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)

The effects of postweaning social isolation (pwSI) on the morphology of the pyramidal neurons from the medial part of the prefrontal cortex (mPFC) and hippocampus were investigated in rats. The animals were weaned on day 21 postnatal (P21) and isolated 8 weeks. After the isolation period, locomotor activity was evaluated through 60 min in the locomotor activity chambers and the animals were sacrificed by overdoses of sodium pentobarbital and perfused intracardially with 0.9% saline solution. The brains were removed, processed by the Golgi-Cox stain and analyzed by the Sholl method. The locomotor activity in the novel environment from the isolated rats was increased with respect to the controls. The dendritic morphology clearly showed that the pwSI animals presented a decrease in dendritic length of pyramidal cells from the CA1 of the hippocampus without changes in the pyramidal neurons of the mPFC. However, the density of dendritic spines was decreased in the pyramidal cells from mPFC and Hippocampus. In addition, the Sholl analyses showed that pwSI produced a decrease in the number of sholl intersections compared with the control group only in the hippocampus region. The present results suggest that pwSI may in part affect the dendritic morphology in the limbic structures such as mPFC and hippocampus that are implicated in schizophrenia.
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PMID:Decreased dendritic spine density on prefrontal cortical and hippocampal pyramidal neurons in postweaning social isolation rats. 1291 73

Mood disorders and schizophrenia share a number of common properties, including: genetic susceptibility; differences in brain structure and drug based therapy. Some genetic loci may even confer susceptibility for bipolar mood disorder and schizophrenia, and some atypical antipsychotic drugs are used as mood stabilizers. As schizophrenia is associated with aberrant neurodevelopment, could this also be true for mood disorders? Such changes could arise pre- or post-natal, however the recent interest in neurogenesis in the adult brain has suggested involvement of these later processes in the origins of mood disorders. Interestingly, the common mood stabilizing drugs, lithium, valproic acid (VPA) and carbamazepine, are teratogens, affecting a number of aspects of animal development. Recent work has shown that lithium and VPA interfere with normal cell development, and all three drugs affect neuronal morphology. The molecular basis for mood stabilizer action in the treatment of mood is unknown, however these studies have suggested both targets and potential mechanisms. Lithium directly inhibits two evolutionarily conserved signal transduction pathways: the protein kinase Glycogen Synthase Kinase-3 (GSK-3) and inositol signaling. VPA can up-regulate gene expression through inhibition of histone deacetylase (HDAC) and indirectly reduce GSK-3 activity. VPA effects are not conserved between cell types, and carbamazepine has no effect on the GSK-3 pathway. All three mood stabilizers suppress inositol signaling, results further supported by studies on the enzyme prolyl oligopeptidase (PO) and the sodium myo-inositol transporter (SMIT). Despite these intriguing observations, it remains unclear whether GSK-3, inositol signaling or both underlie the origins of bipolar disorder.
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PMID:Neurodevelopment and mood stabilizers. 1294

The metabolism of biogenic amines and blood chemistry of psychiatric patients were investigated. Eighty newly admitted psychiatric patients suffering from schizophrenia, hypomania, mania and paranoid disorder, and matched with fifteen normal subjects were used for the study. Blood was collected and centrifuged, after which serum was extracted. Serum concentrations of biogenic amines, namely epinephrine, norepinephrine, dopamine and serotonin were determined using spectrofluorimetric method. Serum concentration of 5-HIAA, activities of alanine transaminase and aspartate transaminase were determined. The concentrations of serum protein, albumin, Na+, K+, Cl- and CO2 in the psychiatric patients and control subjects were determined using Synchron CX5 automated spectrophotometer. Results of the study showed that the concentrations of serum epinephrine and norepinephrine in the psychiatric patients were significantly increased, while the concentrations of dopamine and serotonin were significantly decreased, as compared with the controls. Serum 5-HIAA levels were significantly elevated in all psychiatric patients compared with the controls. There was a marked elevation of the activities of alanine transaminase and aspartate transaminase in all psychiatric syndromes, with the exception of paranoid disorder, which was reduced. Data of the study indicate that metabolism of biogenic amines and concentrations of serum proteins, enzymes and some electrolytes were significantly affected in psychiatric patients suffering form schizophrenia, hypomania, mania and paranoid disorder.
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PMID:Biogenic amines metabolism and blood chemistry of psychiatric patients. 1451 Jan 2

The amino acid glycine (Gly) serves as a neurotransmitter at excitatory and inhibitory synapses in the mammalian central nervous system. Gly concentrations at post-synaptic neurotransmitter receptors are regulated by Na+/Cl(-)-dependent Gly transporters, which are expressed in neurons and in glial cells. Recent evidence suggests that these transporters are promising targets for the treatment of psychiatric and neurological disorders, such as schizophrenia and pain. Here, recent research on the structure, regulation and pharmacology of mammalian Gly transporters is reviewed.
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PMID:Glycine transporter isoforms in the mammalian central nervous system: structures, functions and therapeutic promises. 1457 17

The membrane composition and the isoprenoid pathway metabolites important in maintaining cell membrane integrity was studied in neurological and psychiatric disorders. The results indicate alteration in cholesterol:phospholipid ratio of the RBC membrane which is increased in glioma, schizophrenia, and bipolar mood disorder (MDP); decreased in multiple sclerosis and Parkinson's disease; and not significantly altered in epilepsy. The concentration of total glycosaminoglycans (GAG), hexose, and fucose decreased in the RBC membrane and increased in the serum. The RBC membrane Na+-K+ ATPase activity was reduced and serum HMG CoA reductase activity was increased. There were increased serum levels of digoxin, cholesterol, and dolichol and decreased levels of ubiquinone. The serum magnesium and tyrosine levels were reduced and tryptophan increased. The results indicate a defect in membrane formation and a decreased membrane Na+-K+ ATPase activity in all the disorders studied. The results are discussed, and a hypothesis regarding the relationship between these disorders and defective membrane architecture and membrane Na+-K+ ATPase inhibition is presented.
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PMID:Isoprenoid pathway-related membrane dysfunction in neuropsychiatric disorders. 1458 55

Glycine exerts multiple functions in the central nervous system, as an inhibitory neurotransmitter through activation of specific, Cl--permeable, ligand-gated ionotropic receptors and as an obligatory co-agonist with glutamate on the activation of N-methyl-D-aspartate (NMDA) receptors. In some areas of the central nervous system, glycine seems to be co-released with gamma-aminobutyric acid (GABA), the main inhibitory amino acid neurotransmitter. The synaptic action of glycine ends by active recapture through sodium- and chloride-coupled glycine transporters located in glial and neuronal plasma membranes, whose structure-function relationship is being studied. The trafficking and plasma membrane expressions of these proteins are controlled by regulatory mechanisms. Glycine transporter inhibitors may find application in the treatment of muscle tone defects, epilepsy, schizophrenia, pain and neurodegenerative disorders. This review deals on recent progress on localization, transport mechanisms, structure, regulation and pharmacology of the glycine transporters (GLYTs).
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PMID:Structure, function and regulation of glycine neurotransporters. 1461 55

Nicotine addiction is the single largest preventable cause of morbidity and mortality in the Western World. Smoking is not any more just a bad habit, but a substance addiction problem. The pharmacological aspects of nicotine show that this substance has a broad distribution in the different body compartnents, due mainly to its lipophilic characteristic. There are nicotinic receptors as members of cholinergic receptors' family. They are located in neuromuscular junction and in the central nervous system (CNS). Although they are similar, pentameric structure with an ionic channel to sodium, there are some differences in the protein chains characteristics. Repeated administration of nicotine in rats, results in the sensitization phenomenon, which produces increase in the behavioral locomotor activity response. It has been found that most psychostimulants-induced behavioral sensitization through a nicotine receptor activation. Nicotine receptors in CNS are located mainly in presynaptic membrane and in that way they regulated the release of several neurotransmitters, among them acetylcholine, dopamine, serotonin, and norepinephrine. In some activities like sleep-wake cycle, nicotine receptors have a functional significance. Nicotine receptor stimulation promotes wake time, reduces both, total sleep time and rapid eye movement sleep (REMS). About nicotine dependence, this substance full fills all the criteria for dependence and withdrawal syndrome. There are some people that have more vulnerability for to become nicotine dependent, those are psychiatric patients. Among them schizophrenia, major depression, anxiety disorders and attention deficit disorder, represent the best example in this area. Nicotine may have some beneficial effects, among them are some neuroprotective effects in disorders like Parkinson's disease, and Gilles de la Tourette' syndrome. Also there are several evidences that support the role of nicotine in cognitive improvement functions like attention, concentration, and memory. Finally there are several strategies to deal with nicotine dependence, Nicotine Replacement Therapy (NRT), which are nicotine chewing-gum, transdermal nicotine patches, and nicotine inhalators device. Also some antidepressants like bupropion has shown to be effective in smoking cessation treatment. To know more about nicotine phenomenon would be important, because that will allow a more mature perspective about the damage and beneficial effects of that substance.
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PMID:Nicotine dependence and psychiatric disorders. 1501 38

Valproate (the active moiety of both valproic acid and divalproex sodium) is commonly used as an adjunctive agent for the treatment of schizophrenia. Among the anticonvulsants, valproate is the most extensively studied in patients with schizophrenia. Theoretical underpinnings for valproate in schizophrenia include its effect on voltage-gated ion channels and on the g-aminobutyric acid (GABA) system, thus modulating mesolimbic dopaminergic activity. Case reports, retrospective studies, and randomized clinical trials support the use of valproate combined with antipsychotics in managing schizophrenia. A recently completed 28-day, double-blind, randomized clinical trial of 249 patients with schizophrenia demonstrated faster improvement in psychopathology with a combination therapy of divalproex and risperidone or olanzapine, compared to monotherapy with risperidone or olanzapine. Additional research is needed to assess the utility of valproate in specialized populations such as those with treatment-refractory schizophrenia or agitation in schizophrenia. Regarding the latter, positive double-blind, randomized clinical trials have already been conducted in patients with borderline personality disorder, dementia, and with disruptive adolescents. It is anticipated that future research will focus on the new extended-release formulation of divalproex that can be administered on a once-daily basis.
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PMID:Schizophrenia and valproate. 1502 63

Polydipsia is a condition whereby individuals consume excessive amounts of liquids, which is common in patients with schizophrenia. A 17-item Polydipsia Screening Tool (PST; Copyright 2000 by Sheila Reynolds) was evaluated for psychometric properties. Five nurses and 70 psychiatric residents in a 92-bed nursing home comprised the samples. The interrater reliability (mean intraclass correlation coefficient) was 0.84. The average test-retest agreement was 92.4% with agreement ranging from 75% to 100%. Internal consistency of the tool was 0.79. Sensitivity and specificity were 80% and 68%, respectively. Additionally, validity of the PST was supported using a medical record history of polydipsia, low serum sodium, and low specific gravity.
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PMID:Polydipsia screening tool. 1510 35

Both omega-6 and omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) modulate TH1 and TH2 cell generation, their cytokine production, and cell proliferation and thus may serve as endogenous anti-inflammatory molecules. LCPUFAs suppress the production of tumor necrosis factor-alpha (TNF-alpha) (and so also of OX40, since it belongs to the family of TNFR) and the expression of Bcl-2, suggesting that these fatty acids have the ability to prevent/suppress autoimmune diseases. Human breast milk contains substantial amounts of both omega-3 and omega-6 fatty acids. This indicates that LCPUFAs present in human breast milk suppress the levels of OX40 and decrease the expression of Bcl-xL and Bcl-2 on exposure to self-antigens and thus, protects against the development of autoimmune diseases in later life. In view of this, I propose that supplementation of appropriate amounts of LCPUFAs during perinatal period protects against atopy, asthma, auto-immune diseases, type 1 and type 2 diabetes mellitus, hypertension, coronary heart disease, metabolic syndrome X, lymphomas, leukemias and other cancers, schizophrenia, depression and other adult diseases in which low-grade systemic inflammation plays a significant role. It is also likely that perinatal supplementation of LCPUFAs in adequate amounts modulates the expression of genes concerned with immune response, angiogenesis, central osmo/sodium and glucose sensors etc. This renders various tissues and organs including T cells and macrophages, endothelial cells, hypothalamic neurons, and various cardiovascular tissues to be able to counteract the pathological mechanisms that tend to induce various adult diseases by blunting the inflammatory responses in those who received adequate amounts of LCPUFAs during the perinatal period compared to those who did not.
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PMID:Perinatal supplementation of long-chain polyunsaturated fatty acids, immune response and adult diseases. 1511 76


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