UMLS:C0036341 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0036341 (schizophrenia)
60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Schisandra chinensis (Turcz.) Bail. is often referred to as an example of a medicinal plant with use in modern Chinese medicine. However, Schisandra chinensis first gained recognition as an adaptogen in the official medicine of the USSR in the early 1960s, principally as a result of the large number of pharmacological and clinical studies carried out by Russian scientists in the preceding two decades. Schizandra has now secured an established position within the medicine of Russia/USSR as evidenced by the inclusion of the drug in recent editions of the National Pharmacopoeia of the USSR and in the State Register of Drugs. Pharmacological studies on animals have shown that Schizandra increases physical working capacity and affords a stress-protective effect against a broad spectrum of harmful factors including heat shock, skin burn, cooling, frostbite, immobilisation, swimming under load in an atmosphere with decreased air pressure, aseptic inflammation, irradiation, and heavy metal intoxication. The phytoadaptogen exerts an effect on the central nervous, sympathetic, endocrine, immune, respiratory, cardiovascular, gastrointestinal systems, on the development of experimental atherosclerosis, on blood sugar and acid-base balance, and on uterus myotonic activity. Studies on isolated organs, tissues, cells and enzymes have revealed that Schizandra preparations exhibit strong antioxidant activities and affect smooth muscles, arachidonic acid release, biosynthesis of leukotriene B(4) in leukocytes, platelet activating factor activity, carbohydrate-phosphorus metabolism, the formation of heat shock protein and polyamines, tissue respiration and oxygen consumption, and the tolerance of an organism to oxygen intoxication. In healthy subjects, Schizandra increases endurance and accuracy of movement, mental performance and working capacity, and generates alterations in the basal levels of nitric oxide and cortisol in blood and saliva with subsequent effects on the blood cells, vessels and CNS. Numerous clinical trials have demonstrated the efficiency of Schizandra in asthenia, neuralgic and psychiatric (neurosis, psychogenic depression, astheno-depressive states, schizophrenia and alcoholism) disorders, in impaired visual function, hypotension and cardiotonic disorders, in epidemic waves of influenza, in chronic sinusitis, otitis, neuritis and otosclerosis, in pneumonia, radioprotection of the fetoplacental system of pregnant women, allergic dermatitis, acute gastrointestinal diseases, gastric hyper- and hypo-secretion, chronic gastritis, stomach and duodenal ulcers, wound healing and trophic ulcers. This review describes the considerable diversity of pharmacological effects of Schisandra chinensis reported in numerous studies carried out in the former USSR and which have been confirmed over more than 40 years of use of the plant as an official medicinal remedy. Such knowledge can be applied in the expansion of the use of Schizandra in the pharmacotherapy of European and other countries as well as for the further discovery of new drugs based on the lignans that constitute the main secondary metabolites of this plant.
...
PMID:Pharmacology of Schisandra chinensis Bail.: an overview of Russian research and uses in medicine. 1851 24

Nitric oxide (NO) plays an important role in the dopaminergic and serotonergic system as the second messenger of the NMDA receptor and has possible roles in neurotransmission, neurosecretion, synaptic plasticity, and tissue injury in many neurological disorders, including schizophrenia. There is also genetic evidence to support the human NOS1 (neuronal nitric oxide synthase 1) gene as a promising candidate gene associated with schizophrenia. In this paper we conducted a case-control association study involving 1705 Chinese subjects and 12 genetic markers [11 single nucleotide polymorphisms (SNPs) and 1 microsatellite] mainly in the 5' flank region of the gene by direct sequencing and capillary electrophoresis. We identified SNP rs3782206 and several haplotypes derived from it as being significantly associated with schizophrenia and, specifically, in a paranoid subgroup. Our results strongly support a previous hypothesis that NOS1 contributes to the genetic risk of schizophrenia and suggest that further research on more NOS1 variants and its regular elements are warranted.
...
PMID:Evidence for association between the 5' flank of the NOS1 gene and schizophrenia in the Chinese population. 1854 80

There is evidence that brain lateralization underlying hemispheric specialization can be observed also at biochemical level. However, hemispheric differences in nitric oxide mediator system have not yet been evaluated. The hippocampus and planum temporale are highly asymmetrical regions but the degree of their laterality is altered in demented or psychotic people. In the study, l-glutamate/l-arginine/l-citrulline concentrations, nitric oxide synthase activities/expressions and nitrites/nitrates levels were estimated in autoptic hippocampi. Right/left laterality in endothelial synthase activity and in nitrites/nitrates was observed in controls. Lateral changes were estimated in patients with Alzheimer disease (a marked increase in activities of constitutive synthases and in expression of inducible enzyme in the left side) and schizophrenia (an increase in activities of all enzymes especially in the right side). Significant shifts from positive to negative correlations were found between laterality of some components of nitric oxide pathway and of planum temporale volumetry under pathological conditions. The hippocampal nitric oxide system appears to be globally right/left lateralized, especially via actions of highly asymmetrical endothelial synthase. The results suggest a specific involvement of all synthases in the development of selected diseases and show that lateral analyses are of sufficient sensitivity to reveal subtle links. The volumetric asymmetry of the planum temporale as a marker of handedness is not probably simply linked to brain laterality at biochemical level but reflects alterations due to pathological processes.
...
PMID:Lateralization of hippocampal nitric oxide mediator system in people with Alzheimer disease, multi-infarct dementia and schizophrenia. 1864 32

Glial activation and neuroinflammatory processes play an important role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and HIV dementia. Activated glia cells can secrete various proinflammatory cytokines and neurotoxic mediators, which may influence neuronal cell survival. Recent studies have demonstrated that glia cell-mediated neuroinflammation is also related to the pathophysiology of schizophrenia. In the present study, anti-inflammatory and neuroprotective effects of antipsychotics were investigated using cultured brain cells as a model. The results showed that spiperone significantly decreased the production of nitric oxide in lipopolysaccharide-stimulated BV-2 microglia cells, primary microglia and primary astrocyte cultures. Spiperone also significantly inhibited nitric oxide production in adenosine 5'-triphosphate (ATP)-stimulated primary microglia cultures. Spiperone markedly decreased the production of tumor necrosis factor-alpha in BV-2 microglia cells. Spiperone attenuated the expression of inducible nitric oxide synthase and proinflammatory cytokines such as interleukin-1beta and tumor necrosis factor-alpha at mRNA levels in BV-2 microglia cells. Spiperone inhibited nuclear translocation and DNA binding of the p65 subunit of nuclear factor kappa B (NF-kappaB), inhibitor of kappa B (IkappaB) degradation, and phosphorylation of p38 mitogen-activated protein kinase in the lipopolysaccharide-stimulated BV-2 microglia cells. Moreover, spiperone was neuroprotective, as the drug reduced microglia-mediated neuroblastoma cell death in the microglia/neuron co-culture. These results imply that the antipsychotic spiperone has anti-inflammatory and neuroprotective effects in the central nervous system by modulating glial activation.
...
PMID:The antipsychotic spiperone attenuates inflammatory response in cultured microglia via the reduction of proinflammatory cytokine expression and nitric oxide production. 1878 64

Tardive dyskinesia (TD) has been considered as a major clinical issue in the treatment of schizophrenia. Various animal studies have indicated the role of oxidative stress and nitric oxide pathway in haloperidol-induced TD. The present study investigated the effect of NO donors (molsidomine and l-arginine) in haloperidol-induced TD in rats. Chronic administration of haloperidol (1 mg/kg i.p. for 21 days) significantly increased vacuous chewing movements (VCMs), tongue protrusions, and facial jerking in rats which was dose dependently inhibited by NO donors. Besides, haloperidol also increased striatal superoxide anion levels and decreased striatal NO and citrulline levels which were prevented by molsidomine and l-arginine. On chronic administration of haloperidol, there was a decrease in the striatal levels of dopamine, which was again reversed by treatment with NO donors. The findings of the present study suggested for the involvement of NO in the development of neuroleptic-induced TD and indicated the potential of NO donors as a possible therapeutic option. Furthermore, a sub-study on a possible schizophrenic phenotype, i.e. a possible clinical worsening in the animals receiving NO donors and neuroleptics will substantiate the clinical utility of the study.
...
PMID:Co-administration of nitric oxide (NO) donors prevents haloperidol-induced orofacial dyskinesia, oxidative damage and change in striatal dopamine levels. 1878 60

Nitric oxide (NO) is associated with dopamine (DA) release. Previously, we demonstrated that rats treated with a non-selective nitric oxide synthase inhibitor, N-omega-nitro-L-arginine (L-NNA) at postnatal days 4-6 (PD4-6) show increased locomotion and disrupt neuronal cytoarchitecture after puberty (PD60). Here, we investigate whether the modulation of NO production in rats at PD4-6 causes long term changes of NO system, its impact on DA innervation, and schizophrenia-like behaviors. NO levels were measured in seven brain areas at PD35, PD60, PD90, and PD120. Autoradiographic studies explored the effect of l-NNA on the expression of D1 and D2 receptors in the caudate-putamen (CPu) and nucleus accumbens (NAcc) at PD60. Locomotor activity was assessed at PD60 using the non-selective DA agonists, amphetamine and apomorphine, and the selective DA receptor agonist [D2, quinpirole; D3, 7-hydroxy-N,N-di-n-propylaminotetralin ((+/-)-7-OH-DPAT)]. L-NNA treatment produced decreases in NO levels in the frontal cortex, striatum, brainstem and cerebellum, while in the occipital cortex changes were observed at PD120. Hippocampus and temporoparietal cortex showed differential levels of NO. Receptor autoradiography revealed increases in D1 receptor levels in the NAcc (shell), while decreases in D2 receptor binding were observed in the CPu and NAcc (core). Amphetamine and quinpirole treatments resulted in increases in locomotion. In contrast, treatment with 7-OH-DPAT produced hypolocomotion at low doses, while increased locomotion was seen at the highest dose. These results show that modulation of NO levels early postnatally (PD4-6) produces long term alteration in NO levels, with possible consequences on DA transmission, and related behaviors relevant to schizophrenia.
...
PMID:Neonatal administration of N-omega-nitro-L-arginine induces permanent decrease in NO levels and hyperresponsiveness to locomotor activity by D-amphetamine in postpubertal rats. 1879 Jul 2

Cognitive deficits are a core feature of schizophrenia that may be linked to abnormalities in GABA and nitric oxide (NO). Subchronic treatment with glutamate receptor antagonists produces similar deficits, providing a useful model to examine potential therapeutics. The present study investigated the effects of subchronic MK-801 (intraperitoneally; 0.5 mg/kg twice daily for 7 days) on amphetamine-induced locomotor activity and reversal learning in the water maze in rats, and the ability of the novel compound GT 1061 (4-methyl-5-(2-nitroxyethyl) thiazole HCl), containing dual pharmacophores producing NO- and GABA-mimetic activity, to ameliorate these effects. MK-801 enhanced locomotor responses to amphetamine. GT 1061 (0.1; not 0.0001, 0.001, 0.01, 1.0 mg/kg) further enhanced locomotion; the pro-GABA drug chlormethiazole (0.1, 1.0 mg/kg) had no significant effect. In saline-pretreated rats GT 1061 (0.1; not 0.0001, 0.001 mg/kg) increased amphetamine-induced locomotion; chlormethiazole (0.1, 1.0 mg/kg) had no effect. In the water maze, MK-801 impaired reversal learning after platform relocation. GT 1061 (0.001, 0.01, 0.1; not 0.0001 or 1.0 mg/kg) attenuated this impairment; chlormethiazole had no significant effect. These ameliorative effects of GT 1061 may be linked to the activation of NO- and GABA-dependent signaling and suggests a new direction for treating cognitive dysfunction in schizophrenia.
...
PMID:Subchronic MK-801 behavioural deficits in rats: partial reversal by the novel nitrate GT 1061. 1883 99

Lowering plasma low density lipoprotein-cholesterol (LDL-C), blood pressure, homocysteine, and preventing platelet aggregation using a combination of a statin, three blood pressure lowering drugs such as a thiazide, a beta blocker, and an angiotensin converting enzyme (ACE) inhibitor each at half standard dose; folic acid; and aspirin-called as polypill- was estimated to reduce cardiovascular events by approximately 80%. Essential fatty acids (EFAs) and their long-chain metabolites: gamma-linolenic acid (GLA), dihomo-GLA (DGLA), arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) and other products such as prostaglandins E1 (PGE1), prostacyclin (PGI2), PGI3, lipoxins (LXs), resolvins, protectins including neuroprotectin D1 (NPD1) prevent platelet aggregation, lower blood pressure, have anti-arrhythmic action, reduce LDL-C, ameliorate the adverse actions of homocysteine, show anti-inflammatory actions, activate telomerase, and have cytoprotective properties. Thus, EFAs and their metabolites show all the classic actions expected of the "polypill". Unlike the proposed "polypill", EFAs are endogenous molecules present in almost all tissues, have no significant or few side effects, can be taken orally for long periods of time even by pregnant women, lactating mothers, and infants, children, and adults; and have been known to reduce the incidence cardiovascular diseases including stroke. In addition, various EFAs and their long-chain metabolites not only enhance nitric oxide generation but also react with nitric oxide to yield their respective nitroalkene derivatives that produce vascular relaxation, inhibit neutrophil degranulation and superoxide formation, inhibit platelet activation, and possess PPAR-gamma ligand activity and release NO, thus prevent platelet aggregation, thrombus formation, atherosclerosis, and cardiovascular diseases. Based on these evidences, I propose that a rational combination of omega-3 and omega-6 fatty acids and the co-factors that are necessary for their appropriate action/metabolism is as beneficial as that of the combined use of a statin, thiazide, a beta blocker, and an angiotensin converting enzyme (ACE) inhibitor, folic acid, and aspirin. Furthermore, appropriate combination of omega-3 and omega-6 fatty acids may even show additional benefits in the form of protection from depression, schizophrenia, Alzheimer's disease, and enhances cognitive function; and serve as endogenous anti-inflammatory molecules; and could be administered from childhood for life long.
...
PMID:Essential fatty acids and their metabolites could function as endogenous HMG-CoA reductase and ACE enzyme inhibitors, anti-arrhythmic, anti-hypertensive, anti-atherosclerotic, anti-inflammatory, cytoprotective, and cardioprotective molecules. 1892 79

The second messenger cyclic guanosine 3',5'-monophosphate (cGMP) plays a crucial role in the control of cardiovascular and gastrointestinal homeostastis, but its effects on neuronal functions are less established. This review summarizes recent biochemical and functional data on the role of the cGMP signalling pathway in the mammalian brain, with a focus on the regulation of synaptic plasticity, learning, and other complex behaviours. Expression profiling, along with pharmacological and genetic manipulations, indicates important functions of nitric oxide (NO)-sensitive soluble guanylyl cyclases (sGCs), cGMP-dependent protein kinases (cGKs), and cGMP-regulated phosphodiesterases (PDEs) as generators, effectors, and modulators of cGMP signals in the brain, respectively. In addition, neuronal cGMP signalling can be transmitted through cyclic nucleotide-gated (CNG) or hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels. The canonical NO/sGC/cGMP/cGK pathway modulates long-term changes of synaptic activity in the hippocampus, amygdala, cerebellum, and other brain regions, and contributes to distinct forms of learning and memory, such as fear conditioning, motor adaptation, and object recognition. Behavioural studies indicate that cGMP signalling is also involved in anxiety, addiction, and the pathogenesis of depression and schizophrenia. At the molecular level, different cGK isoforms appear to mediate effects of cGMP on presynaptic transmitter release and postsynaptic functions. The cGKs have been suggested to modulate cytoskeletal organization, vesicle and AMPA receptor trafficking, and gene expression via phosphorylation of various substrates including VASP, RhoA, RGS2, hSERT, GluR1, G-substrate, and DARPP-32. These and other components of the cGMP signalling cascade may be attractive new targets for the treatment of cognitive impairment, drug abuse, and psychiatric disorders.
...
PMID:cGMP signalling in the mammalian brain: role in synaptic plasticity and behaviour. 1908 45

Recent theories propose that both GABA and glutamate signaling are compromised in patients with schizophrenia. These deficits can be observed in several brain regions including the prefrontal cortex (PFC), an area extensively linked to the cognitive dysfunction in this disease and notably affected by NMDA receptor antagonists such as phencyclidine (PCP). We have previously demonstrated that inhibition of the nitric oxide (NO) pathways in the brain, particularly in the PFC, prevents a wide range of PCP-induced behavioral deficits including disruption of prepulse inhibition (PPI). This study investigated the role of GABA(B) receptor signaling and NO in the effects of PCP on PPI. Mice received systemic or prefrontal injections of the GABA(B) receptor agonist baclofen (2.5-5 mg/kg and 1 mM) before PCP treatment (5 mg/kg) and were thereafter tested for PPI. GABA/NO interactions were studied by combining baclofen and the NO synthase inhibitor L-NAME (20 mg/kg) in subthreshold doses. The role of GABA(B) receptors for NO production in vivo was assessed using NO-sensors implanted into the rat PFC. PCP-induced PPI deficits were attenuated in an additive manner by systemic baclofen treatment, whereas prefrontal microinjections of baclofen completely blocked the effects of PCP, without affecting PPI per se. The combination of baclofen and L-NAME was more effective in preventing the effects of PCP than any compound by itself. Additionally, baclofen decreased NO release in the PFC in a dose-related manner. This study proposes a role for GABA(B) receptor signaling in the effects of PCP, with altered NO levels as a downstream consequence. Thus, prefrontal NO signaling mirrors an altered level of cortical inhibition that may be of importance for information processing deficits in schizophrenia.
...
PMID:Prefrontal GABA(B) receptor activation attenuates phencyclidine-induced impairments of prepulse inhibition: involvement of nitric oxide. 1914 29

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>