RESUMEN
Previous studies have demonstrated that macromolecular synthesis in the brain is modulated in association with the occurrence of sleep and wakefulness. Similarly, the spectral composition of electroencephalographic activity that occurs during sleep is dependent on the duration of prior wakefulness. Since this homeostatic relationship between wake and sleep is highly conserved across mammalian species, genes that are truly involved in the electroencephalographic response to sleep deprivation might be expected to be conserved across mammalian species. Therefore, in the rat cerebral cortex, we have studied the effects of sleep deprivation on the expression of immediate early gene and heat shock protein mRNAs previously shown to be upregulated in the mouse brain in sleep deprivation and in recovery sleep after sleep deprivation. We find that the molecular response to sleep deprivation and recovery sleep in the brain is highly conserved between these two mammalian species, at least in terms of expression of immediate early gene and heat shock protein family members. Using Affymetrix Neurobiology U34 GeneChips , we also screened the rat cerebral cortex, basal forebrain, and hypothalamus for other genes whose expression may be modulated by sleep deprivation or recovery sleep. We find that the response of the basal forebrain to sleep deprivation is more similar to that of the cerebral cortex than to the hypothalamus. Together, these results suggest that sleep-dependent changes in gene expression in the cerebral cortex are similar across rodent species and therefore may underlie sleep history-dependent changes in sleep electroencephalographic activity.
Asunto(s)
Encéfalo/metabolismo , Regulación de la Expresión Génica/fisiología , Genes Inmediatos-Precoces/genética , Proteínas de Choque Térmico/genética , Privación de Sueño/genética , Sueño/fisiología , Potenciales de Acción/genética , Animales , Núcleo Basal de Meynert/anatomía & histología , Núcleo Basal de Meynert/metabolismo , Núcleo Basal de Meynert/fisiopatología , Encéfalo/anatomía & histología , Corteza Cerebral/anatomía & histología , Corteza Cerebral/metabolismo , Corteza Cerebral/fisiopatología , Electroencefalografía , Perfilación de la Expresión Génica , Proteínas de Choque Térmico/biosíntesis , Hipotálamo/anatomía & histología , Hipotálamo/metabolismo , Hipotálamo/fisiopatología , Masculino , Ratones , Análisis de Secuencia por Matrices de Oligonucleótidos , Ratas , Ratas Wistar , Recuperación de la Función/genética , Privación de Sueño/metabolismo , Especificidad de la EspecieRESUMEN
The hypocretin/orexin ligand-receptor system has recently been implicated in the sleep disorder narcolepsy. During the dark (active) period, null mutants of the prepro-orexin (prepro-hypocretin) gene have cataplectic attacks and increased levels of both rapid eye movement (REM) and non-REM (NREM) sleep. Intracerebroventricular injection of one of the encoded neuropeptides, orexin-A, early in the light period increases wakefulness and reduces REM sleep in the rat, suggesting that this system may be involved in the normal regulation of sleep and wakefulness. To further test this hypothesis, we measured hypocretin (hcrt) mRNA levels by both Northern hybridization and Taqman analysis in mouse and rat hypothalamus after short-term (6 h) sleep deprivation (SD) and 2-4 hours after recovery from SD. Although our SD procedures effectively induced a sleep debt and increased c-fos mRNA expression in the cortex and hypothalamus as described by other investigators, we found that hcrt mRNA levels were not significantly changed in either species either after SD or after recovery from SD. If the hcrt system is involved in normal regulation of sleep and wakefulness, longer periods of SD may be necessary to affect hcrt mRNA levels or changes may occur at the protein rather than mRNA level. Alternatively, this system may also be involved in another function that counterbalances any SD-induced changes in hcrt mRNA levels.
Asunto(s)
Hipotálamo/metabolismo , Neuropéptidos/genética , Neuropéptidos/metabolismo , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Privación de Sueño/metabolismo , Sueño REM/fisiología , Animales , Northern Blotting , Electrodos Implantados , Electroencefalografía , Electromiografía , Expresión Génica , Péptidos y Proteínas de Señalización Intracelular , Ratones , Ratones Endogámicos C57BL , Orexinas , Reacción en Cadena de la Polimerasa/métodos , ARN Mensajero/genética , Ratas , Vigilia/fisiologíaRESUMEN
The effect of temperature on the duration of both population spikes and action potentials of single neurons has been investigated in a variety of in vitro preparations. A few studies have examined the influence of temperature on spike potentials from spinal motoneurons of intact, anesthetized mammals. In all cases, the duration of the action potential or population spike increased as temperature decreased. A similar increase in the duration of action potentials accompanied hibernation in the ground squirrel (Spermophilus lateralis). Oscilloscope traces of 2 brainstem reticular formations, and 8 posterior thalamic single units were photographed at a body temperature (Tb) of 34-36 degrees C during euthermia prior to entrance into hibernation and at Tb's ranging from 10 to 27 degrees C during hibernation. There was a significant increase in the duration of the second component of the diphasic action potential at the lower Tb (P less than 0.01). This temperature effect was reversible, i.e. action potential durations returned to preentrance euthermic values following arousal from hibernation (Tb = 34-36 degrees C). This study is the first to use behaving animals to demonstrate that changes in biophysical characteristics of central nervous system neurons occur at low Tb. These changes in membrane characteristics probably result in alterations in neuronal functioning and information processing during hibernation.