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)

N-acetylaspartate (NAA) is present in high concentrations in the CNS and is found primarily in neurons. NAA is considered to be a marker of neuronal viability. Numerous magnetic resonance spectroscopy (MRS) and postmortem studies have shown reductions of NAA in different brain regions in schizophrenia. Most of these studies involved patients chronically treated with antipsychotic drugs. However, the effect of chronic antipsychotic treatment on NAA remains unclear. In the present study, we measured NAA in brain tissue taken from 43 male Long-Evans rats receiving 28.5 mg/kg haloperidol decanoate i.m. every 3 weeks for 24 weeks and from 21 controls administered with vehicle. Determination of tissue concentrations of NAA was achieved by HPLC of sections of frozen tissue from several brain regions with relevance to schizophrenia. Chronic administration of haloperidol was associated with a significant increase (+23%) in NAA in the striatum (p<0.05) when compared to controls, with no significant changes in the other regions investigated (frontal and temporal cortex, thalamus, hippocampus, amygdala, and nucleus accumbens). NAA appears to be selectively increased in the striatum of rats chronically receiving haloperidol. This increase may reflect a hyperfunction of striatal neurons and relate to the reported increase in somal size of these cells and/or the increase in synaptic density seen in this region following antipsychotic administration. The lack of effect in other regions indicates that the well-documented NAA deficits seen in chronically treated schizophrenia patients is not an effect of antipsychotic medication and may in fact be related to the disease process.
 ...
PMID:Increased N-acetylaspartate in rat striatum following long-term administration of haloperidol. 1588 21

We reported heritable differences between Sprague-Dawley (SD) and Long Evans (LE) rats in their sensitivity to the disruption of prepulse inhibition of startle (PPI) by dopamine (DA) agonists, and in their basal levels and turnover of forebrain DA. In an effort to better understand these differences, we assessed strain patterns in the efficacy of D2-like receptor-G-protein coupling using [35S]GTPgammaS binding in brain regions that contribute to the dopaminergic regulation of PPI. Sensitivity to the PPI-disruptive effects of apomorphine (APO) was examined in SD, LE, and F1 (SD x LE) rats. Basal and DA-stimulated [35S]GTPgammaS binding were then assessed in these rats using conditions that preferentially exclude Gs proteins to favor visualization of D2-like receptors. To explore the behavioral specificity of these strain differences, locomotor responses to APO and amphetamine (AMPH) were also assessed in SD, LE, and F1 rats. Strain differences were evident in the PPI-disruptive effects of APO (SD>F1>LE), and in the locomotor responses to AMPH (LE>F1>SD) and APO (SD exhibited motor suppression, LE exhibited motor activation). Compared to SD rats, LE rats exhibited greater DA-stimulated [35S]GTPgammaS binding in nucleus accumbens and caudatoputamen, while F1 progeny had intermediate levels. In conclusion, SD and LE rats exhibit heritable differences in D2-mediated behavioral and biochemical measures. Conceivably, genes that regulate heritable differences in forebrain D2 function may contribute to heritable differences in PPI in patients with specific neuropsychiatric disorders, including schizophrenia and Tourette Syndrome.
 ...
PMID:Heritable differences in the dopaminergic regulation of behavior in rats: relationship to D2-like receptor G-protein function. 1612 42

Performance of Long-Evans rats repeatedly treated with a high dose of phencyclidine (PCP) was compared with that of controls on two tasks involving rule shifts. Fifteen hours after receiving 12 daily doses of PCP (10mg/kg) or saline, rats were tested in the first task where a fixed or variable goal had to be recognized among four maze-arm locations. After receiving the last of 33 injections, rats were subjected to a second task: they had to discriminate the relevant perceptual dimension in a pair of stimuli and choose the appropriate stimulus in each problem. Results from both tasks revealed no difference between controls and rats injected with PCP either during acquisition using a constant rule or during testing with rule shifts. Consequently, PCP appears to lack consistency in disturbing frontal cognitive functions in animal models of schizophrenia.
 ...
PMID:Rule shift under long-term PCP challenge in rats. 1619 31

Self-grooming in rodents is stereotypically sequenced and naturally occurs after arousal, novelty, or stress. Grooming expression and syntax resulting from stressful and appetitive conditions were assessed in male Long Evans rats treated daily with 10mg/kg of phencyclidine (PCP) for 15 days. Approximately 20 h after the 1st, the 8th, and/or the 15th injection, grooming was induced with water sprays, a loud sound, or smearing food. Behaviors expressed during the seconds or minutes that followed induction were videotaped and codified. Results showed that subchronic treatment with PCP amplified the grooming response in all stressful and appetitive conditions, but provoked a disorganization of grooming sequences only under the stressful, water condition. Thus, PCP enhanced grooming expression indiscriminately. However, this behavior had to serve both hygienic and stress managing purposes in order for chain sequencing to become disorganized as a consequence of drug treatment. These results suggest that the detailed examination of grooming expression and organization is an appropriate tool to measure stress-induced behavioral sensitization and motor functions in animal models of neuropsychiatric disorders such as schizophrenia.
 ...
PMID:Repeated subchronic exposure to phencyclidine elicits excessive atypical grooming in rats. 1625 55

Gene expression profiles in the cortex of adult Long-Evans rats as a function of a stressful social loss and victory in inter-male fighting encounters were examined. This social dominance and subordination model has been postulated to simulate early changes in the onset of depression in the losers. Microarrays were fabricated containing 45mer oligonucleotides spotted in quadruplicate and representing 1178 brain-associated genes. Dynamic range, discrimination power, accuracy and reproducibility were determined with standard mRNA "spiking" studies. Gene expression profiles in dominant and subordinate animals were compared using a "universal" reference design [Churchill GA (2002) Fundamentals of experimental design for cDNA microarrays. Nat Genet 32 (Suppl):490-495]. Data were analyzed by significance analysis of microarrays using rank scores [Tusher VG, Tibshirani R, Chu G (2001) Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA 98:5116-5121; van de Wiel MA (2004) Significance analysis of microarrays using rank scores. Kwantitatieve Methoden 71:25-37]. Ontological analyses were then performed using the GOMiner algorithm [Zeeberg BR, Feng W, Wang G, Wang MD, Fojo AT, Sunshine M, Narasimhan S, Kane DW, Reinhold WC, Lababidi S, Bussey KJ, Riss J, Barrett JC, Weinstein JN (2003) GoMiner: a resource for biological interpretation of genomic and proteomic data. Genome Biol 4(4):R28]. And finally, genes of special interest were further studied using quantitative reverse transcriptase polymerase chain reaction. Twenty-two transcripts were statistically significantly differentially expressed in the neocortex between dominant and subordinate animals. Ontological analyses revealed that significant gene changes were clustered primarily into functional neurochemical pathways associated with protein biosynthesis and cytoskeletal dynamics. The most robust of these were the increased expression of interleukin-18, heat shock protein 27, beta3-tubulin, ribosome-associated membrane protein 4 in subordinate animals. Interleukin-18 has been found to be over-expressed in human depression and panic disorder as well as other physiological stress paradigms [Takeuchi M, Okura T, Mori T, Akita K, Ohta T, Ikeda M, Ikegami H, Kurimoto M (1999) Intracellular production of interleukin-18 in human epithelial-like cell lines is enhanced by hyperosmotic stress in vitro. Cell Tissue Res 297(3):467-473] and heat shock proteins have been shown to be involved in the pathogenesis of many neurodegenerative and psychiatric disorders [Iwamoto K, Kakiuchi C, Bundo M, Ikeda K, Kato T (2004) Molecular characterization of bipolar disorder by comparing gene expression profiles of postmortem brains of major mental disorders. Mol Psychiatry 9(4):406-416; Pongrac JL, Middleton FA, Peng L, Lewis DA, Levitt P, Mirnics K (2004) Heat shock protein 12A shows reduced expression in the prefrontal cortex of subjects with schizophrenia. Biol Psychiatry 56(12):943-950]. Thus, the gene expression changes that we have observed here are consistent with and extend the observations found in the clinical literature and link them to the animal model used here thereby reinforcing its use to better understand the genesis of depression and identify novel therapeutic targets for its treatment.
 ...
PMID:Modeling depression: social dominance-submission gene expression patterns in rat neocortex. 1628 86

The psychotomimetic drug phencyclidine (PCP) induces symptoms closely related to those of schizophrenia in humans. In order to test the hypothesis that cytokines may be involved in the aetiology and treatment of schizophrenia, this study investigated the levels of cytokine mRNAs in rat brain after acute and chronic administration of PCP, in the presence and absence of antipsychotic drugs. The levels of the mRNAs encoding TNF, IL-2, IL-6, TGF 1, 2, 3, IL-3 and GM-CSF were measured in the prefrontal cortex, cortex, hippocampus, ventral and dorsal striatum regions of male hooded Long Evans rats after acute drug administration. Antipsychotic drugs and PCP significantly reduced the levels of TNF in the prefrontal cortex compared to vehicle-treated animals, whilst other cytokines remained unchanged. In addition, significant reductions in the levels of TNF mRNA in the prefrontal cortex still occurred 24h after acute PCP administration. However, levels of TNF mRNA were restored to control values after chronic PCP treatment, whereas increased expression was detected in animals co-administered with haloperidol. Levels of TNF mRNA were also found to be significantly increased in the prefrontal cortex of schizophrenic subjects. The relationship between TNF levels and schizophrenia are discussed.
 ...
PMID:Selective increases in the cytokine, TNFalpha, in the prefrontal cortex of PCP-treated rats and human schizophrenic subjects: influence of antipsychotic drugs. 1647 54

The aims of the present study were to compare the effect of subchronic administration of MK-801 on performance in the active allothetic place avoidance (AAPA) task and in the working version of Morris water maze (MWM) in Long-Evans and Wistar rats. Animals were trained for four daily sessions either in the AAPA or in the working memory version of the MWM. Wistar rats treated by MK-801 (0.1 mg/kg) showed a cognitive deficit in the AAPA task without a significant hyperlocomotion, whereas they were not impaired in the working memory version of the MWM compared to controls. Long-Evans rats treated by MK-801 (0.1 mg/kg) were not impaired either in the AAPA task or in the MWM task. Higher doses of MK-801 (0.2 and 0.3 mg/kg) produced hyperlocomotion in both strains which corresponded to an inability to solve both spatial tasks. Long-Evans rats were superior in the MWM to the Wistar rats in the groups treated with the low dose of MK-801. In conclusion, intact Wistar rats can efficiently solve both spatial tasks; however, they are more sensitive to MK-801-induced behavioural deficit. This has relevance for modeling of the schizophrenia-related deficits and for screening substances for their therapeutic potential.
 ...
PMID:Analysis of sensitivity to MK-801 treatment in a novel active allothetic place avoidance task and in the working memory version of the Morris water maze reveals differences between Long-Evans and Wistar rats. 1671 95

Although it might seem that people with schizophrenia would perform poorly on measures of emotion-based learning, several studies have shown normal levels of performance on the Iowa Gambling Task (IGT; C. E. Y. Evans, C. H. Bowman, & O. H. Turnbull, 2005; L. M. Ritter, J. H. Meador-Woodruff, & G. W. Dalack, 2004; B. Shurman, W. P. Horan, & K. H. Nuechterlein, 2005; K. E. Wilder, D. R. Weinberger, & T. E. Goldberg, 1998). The present article describes a newly developed modification of the IGT involving initial familiarization with the basic contingency pattern then 3 periods of contingency shift. Control participants showed substantial gains during the later trials of each shift period. Analyzed in terms of positive symptoms, those with schizophrenia were little different from control participants. Those high in negative symptoms could perform the basic task but showed remarkably poor performances (no better than chance) in the shift phases, retaining a preference for decks that had previously been "good," even when they experienced substantial losses.
 ...
PMID:A novel set-shifting modification of the iowa gambling task: flexible emotion-based learning in schizophrenia. 1671 22

Insufficient availability of n-3 polyunsaturated fatty acids (PUFAs) during pre- and neonatal development decreases accretion of docosahexaenoic acid (DHA, 22:6n-3) in the developing brain and is associated with sub-optimal sensory and cognitive function in humans, altered behavior in animals, and may contribute to neurodevelopmental disorders such as attention deficit hyperactivity disorder and schizophrenia. This study examined the effects of variation in dietary availability of n-3 PUFAs on brain fatty acid composition and the consequent effects on locomotor activity in male and female Long-Evans rats. Rats were raised from conception using purified diets and breeding protocols designed to produce four groups with distinct brain phospholipid compositions varying in DHA content and/or the proportion of n-3 and n-6 PUFAs. Locomotor behavior was measured for a 2-h period on postnatal days 28, 42, 56, and 70. In males, decreased brain DHA produced alterations in activity that were most pronounced post-adolescence and with the greatest decrease in DHA. However, the behavioral effects in males were not linearly related to brain DHA level. In contrast, no significant effects of variation in brain fatty acid composition were observed in females. This suggests that variation in brain DHA content produces sex-specific alterations in locomotor activity and that the neurochemical alterations underlying the observed behavioral changes vary depending on the degree of DHA depletion.
 ...
PMID:Sex-specific effects of brain LC-PUFA composition on locomotor activity in rats. 1687 5

Neurophysiologic research has shown a Neurological Soft Sign (NSS) characteristic prevalence in schizophrenic patients, and correlations between NSS and the most frequently cerebral alterations. The aim of this study was to investigate, by means of MRI, the quantitative alterations of cortical and subcortical structures and their correlation with NSS in a sample of schizophrenic patients. Linear measures of lateral ventricular (Evans ratio), third ventricular (Third Ventricular Width), hippocampal (Interuncal Index) and cerebellar (Verm Cerebellar Atrophy) atrophy were made on magnified MR images of 33 patients with a DSM IV diagnoses of chronic schizophrenia. NSS were evaluated with the Buchanan and Heinrichs's Neurological Evaluation Scale (NES). Lateral ventricular enlargement showed to be correlated with right stereoagnosia item (p=0.001). Hippocampal atrophy, with right stereoagnosia item (p=0.023), with forefinger-right thumb opposition (p=0.004), forefinger-left thumb opposition (p=0.029 and face-hand extinction (0.26). Third ventricle enlargement showed to be correlated with forefinger-right thumb opposition (p=0.001), forefinger-left thumb opposition(p=0.021) and total sensorial integration (p=0.012). Cerebellar atrophy showed to be correlated with rhythmic drumming item (p=0.042), forefinger-right thumb opposition (p=0.007), forefinger-left thumb opposition (p=0.026), left specular movements (p=0.049), face-hand extinction (p=0.001), right-left confusion (p=0.005) and with left forefinger-nose index (p=0.032). Results obtained confirm the correlation between NSS and neuroanatomical alterations in schizophrenia.
 ...
PMID:Neurological soft signs and cerebral measurements investigated by means of MRI in schizophrenic patients. 1717 77


<< Previous 1 2 3 4 5 6 7 Next >>