Assessing a Novel Adaptation to CCI Devices to Model Human Mild Traumatic Brain Injury

Background: Traumatic Brain Injuries (TBIs) are a health crisis with over a million people suffering injuries each year in the United States. The majority of TBIs are mild injuries which often produce no period of unconsciousness and no gross damage to the brain or skull. A range of TBI animal models exist but many produce injuries too severe to characterize as mild. One TBI induction method commonly used is Controlled Cortical Impact (CCI) devices. New Method: The purpose of this study is to assess a novel adaptation to CCI devices that allows for the induction of mild injuries that mimic human mild TBI (mTBI). In this apparatus, the mouse is placed on an elevated platform which utilizes a sensor to collapse the platform as the impactor hits the head. Results: On the first day of injury, the repetitive dropping platform group had a significantly lower Time to Righting (TTR) than both control and single hit stationary platform groups. Additionally, on the first day of injury the single-hit stationary group had a significantly increased Time to Ambulation (TTA) compared to all other groups. Furthermore, this adaptation produces significantly less GFAP than CCI injuries performed without the falling platform. Comparison with existing models: This model incorporates the high control of the CCI device that may be lost in weight-drop models of mild injury while also producing translational mild injuries. Conclusion: This adaptation can be used in any CCI research lab to translationally study mild injuries. This will facilitate murine research into mTBI

A Novel hAPP/htau Mouse Model of Alzheimer's Disease: Inclusion of APP With Tau Exacerbates Behavioral Deficits and Zinc Administration Heightens Tangle Pathology

The brains of those with Alzheimer's disease have amyloid and tau pathology; thus, mice modeling AD should have both markers. In this study, we characterize offspring from the cross of the J20 (hAPP) and rTg4510 (htau) strains (referred to as dual Tg). Behavior was assessed at both 3.5 and 7 months, and biochemical differences were assessed at 8 months. Additionally, mice were placed on zinc (Zn) water or standard lab water in order to determine the role of this essential biometal. Behavioral measures examined cognition, emotion, and aspects of daily living. Transgenic mice (dual Tg and htau) showed significant deficits in spatial memory in the Barnes Maze at both 3.5 and 7 months compared to controls. At 7 months, dual Tg mice performed significantly worse than htau mice (p < 0.01). Open field and elevated zero maze (EZM) data indicated that dual Tg and htau mice displayed behavioral disinhibition compared to control mice at both 3.5 and 7 months (p < 0.001). Transgenic mice showed significant deficits in activities of daily living, including burrowing and nesting, at both 3.5 and 7 months compared to control mice (p < 0.01). Dual Tg mice built very poor nests, indicating that non-cognitive tasks are also impacted by AD. Overall, dual Tg mice demonstrated behavioral deficits earlier than those shown by the htau mice. In the brain, dual Tg mice had significantly less free Zn compared to control mice in both the dentate gyrus and the CA3 of the hippocampus (p < 0.01). Dual Tg mice had increased tangles and plaques in the hippocampus compared to htau mice and the dual Tg mice given Zn water displayed increased tangle pathology in the hippocampus compared to htau mice on Zn water (p < 0.05). The dual Tg mouse described here displays pathology reminiscent of the human AD condition and is impaired early on in both cognitive and non-cognitive behaviors. This new mouse model allows researchers to assess how both amyloid and tau in combination impact behavior and brain pathology

Identification of hydroxyapatite spherules provides new insight into sub-retinal pigment epithelial deposit formation in the aging eye

Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye. Proc Natl Acad Sci U S A , 112 Keywords: Hydroxyapatite, calcium, drusen, macula, retinal pigment epithelium, RPE, age-related macular degeneration, AMD, cholesterol, complement factor H, CFH, amyloid-beta, vitronectin Significance Statement Proteins and lipids accumulating in deposits external to the RPE represent a barrier to metabolic exchange between the retina and the choroidal capillaries. With time, these deposits can lead to age-related macular degeneration (AMD), the most common cause of blindness in the elderly in the developed world. It remains unclear how sub-RPE deposits are initiated and grow to clinically relevant features. Using a combination of high resolution analytical techniques we found that tiny hydroxyapatite (bone mineral) spherules with cholesterol-containing cores are present in all examined sub-RPE deposits, providing a scaffold to which proteins adhere. If the spherules are important in initiating sub-RPE deposit formation this may provide attractive new approaches for early identification and treatment of AMD

Localization of Free and Bound Metal Species through X-Ray Synchrotron Fluorescence Microscopy in the Rodent Brain and Their Relation to Behavior

Biometals in the brain, such as zinc, copper, and iron, are often discussed in cases of neurological disorders; however, these metals also have important regulatory functions and mediate cell signaling and plasticity. With the use of synchrotron X-ray fluorescence, our lab localized total, both bound and free, levels of zinc, copper, and iron in a cross section of one hemisphere of a rat brain, which also showed differing metal distributions in different regions within the hippocampus, the site in the brain known to be crucial for certain types of memory. This review discusses the several roles of these metals in brain regions with an emphasis on hippocampal cell signaling, based on spatial mapping obtained from X-ray fluorescence microscopy. We also discuss the localization of these metals and emphasize different cell types and receptors in regions with metal accumulation, as well as the potential relationship between this physiology and behavior

Participation in Active Singing Leads to Cognitive Improvements in Individuals With Dementia

Present study aims to examine effect of music in cognitive improvements in individuals with dementia. Music has been shown to be an effective management strategy for individuals with Alzheimer’s disease and has been shown to reduce agitation, antisocial behavior, depression, aggression, and anxiety. Thus, the effect of active singing on measures of cognition and life satisfaction was examined. The study was performed at an east coast assisted living facility. Singing and listening groups (N = 45) received three vocal music sessions per week. Vocal music programming included familiar (nostalgic) and nonfamiliar (novel) vocal music selections in four, 50-minute singing programs. Music has been shown to be an effective management strategy for individuals with Alzheimer’s disease and has been shown to reduce agitation, antisocial behavior, depression, aggression, and anxiety. Thus, the effect of active singing on measures of cognition and life satisfaction was examined. (PsycINFO Database Record (c) 2016 APA, all rights reserved

White Button Mushroom (<i>Agaricus bisporus)</i> Supplementation Ameliorates Spatial Memory Deficits and Plaque Formation in an Amyloid Precursor Protein Mouse Model of Alzheimer’s Disease

Alzheimer’s Disease (AD) is characterized by cognitive impairment and the presence of amyloid-β (Aβ) plaques and tau tangles. This study was conducted to assess the effects of white button mushroom (WBM) supplementation on spatial memory and plaque formation in mice with mutations in amyloid (Aβ). Mice with amyloid precursor protein (hAPP) mutations and their wildtype (WT) littermates were fed a 10% white button mushroom (WBM) feed ad libitum three times per week, in addition to their normal diet. Morris water maze (MWM) was conducted at 14 and 32 weeks of age to assess spatial memory and Aβ plaque pathology in the hippocampus was analyzed. Our results showed that hAPP mice on the WBM diet were faster in reaching the platform in the MWM compared to hAPP mice on the control diet at 32 weeks (p p < 0.05). Overall, hAPP mice on the WBM diet had improved spatial memory at 32 weeks of age compared to those on the control diet and exhibited fewer amyloid plaques