Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have demonstrated that the function of glia is not restricted to the support of neuronal function. In fact, astrocytes are essential for neuronal activity in the brain and play an important role in the regulation of complex behavior. Astrocytes actively participate in synapse formation and brain information processing by releasing and uptaking glutamate, D-serine, adenosine 5'-triphosphate (ATP), and adenosine. In the central nervous system, adenosine-mediated neuronal activity modulates the actions of other neurotransmitter systems. Adenosinergic fine-tuning of the glutamate system in particular has been shown to regulate circadian rhythmicity and sleep, as well as alcohol-related behavior and drinking. Adenosine gates both photic (light-induced) glutamatergic and nonphotic (alerting) input to the circadian clock located in the suprachiasmatic nucleus of the hypothalamus. Astrocytic, SNARE-mediated ATP release provides the extracellular adenosine that drives homeostatic sleep. Acute ethanol increases extracellular adenosine, which mediates the ataxic and hypnotic/sedative effects of alcohol, while chronic ethanol leads to downregulated adenosine signaling that underlies insomnia, a major predictor of relapse. Studies using mice lacking the equilibrative nucleoside transporter 1 have illuminated how adenosine functions through neuroglial interactions involving glutamate uptake transporter GLT-1 [referred to as excitatory amino acid transporter 2 (EAAT2) in human] and possibly water channel aquaporin 4 to regulate ethanol sensitivity, reward-related motivational processes, and alcohol intake.
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PMID:Adenosine and glutamate in neuroglial interaction: implications for circadian disorders and alcoholism. 2523 26

Neuromyelitis optica (NMO; also termed Devic's disease) is a severely disabling autoimmune disorder of the central nervous system (CNS), which predominantly affects the optic nerves and spinal cord. In up to 80% of cases, NMO is associated with antibodies to aquaporin-4 (AQP4-IgG), the most abundant water channel in the CNS. AQP4-IgG have been demonstrated to be directly pathogenic. Gamma-aminobutyric acid A receptor (GABAAR) agonists are frequently used in patients with NMO, e.g., for symptomatic treatment of spasticity or epilepsy or for non-NMO-related indications such as treatment of insomnia. However, GABAAR signaling has recently been shown to strongly promote AQP4 expression. This is of potential clinical importance since any increase in AQP4 membrane expression during acute NMO attacks may enhance the complement-mediated humoral immune reaction against AQP4-expressing cells characteristic for NMO and, thus, result in more severe CNS damage. We therefore hypothesize that GABAAR agonist-induced AQP4 upregulation may be a potential risk factor in NMO. This would also include a potential role for (GABAAR-enhanced) damage to the subependymal zone neural stem cells, the major source of both glial cells and neuroblasts in the adult brain, in NMO. We also make proposals on how to test that hypothesis and underline the general need for evaluating possible detrimental effects of commonly used drugs affecting AQP4 expression in NMO.
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PMID:Gamma-aminobutyric acid receptor agonists, aquaporin-4, and neuromyelitis optica: a potential link. 2632 47

Aquaporins (AQPs) are widely expressed in various types of tissues, among them AQP1, AQP4 and AQP9 are expressed predominately with relatively special distributing features in various brain regions. The aberrant changes of AQP1 and AQP4 have been observed in the brains of Alzheimer disease (AD). To evaluate the underlying alteration of brain AQPs in prion diseases, scrapie strains of 139A, ME7 and S15 infected mice were tested in this study. Western blots revealed markedly increased levels of AQP1, AQP4 and AQP9 in the brain tissues of all tested scrapie-infected mice collected at terminal stage. Analyses of the AQPs levels in the brain tissues collected at different time-points during incubation period showed time-dependent increased in 139A and ME7-infected mice, especially at the middle-late stage. The AQP1 levels also increased in the cortex regions of some human prion diseases, including the patients with sporadic Creutzfeldt-Jakob disease (CJD), fatal familial insomnia (FFI) and G114V genetic CJD (gCJD). Immunohistochemistry (IHC) assays verified that the AQPs-positive cells were astrocyte-like morphologically; meanwhile, numerous various sizes of AQPs-positive particles and dots were also observable in the brain sections of scrapie-infected mice. Immunofluorescent assays (IFAs) illustrated that the signals of AQPs colocalized with those of the GFAP positive proliferative astrocytes, and more interestingly, appeared to overlap also with the signals of PrP in the brains of scrapie-infected mice. Moreover, IHC assays with a commercial doublestain system revealed that distributing areas of AQPs overlapped not only with that of the activated large astrocytes, but also with that of abundantly deposited PrPSc in the brain tissues of scrapie murine models. Our data here propose the solid evidences that the expressions of brain AQP1, AQP4 and AQP9 are all aberrantly enhanced in various murine models of scrapie infection. The closely anatomical association between the accumulated AQPs and deposited PrPSc in the brain tissues indicates that the abnormally increased water channel proteins participate in the pathogenesis of prion diseases.
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PMID:Significant enhanced expressions of aquaporin-1, -4 and -9 in the brains of various prion diseases. 3181 27