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Dr Steve Kassem completed his BSc at the University of Sydney in Neuroscience and Psychology. He then went on to complete his honours year at the Brain and Mind Research Institute, looking into the morphological changes of chronic stress on neurons, glia and gray matter. Where he published work revealing the composition of gray matter represented by its cellular bodies, and how changes to these cellular bodies resulted in concomitant changes in gray matter volume. Subsequently, he went on to complete his PhD, in a dual supervision, at the University of Sydney and the University of NSW, looking into the effects chronic stress and its morphological changes had on learning behaviours and their neural circuits. In addition, he modernised the Golgi Stain, a histological method over a century old and recognised as the gold standard to visualising the neuron, it fell out of common use due to it not being compatible with modern techniques, however, it now called the Ultra-Rapid Golgi or URG stain, and has revealed to be fluorescent and not only compatible but advantageous when combined with modern techniques. For his PhD, he won the Peter Bancroft Award for research excellence and a thesis which did not require emendment. Dr Kassem is an avid supporter of science communication and in 2017 joined NeuRA originally under the media and communications department, coming from his management role with the Sydney Science Festival, however as of 2018, Dr Kassem was appointed a postdoctoral fellowship to work with Scientia Professor George Paxinos AO, bringing his novel histological and MRI skills to Prof Paxinos’ work on visualising and defining the brain.
This project aims to deliver the most comprehensive, detailed and stereotaxically accurate MRI atlas of the canonical human brain.
In human neuroscience, researchers and clinicians almost always investigate images obtained from living individuals. Yet, there is no satisfactory MRI atlas of the human brain in vivo or post-mortem. There are some population-based atlases, which valiantly solve a number of problems, but they fail to address major needs. Most problematically, they segment only a small number of brain structures, typically about 50, and they are of limited value for the interpretation of a single subject/patient.
In contrast to population-based approaches, the present project will investigate normal, living subjects in detail. We aim to define approximately 800 structures, as in the histological atlas of Mai, Majtanik and Paxinos (2016), and, thus, provide a “gold standard” for science and clinical practice. We will do this by obtaining high-resolution MRI at 3T and 7T of twelve subjects through a collaboration with Markus Barth from the Centre for Advanced Imaging at the University of Queensland (UQ). The limited number of subjects will allow us to image each for longer periods, obtaining higher resolution and contrast, and to invest the required time to produce unprecedented detail in segmentation.
We will produce an electronic atlas for interpreting MR images, both as a tablet application and as an online web service. The tablet application will provide a convenient and powerful exegesis of brain anatomy for researchers and clinicians. The open access web service will additionally provide images, segmentation and anatomical templates to be used with most common MR-analysis packages (e.g., SPM, FSL, MINC, BrainVoyager). This will be hosted in collaboration with UQ, supporting and complementing their population-based atlas.
DR TERI FURLONG Postdoctoral Fellow
DR CHRISTODOULOS SKLIROS PhD Fellow
KEIRA MCCLOSKEY Research Assistant
KATERINA ARVANITAKIS Research Assistant
This is the first application of a Golgi-Cox stain to cleared brain tissue, it is investigated and discussed in detail, describing different methodologies that may be used, a comparison between the different clearing techniques and lastly the novel interaction of these techniques with this ultra-rapid stain.
Alterations in the gray matter volume of several brain regions have been reported in people with chronic pain. The most consistent observation is a decrease of gray matter volume in the medial prefrontal cortex. These findings are important as the medial prefrontal cortex plays a critical role in emotional and cognitive processing in chronic pain. Although a logical cause of gray matter volume decrease may be neurodegeneration, this is not supported by the current evidence. Therefore, the purpose of this review is to evaluate the existing literature to unravel what the decrease in medial prefrontal cortex gray matter volume of people with chronic pain may represent on a biochemical and cellular level. Our model proposes new mechanisms in chronic pain pathophysiology responsible for mPFC gray matter loss as alternatives to neurodegeneration. This article is protected by copyright. All rights reserved.
One neuropathological feature of schizophrenia is a diminished number of dendritic spines in the prefrontal cortex and hippocampus. The neuregulin 1 (Nrg1) system is involved in the plasticity of dendritic spines, and chronic stress decreases dendritic spine densities in the prefrontal cortex and hippocampus. Here, we aimed to assess whether Nrg1 deficiency confers vulnerability to the effects of adolescent stress on dendritic spine plasticity. We also assessed other schizophrenia-relevant neurobiological changes such as microglial cell activation, loss of parvalbumin (PV) interneurons, and induction of complement factor 4 (C4). Adolescent male wild-type (WT) and Nrg1 heterozygous mice were subjected to chronic restraint stress before their brains underwent Golgi impregnation or immunofluorescent staining of PV interneurons, microglial cells, and C4. Stress in WT mice promoted dendritic spine loss and microglial cell activation in the prefrontal cortex and the hippocampus. However, Nrg1 deficiency rendered mice resilient to stress-induced dendritic spine loss in the infralimbic cortex and the CA3 region of the hippocampus without affecting stress-induced microglial cell activation in these brain regions. Nrg1 deficiency and adolescent stress combined to trigger increased dendritic spine densities in the prelimbic cortex. In the hippocampal CA1 region, Nrg1 deficiency accentuated stress-induced dendritic spine loss. Nrg1 deficiency increased C4 protein and decreased C4 mRNA expression in the hippocampus, and the number of PV interneurons in the basolateral amygdala. This study demonstrates that Nrg1 modulates the impact of stress on the adolescent brain in a region-specific manner. It also provides first evidence of a link between Nrg1 and C4 systems in the hippocampus.