Modulators of Cytoskeletal Reorganization in CA1 Hippocampal Neurons Show Increased Expression in Patients at Mid-Stage Alzheimer's Disease

During the progression of Alzheimer's disease (AD), hippocampal neurons undergo cytoskeletal reorganization, resulting in degenerative as well as regenerative changes. As neurofibrillary tangles form and dystrophic neurites appear, sprouting neuronal processes with growth cones emerge. Actin and tubulin are indispensable for normal neurite development and regenerative responses to injury and neurodegenerative stimuli. We have previously shown that actin capping protein beta2 subunit, Capzb2, binds tubulin and, in the presence of tau, affects microtubule polymerization necessary for neurite outgrowth and normal growth cone morphology. Accordingly, Capzb2 silencing in hippocampal neurons resulted in short, dystrophic neurites, seen in neurodegenerative diseases including AD. Here we demonstrate the statistically significant increase in the Capzb2 expression in the postmortem hippocampi in persons at mid-stage, Braak and Braak stage (BB) III-IV, non-familial AD in comparison to controls. The dynamics of Capzb2 expression in progressive AD stages cannot be attributed to reactive astrocytosis. Moreover, the increased expression of Capzb2 mRNA in CA1 pyramidal neurons in AD BB III-IV is accompanied by an increased mRNA expression of brain derived neurotrophic factor (BDNF) receptor tyrosine kinase B (TrkB), mediator of synaptic plasticity in hippocampal neurons. Thus, the up-regulation of Capzb2 and TrkB may reflect cytoskeletal reorganization and/or regenerative response occurring in hippocampal CA1 neurons at a specific stage of AD progression

Prevalence of childhood eczema and food sensitization in the First Nations reserve of Natuashish, Labrador, Canada

Background: The Mushua Innu of Natuashish, Labrador, Canada seem to have a high rate of childhood eczema. Anecdotally this problem seems to be more common now than 20 years ago. There has been speculation that this could be related to food sensitization that may have arisen coincident with a move away from a traditional Innu diet. We undertook to assess the prevalence and severity of pediatric eczema in Natuashish (population 792), and investigate the level of sensitization to common food antigens. Methods: Over a three-month period we performed a population survey of all children in the community from the ages of 2–12 inclusive. The one-year prevalence of eczema was assessed using the United Kingdom Working Party’s diagnostic criteria, and graded on the Nottingham Severity Scale. All children with eczema and twice as many age/sex matched controls were offered complete blood counts, total IgE, and food specific IgE levels for egg white, cow’s milk protein and wheat. Results: One hundred and eighty two (95% of the eligible children) were assessed. Of the 182 children examined eczema was diagnosed in 30 (16.5%) - 22 females and 8 males. The majority of children with eczema (20/30) were classified as being in the moderate and severe category. Of the 22 with eczema and 40 controls who consented to venipuncture all but 3 had IgE levels above the lab's reference range. Food specific antibody assays showed that 32, 23, and 5 percent of children with eczema were sensitized to egg, milk, and wheat respectively. None of the controls were sensitized. Conclusions: The children of Natuashish, Labrador have a high rate of eczema, much of it graded as moderate or severe. IgE levels were markedly elevated in children with and without eczema, with average values at least ten-fold higher than other populations. There is no evidence of an unusual amount of sensitization to egg, milk or wheat