Families' reflections on the process of brain donation following coronial autopsy.

This study aims to explore families' reflections on their decision to donate brain tissue to the NSW Tissue Resource Centre (NSW TRC), Australia. Specifically, the study aims to investigate respondents' initial reactions to the request for donation, primary reasons for their decision, and subsequent satisfaction levels. Participants were next-of-kin (NOK) contacted between May 2002 and May 2008, on the day of their relative's autopsy, who agreed to donate brain tissue to the NSW TRC for medical research.

Selection of reference gene expression in a schizophrenia brain cohort.

Objective: In order to conduct postmortem human brain research into the neuropatho-logical basis of schizophrenia, it is critical to establish cohorts that are well-characterized and well-matched. The aim of the present study was therefore to determine if specimen characteristics including: diagnosis, age, postmortem interval (PMI), brain acidity (pH), and/or the agonal state of the subject at death related to RNA quality, and to determine the most appropriate reference gene mRNAs.

Methods: A matched cohort was selected of 74 subjects (schizophrenia/schizoaffective disorder, n = 37; controls, n = 37).

The effect of moderate to heavy alcohol consumption on neuropsychological performance as measured by the repeatable battery for the assessment of neuropsychological status.

Background: Excessive alcohol use is associated with damage to the structure and function of the brain and impairment of cognition and behavior. Traditional test batteries used to assess cognitive performance in alcoholics are extensive and costly, limiting their use across various clinical and research settings. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a relatively new instrument that attempts to overcome some of these limitations.

FOSB proteins in the orbitofrontal and dorsolateral prefrontal cortices of human alcoholics.

The transcription factor DeltaFosB is accumulated in the addiction circuitry, including the orbitofrontal and medial prefrontal cortices of rodents chronically exposed to ethanol or other drugs of abuse, and has been suggested to play a direct role in addiction maintenance. To address this hypothesis in the context of substance dependence in humans, we compared the immunoreactivities of FOSB proteins in the orbitofrontal and dorsolateral prefrontal cortices (OFC and DLPFC respectively) between controls and alcoholics using semiquantitative immunoblotting. In both structures, we detected three forms of FOSB, one of which was DeltaFOSB, but in neither case did their immunoreactivities differ between the groups.

Factors that influence decisions by families to donate brain tissue for medical research.

Whilst mainstream transplant literature provides valuable insights into the influences on families to donate organs and tissues for transplant, the relevance of these findings in relation to organ donation for research remain speculative. The present study aims to expand the research donation literature, by exploring factors that influence a family's decision to donate brain tissue to neuroscience research. The verbal responses of the senior available next-of-kin (NOK), to the question of brain donation for research, are analysed.

Expression of pronociceptin and its receptor is downregulated in the brain of human alcoholics.

Animal studies demonstrated a role of neuropeptide nociceptin (NC) and its receptor (opiate receptor like-1, OPRL1) in ethanol-induced reward; activation of the OPRL1 by natural or synthetic ligands reduced ethanol self-administration and prevented relapse to ethanol drinking. The endogenous NC may function in neuronal circuits involved in reinforcing or conditioning effects of ethanol as a "brake" to limit ethanol intake (Roberto, M., Siggins, G.

The importance of brain banks for molecular neuropathological research: The New South Wales Tissue Resource Centre experience.

New developments in molecular neuropathology have evoked increased demands for postmortem human brain tissue. The New South Wales Tissue Resource Centre (TRC) at The University of Sydney has grown from a small tissue collection into one of the leading international brain banking facilities, which operates with best practice and quality control protocols. The focus of this tissue collection is on schizophrenia and allied disorders, alcohol use disorders and controls.

Brain donation: who and why?

Understanding what influences people to donate, or not donate, body organs and tissues is very important for the future of transplant surgery and medical research (Garrick in J Clin Neurosci 13:524-528, 2006). A previous web-based motivation survey coordinated by the New South Wales Tissue Resource Centre found that most people who participated in brain donation were young, female, educated Australians, not affiliated with any particular religion, and with a higher prevalence of medical illness than the general Australian population. It discussed the main motivating factors for brain donation to be "the benefits of the research to medicine and science".

Dysregulation of cell death machinery in the prefrontal cortex of human alcoholics.

In human alcoholics, the cell density is decreased in the prefrontal cortex (PFC) and other brain areas. This may be due to persistent activation of cell death pathways. To address this hypothesis, we examined the status of cell death machinery in the dorsolateral PFC in alcoholics.

Elevated synaptophysin I in the prefrontal cortex of human chronic alcoholics.

Convergent lines of evidence suggest potentiation of glutamatergic synapses after chronic ethanol exposure, and indicate that the presynaptic effect hereof is on modulators of synaptic strength rather than on executors of glutamate release. To address this hypothesis in the context of ethanol dependence in humans, we used semiquantitative immunoblotting to compare the immunoreactivities of synaptophysin I, syntaxin 1A, synaptosome-associated protein 25, and vesicle-associated membrane protein in the prefrontal and motor cortices between chronic alcoholics and control subjects. We found a region-specific elevation in synaptophysin I immunoreactivity in the prefrontal cortex of alcoholics, but detected no significant differences between the groups in the immunoreactivities of the other three proteins.

Reliability of post-mortem psychiatric diagnosis for neuroscience research.

Objective: The validity of post-mortem human brain research relies upon accurate clinical and psychopathological diagnosis. Current literature indicates few instances where standardized diagnostic assessment tools such as the Diagnostic Instrument for Brain Studies have been utilized. The primary aim of the present study was to investigate the degree of concordance between predominant ante-mortem psychiatric diagnoses indicated in medical records, and post-mortem diagnoses derived through structured diagnostic instruments such as the Diagnostic Instrument for Brain Studies and the Item Group Checklist of the Schedules for Clinical Assessment in Neuropsychiatry.

Neuroadaptations in human chronic alcoholics: dysregulation of the NF-kappaB system.

Background: Alcohol dependence and associated cognitive impairments apparently result from neuroadaptations to chronic alcohol consumption involving changes in expression of multiple genes. Here we investigated whether transcription factors of Nuclear Factor-kappaB (NF-kappaB) family, controlling neuronal plasticity and neurodegeneration, are involved in these adaptations in human chronic alcoholics.

Methods And Findings: Analysis of DNA-binding of NF-kappaB (p65/p50 heterodimer) and the p50 homodimer as well as NF-kappaB proteins and mRNAs was performed in postmortem human brain samples from 15 chronic alcoholics and 15 control subjects.

Validation of endogenous controls for quantitative gene expression analysis: application on brain cortices of human chronic alcoholics.

Real-time PCR is frequently used for gene expression quantification due to its methodological sensitivity and reproducibility. The gene expression is quantified by normalization to one or more reference genes, usually beta-actin (ACTB), glyceraldehyde-3-phosphate dehydrogenase (GAPD) or to ribosomal RNA (18S). However, different environmental or pathological conditions might also influence the expression of normalizing genes, which could severely skew the interpretation of quantitative results.

Preliminary evidence for a link between schizophrenia and NMDA-glycine site receptor ligand metabolic enzymes, d-amino acid oxidase (DAAO) and kynurenine aminotransferase-1 (KAT-1).

Preliminary investigations, studying gene expression and biochemical activities of enzymes d-amino acid oxidase (DAAO) and kynurenine aminotransferase-1 (KAT-1), revealed elevated cerebellar KAT-1 and DAAO activities in post-mortem brain samples from schizophrenic versus normal individuals. In addition, we have identified a transcript of DAAO, which was expressed in significantly higher quantities in the diseased cerebellum but not detected in the parietal cortex where DAAO activity is absent.

Postmortem MR imaging of formalin-fixed human brain.

High-resolution postmortem neuroimaging of the brain can play a role in research programs by providing archival and reslicable images of brain specimens before permanent sectioning. These images can supplement evidence attained from both traditional neuropathological observations and in vivo neuroimaging. Differential brain tissue conspicuity, detectable with MRI, is determined by the density and mobility of water protons.

Selective antagonist [3H]SR141716A binding to cannabinoid CB1 receptors is increased in the anterior cingulate cortex in schizophrenia.

Previous studies suggest that long-term cannabis use causes cognitive impairment, including lack of motivation and impaired attention, conditions that also resemble core negative symptoms of schizophrenia. The anterior cingulate cortex (ACC) plays an important role in normal cognition, particularly in relation to motivation and attention. This could suggest that changes in the cannabinoid (CB) system might be present in the ACC of patients suffering schizophrenia.

Neuropathological alterations in alcoholic brains. Studies arising from the New South Wales Tissue Resource Centre.

Alcohol dependence and abuse are among the most costly health problems in the world from both social and economic points of view. Patterns of drinking appear to be changing throughout the world with more women and young people drinking heavily. Excessive drinking can lead to impairment of cognitive function and structural brain changes--some permanent, some reversible.

Changing trends in heroin-related deaths in Sydney, Australia-1995 to 1999.

This 1997-1999 study replicates an earlier one (1995-1997) in which coronial cases were reviewed at the Department of Forensic Medicine in Australia. Ten percent of the 2945 cases were considered accidental illicit drug deaths, compared to 4% in the previous study. Heroin was associated with 90% of the deaths, but in only 17% of these cases as a single drug.

How important are brain banks for alcohol research?

This article contains the proceedings of a symposium at the 2002 RSA/ISBRA Meeting in San Francisco, organized and chaired by Clive Harper and co-chaired by Izuru Matsumoto. The presentations were (1) Introduction, by Clive Harper; (2) The quality of tissue-a critical issue, by Therese Garrick; (3) The first systematic brain tissue donor program in Japan, by Izuru Matsumoto; (4) Brain scans after death-really! by Adolf Pfefferbaum, Elfar Adalsteinsson, and Edith Sullivan; (5) Capture that (genial) expression, by Joanne Lewohl and Peter Dodd; and (6) Neurochemical/pharmacological studies: experimental design and limitations, by Roger Butterworth.