Neurosciences Commons^™

Brain Ageing In Schizophrenia: Evidence From 26 International Cohorts Via The Enigma Schizophrenia Consortium, Constantinos Constantinides, Laura K M Han, Clara Alloza, Linda Antonella Antonucci, Celso Arango, Rosa Ayesa-Arriola, Nerisa Banaj, Alessandro Bertolino, Stefan Borgwardt, Jason Bruggemann, Juan Bustillo, Oleg Bykhovski, Vince Calhoun, Vaughan Carr, Stanley Catts, Young-Chul Chung, Benedicto Crespo-Facorro, Covadonga M Díaz-Caneja, Gary Donohoe, Stefan Du Plessis, Jesse Edmond, Stefan Ehrlich, Robin Emsley, Lisa T Eyler, Paola Fuentes-Claramonte, Foivos Georgiadis, Melissa Green, Amalia Guerrero-Pedraza, Minji Ha, Tim Hahn, Frans A Henskens, Laurena Holleran, Stephanie Homan, Philipp Homan, Neda Jahanshad, Joost Janssen, Ellen Ji, Stefan Kaiser, Vasily Kaleda, Minah Kim, Woo-Sung Kim, Matthias Kirschner, Peter Kochunov, Yoo Bin Kwak, Jun Soo Kwon, Irina Lebedeva, Jingyu Liu, Patricia Mitchie, Stijn Michielse, David Mothersill, Bryan Mowry, Víctor Ortiz-García De La Foz, Christos Pantelis, Giulio Pergola, Fabrizio Piras, Edith Pomarol-Clotet, Adrian Preda, Yann Quidé, Paul E Rasser, Kelly Rootes-Murdy, Raymond Salvador, Marina Sangiuliano, Salvador Sarró, Ulrich Schall, André Schmidt, Rodney J Scott, Pierluigi Selvaggi, Kang Sim, Antonin Skoch, Gianfranco Spalletta, Filip Spaniel, Sophia I Thomopoulos, David Tomecek, Alexander S Tomyshev, Diana Tordesillas-Gutiérrez, Therese Van Amelsvoort, Javier Vázquez-Bourgon, Daniela Vecchio, Aristotle Voineskos, Cynthia S Weickert, Thomas Weickert, Paul M Thompson, Lianne Schmaal, Theo G M Van Erp, Jessica Turner, James H Cole, Enigma Schizophrenia Consortium, Danai Dima, Esther Walton

Faculty, Staff and Students Publications

Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18–72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18–73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on …

Circadian Rhythms As Modulators Of Brain Health During Development And Throughout Aging, Rachel Van Drunen, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

The circadian clock plays a prominent role in neurons during development and throughout aging. This review covers topics pertinent to the role of 24-h rhythms in neuronal development and function, and their tendency to decline with aging. Pharmacological or behavioral modification that augment the function of our internal clock may be central to decline of cognitive disease and to future chronotherapy for aging-related diseases of the central nervous system.

Transcriptional Profiles In Olfactory Pathway-Associated Brain Regions Of African Green Monkeys: Associations With Age And Alzheimer’S Disease Neuropathology, Jacob D Negrey, Dorothy L Dobbins, Timothy D Howard, Karin E Borgmann-Winter, C G Hahn, Sergey Kalinin, Douglas L Feinstein, Suzanne Craft, Carol A Shively, Thomas C Register

Department of Neuroscience Faculty Papers

Introduction: Olfactory impairment in older individuals is associated with an increased risk of Alzheimer's disease (AD). Characterization of age versus neuropathology-associated changes in the brain olfactory pathway may elucidate processes underlying early AD pathogenesis. Here, we report age versus AD neuropathology-associated differential transcription in four brain regions in the olfactory pathway of 10 female African green monkeys (vervet, Chlorocebus aethiops sabaeus), a well-described model of early AD-like neuropathology.

Methods: Transcriptional profiles were determined by microarray in the olfactory bulb (OB), piriform cortex (PC), temporal lobe white matter (WM), and inferior temporal cortex (ITC). Amyloid beta (Aβ) plaque load in …

Aging After Stroke: How To Define Post-Stroke Sarcopenia And What Are Its Risk Factors?, Sheng Li, Javier Gonzalez-Buonomo, Jaskiran Ghuman, Xinran Huang, Aila Malik, Nuray Yozbatiran, Elaine Magat, Gerard E Francisco, Hulin Wu, Walter R Frontera

Faculty, Staff and Student Publications

BACKGROUND: Sarcopenia, generally described as "aging-related loss of skeletal muscle mass and function", can occur secondary to a systemic disease.

AIM: This project aimed to study the prevalence of sarcopenia in chronic ambulatory stroke survivors and its associated risk factors using the two most recent diagnostic criteria.

DESIGN: A cross-sectional observational study.

SETTING: A scientific laboratory.

POPULATION: Chronic stroke.

METHODS: Twenty-eight ambulatory chronic stroke survivors (12 females; mean age=57.8±11.8 years; time after stroke=76±45 months), hand-grip strength, gait speed, and appendicular skeletal muscle mass (ASM) were measured to define sarcopenia. Risk factors, including motor impairment and spasticity, were identified using regression …

Aging After Stroke: How To Define Post-Stroke Sarcopenia And What Are Its Risk Factors?, Sheng Li, Javier Gonzalez-Buonomo, Jaskiran Ghuman, Xinran Huang, Aila Malik, Nuray Yozbatiran, Elaine Magat, Gerard E Francisco, Hulin Wu, Walter R Frontera

Faculty, Staff and Student Publications

BACKGROUND: Sarcopenia, generally described as "aging-related loss of skeletal muscle mass and function", can occur secondary to a systemic disease.

AIM: This project aimed to study the prevalence of sarcopenia in chronic ambulatory stroke survivors and its associated risk factors using the two most recent diagnostic criteria.

DESIGN: A cross-sectional observational study.

SETTING: A scientific laboratory.

POPULATION: Chronic stroke.

METHODS: Twenty-eight ambulatory chronic stroke survivors (12 females; mean age=57.8±11.8 years; time after stroke=76±45 months), hand-grip strength, gait speed, and appendicular skeletal muscle mass (ASM) were measured to define sarcopenia. Risk factors, including motor impairment and spasticity, were identified using regression …

Aging After Stroke: How To Define Post-Stroke Sarcopenia And What Are Its Risk Factors?, Sheng Li, Javier Gonzalez-Buonomo, Jaskiran Ghuman, Xinran Huang, Aila Malik, Nuray Yozbatiran, Elaine Magat, Gerard E Francisco, Hulin Wu, Walter R Frontera

Faculty, Staff and Student Publications

BACKGROUND: Sarcopenia, generally described as "aging-related loss of skeletal muscle mass and function", can occur secondary to a systemic disease.

AIM: This project aimed to study the prevalence of sarcopenia in chronic ambulatory stroke survivors and its associated risk factors using the two most recent diagnostic criteria.

DESIGN: A cross-sectional observational study.

SETTING: A scientific laboratory.

POPULATION: Chronic stroke.

METHODS: Twenty-eight ambulatory chronic stroke survivors (12 females; mean age=57.8±11.8 years; time after stroke=76±45 months), hand-grip strength, gait speed, and appendicular skeletal muscle mass (ASM) were measured to define sarcopenia. Risk factors, including motor impairment and spasticity, were identified using regression …

Epigenetic Pathogenesis Of Neurological Disorders In Utero And Considerations For Genetic Counseling, Lauren Juga

Senior Honors Theses

Epigenetic modifications are a major focus of study in the pathogenesis of many disorders regarding metabolism, aging, neurodevelopment, and neurodegeneration. Epigenetic mechanisms are present throughout life but are especially vital to guiding fetal development. The precise timing of gene activation and deactivation guides stem cell differentiation through each embryonic stage. After exposure to environmental stimuli, gene expression can be altered by transcription factors, resulting in observable phenotypes and even pathology. Here, the epigenetic mechanisms responsible for the pathogenesis of neurodevelopmental and neuropsychiatric disorders are explored in response to environmental perturbations in utero. The present goal is to identify correlations between …

Pathogenic Tau Accelerates Aging-Associated Activation Of Transposable Elements In The Mouse Central Nervous System, Paulino Ramirez, Gabrielle Zuniga, Wenyan Sun, Adrian Beckmann, Elizabeth Ochoa, Sarah L Devos, Bradley Hyman, Gabriel Chiu, Ethan R Roy, Wei Cao, Miranda Orr, Virginie Buggia-Prevot, William J Ray, Bess Frost

Faculty, Staff and Student Publications

Transposable elements comprise almost half of the mammalian genome. A growing body of evidence suggests that transposable element dysregulation accompanies brain aging and neurodegenerative disorders, and that transposable element activation is neurotoxic. Recent studies have identified links between pathogenic forms of tau, a protein that accumulates in Alzheimer's disease and related "tauopathies," and transposable element-induced neurotoxicity. Starting with transcriptomic analyses, we find that age- and tau-induced transposable element activation occurs in the mouse brain. Among transposable elements that are activated at the RNA level in the context of brain aging and tauopathy, we find that the endogenous retrovirus (ERV) class …

Investigating The Mitochondrial Protein Mitoneet In C. Elegans Models Of Aging And Alzheimer's Disease, Jacob Ryan Boos

Graduate Theses, Dissertations, and Problem Reports (ETD)

Oxidative stress is an imbalance between reactive oxygen species production and elimination, favoring the former. Reactive oxygen species serve as important signaling molecules for physiological homeostasis. However, when produced in excess, these once important signaling molecules become detrimental, disrupting cellular functions, and ultimately leading to cell death. In aging, reactive oxygen species production is increased, accompanied with reductions in oxidative stress resistance, increasing the risk for developing age-related diseases including cardiovascular disease, cancer, stroke, and neurodegenerative diseases. The outer mitochondrial membrane iron-sulfur cluster containing protein mitoNEET (CISD1; gene CISD1) has shown to be a mediator of mitochondrial function and …

Enhancing Mask Activity In Dopaminergic Neurons Extends Lifespan In Flies, Xiaolin Tian

School of Medicine Faculty Publications

Dopaminergic neurons (DANs) are essential modulators for brain functions involving memory formation, reward processing, and decision-making. Here I demonstrate a novel and important function of the DANs in regulating aging and longevity. Overexpressing the putative scaffolding protein Mask in two small groups of DANs in flies can significantly extend the lifespan in flies and sustain adult locomotor and fecundity at old ages. This Mask-induced beneficial effect requires dopaminergic transmission but cannot be recapitulated by elevating dopamine production alone in the DANs. Independent activation of Gαs in the same two groups of DANs via the drug-inducible DREADD system also extends fly …

Dysregulation Of Systemic Immunity In Aging And Dementia, Jenny Lutshumba, Barbara S. Nikolajczyk, Adam D. Bachstetter

Pharmacology and Nutritional Sciences Faculty Publications

Neuroinflammation and the tissue-resident innate immune cells, the microglia, respond and contribute to neurodegenerative pathology. Although microglia have been the focus of work linking neuroinflammation and associated dementias like Alzheimer’s Disease, the inflammatory milieu of brain is a conglomerate of cross-talk amongst microglia, systemic immune cells and soluble mediators like cytokines. Age-related changes in the inflammatory profile at the levels of both the brain and periphery are largely orchestrated by immune system cells. Strong evidence indicates that both innate and adaptive immune cells, the latter including T cells and B cells, contribute to chronic neuroinflammation and thus dementia. Neurodegenerative hallmarks …

Acute Inflammatory Profiles Differ With Sex And Age After Spinal Cord Injury, Andrew N. Stewart, John L. Lowe, Ethan P. Glaser, Caitlin A. Mott, Ryan K. Shahidehpour, Katelyn E. Mcfarlane, William M. Bailey, Bei Zhang, John C. Gensel

Physiology Faculty Publications

Background

Sex and age are emerging as influential variables that affect spinal cord injury (SCI) recovery. Despite a changing demographic towards older age at the time of SCI, the effects of sex or age on inflammation remain to be elucidated. This study determined the sex- and age-dependency of the innate immune response acutely after SCI.

Methods

Male and female mice of ages 4- and 14-month-old received T9 contusion SCI and the proportion of microglia, monocyte-derived macrophages (MDM), and neutrophils surrounding the lesion were determined at 3- and 7-day post-injury (DPI) using flow cytometry. Cell counts of microglia and MDMs were …

Multimodal Neuroimaging Of Hiv And Aging, Brandon Lew

Theses & Dissertations

HIV infection remains a significant contributor to disease burden, and with the success of antiretroviral therapies, the population of people with HIV is aging. A growing literature suggests a relationship between HIV-infection and a profile of age advancement, most notably in molecular studies of epigenetics. However, despite the widely-known high prevalence of HIV-related brain atrophy, functional deficits, and HIV-associated neurocognitive disorder (HAND), epigenetic age advancement has not been linked to HIV-related changes in neuroimaging metrics.

We applied three neuroimaging methods, structural MRI, resting state functional MRI, and resting state MEG, to study the brain structure and function of 121 virally-suppressed …

Dystrophic Microglia Are Associated With Neurodegenerative Disease And Not Healthy Aging In The Human Brain, Ryan K. Shahidehpour, Rebecca E. Higdon, Nicole G. Crawford, Janna H. Neltner, Eseosa T. Ighodaro, Ela Patel, Douglas Price, Peter T. Nelson, Adam D. Bachstetter

Spinal Cord and Brain Injury Research Center Faculty Publications

Loss of physiological microglial function may increase the propagation of neurodegenerative diseases. Cellular senescence is a hallmark of aging; thus, we hypothesized age could be a cause of dystrophic microglia. Stereological counts were performed for total microglia, 2 microglia morphologies (hypertrophic and dystrophic) across the human lifespan. An age-associated increase in the number of dystrophic microglia was found in the hippocampus and frontal cortex. However, the increase in dystrophic microglia was proportional to the age-related increase in the total number of microglia. Thus, aging alone does not explain the presence of dystrophic microglia. We next tested if dystrophic microglia could …

Electrophysiological And Imaging Calcium Biomarkers Of Aging In Male And Female 5×Fad Mice, Adam O. Ghoweri, Lara Ouillette, Hilaree N. Frazier, Katie L. Anderson, Ruei-Lung Lin, John C. Gant, Rachel Parent, Shannon Moore, Geoffrey G. Murphy, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: In animal models and tissue preparations, calcium dyshomeostasis is a biomarker of aging and Alzheimer's disease that is associated with synaptic dysfunction, neuritic pruning, and dysregulated cellular processes. It is unclear, however, whether the onset of calcium dysregulation precedes, is concurrent with, or is the product of pathological cellular events (e.g., oxidation, amyloid-β production, and neuroinflammation). Further, neuronal calcium dysregulation is not always present in animal models of amyloidogenesis, questioning its reliability as a disease biomarker.

OBJECTIVE: Here, we directly tested for the presence of calcium dysregulation in dorsal hippocampal neurons in male and female 5×FAD mice on …

Immune Modulation As A Therapeutic Target In An Α-Synuclein Model Of Parkinson’S Disease, Meena Subhashini Subbarayan

USF Tampa Graduate Theses and Dissertations

Parkinson’s disease (PD) is the second most common neurodegenerative disorder affecting about 1.5 million people in the United States with more than 60,000 people diagnosed each year. It is classically characterized by four major symptoms: tremor, postural instability, stiffness in joints, and slow movement (bradykinesia). Pathologically PD is characterized by up to 70% loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) of midbrain and accumulation of presynaptic protein called α-synuclein (α-syn) within dopaminergic neurons that extend to the striatum. This disrupts the nigrostriatal pathway leading to the motor symptoms seen in PD patients. Microglia, the innate immune cells …

Neuronal Calcium Imaging, Excitability, And Plasticity Changes In The Aldh2-/- Mouse Model Of Sporadic Alzheimer's Disease, Adam O. Ghoweri, Peter Gagolewicz, Hilaree N. Frazier, John C. Gant, R. David Andrew, Brian M. Bennett, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Dysregulated signaling in neurons and astrocytes participates in pathophysiological alterations seen in the Alzheimer's disease brain, including increases in amyloid-β, hyperphosphorylated tau, inflammation, calcium dysregulation, and oxidative stress. These are often noted prior to the development of behavioral, cognitive, and non-cognitive deficits. However, the extent to which these pathological changes function together or independently is unclear.

OBJECTIVE: Little is known about the temporal relationship between calcium dysregulation and oxidative stress, as some reports suggest that dysregulated calcium promotes increased formation of reactive oxygen species, while others support the opposite. Prior work has quantified several key outcome measures associated with …

Cardiorespiratory Fitness Diminishes The Effects Of Age On White Matter Hyperintensity Volume, Nathan F. Johnson, Ahmed A. Bahrani, David K. Powell, Gregory A. Jicha, Brian T. Gold

Physical Therapy Faculty Publications

White matter hyperintensities (WMHs) are among the most commonly observed marker of cerebrovascular disease. Age is a key risk factor for WMH development. Cardiorespiratory fitness (CRF) is associated with increased vessel compliance, but it remains unknown if high CRF affects WMH volume. This study explored the effects of CRF on WMH volume in community-dwelling older adults. We further tested the possibility of an interaction between CRF and age on WMH volume. Participants were 76 adults between the ages of 59 and 77 (mean age = 65.36 years, SD = 3.92) who underwent a maximal graded exercise test and structural brain …

Indicators Of Mild Cognitive Impairment Associated With Language Processing And Production, Diana Julbe-Delgado

USF Tampa Graduate Theses and Dissertations

The research purpose of the present study was to (1) examine cognitive-linguistic features related to processing and production across a series of tasks that are representative of everyday discourse and (2) compare older adults with and without mild cognitive impairment (MCI) across linguistic features. Twenty-seven participants, including 12 individuals with- and 15 individuals without MCI, were enrolled from a larger study (Hudak et al., 2019). Cognitive status was initially assessed as part of the larger study using the Montreal Cognitive Assessment (MoCA; Nasreddine et al., 2005). Participants who scored ≤ 25 on the MoCA received a standardized neuropsychological evaluation and …

Brain Structure Changes Over Time In Normal And Mildly Impaired Aged Persons, Charles D. Smith, Linda J. Van Eldik, Gregory A. Jicha, Frederick A. Schmitt, Peter T. Nelson, Erin L. Abner, Richard J. Kryscio, Richard R. Murphy, Anders H. Andersen

Neurology Faculty Publications

Structural brain changes in aging are known to occur even in the absence of dementia, but the magnitudes and regions involved vary between studies. To further characterize these changes, we analyzed paired MRI images acquired with identical protocols and scanner over a median 5.8-year interval. The normal study group comprised 78 elders (25M 53F, baseline age range 70-78 years) who underwent an annual standardized expert assessment of cognition and health and who maintained normal cognition for the duration of the study. We found a longitudinal grey matter (GM) loss rate of 2.56 ± 0.07 ml/year (0.20 ± 0.04%/year) and a …

Mass Spectrometry Discovery-Based Proteomics To Examine Anti-Aging Effects Of The Nutraceutical Nt-020 In Rat Serum, Samantha M. Portis

USF Tampa Graduate Theses and Dissertations

Aging is a complex physiological process that leads to the deterioration of all cells and tissues throughout the body. Aging is a major risk factor for the onset of many degenerative diseases in both the central nervous system (CNS) and the periphery, but even nonpathological aging (“normal” aging) is associated with chronic inflammation, oxidative stress, and decreased stem cell proliferation and regenerative capacity. This decreased regenerative capacity in stem cell niches is thought to be a key component underlying the aging process and many disease states associated with aging.

While the exact biological mechanisms underlying impaired stem cell proliferation and …

Age Differences In Hippocampal Glutamate Modulation During Associative Learning And Memory: A Proton Functional Magnetic Resonance Spectroscopy (1h Fmrs) Study, Chaitali Anand

Wayne State University Dissertations

Episodic and associative memory decline is one of the earliest cognitive impairments in normal aging and among the defining cognitive features of Alzheimer’s disease (AD). Since, age-related cognitive decline gradually devolves into AD, with neuropathology preceding cognitive changes by many years, the identification of biomarkers of early disease progression is crucial. Reduction in glutamate, the main excitatory neurotransmitter involved in associative memory, in key brain regions such as the hippocampus, has been theorized as one of the cellular mechanisms underlying cognitive decline in aging and AD. A few neuroimaging studies that demonstrated a link between older adults’ weaker cognitive performance …

Thirty-Five Years Of Computerized Cognitive Assessment Of Aging — Where Are We Now?, Avital Sternin, Alistair Burns, Adrian M. Owen

Brain and Mind Institute Researchers' Publications

Over the past 35 years, the proliferation of technology and the advent of the internet have resulted in many reliable and easy to administer batteries for assessing cognitive function. These approaches have great potential for affecting how the health care system monitors and screens for cognitive changes in the aging population. Here, we review these new technologies with a specific emphasis on what they offer over and above traditional ‘paper-and-pencil’ approaches to assessing cognitive function. Key advantages include fully automated administration and scoring, the interpretation of individual scores within the context of thousands of normative data points, the inclusion of …

Non-Fasting High-Density Lipoprotein Is Associated With White Matter Microstructure In Healthy Older Adults, Nathan F. Johnson, Brian T. Gold, Dorothy Ross, Alison L. Bailey, Jody L. Clasey, Vedant Gupta, Steve W. Leung, David K. Powell

Physical Therapy Faculty Publications

A growing body of evidence indicates that biomarkers of cardiovascular risk may be related to cerebral health. However, little is known about the role that non-fasting lipoproteins play in assessing age-related declines in a cerebral biomarker sensitive to vascular compromise, white matter (WM) microstructure. High-density lipoprotein cholesterol (HDL-C) is atheroprotective and low-density lipoprotein cholesterol (LDL-C) is a major atherogenic lipoprotein. This study explored the relationships between non-fasting levels of cholesterol and WM microstructure in healthy older adults. A voxelwise and region of interest approach was used to determine the relationship between cholesterol and fractional anisotropy (FA). Participants included 87 older …

Using Genetic Diversity To Understand Susceptibility To Cognitive Decline In Aging And Alzheimer’S Disease, Sarah M. Neuner

Theses and Dissertations (ETD)

An individual's genetic makeup plays an important role in determining susceptibility to cognitive aging and transition to dementia such as Alzheimer's disease (AD). Identifying the specific genetic variants that contribute to cognitive aging and AD may aid in early diagnosis of at-risk patients, as well as identify novel therapeutics targets to treat or prevent development of symptoms. Challenges to identifying these specific genes in human studies include complex genetics, difficulty in controlling environmental factors, and limited access to human brain tissue. Here, we turned to genetically diverse mice from the BXD genetic reference panel (GRP) to overcome some of the …

Efficacy Of Leukemia Inhibitory Factor As A Therapeutic For Permanent Large Vessel Stroke Differs Among Aged Male And Female Rats, Stephanie M. Davis, Lisa A. Collier, Sarah J. Goodwin, Douglas E. Lukins, David K. Powell, Keith R. Pennypacker

Neurology Faculty Publications

Preclinical studies using rodent models of stroke have had difficulty in translating their results to human patients. One possible factor behind this inability is the lack of studies utilizing aged rodents of both sexes. Previously, this lab showed that leukemia inhibitory factor (LIF) promoted recovery after stroke through antioxidant enzyme upregulation. This study examined whether LIF promotes neuroprotection in aged rats of both sexes. LIF did not reduce tissue damage in aged animals, but LIF-treated female rats showed partial motor skill recovery. The LIF receptor (LIFR) showed membrane localization in young male and aged rats of both sexes after stroke. …

Micrornas And The Genetic Nexus Of Brain Aging, Neuroinflammation, Neurodegeneration, And Brain Trauma, Saumyendra N. Sarkar, Ashley E. Russell, Russell Elizabeth B. Engler-Chiurazzi, Keyana N. Porter, James W. Simpkins

Faculty & Staff Scholarship

ABSTRACT: Aging is a complex and integrated gradual deterioration of cellular activities in specific organs of the body, which is associated with increased mortality. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, neurovascular disorders, and neurodegenerative diseases. There are nine tentative hallmarks of aging. In addition, several of these hallmarks are increasingly being associated with acute brain injury conditions. In this review, we consider the genes and their functional pathways involved in brain aging as a means of developing new strategies for therapies targeted to the neuropathological processes themselves, but also as …

Can Self-Efficacy Training Improve Memory And Functional Activation In Older Adults With Mild Cognitive Impairment? A Proof-Of-Concept Intervention Study, Brainscan, Western University, Lindsay Nagamatsu, Derek Mitchell, Paul Minda, Amer Burhan, Becky Horst

Project Summaries

The goal of this study is to examine the changes in brain activity after a memory self-efficacy training program to better understand the mechanisms of memory self-efficacy. We will conduct a proof-of-concept six-week memory self-efficacy intervention in older adults with MCI, in order to demonstrate that self-efficacy impacts brain function. This will allow us to determine whether self-efficacy interventions may be a potential strategy for combating AD in the future.

Gender- And Region-Specific Changes In Estrogen Signaling In Aging Rat Brain Mitochondria, Christopher M. Evola, Tanner L. Hudson, Luping Huang, Adrian M. Corbett, Debra A. Mayes

Neuroscience, Cell Biology & Physiology Faculty Publications

Recently epidemiological studies suggest females lose neuroprotection from neurodegenerative diseases as they go through menopause. It has been hypothesized that this neuroprotection is hormone‐dependent. The current study characterized cell signaling molecules downstream of estrogen receptor beta that are known to play a role in memory, PKC, ERK, and connexin‐43, in regions of the brain associated with memory decline in an attempt to elucidate significant changes that occur post‐estrus. Total whole cell lysates were compared to isolated mitochondrial protein because mitochondrial function is known to be altered during aging. As hypothesized, protein concentrations differed depending on age, gender, and brain region. …

Neuroimaging Biomarkers Of Mtor Inhibition On Vascular And Metabolic Functions In Aging Brain And Alzheimer’S Disease, Jennifer Lee, Lucille M. Yanckello, David Ma, Jared D. Hoffman, Ishita Parikh, Scott Thalman, Bjoern Bauer, Anika M. S. Hartz, Fahmeed Hyder, Ai-Ling Lin

Pharmacology and Nutritional Sciences Faculty Publications

The mechanistic target of rapamycin (mTOR) is a nutrient sensor of eukaryotic cells. Inhibition of mechanistic mTOR signaling can increase life and health span in various species via interventions that include rapamycin and caloric restriction (CR). In the central nervous system, mTOR inhibition demonstrates neuroprotective patterns in aging and Alzheimer’s disease (AD) by preserving mitochondrial function and reducing amyloid beta retention. However, the effects of mTOR inhibition for in vivo brain physiology remain largely unknown. Here, we review recent findings of in vivo metabolic and vascular measures using non-invasive, multimodal neuroimaging methods in rodent models for brain aging and AD. …