Extravasated Brain-Reactive Autoantibodies Perturb Neuronal Surface Protein Expression in Alzheimer\u27s Pathology

Background: Increased blood-brain barrier (BBB) permeability is reported in both the neuropathological and in vivo studies in both Alzheimer’s Disease (AD) and age matched cognitively normal, no cognitive impairment (NCI), subjects. Impaired BBB allows various vascular components such as immunoglobulin G (IgG) to extravasate into the brain and specifically bind to various neuronal surface proteins (NSP), also known as brain reactive autoantibodies (BrABs). This interaction is predicted to further enhance deposition of amyloid plaques. Hypothesis: Interaction between extravasated BrABs and its cognate NSPs lower the expression of that NSPs in AD patients. Methods: We selected Western blotting technique to study the expression of various brain proteins and test our hypothesis. Fresh frozen brain samples of AD and NCI subjects were acquired, and total brain protein was extracted using protocol established in Acharya lab. We also identified various NSPs to study the impact of BrABs-NSPs interactions. Additionally, we investigated the expression of amyloid plaques ((amyloid precursor protein (APP)) and apoptosis (Caspase-3) markers. Specific NSPs examined included the alpha7 nicotinic acetylcholine receptor (α7nAChR) and anti-choline acetyltransferase (ChAT). To image the membranes, fluorescent imaging was used initially, which was later switched to chemiluminescence, after much troubleshooting. Results: Most of the work done through these experiments was focused on establishing a thorough Western blot protocol that can be used to reliably perform these experiments. This involved determining the appropriate primary and secondary antibodies concentrations, loading concentrations, and testing different imaging settings to determine the most ideal image-acquisition conditions. Towards the end of the fellowship, we were successful in developing a protocol to further explore our investigation. Using this protocol, we were able to visualize bands for ChAT, α7nAChR, and caspase – 3. Conclusions: Using this protocol further Western blot experiments can be run to study and compare the expression levels of various NSP in AD and control samples for testing our hypothesi

A Preliminary Report: The Hippocampus and Surrounding Temporal Cortex of Patients With Schizophrenia Have Impaired Blood-Brain Barrier

Schizophrenia (SZ) is one of the most severe forms of mental illness, yet mechanisms remain unclear. A widely established brain finding in SZ is hippocampal atrophy, and a coherent explanation similarly is lacking. Epidemiological evidence suggests increased cerebrovascular and cardiovascular complications in SZ independent of lifestyle and medication, pointing to disease-specific pathology. Endothelial cell contributions to blood-brain barrier (BBB) compromise may influence neurovascular unit and peripheral vascular function, and we hypothesize that downstream functional and structural abnormalities may be explained by impaired BBB

The Brodmann Area 39/40 of the Brain in Alzheimer’s, Mild Cognitive Impairment, and No Cognitive Impairment Subjects at Advanced Age Demonstrate Comparable Levels of Blood-Brain Barrier Breach

• Alzheimer’s disease (AD) is one of the most common form of dementia • Mild cognitive impairment (MCI), specifically amnestic subtype, more likely to progress to AD • Pathogenesis Theories: o Accumulation of amyloid-beta peptides and neurofibrillary tangles containing hyperphosphorylated neuronal tau protein o Blood Brain Barrier (BBB) dysfunction is associated with AD pathogenesis • Brodmann area 39/40: regions of parietal cortex are responsible for language, spatial cognition, memory retrieval, attention, phonological processing, and emotional processing • Hypothesis: An increased BBB permeability in Brodmann area 39/40 of AD and age-matched MCI and no cognitive impairment (NCI) subject

Beyond the Stalemate of Economics versus Ethics: Corporate Social Responsibility and the Discourse of the Organizational Self

The purpose of this paper is to advance research on CSR beyond the stalemate of economic versus ethical models by providing an alternative perspective integrating existing views and allowing for more shared dialog and research in the field. It is suggested that we move beyond making a normative case for ethical models and practices of CSR by moving beyond the question of how to manage organizational self-interest toward the question of how accurate current conceptions of the organizational self seem to be. Specifically, it is proposed that CSR is not a question of how self-interested the corporation should be, but how this self is defined. Economic and ethical models of CSR are not models of opposition but exist on a continuum between egoic and post-egoic, illusory and authentic conceptions of the organizational self. This means that moving from one to the other is not a question of adopting different paradigms but rather of moving from illusion and dysfunction to authenticity and functionality, from pathology to health. Copyright Springer 2006corporate social responsibility, economic and ethical models, economic, egoic and post-egoic approaches, narratives, organizational self, psychoanalysis,