Inter-relationship of plasma markers of oxidative stress and thyroid hormones in schizophrenics

<p>Abstract</p> <p>Background</p> <p>The relationship of oxidative stress to thyroid hormones has not been studied in the schizophrenics. The present study determined the status and interrelationship of plasma markers of oxidative stress, nitric oxide and thyroid hormones in thirty (17 males and 13 females) newly diagnosed patients with acute schizophrenia before initiation of chemotherapy. Twenty five (13 males and 12 females) mentally healthy individuals served as controls. Patients and controls with history of hard drugs (including alcohol and cigarette), pre-diagnosis medications (e.g. antiparkinsonian/antipsychotic drugs), chronic infections, liver disease and diabetes mellitus were excluded from the study. Plasma levels of total antioxidant potential (TAP), total plasma peroxides (TPP), nitric oxide (NO), malondialdehyde (MDA), thyroxine (T4), tri-iodothyronine (T3) and thyroid stimulating hormone (TSH) were determined in all participants using spectrophotometric and enzyme linked immunosorbent assay (ELISA) methods respectively. Oxidative stress index (OSI) was calculated as the percent ratio of total plasma peroxides and total antioxidant potential.</p> <p>Findings</p> <p>Significantly higher plasma levels of MDA (p < 0.01), TPP (p < 0.01), OSI (p < 0.01), T3 (p < 0.01) and T4 (p < 0.05) were observed in schizophrenics when compared with the controls. The mean levels of TAP, NO and TSH were significantly lower in schizophrenics (p < 0.01) when compared with the controls. The result shows that T3 values correlate significantly with MDA (p < 0.05) and TPP (p < 0.01) in schizophrenics.</p> <p>Conclusions</p> <p>Higher level of TPP may enhance thyroid hormogenesis in schizophrenics. Adjuvant antioxidant therapy may be a novel approach in the treatment of schizophrenic patients.</p

Neuropathological Similarities and Differences between Schizophrenia and Bipolar Disorder: A Flow Cytometric Postmortem Brain Study

Recent studies suggest that schizophrenia (SCH) and bipolar disorder (BPD) may share a similar etiopathology. However, their precise neuropathological natures have rarely been characterized in a comprehensive and quantitative fashion. We have recently developed a rapid, quantitative cell-counting method for frozen unfixed postmortem brains using a flow cytometer. In the present study, we not only counted stained nuclei, but also measured their sizes in the gray matter of frontopolar cortices (FPCs) and inferior temporal cortices (ITCs) from patients with SCH or BPD, as well as in that from normal controls. In terms of NeuN(+) neuronal nuclei size, particularly in the reduced densities of small NeuN(+) nuclei, we found abnormal distributions present in the ITC gray matter of both patient groups. These same abnormalities were also found in the FPCs of SCH patients, whereas in the FPCs of BPD patients, a reduction in oligodendrocyte lineage (olig2(+)) cells was much more common. Surprisingly, in the SCH FPC, normal left-greater-than-right asymmetry in neural nuclei densities was almost completely reversed. In the BPD FPC, this asymmetry, though not obvious, differed significantly from that in the SCH FPC. These findings indicate that while similar neuropathological abnormalities are shared by patients with SCH or BPD, differences also exist, mainly in the FPC, which may at least partially explain the differences observed in many aspects in these disorders

fMRI BOLD signal changes in elite swimmers while viewing videos of personal failure

Athletes who fail are susceptible to negative affect (NA) and impaired future performance. Functional magnetic resonance imaging (fMRI) studies have identified prefrontal, anterior cingulate, and limbic activations following negative mood provocation. Little is known about the neural correlates of negative self-reference (SR), especially in athletes. Even less is known about the neural correlates of the effects of cognitive intervention (CI) in modifying negative SR and NA in this population. In an fMRI study, 13 athletes watched a video of their own career-threatening defeat in two controlled blocks. Between fMRI blocks, they received a 20-min CI designed to assist in event reappraisal and planning for future performance. Relative increases post-CI were seen in premotor (BA6) and sensorimotor (BA4/1) cortices. Correlated with mood ratings, relatively higher pre-CI levels were seen in the ventromedial prefrontal cortex, the right dorsomedial prefrontal cortex (PFC; BA10), the right dorsolateral PFC (BA45), the anterior cingulate, and the right parahippocampus. CI may counteract the detrimental effects of NA and negative SR on premotor and motor activity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83878/1/fMRI-BOLD-signal-changes-in-elite-swimmers-while-viewing-videos-of-personal-failure.pd

Food or fear? Predation risk mediates edge refuging in an insectivorous mammal

Understanding space use by animals plays a key role in a wide array of behavioural and ecological fields of study. An insight into how and why species use the space available to them may aid their conservation. The West European hedgehog, . Erinaceus europaeus, a species in decline in part of its range, is relatively mobile and adapted to a wide range of habitat types. However, it is frequently associated with edge habitats. This edge-refuging behaviour is not well understood and may be the result of fear of predators, food availability or other factors. We used radiotelemetry to investigate the movement of hedgehogs in comparable landscapes with high and low predator (badgers, . Meles meles) abundance. Simultaneously, food availability was assessed in both landscapes. Our results suggest that agricultural habitats may be 'landscapes of fear' for hedgehogs in the presence of a high number of predators. On agricultural fields, hedgehogs were on average situated closer to edge cover in areas with predators present. It is thus likely to be beneficial for the conservation of hedgehogs in areas with a high number of predators to increase the complexity of the habitat structure by, among other measures, establishing more and denser hedgerows in rural areas. Our results suggest that enhancing the complexity of the habitat structure might lessen the effects of fear. Additionally, our results emphasize the importance of integrating data on predator abundance and food availability in studies that focus on habitat selection behaviour and species conservation

53BP1 integrates DNA repair and p53-dependent cell fate decisions via distinct mechanisms

The tumor suppressor protein 53BP1, a pivotal regulator of DNA double-strand break (DSB) repair, was first identified as a p53-interacting protein over two decades ago. However, its direct contributions to p53-dependent cellular activities remain undefined. Here, we reveal that 53BP1 stimulates genome-wide p53-dependent gene transactivation and repression events in response to ionizing radiation (IR) and synthetic p53 activation. 53BP1-dependent p53 modulation requires both auto-oligomerization and tandem-BRCT domain-mediated bivalent interactions with p53 and the ubiquitin-specific protease USP28. Loss of these activities results in inefficient p53-dependent cell-cycle checkpoint and exit responses. Furthermore, we demonstrate 53BP1-USP28 cooperation to be essential for normal p53-promoter element interactions and gene transactivation-associated events, yet dispensable for 53BP1-dependent DSB repair regulation. Collectively, our data provide a mechanistic explanation for 53BP1-p53 cooperation in controlling anti-tumorigenic cell-fate decisions and reveal these activities to be distinct and separable from 53BP1’s regulation of DNA double-strand break repair pathway choice

53BP1 integrates DNA repair and p53-dependent cell fate decisions via distinct mechanisms

The tumor suppressor protein 53BP1, a pivotal regulator of DNA double-strand break (DSB) repair, was first identified as a p53-interacting protein over two decades ago. However, its direct contributions to p53-dependent cellular activities remain undefined. Here, we reveal that 53BP1 stimulates genome-wide p53-dependent gene transactivation and repression events in response to ionizing radiation (IR) and synthetic p53 activation. 53BP1-dependent p53 modulation requires both auto-oligomerization and tandem-BRCT domain-mediated bivalent interactions with p53 and the ubiquitin-specific protease USP28. Loss of these activities results in inefficient p53-dependent cell-cycle checkpoint and exit responses. Furthermore, we demonstrate 53BP1-USP28 cooperation to be essential for normal p53-promoter element interactions and gene transactivation-associated events, yet dispensable for 53BP1-dependent DSB repair regulation. Collectively, our data provide a mechanistic explanation for 53BP1-p53 cooperation in controlling anti-tumorigenic cell-fate decisions and reveal these activities to be distinct and separable from 53BP1’s regulation of DNA double-strand break repair pathway choice

Mechanisms of Working Memory Impairment in Schizophrenia

BACKGROUND: The neural correlates of working memory (WM) impairment in schizophrenia remain a key puzzle in understanding the cognitive deficits and dysfunction of dorsolateral prefrontal cortex observed in the disorder. We sought to determine whether patients with schizophrenia exhibit an alteration in the inverted-U relationship between WM load and activation that we recently observed in healthy individuals, and whether this could account for WM deficits in this population. METHODS: Medicated (N=30) and unmedicated (N=21) patients with schizophrenia and healthy controls (N=45) performed the self-ordered WM task during functional Magnetic Resonance Imaging. We identified regions exhibiting an altered fit to an inverted-U relationship between WM load and activation that were also predictive of WM performance. RESULTS: A blunted inverted-U response was observed in left DLPFC in patients and was associated with behavioral deficits in WM capacity. In addition, suppression of medial prefrontal cortex (mPFC) during WM was reduced in patients, and was also associated with poorer WM capacity in patients. Finally, activation of visual cortex in the cuneus was elevated in patients and associated with improved WM capacity. Together, these findings explained 55% of the interindividual variance in WM capacity when combined with diagnostic and medication status, which alone accounted for only 22% of the variance in WM capacity. CONCLUSIONS: These findings identify a novel biomarker and putative mechanism of WM deficits in patients with schizophrenia, a reduction or flattening of the inverted-U relationship between activation and WM load observed in healthy individuals in left dorsolateral prefrontal cortex