A molecule isolated from the cerebrospinal fluid of sleep-deprived cats has been chemically characterized and identified as cis-9,10-octadecenoamide. Other fatty acid primary amides in addition to cis-9,10-octadecenoamide were identified as natural constituents of the cerebrospinal fluid of cat, rat, and human, indicating that these compounds compose a distinct family of brain lipids. Synthetic cis-9,10-octadecenoamide induced physiological sleep when injected into rats. Together, these results suggest that fatty acid primary amides may represent a previously unrecognized class of biological signaling molecules.

Acetylcholine (ACh) plays a key role in the transitions between the different phases of sleep: Slow-wave sleep requires low ACh concentrations in the brain, whereas rapid-eye-movement (REM) sleep is associated with high levels of ACh. Also, these phases of sleep are differentially sensitive to a number of endogenous neuropeptides and cytokines, including somatostatin, which has been shown to increase REM sleep without significantly affecting other phases. Here we report the cloning and initial characterization of cortistatin, a neuropeptide that exhibits strong structural similarity to somatostatin, although it is the product of a different gene. Administration of cortistatin depresses neuronal electrical activity but, unlike somatostatin, induces low-frequency waves in the cerebral cortex and antagonizes the effects of acetylcholine on hippocampal and cortical measures of excitability. This suggests a mechanism for cortical synchronization related to sleep.

Sleep is considered an important modulator of the immune response. Thus, a lack of sleep can weaken immunity, increasing organism susceptibility to infection. For instance, shorter sleep durations are associated with a rise in suffering from the common cold. The function of sleep in altering immune responses must be determined to understand how sleep deprivation increases the susceptibility to viral, bacterial, and parasitic infections. There are several explanations for greater susceptibility to infections after reduced sleep, such as impaired mitogenic proliferation of lymphocytes, decreased HLA-DR expression, the upregulation of CD14+, and variations in CD4+ and CD8+ T lymphocytes, which have been observed during partial sleep deprivation. Also, steroid hormones, in addition to regulating sexual behavior, influence sleep. Thus, we hypothesize that sleep and the immune-endocrine system have a bidirectional relationship in governing various physiological processes, including immunity to infections. This review discusses the evidence on the bidirectional effects of the immune response against viral, bacterial, and parasitic infections on sleep patterns and how the lack of sleep affects the immune response against such agents. Because sleep is essential in the maintenance of homeostasis, these situations must be adapted to elicit changes in sleep patterns and other physiological parameters during the immune response to infections to which the organism is continuously exposed.

Background and purpose: Evidence indicates that the endocannabinoid, 2-arachidonoylglycerol (2-AG), increases food intake when injected into the nucleus accumbens shell (NAcS), thereby potentially activating hypothalamic nuclei involved in food intake regulation. We aimed to evaluate potential orexigenic effects of the endocannabinoid anandamide and of AA5HT, a fatty acid amide hydrolase (FAAH) inhibitor, and OMDM-1, an inhibitor of anandamide uptake, injected in the NAcS, as well as the effect of these treatments on activation of hypothalamic nuclei. Experimental approach: Drugs were given into the NAcS of rats and food intake quantified during the next 4 h. In other groups, after the same treatments the brains were processed for c-Fos immunohistochemistry with focus on hypothalamic nuclei. Additional groups were used to quantify endocannabinoid levels in the nucleus accumbens and the hypothalamus after AA5HT and OMDM-1 intra-NAcS injections. Key results. Our results indicate that the above treatments stimulate food intake during 4 h post-injection. They also increase c-Fos immunoreactivity in hypothalamic nuclei. The CB 1 antagonist, AM251, blocked these effects. Finally, we found elevated levels of 2-AG, but not anandamide, after intra-NAcS injections of AA5HT. Conclusions and implications: These data support the involvement of the endocannabinoid system in feeding behavior at the level of the NAcS and hypothalamus. In addition, this is the first experimental demonstration that the pharmacological inhibition of endocannabinoid inactivation in the NAcS stimulates food intake, suggesting that the endocannabinoid degrading proteins can be a target for treating eating disorders.

We report the isolation of a heretofore unrecognized brain Upid that is present in cerebrospinal fluid of sleep-deprived cats. The molecule appears to be a long-chain base structurally related to sphingosine and sph nane in which a second unsaturated bond has been introduced. An increase in the degree of unsaturation of a key membrane component is expected to have important physiological consequences. (Liberty Laboratories, Liberty Corner, NJ) were used for these studies. Subjects weighed 3.0-4.2 kg at the time of sampling. In order to establish a chronic cerebroventricular cannula, subjects were first placed under general anesthesia (halothane), intubated, and restrained in a feline stereotaxic apparatus (Kopf Instruments, Tujunga, CA). A trephine hole was then drilled in the cranial vault through which a stainless steel cannula (Plastic Products, Roanoke, VA) was inserted, directed toward either the fourth (two cats) or the right lateral (two cats) ventricle. Patency of the cannula placement was confirmed by observing spontaneous flow of clear CSF from the external tip of the cannula or by the ability to draw CSF from the cannula with a microliter syringe (Hamilton). The cannula and a fixed internal stilette were then encased and secured to the cranium by dental acrylic cement. Subjects were allowed at least 2 weeks of recovery prior to sampling of biological fluids. Subjects were group housed in a vivarium with regulated temperature and a 12-hr light/dark cycle (lights on at 6:30 a.m.; lights off at 6:30 p.m.). CSF samples were extracted between 10:00 a.m. and 12:30 a.m. The CSF sampling procedure involved removal of the internal stilette and insertion of a small diameter cannula that extended one millimeter beyond the tip ofthe implanted cannula. CSF was then drawn into a 100-A4 Hamilton syringe and immediately placed into a small plastic container (Eppendorf microcentrifuge tube) and placed into a bucket filled with dry ice. Samples were then transferred to a -700C freezer until analytical analysis. A total of six samples were collected in this fashion. Individual samples varied in volume from 150 to 300 /4. In addition to this procedure, two cats were placed on an enclosed, slow-moving treadmill for 22 hr. thereby enforcing partial sleep deprivation. One CSF sample of these subjects was taken following this period of sleep deprivation. Finally, two additional CSF samples were taken from ketamineanesthetized cats by acute transcutaneous puncture through the cisterna magna.HPLC Experiments. Preparative HPLC analysis of CSF was performed on a Pharmacia LKB Biotechnology SMART system with a MicroPeak monitor. A pRPC C2/C18, SC 2/10 column was used to perform the separation; a flow of 100 /4/min was maintained with a 1% acetonitrile/water (0.1% trifluoroacetic acid) gradient. The fraction collector collected the sample directly from the detector, which monitored absorbance at two wavelengths, 215 and 280 nm. Direct coupling between the mass spectrometer and a Michrom HPLC was also achieved.Mass Spect...