ABSTRACT
With aging there is a significant decline in the normal architecture of sleep and a reduction in the diurnal amplitude of core body temperature. Regular moderate exercise has been shown to have a positive impact in the elderly and here we investigate whether sleep-wake patterning can also be improved. Young (3 months) and old (22 months) F344 rats were exercised once a day for 50min at night onset over an 8-week period. Thereafter, polysomnographic recordings were obtained immediately after exercise. To determine the lasting consequences of exercise, sleep was also recorded 2 days and 2 weeks after exercise had ended. Old rats that were exercised had a significant weight loss, were awake more during the last third of their active period, had less sleep fragmentation and the amplitude of the diurnal rhythm of core body temperature was significantly increased. Old exercised rats also had an overall increase in the amplitude of EEG power (0.5-16Hz) during wake and theta EEG power during REM sleep. In young rats regular exercise increased EEG delta power (0.5-4Hz) during NREM sleep. Our data indicate regular exercise in old rats improves sleep architecture, EEG power and diurnal rhythm of temperature.
Subject(s)
Aging/physiology , Physical Conditioning, Animal/physiology , Sleep/physiology , Animals , Body Temperature/physiology , Electroencephalography , Male , Rats , Rats, Inbred F344ABSTRACT
The neuropeptide hypocretin, also known as orexin, has been implicated in waking since its deletion leads to the sleep disorder narcolepsy. Hypocretin neurons project to major arousal areas, and in an effort to determine which region is responsible for the changes in sleep-wake architecture we have developed the neurotoxin hypocretin2-saporin, which lesions hypocretin receptor bearing neurons. Here, in rats, we investigate the effects of hypocretin2-saporin lesions of the substantia nigra and ventral tegmental area in the regulation of sleep and wakefulness. Bilateral injection of hypocretin2-sap into both the ventral tegmental area and substantia nigra (92 and 184 ng/microl, 0.25 microl in the ventral tegmental area and 0.5 microl in the substantia nigra) or into the substantia nigra alone (184 ng/microl, 0.5 microl) produced insomnia. The insomnia seemed to be associated with a large increase in locomotion on days 4 and 6 postinjection, as hyperactivity and stereotypic movements were consistently observed on the video recordings in all lesioned rats. In these rats, a nearly complete loss of both tyrosine hydroxylase and neuron-specific nuclear protein (neuronal nuclei) immunoreactive cells in the substantia nigra as well as diminution of tyrosine hydroxylase-immunoreactive fibers in the caudate putamen was found. Following bilateral injection of hypocretin2-sap at a lower concentration (46 ng/microl, 0.25 microl in the ventral tegmental area and 0.5 microl in the substantia nigra), very little reduction in the number of tyrosine hydroxylase- and neuronal nuclei-immunoreactive neurons and only a temporary increase in wakefulness (17.4% increase during light-off period on day 6 postinjection) were observed. Ventral tegmental area lesions (184 ng/mul of hypocretin2-sap, 0.25 microl, bilateral injections) did not produce significant changes in sleep, although most of the tyrosine hydroxylase- and neuronal nuclei-immunoreactive neurons in the ventral tegmental area were destroyed. Insomnia following hypocretin2-sap lesions of the substantia nigra could be secondary to increased motor activity resulting from reduction of tonic inhibitory control by the substantia nigra.
Subject(s)
Neuropeptides/toxicity , Plant Proteins/toxicity , Sleep Initiation and Maintenance Disorders/chemically induced , Sleep Initiation and Maintenance Disorders/physiopathology , Substantia Nigra/drug effects , Toxins, Biological/toxicity , Animals , Dose-Response Relationship, Drug , Electroencephalography , Electromyography , Immunohistochemistry , Injections, Intraventricular , Motor Activity/drug effects , Neurons/drug effects , Neurons/metabolism , Neurons/pathology , Neuropeptides/administration & dosage , Plant Proteins/administration & dosage , Rats , Ribosome Inactivating Proteins, Type 1 , Saporins , Sleep Initiation and Maintenance Disorders/pathology , Substantia Nigra/metabolism , Substantia Nigra/pathology , Toxins, Biological/administration & dosage , Tyrosine 3-Monooxygenase/drug effects , Tyrosine 3-Monooxygenase/metabolism , Ventral Tegmental Area/drug effects , Ventral Tegmental Area/pathologyABSTRACT
Rapid eye movement (REM) sleep is hypothesized to result from the activity of REM sleep-generating and REM sleep-inhibiting neurons. The serotoninergic (5-HT) neurons of the dorsal raphe nucleus (DRN) represents one such population of REM-sleep inhibiting neurons since they are silent during REM sleep. Consistent with the decrease in activity of 5-HT neurons, the brain extracellular levels of 5-HT are lower during REM sleep compared to wakefulness. It is not known whether serotonin release is also reduced as a consequence of REM sleep rebound. Using microdialysis sampling coupled to HPLC-ECD, we measured the extracellular levels of 5-HT and its metabolite (5-HIAA) in the medial medullary reticular formation (mMRF) of freely behaving rats during normal sleep, REM sleep deprivation as well as during REM sleep rebound. We found that the levels 5-HT and 5-HIAA were significantly decreased by REM sleep deprivation. The reduction of 5-HT release was maintained during REM sleep rebound but the extracellular level of its main metabolite was increased. In addition, even during REM sleep rebound, 5-HT release during sleep was low compared to wakefulness. Taken together these data support the permissive role of 5-HT neurotransmission for REM sleep expression.
