleep-wake cycle, and the maintenance of LC function depends on light exposure. Light deprivation induces a loss of noradrenergic fibers, which in turn decreases the amplitude of the sleep-wake rhythm.

Visual Abstract

The influence of light on mammalian physiology and behavior is due to the entrainment of circadian rhythms complemented with a direct modulation of light that would be unlikely an outcome of circadian system. In mammals, physiological and behavioral circadian rhythms are regulated by the suprachiasmatic nucleus (SCN) of the hypothalamus. This central control allows organisms to predict and anticipate environmental change, as well as to coordinate different rhythmic modalities within an individual. In adult mammals, direct retinal projections to the SCN are responsible for resetting and synchronizing physiological and behavioral rhythms to the light-dark (LD) cycle. Apart from its circadian effects, light also has direct effects on certain biological functions in such a way that the participation of the SCN would not be fundamental for this network. The objective of this review is to increase awareness, within the scientific community and commercial providers, of the fact that laboratory rodents can experience a number of adverse health and welfare outcomes attributed to commonly-used lighting conditions in animal facilities during routine husbandry and scientific procedures, widely considered as “environmentally friendly.” There is increasing evidence that exposure to dim light at night, as well as chronic constant darkness, challenges mammalian physiology and behavior resulting in disrupted circadian rhythms, neural death, a depressive-behavioral phenotype, cognitive impairment, and the deregulation of metabolic, physiological, and synaptic plasticity in both the short and long terms. The normal development and good health of laboratory rodents requires cyclical light entrainment, adapted to the solar cycle of day and night, with null light at night and safe illuminating qualities during the day. We therefore recommend increased awareness of the limited information available with regards to lighting conditions, and therefore that lighting protocols must be taken into consideration when designing experiments and duly highlighted in scientific papers. This practice will help to ensure the welfare of laboratory animals and increase the likelihood of producing reliable and reproducible results.

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