Effects on prolactin secretion and binding to dopaminergic receptors in sleep-deprived lupus-prone mice

Abstract

Sleep disturbances have far-reaching effects on the neuroendocrine and immune systems and may be linked to disease manifestation. Sleep deprivation can accelerate the onset of lupus in NZB/NZWF 1 mice, an animal model of severe systemic lupus erythematosus. High prolactin (PRL) concentrations are involved in the pathogenesis of systemic lupus erythematosus in human beings, as well as in NZB/NZWF 1 mice. We hypothesized that PRL could be involved in the earlier onset of the disease in sleep-deprived NZB/NZWF 1 mice. We also investigated its binding to dopaminergic receptors, since PRL secretion is mainly controlled by dopamine. Female NZB/NZWF 1 mice aged 9 weeks were deprived of sleep using the multiple platform method. Blood samples were taken for the determination of PRL concentrations and quantitative receptor autoradiography was used to map binding of the tritiated dopaminergic receptor ligands [ 3 H]-SCH23390, [ 3 H]-raclopride and [ 3 H]-WIN35,428 to D 1 and D 2 dopaminergic receptors and dopamine transporter sites throughout the brain, respectively. Sleep deprivation induced a significant decrease in plasma PRL secretion (2.58 ± 0.95 ng/mL) compared with the control group (25.25 ± 9.18 ng/mL). The binding to D 1 and D 2 binding sites was not significantly affected by sleep deprivation; however, dopamine transporter binding was significantly increased in subdivisions of the caudate-putamen -posterior (16.52 ± 0.5 vs 14.44 ± 0.6), dorsolateral (18.84 ± 0.7 vs 15.97 ± 0.7) and ventrolateral (24.99 ± 0.5 vs 22.54 ± 0.7 μCi/g), in the sleep-deprived mice when compared to the control group. These results suggest that PRL is not the main mechanism involved in the earlier onset of the disease observed in sleepdeprived NZB/NZWF 1 mice and the reduction of PRL concentrations after sleep deprivation may be mediated by modifications in the dopamine transporter sites of the caudate-putamen.

Repeated Exposure to Severely Limited Sleep Results in Distinctive and Persistent Physiological Imbalances in Rats

“…As noted above, low or unchanged plasma cortisol in humans is a prevalent finding, for which the present results in rats are consistent. Findings in humans include inappropriately low TSH [88], suppressed growth hormone [103], and perhaps suppressed prolactin [104]; these changes also are observed in sleep-deprived and sleep-restricted rats and mice [14], [15], [75], [105]. Various signs of sympathetic nervous system activation are typically reported in humans [84], [88], [95], [97], [106], [107], [108], [109], [110], [111], as well as in laboratory rats [11], [18].…”

Polygenic autoimmune disease risk alleles impacting B cell tolerance act in concert across shared molecular networks in mouse and in humans

“…Indeed, less than 7 hours of sleep is associated with the onset of human SLE in longitudinal cohort studies ( 490 ). Further, several reports indicate that systematically sleep deprived NZB/NZWF (1) mice develop increased lupus activity ( 491 , 492 ). Thus, differences in circadian cycles may be an additional factor to consider when modeling human autoimmune pathologies in mice.…”

Type 2 diabetes mellitus, drug addiction, bipolar disorder and epilepsy display overlapping aetiopathogenic mechanisms: Implication for prevention and pharmacotherapy

“…Bipolar disorder may be a cyclical process, where increased dopaminergic transmission is responsible for the manic features and receptor down-regulation may correspond to the depression phase (Berk et al, 2007). Pronounced hyperactivity, caffeine hypersensitivity and reduced sleep are typically observed in dopamine transporter (DAT) knock-out animals (Holst et al, 2014) and sleepdeprivation may induce supersensitivity of dopaminergic receptors in the rat brain (Tufik et al, 1978;Palma et al, 2009;De Laurentis et al, 2002;Troncone et al, 1998). Prostaglandin E2 may amplify DI and D2 receptor signalling (Kitaoka et al, 2007;Di Marzo and Piomelli, 1992).…”