Role of glutathione in schizophrenia? The effect of brain glutathione depletion on prepulse inhibition (PPI) in rats and mice

Reductions in brain glutathione (GSH) levels have been reported in schizophrenia. We investigated the effects of brain GSH depletion on prepulse inhibition (PPI), a model of sensorimotor gating which is disrupted in individuals with schizophrenia. It was hypothesized that GSH depletion would lead to disruption of PPI similar to that seen in schizophrenia and enhance the effect of increased dopamine release by amphetamine. Sprague-Dawley rats and C57Bl/6 mice were treated with saline or 2-cyclohexene-1-one (CHX, 75 mg/kg and 120 mg/kg respectively) to deplete brain GSH. 225 minutes later the animals were injected with amphetamine (2.5 mg/kg in rats and 25 mg/kg in mice). Total brain GSH levels were measured using an enzymatic recycling assay. Surprisingly, in rats CHX treatment prevented the disruption of PPI by amphetamine. Thus, while there was the expected disruption of PPI caused by amphetamine on its own (average %PPI reduced from 58 ± 5 to 44 ± 4), in combination with CHX, amphetamine had no significant effect (67 ± 4 vs. 63 ± 3, respectively). In contrast to rats, in mice CHX had no effect on PPI. Thus, amphetamine similarly disrupted PPI after saline (41 ± 5 vs. 28 ± 5) and CHX pretreatment (45 ± 6 vs. 26 ± 5). There were significant 40-63% depletions of GSH in frontal cortex and striatum of CHX-treated rats and mice. These data show that GSH depletion in the brain by CHX treatment did not induce the expected decrease in PPI. Because the levels of GSH depletion in this study were similar to those found in schizophrenia, these results cast doubt on a direct interaction between brain GSH levels and PPI disruption in this illness. In rats, CHX treatment prevented the disruption of PPI caused by amphetamine. We have observed that resting levels of GSH are lower in rats than in mice. It is plausible that some oxidative damage may occur after amphetamine treatment alone, which induces marked release of the electroactive species, dopamine. In mice with their higher levels of GSH (either with or without CHX treatment) and in control rats, this does not cause functional effects. However, in CHX-treated rats GSH levels are reduced to a point where amphetamine-induced dopamine release may cause increased metabolism and lipid peroxidation inducing a decrease in postsynaptic dopamine receptor function and consequently leading to an apparent inhibition of the disruption of PPI. In conclusion, while individuals with schizophrenia show disruption of PPI and reduced brain GSH levels, in rats and mice brain GSH depletion alone does not impact on PPI. In combination with a hyperdopaminergic state, functional effects on PPI regulation were found. These effects warrant further investigation.

Identification of a by-product of nitric oxide synthase activity in human acute brain injury with in vivo proton magnetic resonance spectroscopy

BACKGROUND AND PURPOSE: Laboratory studies have been used to identify nitric oxide as a notable mediator in neuronal death after acute brain injury. To our knowledge, this has not previously been confirmed with in vivo study in humans. Our purpose was to seek in vivo evidence for the induction of nitric oxide synthase (NOS) in human acute brain injury by using proton MR spectroscopy.

METHODS: In vitro proton MR spectra were obtained in neural extracts from 30 human cadavers, and in vivo spectra were obtained in 20 patients with acute brain injury and in a similar number of control subjects.

RESULTS: We identified a unique peak at 3.15 ppm by using in vivo proton MR spectroscopy in eight of 20 patients with acute brain injury but not in 20 healthy volunteers (P < .002). On the basis of in vitro data, we have tentatively assigned this peak to citrulline, a NOS by-product.

CONCLUSION: To our knowledge, our findings suggest, for the first time, that excitotoxicity may occur in human acute brain injury. Confirmation with the acquisition of spectra in very early acute cerebral injury would provide a rationale for the use of neuroprotective agents in these conditions, as well as a new noninvasive method for quantification.

Changes in SWB following injury to different brain lobes

A neurological substrate for subjective wellbeing (SWB) has received little research attention.
Purpose This study was designed to conduct exploratory investigation into the neuroanatomical correlates of SWB, by monitoring the SWB of a head-injured population over a six-month period.
Method Seventy people with head injury (HI), aged 10–65, were studied. The SWB of each participant was measured, and computed tomography (CT) scans were analysed to obtain regional brain injury location (BIL).
Results SWB was associated with BIL. However, the hypothesis that individuals with left frontal injury would report lower SWB was not supported. Instead, it was observed that participants with injury to their right frontal lobe reported higher SWB than individuals with injury to other regions of the brain.
Conclusions This study provides initial exploration into the neuroanatomical correlates of SWB.

The brain in the jar : troubling the truths of discourses of adolescent brain development

Ideas about adolescent brains and their development increasingly function as powerful truths in making sense of young people. And it is the knowledge practices of the neurosciences and evolutionary and developmental psychology that are deemed capable of producing what we have come to understand as the evidence on which policy, interventions and education should be built. In effect these discourses reduce young people to little more than a brain in a jar. The paper examines how the evidence about adolescent brains - their volume, and the functioning and activity of different regions - from neuroscience and evolutionary and developmental psychology works as truth. What knowledge practices are used to produce this evidence, or are deemed capable of producing this evidence? What truth claims are able to attach to this evidence? What makes it true and why is it imagined as evidence of something that is true in policy, public and other research settings that are often far removed from where it was produced? I argue that the discourses of adolescent brain development disembody, reduce and simplify the complexities of these figures we know as adolescents. In effect they render the adolescent as a brain in a jar.

Brain MRI thresholding using incomparability and overlap functions

In this work we present a new image thresholding algorithm for the segmentation of MRI brain images into two classes: gray matter and white matter. The proposed algorithm is based on the concept of incomparability proposed by Fodor and Roubens for fuzzy preference relations. We test our algorithm for local and global segmentation of brain images. We proof that global segmentation performs better results than local segmentation and improves the results obtained by other thresholding algorithm.

Clusters driven implementation of a brain inspired model for multi-view pattern identifications

The human brain processes information in both unimodal and multimodal fashion where information is progressively captured, accumulated, abstracted and seamlessly fused. Subsequently, the fusion of multimodal inputs allows a holistic understanding of a problem. The proliferation of technology has produced various sources of electronic data and continues to do so exponentially. Finding patterns from such multi-source and multimodal data could be compared to the multimodal and multidimensional information processing in the human brain. Therefore, such brain functionality could be taken as an inspiration to develop a methodology for exploring multimodal and multi-source electronic data and further identifying multi-view patterns. In this paper, we first propose a brain inspired conceptual model that allows exploration and identification of patterns at different levels of granularity, different types of hierarchies and different types of modalities. Secondly, we present a cluster driven approach for the implementation of the proposed brain inspired model. Particularly, the Growing Self Organising Maps (GSOM) based cross-clustering approach is discussed. Furthermore, the acquisition of multi-view patterns with clusters driven implementation is demonstrated with experimental results.

A head mountable deep brain stimulation device for laboratory animals

Deep brain stimulation has emerged as an effective method to treat certain medical conditions. Electrical charges are injected into the target tissue through a conducting electrode exciting the tissue. A variety of DBS devices have been developed based on different operation principles. Majority of these devices, however, employ complex circuitry and are bulky. In clinical trials, laboratory animals need to freely move around and perform activities whilst receiving brain stimulation for days. This paper presents a simple lightweight head mountable deep brain stimulation device that can be carried by the animal during the course of a clinical trial. The device produces continuous current pulses of specific characteristics. It employs passive charge balancing to minimize undesirable effects on the target tissue. The device is constructed and its performance tested.

Chronic stress alters the density and morphology of microglia in a subset of stress-responsive brain regions

The current study, in parallel experiments, evaluated the impact of chronic psychological stress on physiological and behavioural measures, and on the activation status of microglia in 15 stress-responsive brain regions. Rats were subjected, for 14 days, to two 30 min sessions of restraint per day, applied at random times each day. In one experiment the effects of stress on sucrose preference, weight gain, core body temperature, and struggling behaviour during restraint, were determined. In the second experiment we used immunohistochemistry to investigate stress-induced changes in ionized calcium-binding adaptor molecule-1 (Iba1), a marker constitutively expressed by microglia, and major histocompatibility complex-II (MHC-II), a marker often expressed on activated microglia, in a total of 15 stress-responsive nuclei. We also investigated cellular proliferation in these regions using Ki67 immunolabelling, to check for the possibility of microglial proliferation. Collectively, the results we obtained showed that chronic stress induced a significant increase in anhedonia, a decrease in weight gain across the entire observation period, a significant elevation in core body temperature during restraint, and a progressive decrease in struggling behaviour within and over sessions. With regard to microglial activation, chronic stress induced a significant increase in the density of Iba1 immunolabelling (nine of 15 regions) and the number of Iba1-positive cells (eight of 15 regions). Within the regions that exhibited an increased number of Iba1-positive cells after chronic stress, we found no evidence of a between group difference in the number of MHC-II or Ki67 positive cells. In summary, these results clearly demonstrate that chronic stress selectively increases the number of microglia in certain stress-sensitive brain regions, and also causes a marked transition of microglia from a ramified-resting state to a non-resting state. These findings are consistent with the view that microglial activation could play an important role in controlling and/or adapting to stress.