RESUMO
Neurons that utilize melanin-concentrating hormone (MCH) as neuromodulator are located in the lateral hypothalamus and incerto-hypothalamic area. These neurons project throughout the central nervous system and play a role in sleep regulation. With the hypothesis that the MCHergic system function would be modified by the time of the day as well as by disruptions of the sleep-wake cycle, we quantified in rats the concentration of MCH in the cerebrospinal fluid (CSF), the expression of the MCH precursor (Pmch) gene in the hypothalamus, and the expression of the MCH receptor 1 (Mchr1) gene in the frontal cortex and hippocampus. These analyses were performed during paradoxical sleep deprivation (by a modified multiple platform technique), paradoxical sleep rebound and chronic sleep restriction, both at the end of the active (dark) phase (lights were turned on at Zeitgeber time zero, ZT0) and during the inactive (light) phase (ZT8). We observed that in control condition (waking and sleep ad libitum), Mchr1 gene expression was larger at ZT8 (when sleep predominates) than at ZT0, both in frontal cortex and hippocampus. In addition, compared to control, disturbances of the sleep-wake cycle produced the following effects: paradoxical sleep deprivation for 96 and 120 h reduced the expression of Mchr1 gene in frontal cortex at ZT0. Sleep rebound that followed 96 h of paradoxical sleep deprivation increased the MCH concentration in the CSF also at ZT0. Twenty-one days of sleep restriction produced a significant increment in MCH CSF levels at ZT8. Finally, sleep disruptions unveiled day/night differences in MCH CSF levels and in Pmch gene expression that were not observed in control (undisturbed) conditions. In conclusion, the time of the day and sleep disruptions produced subtle modifications in the physiology of the MCHergic system.
Assuntos
Hormônios Hipotalâmicos/líquido cefalorraquidiano , Hormônios Hipotalâmicos/genética , Hipotálamo/metabolismo , Melaninas/líquido cefalorraquidiano , Hormônios Hipofisários/líquido cefalorraquidiano , Precursores de Proteínas/genética , Receptores de Somatostatina/genética , Privação do Sono/metabolismo , Sono REM , Animais , Lobo Frontal/metabolismo , Expressão Gênica , Hipocampo/metabolismo , Masculino , Ratos , Ratos WistarRESUMO
Millions of people worldwide are affected by anthropogenic air pollution derived from the combustion of fossil fuels. In this work, we tested the effects of fetal, lactation and post-weaning ambient air pollution exposure on total homocysteine (tHcy) concentrations and on a downstream pathway element, the plasma cysteine (Cys) concentration. Two similar exposure chambers (polluted and filtered chamber) were located near an area with heavy traffic in São Paulo, Brazil, and male Swiss mice were housed there from the pre-natal period until 3 months of age. Groups during fetal, lactation and adult periods of exposure were apportioned, and tHcy and Cys plasma concentrations were assessed when the animals were 3 months old. In our study, both the tHcy and Cys concentrations were decreased in groups that spent their final stage of life in polluted chambers, suggesting recent alterations in tHcy and Cys concentrations due to air pollution exposure. The possible relationship of these data with cardiovascular dysfunction is still a matter of controversy in animals; nevertheless, epigenetic mechanisms emerge as a possible issue to consider in the investigation of the link between air pollution and Hcy measurement.