Social and Behavioral Sciences Commons^™

Selective Suppression Of The Α Isoform Of P38 Mapk Rescues Late-Stage Tau Pathology, Nicole Maphis, Shanya Jiang, Guixiang Xu, Olga N. Kokiko-Cochran, Saktimayee M. Roy, Linda J. Van Eldik, D. Martin Watterson, Bruce T. Lamb, Kiran Bhaskar

Sanders-Brown Center on Aging Faculty Publications

Background: Hyperphosphorylation and aggregation of tau protein are the pathological hallmarks of Alzheimer’s disease and related tauopathies. We previously demonstrated that the microglial activation induces tau hyperphosphorylation and cognitive impairment via activation of p38 mitogen-activated protein kinase (p38 MAPK) in the hTau mouse model of tauopathy that was deficient for microglial fractalkine receptor CX3CR1.

Method: We report an isoform-selective, brain-permeable, and orally bioavailable small molecule inhibitor of p38α MAPK (MW181) and its effects on tau phosphorylation in vitro and in hTau mice.

Results: First, pretreatment of mouse primary cortical neurons with MW181 completely blocked inflammation-induced p38α MAPK activation and AT8 …

Individual And Family Protective Factors Of Intentional And Unintentional Consumption Of Online Pornography In Hong Kong, Cecilia M. S. Ma, Daniel T. L. Shek, Catie C. W. Lai

Pediatrics Faculty Publications

The purpose of the current study was to explore how positive youth development and family functioning were related to unintentional and intentional exposure to online pornography in Chinese adolescents. A total of 1401 secondary school students (mean age=12.43) participated in the study. Findings suggested that positive youth development and family functioning were associated with lower exposure to online pornography. In particular, higher levels of spirituality, social competence, mutuality and communication were associated with lower levels of both types of exposure to online pornography. Discussion focuses on the importance of promoting positive youth development and family functioning as protective factors against …

Caloric Restriction Preserves Memory And Reduces Anxiety Of Aging Mice With Early Enhancement Of Neurovascular Functions, Ishita Parikh, Janet Guo, Kai-Hsiang Chuang, Yu Zhong, Ralf G. Rempe, Jared D. Hoffman, Rachel Armstrong, Björn Bauer, Anika M. S. Hartz, Ai-Ling Lin

Sanders-Brown Center on Aging Faculty Publications

Neurovascular integrity plays an important role in protecting cognitive and mental health in aging. Lifestyle interventions that sustain neurovascular integrity may thus be critical on preserving brain functions in aging and reducing the risk for age-related neurodegenerative disorders. Here we show that caloric restriction (CR) had an early effect on neurovascular enhancements, and played a critical role in preserving vascular, cognitive and mental health in aging. In particular, we found that CR significantly enhanced cerebral blood flow (CBF) and blood-brain barrier function in young mice at 5-6 months of age. The neurovascular enhancements were associated with reduced mammalian target of …

Immunomodulators As Therapeutic Agents In Mitigating The Progression Of Parkinson's Disease, Bethany Grimmig, Josh Morganti, Kevin Nash, Paula C. Bickford

Sanders-Brown Center on Aging Faculty Publications

Parkinson’s disease (PD) is a common neurodegenerative disorder that primarily afflicts the elderly. It is characterized by motor dysfunction due to extensive neuron loss in the substantia nigra pars compacta. There are multiple biological processes that are negatively impacted during the pathogenesis of PD, and are implicated in the cell death in this region. Neuroinflammation is evidently involved in PD pathology and mitigating the inflammatory cascade has been a therapeutic strategy. Age is the number one risk factor for PD and thus needs to be considered in the context of disease pathology. Here, we discuss the role of neuroinflammation within …

Extracellular Vesicle-Associated Aβ Mediates Trans-Neuronal Bioenergetic And Ca2+-Handling Deficits In Alzheimer's Disease Models, Erez Eitan, Emmette R. Hutchison, Krisztina Marosi, James Comotto, Maja Mustapic, Saket M. Nigam, Caitlin Suire, Chinmoyee Maharana, Gregory A. Jicha, Dong Liu, Vasiliki Machairaki, Kenneth W. Witwer, Dimitrios Kapogiannis, Mark P. Mattson

Sanders-Brown Center on Aging Faculty Publications

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder in which aggregation-prone neurotoxic amyloid β-peptide (Aβ) accumulates in the brain. Extracellular vesicles (EVs), including exosomes, are small 50–150 nm membrane vesicles that have recently been implicated in the prion-like spread of self-aggregating proteins. Here we report that EVs isolated from AD patient cerebrospinal fluid and plasma, from the plasma of two AD mouse models, and from the medium of neural cells expressing familial AD presenilin 1 mutations, destabilize neuronal Ca²⁺ homeostasis, impair mitochondrial function, and sensitize neurons to excitotoxicity. EVs contain a relatively low amount of Aβ but have an …

Reduced Efficacy Of Anti-AΒ Immunotherapy In A Mouse Model Of Amyloid Deposition And Vascular Cognitive Impairment Comorbidity, Erica M. Weekman, Tiffany L. Sudduth, Carly N. Caverly, Timothy J. Kopper, Oliver W. Phillips, David K. Powell, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Vascular cognitive impairment and dementia (VCID) is the second most common form of dementia behind Alzheimer's disease (AD). It is estimated that 40% of AD patients also have some form of VCID. One promising therapeutic for AD is anti-Aβ immunotherapy, which uses antibodies against Aβ to clear it from the brain. While successful in clearing Aβ and improving cognition in mice, anti-Aβ immunotherapy failed to reach primary cognitive outcomes in several different clinical trials. We hypothesized that one potential reason the anti-Aβ immunotherapy clinical trials were unsuccessful was due to this high percentage of VCID …

Opportunities And Challenges In Incorporating Ancillary Studies Into A Cancer Prevention Randomized Clinical Trial, Phyllis J. Goodman, Catherine M. Tangen, Amy K. Darke, Kathryn B. Arnold, Joann Hartline, Monica Yee, Karen Anderson, Allison Caban-Holt, William G. Christen, Patricia A Cassano, Peter Lance, Eric A. Klein, John J. Crowley, Lori M. Minasian, Frank L. Meyskens

Sanders-Brown Center on Aging Faculty Publications

Background: The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was a randomized, double-blind, placebo-controlled, prostate cancer prevention study funded by the National Cancer Institute and conducted by SWOG (Southwest Oncology Group). A total of 35,533 men were assigned randomly to one of four treatment groups (vitamin E + placebo, selenium + placebo, vitamin E + selenium, placebo + placebo). At the time of the trial’s development, NIH had invested substantial resources in evaluating the potential benefits of these antioxidants. To capitalize on the knowledge gained from following a large cohort of healthy, aging males on the effects of selenium …

Mtor: Alzheimer's Disease Prevention For Apoe4 Carriers, Ai-Ling Lin, D. Allan Butterfield, Arlan Richardson

Sanders-Brown Center on Aging Faculty Publications

No abstract provided.

1H-Mrs Metabolites In Adults With Down Syndrome: Effects Of Dementia, Ai-Ling Lin, David Powell, Allison Caban-Holt, Gregory A. Jicha, William C. Robertson, Brian T. Gold, Roberta Davis, Erin L. Abner, Donna M. Wilcock, Frederick A. Schmitt, Elizabeth Head

Sanders-Brown Center on Aging Faculty Publications

To determine if proton magnetic resonance spectroscopy (¹H-MRS) detect differences in dementia status in adults with Down syndrome (DS), we used ¹H-MRS to measure neuronal and glial metabolites in the posterior cingulate cortex in 22 adults with DS and in 15 age- and gender-matched healthy controls. We evaluated associations between ¹H-MRS results and cognition among DS participants. Neuronal biomarkers, including N-acetylaspartate (NAA) and glutamate-glutamine complex (Glx), were significantly lower in DS patients with Alzheimer's should probably be changed to Alzheimer (without ' or s) through ms as per the new naming standard disease (DSAD) when …

Interaction Of Tau With The Rna-Binding Protein Tia1 Regulates Tau Pathophysiology And Toxicity, Tara Vanderweyde, Daniel J. Apicco, Katherine Youmans-Kidder, Peter E. A. Ash, Casey Cook, Edroaldo Lummertz Da Rocha, Karen Jansen-West, Alissa A. Frame, Allison Citro, John D. Leszyk, Pavel Ivanov, Jose F. Abisambra, Martin Steffen, Hu Li, Leonard Petrucelli, Benjamin Wolozin

Sanders-Brown Center on Aging Faculty Publications

Dendritic mislocalization of microtubule associated protein tau is a hallmark of tauopathies, but the role of dendritic tau is unknown. We now report that tau interacts with the RNA-binding protein (RBP) TIA1 in brain tissue, and we present the brain-protein interactome network for TIA1. Analysis of the TIA1 interactome in brain tissue from wild-type (WT) and tau knockout mice demonstrates that tau is required for normal interactions of TIA1 with proteins linked to RNA metabolism, including ribosomal proteins and RBPs. Expression studies show that tau regulates the distribution of TIA1, and tau accelerates stress granule (SG) formation. Conversely, TIA1 knockdown …

Plasma Neuronal Exosomal Levels Of Alzheimer's Disease Biomarkers In Normal Aging, Erin L. Abner, Gregory A. Jicha, Leslie M. Shaw, John Q. Trojanowski, Edward J. Goetzl

Sanders-Brown Center on Aging Faculty Publications

Plasma neuronal exosomal levels of pathogenic Alzheimer's disease (AD) proteins, cellular survival factors, and lysosomal proteins distinguish AD patients from control subjects, but changes in these exosomal proteins associated with normal aging have not been described for cognitively intact subjects. Plasma neuronal exosomal levels of P-T181-tau, P-S396-tau, Aβ_1-42, cathepsin D, repressor element 1-silencing transcription factor, and neurogranin were quantified longitudinally in cognitively intact older adults using two samples collected at 3- to 11-year intervals. Except for P-S396-tau, exosomal protein levels changed significantly with aging, but were largely outside the range observed in AD patients.

Transnational Ties Within Azorean Multigenerational Kinship Groups: Multi-Connectedness And Icts, Ana Gherghel, Josiane Le Gall

disClosure: A Journal of Social Theory

This article analyzes the influence of ICTs use on transnational connections and on their perpetuation over time within multigenerational kinship groups dispersed in several countries. Evidence from a multi-sited ethnographic research dedicated to migration from the Azores archipelago (Portugal) to the province of Quebec (Canada) provides information about factors explaining transnational practice over several decades. Our data indicate an overall intensification of transnational contacts due to increasing accessibility of new technologies. However, this process takes place in a family environment characterized by multi-connectedness, a capacity to maintain multiple active ties with siblings living in various countries and using multiple modalities. …

The Tnfα-Transgenic Rat: Hippocampal Synaptic Integrity, Cognition, Function, And Post-Ischemic Cell Loss, L. Creed Pettigrew, Richard J. Kryscio, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

The cytokine, tumor necrosis factor α (TNFα), is a key regulator of neuroinflammation linked to numerous neurodegenerative conditions and diseases. The present study used transgenic rats that overexpress a murine TNFα gene, under the control of its own promoter, to investigate the impact of chronically elevated TNFα on hippocampal synaptic function. Neuronal viability and cognitive recovery in TNFα Tg rats were also determined following an ischemic insult arising from reversible middle cerebral artery occlusion (MCAO). Basal CA3-CA1 synaptic strength, recorded in acute brain slices, was not significantly different between eight-week-old TNFα Tg rats and non-Tg rats. In contrast, slices from …

Mw151 Inhibited Il-1Β Levels After Traumatic Brain Injury With No Effect On Microglia Physiological Responses, Adam D. Bachstetter, Zhengqiu Zhou, Rachel K. Rowe, Bin Xing, Danielle S. Goulding, Alyssa N. Conley, Pradoldej Sompol, Shelby Meier, Jose F. Abisambra, Jonathan Lifshitz, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

A prevailing neuroinflammation hypothesis is that increased production of proinflammatory cytokines contributes to progressive neuropathology, secondary to the primary damage caused by a traumatic brain injury (TBI). In support of the hypothesis, post-injury interventions that inhibit the proinflammatory cytokine surge can attenuate the progressive pathology. However, other post-injury neuroinflammatory responses are key to endogenous recovery responses. Therefore, it is critical that pharmacological attenuation of detrimental or dysregulated neuroinflammatory processes avoid pan-suppression of inflammation. MW151 is a CNS-penetrant, small molecule experimental therapeutic that restores injury- or disease-induced overproduction of proinflammatory cytokines towards homeostasis without immunosuppression. Post-injury administration of MW151 in a …

AΒ40 Reduces P-Glycoprotein At The Blood-Brain Barrier Through The Ubiquitin-Proteasome Pathway, Anika M. S. Hartz, Yu Zhong, Andrea Wolf, Harry Levine Iii, David S. Miller, Björn Bauer

Sanders-Brown Center on Aging Faculty Publications

Failure to clear amyloid-β (Aβ) from the brain is in part responsible for Aβ brain accumulation in Alzheimer's disease (AD). A critical protein for clearing Aβ across the blood–brain barrier is the efflux transporter P-glycoprotein (P-gp) in the luminal plasma membrane of the brain capillary endothelium. P-gp is reduced at the blood–brain barrier in AD, which has been shown to be associated with Aβ brain accumulation. However, the mechanism responsible for P-gp reduction in AD is not well understood. Here we focused on identifying critical mechanistic steps involved in reducing P-gp in AD. We …

Factors Associated With Unmet Needs Among African-American Dementia Care Providers, P. J. Desin, Allison M. Caban-Holt, Erin L. Abner, Linda J. Van Eldik, Frederick A. Schmitt

Sanders-Brown Center on Aging Faculty Publications

Racial and ethnic minorities currently comprise 20% of the U.S. population; in 2050, this figure is expected to rise to 42%. As a result, Alzheimer’s disease (AD), the 5th leading cause of death for people aged 65 and older, is likely to increase in these groups. Most dementia caregiving for these populations comes from family and friends, especially among families with lower socioeconomic status. A convenience sample of 30 African-American dementia caregivers was interviewed to determine unmet needs. Participants expressed a limited desire for formal services, such as support groups, legal advice, case management, and homemaker services. Instead, commonly expressed …

Pathological Tau Promotes Neuronal Damage By Impairing Ribosomal Function And Decreasing Protein Synthesis, Shelby Meier, Michelle Bell, Danielle N. Lyons, Jennifer Rodriguez-Rivera, Alexandria Ingram, Sarah N. Fontaine, Elizabeth Mechas, Jing Chen, Benjamin Wolozin, Harry Levine Iii, Haining Zhu, Jose F. Abisambra

Sanders-Brown Center on Aging Faculty Publications

One of the most common symptoms of Alzheimer's disease (AD) and related tauopathies is memory loss. The exact mechanisms leading to memory loss in tauopathies are not yet known; however, decreased translation due to ribosomal dysfunction has been implicated as a part of this process. Here we use a proteomics approach that incorporates subcellular fractionation and coimmunoprecipitation of tau from human AD and non-demented control brains to identify novel interactions between tau and the endoplasmic reticulum (ER). We show that ribosomes associate more closely with tau in AD than with tau in control brains, and that this abnormal association leads …

"Don't Have Sex, You'll Get Pregnant And Die!": Female University Students' Experiences With Abstinence-Only Education, Jillian Grace Norwick

Theses and Dissertations--Family Sciences

Based on the various changes in sexual education, many schools throughout the United States still teach abstinence-only education. There is a plethora of literature on the effectiveness of sexual education programs as well as adolescent sexual practices. However, there is a deep gap in literature on students' perspectives of their sexual education and the possible effects it has on their experiences while in college. Therefore, this phenomenological study aims to explore and describe the essence of the experience female university students have regarding the abstinence-only education they received during secondary schooling. The informants (n=12) were 19-22 year old female university …

Family Dinner Across Generations: My How Times Have Changed?, Dayna E. Parrett

Theses and Dissertations--Family Sciences

In an effort to determine differences between family dinners across generations, this study examined typical family dinners of participants and how they have changed across the four generations addressed. Previous qualitative research has been conducted to determine communication frames that occur during family dinners and the effect of parenting styles on family dinners, but little research connecting generational differences to family dinners has been published. Data were collected from a homogeneous sample of twenty-four women living in three counties across the Commonwealth of Kentucky. By asking open ended questions during interviews, similarities and differences between family dinners across generations were …

Effects Of Timing Of Parental Divorce On Children’S Romantic Relationships In Adulthood: A Review, Adrian Weldon

Lewis Honors College Capstone Collection

A literature review was conducted to determine what age children are most vulnerable to the impact of parental divorce on their romantic relationships in adulthood. Fourteen articles were included in this review. Results of the review showed different outcomes based on stage of life. Parental divorce in infancy, early childhood, late childhood, and adolescence resulted in the most negative long-term effects on the children’s intimate relationships later in life. Children in middle childhood and young adulthood at the time of their parents’ marital dissolution appeared to be most resilient to its impact on their romantic relationships in adulthood. Literature on …

Reducing Depression Among Older Adults: Informal Helping Versus Volunteering, Salih Salihoglu

MPA/MPP/MPFM Capstone Projects

Volunteerism is an unpaid productive activity that is exercised within a formal organization to benefit others that are not part of family or friends (Musick & Wilson, 2008). Alternatively, individuals could engage in informal helping which would be an activity undertaken outside a formal, structured organization. This paper addresses whether informal helping is also effective in reducing depression for older adults alongside volunteering. I hypothesize that informal helping is effective in reducing depression only when exercised for short durations. On the other hand, I hypothesize that volunteerism is only effective when exercised for long periods of time. I try to …

College-Educated, African American Women's Marital Choices, Katherine M. Oliver

Theses and Dissertations--Family Sciences

This study explores the desire to marry, marriageable mate criteria, and marital choices/options as they pertain to college-educated, African American women within today’s society. A purposive, nationally based sample (N = 95) of never married, college-educated, African American women (i.e., 18 to 40 years of age) was gathered via an online survey accessed by an emailed link. A mixed methods approach was utilized within the survey design, followed by data analyses (i.e., frequencies, two-way analyses) interpreted through a theoretical framework of social exchange. Areas discussed include life goals of marriage, cohabitation, and career; romantic barriers; the perceived availability of …

Effect Of Mass Media On Family Planning Choices In Indonesia, Beta Ardiansyah

MPA/MPP/MPFM Capstone Projects

Realizing the necessity of family planning, the Indonesian government started family planning programs in the late 1960s, long before the global Program of Action from the International Conference of Population (ICPD) in 1994.

Many studies have tried to draw plausible explanations for the prevalence of family planning focused mainly on socio-economic factors but few studies have approached the issue from the perspective of mass media influence as the variable of interest. This study attempts to fill this gap created by the lack of empirical evidence about mass media effects of family planning choices by examining the contraceptive behavior of Indonesian …

Retrospective Frames Of Disability: Themes Derived From Parents Of Children Who Grew Up With Congenital Disability, Sheryl L. Holt

Theses and Dissertations--Rehabilitation Sciences

Introduction: For children born with physical disabilities, the perspectives and actions of their parents prove significant to their childhood developmental outcomes clinically, educationally, socially, and with regard to community participation. The lived world and perceptions of parents who have children with disabilities however is not well investigated. This study sought to understand parents’ framing of theirs and their children’s disability experiences. Family systems together with family systems intervention models, and disability theory were used to provide structure to interview instrumentation and subsequent analysis. Child-centered and ecologic influences were also used to track the transformative processes over time that infuses parental …

Hosting An International Exchange Youth: The Influence On The Family, Mark Mains

Theses and Dissertations--Family Sciences

This study explores how hosting an international exchange youth influences families. Participants in the study took part in a four-week summer exchange by hosting a middle school aged Japanese youth through the Kentucky 4-H/Labo program. Labo is a Japanese club program that encourages youth to learn about American culture through international travel. As society becomes more globalized, the skills and abilities associated with international travel are increasingly important (Anderson, Lawton, Rexeisen & Hubbard, 2006). Hosting international youth through exchange programs is one method of developing these skills and abilities. This qualitative study uses thematic analysis to analyze three primary data …