Neuroscience and Neurobiology Commons^™

Aβ Vaccination In Combination With Behavioral Enrichment In Aged Beagles: Effects On Cognition, Aβ, And Microhemorrhages, Paulina R. Davis, Ginevra Giannini, Karin Rudolph, Nathaniel Calloway, Christopher M. Royer, Tina L. Beckett, M. Paul Murphy, Frederick Bresch, Dieter Pagani, Thomas Platt, Xiaohong Wang, Amy Skinner Donovan, Tiffany L. Sudduth, Wenjie Lou, Erin L. Abner, Richard J. Kryscio, Donna M. Wilcock, Edward G. Barrett, Elizabeth Head

Sanders-Brown Center on Aging Faculty Publications

Beta-amyloid (Aβ) immunotherapy is a promising intervention to slow Alzheimer’s disease (AD). Aging dogs naturally accumulate Aβ and show cognitive decline. An active vaccine against fibrillar Aβ 1–42 (VAC) in aged beagles resulted in maintenance but not improvement of cognition along with reduced brain Aβ. Behavioral enrichment (ENR) led to cognitive benefits but no reduction in Aβ. We hypothesized cognitive outcomes could be improved by combining VAC with ENR in aged dogs. Aged dogs (11–12 years) were placed into 4 groups: (1) control/control (C/C); (2) control/VAC (C/V); (3) ENR/control (E/C); (4) ENR and VAC (E/V) and treated for 20 months. …

The Default Mode Network And Executive Function: Influence Of Age, White Matter Connectivity, And Alzheimer’S Pathology, Christopher A. Brown

Theses and Dissertations--Neuroscience

The default mode network (DMN) consists of a set of interconnected brain regions supporting autobiographical memory, our concept of the self, and the internal monologue. These processes must be maintained at all times and consume the highest amount of the brain’s energy during its baseline state. However, when faced with an active, externally-directed cognitive task, the DMN shows a small, but significant, decrease in activity. The reduction in DMN activity during the performance of an active, externally-directed task compared to a baseline state is termed task-induced deactivation (TID), which is thought to ‘free-up’ resources required to respond to external demands. …

Age- And Sex-Related Changes In Fasting Plasma Glucose And Lipoprotein In Cynomolgus Monkeys, Feng Yue, Guodong Zhang, Rongping Tang, Zhouquan Zhang, Liqiong Teng, Zhiming Zhang

Neuroscience Faculty Publications

Background: The age-related dysfunction of glucose and lipid metabolism has a long-standing relationship with cardiovascular and neurodegenerative disease. However, the effects of metabolic dysfunction on men and women are different. Reasons for these sex differences remains unclear. Cynomolgus monkeys have been used, in the past, for the study of human metabolic diseases due to their biologically proximity to humans. Nevertheless, few studies to date have focused on both age- and sex-related differences in glucose and lipid metabolism. The present study was designed to specifically address these questions by using a large cohort of cynomolgus monkeys (N = 1,399) including …

White Matter Microstructure Contributes To Age-Related Declines In Task-Induced Deactivation Of The Default Mode Network, Christopher A. Brown, Jonathan G. Hakun, Zude Zhu, Nathan F. Johnson, Brian T. Gold

Neuroscience Faculty Publications

Task-induced deactivations within the brain’s default mode network (DMN) are thought to reflect suppression of endogenous thought processes to support exogenous goal-directed task processes. Older adults are known to show reductions in deactivation of the DMN compared to younger adults. However, little is understood about the mechanisms contributing to functional dysregulation of the DMN in aging. Here, we explored the relationships between functional modulation of the DMN and age, task performance and white matter (WM) microstructure. Participants were 117 adults ranging from 25 to 83 years old who completed an fMRI task switching paradigm, including easy (single) and difficult (mixed) …

Apoe Stabilization By Exercise Prevents Aging Neurovascular Dysfunction And Complement Induction, Ileana Soto Reyes, Leah C. Graham, Hannah J. Richter, Stephen N. Simeone, Jake E. Radell, Weronika Grabowska, W. Keith Funkhouser, Megan C. Howell, Gareth R. Howell

College of Science & Mathematics Departmental Research

Aging is the major risk factor for neurodegenerative diseases such as Alzheimer's disease, but little is known about the processes that lead to age-related decline of brain structures and function. Here we use RNA-seq in combination with high resolution histological analyses to show that aging leads to a significant deterioration of neurovascular structures including basement membrane reduction, pericyte loss, and astrocyte dysfunction. Neurovascular decline was sufficient to cause vascular leakage and correlated strongly with an increase in neuroinflammation including up-regulation of complement component C1QA in microglia/monocytes. Importantly, long-term aerobic exercise from midlife to old age prevented this age-related neurovascular decline, …

Disease-Related Microglia Heterogeneity In The Hippocampus Of Alzheimer's Disease, Dementia With Lewy Bodies, And Hippocampal Sclerosis Of Aging, Adam D. Bachstetter, Linda J. Van Eldik, Frederick A. Schmitt, Janna H. Neltner, Eseosa T. Ighodaro, Scott J. Webster, Ela Patel, Erin L. Abner, Richard J. Kryscio, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Introduction: Neuropathological, genetic, and biochemical studies have provided support for the hypothesis that microglia participate in Alzheimer's disease (AD) pathogenesis. Despite the extensive characterization of AD microglia, there are still many unanswered questions, and little is known about microglial morphology in other common forms of age-related dementia: particularly, dementia with Lewy bodies (DLB) and hippocampal sclerosis of aging (HS-Aging). In addition, no prior studies have attempted to compare and contrast the microglia morphology in the hippocampus of various neurodegenerative conditions.

Results: Here we studied cases with pathologically-confirmed AD (n = 7), HS-Aging (n = 7), AD + HS-aging …

Efficient In Vitro Development Of Photoreceptors From Human Pluripotent Stem Cells, Joseph C. Reynolds

Dissertations, Masters Theses, Capstones, and Culminating Projects

Degeneration of the rod and cone photoreceptors in the human retina is among the most common causes of blindness. Replacing these damaged photoreceptors may help to restore vision. Repairing the damaged retina relies on the insertion of new, healthy cells. Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are two possible sources of photoreceptors to restore vision. Previous data shows that human ES cells and iPS cells can be differentiated into photoreceptors and transplanted into the eye to restore some vision. However, this process is inefficient, and costly. Here, we show a new method for inducing photoreceptor production …

Effects Of 17Β-Estradiol On Learning And Memory And Strategy Use During A Hole Board Spatial Navigation Task In Aged Male Rats, Megan Berthiaume

Seton Hall University Dissertations and Theses (ETDs)

Treatment with 17β- estradiol has been shown to ameliorate age related deficits in spatial learning and memory as well as to promote the use of an allocentric strategy during spatial navigation. While the majority of research using 17β- estradiol has been done using females rodents, there have been studies showing an improvement in spatial learning and memory and promoted use of allocentric strategies in spatial navigation in males as well. In males testosterone (T) is metabolized into estradiol by aromatase. As circulating levels of T decline with aging there is less available T to be metabolized into estradiol. The current …

Neural Correlates Of Audiovisual Speech Perception In Aphasia And Healthy Aging, Sarah H. Baum

Dissertations and Theses (Open Access)

Understanding speech in face-to-face conversation utilizes the integration of multiple pieces of information, most importantly the auditory vocal sounds and visual lip movements. Prior studies of the neural underpinnings of audiovisual integration in the brain have provided converging evidence to suggest that neurons within the left superior temporal sulcus (STS) provide a critical neural hub for the integration of auditory and visual information in speech. While most studies of audiovisual processing focus on neural mechanisms within healthy, young adults, we currently know very little about how changes to the brain can affect audiovisual integration in speech. To examine this further, …

The Effects Of Aging And Injury On The Murine Ependymal Barrier And Subventricular Zone, John J. Peters

Honors Scholar Theses

Previous research has shown that numerous age-related changes occur in the subventricular zone (SVZ) and diminish the neurogenic output of the region. Here, various age-related changes in the structure of the lateral ventricle, the ependymal barrier, and the SVZ were examined. It was found that the walls of the lateral ventricles move together, adhere, and eventually fuse. This results in a degradation of the SVZ. Other changes associated with aging were found, including ependymal cell stretching, heightened, ependymal repair, changes in CSF flow velocity and dynamics, and altered ependymal cell polarity. These changes may be related to the process of …

Exercise Alters Glial Cell Line-Derived Neurotrophic Factor (Gdnf) Protein Content In The Spinal Cord, Monica Janine Mccullough

Dissertations

Neurotrophic factors may play a role in exercise-induced neuroprotective effects; however, it is not known if exercise mediates changes in glial cell line-derived neurotrophic factor (GDNF) protein levels in the spinal cord. The aim of the studies described herein was to determine if exercise alters GDNF protein expression in the lumbar spinal cord of healthy and diseased animals. The lumbar spinal cord was analyzed from adult rats aged 6-, 12-, 18- and 24-months, and from transgenic amyotrophic lateral sclerosis (ALS) mice and wild-type mice aged 3 months. Animals had undergone either forced wheel running, voluntary wheel running or swimming for …

Lifelong Bilingualism Maintains Neural Efficiency For Cognitive Control In Aging, Brian T. Gold, Chobok Kim, Nathan F. Johnson, Richard J. Kryscio, Charles D. Smith

Neuroscience Faculty Publications

Recent behavioral data have shown that lifelong bilingualism can maintain youthful cognitive control abilities in aging. Here, we provide the first direct evidence of a neural basis for the bilingual cognitive control boost in aging. Two experiments were conducted, using a perceptual task-switching paradigm, including a total of 110 participants. In Experiment 1, older adult bilinguals showed better perceptual switching performance than their monolingual peers. In Experiment 2, younger and older adult monolinguals and bilinguals completed the same perceptual task-switching experiment while functional magnetic resonance imaging (fMRI) was performed. Typical age-related performance reductions and fMRI activation increases were observed. However, …

Effects Of Intranasally Administered Dnsp-11 On The Central Dopamine System Of Normal And Parkinsonian Fischer 344 Rats, James H. Sonne

Theses and Dissertations--Neuroscience

Due to the blood-brain barrier, delivery of many drugs to the brain has required intracranial surgery which is prone to complication. Here we show that Dopamine Neuron Stimulating Peptide 11 (DNSP-11), following non-invasive intranasal administration, protects dopaminergic neurons from a lesion model of Parkinson’s disease in the rat. A significant and dose-dependent increase in an index of dopamine turnover (the ratio of DOPAC to dopamine) was observed in the striatum of normal young adult Fischer 344 rats by whole-tissue neurochemistry compared to vehicle administered controls.

Among animals challenged with a moderate, unilateral 6-hydroxy-dopamine (6-OHDA) lesion of the substantia nigra, those …

Changes In Sleep Architecture And Cognition With Age And Psychosocial Stress: A Study In Fischer 344 Rats, Heather M. Buechel

Theses and Dissertations--Pharmacology and Nutritional Sciences

Changes in both sleep architecture and cognition are common with age. Typically these changes have a negative connotation: sleep fragmentation, insomnia, and deep sleep loss as well as forgetfulness, lack of focus, and even dementia and Alzheimer’s disease. Research has shown that psychosocial stressors, such as isolation from family and friends or loss of a loved one can also have significant negative effects on sleep architecture and cognitive capabilities. This leaves the elderly in a particularly vulnerable situation: suffering from cognitive decline and sleep dysregulation already, and more likely to respond negatively to psychosocial stressors. Taking all of these factors …

Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction In A Mouse Model That Exhibits Age-Dependent Progression Of Alzheimer's Disease-Related Pathology, Adam D. Bachstetter, Christopher M. Norris, Pradoldej Sompol, Donna M. Wilcock, Danielle Goulding, Janna H. Neltner, Daret St. Clair, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Overproduction of proinflammatory cytokines in the CNS has been implicated as a key contributor to pathophysiology progression in Alzheimer's disease (AD), and extensive studies with animal models have shown that selective suppression of excessive glial proinflammatory cytokines can improve neurologic outcomes. The prior art, therefore, raises the logical postulation that intervention with drugs targeting dysregulated glial proinflammatory cytokine production might be effective disease-modifying therapeutics if used in the appropriate biological time window. To test the hypothesis that early stage intervention with such drugs might be therapeutically beneficial, we examined the impact of intervention with MW01-2-151SRM (MW-151), an experimental therapeutic that …

Aging Is Associated With Positive Responding To Neutral Information But Reduced Recovery From Negative Information, Carien M. Van Reekum, Stacey M. Schaefer, Regina C. Lapate, Catherine J. Norris, Lawrence L. Greischar, Richard J. Davidson

Dartmouth Scholarship

Studies on aging and emotion suggest an increase in reported positive affect, a processing bias of positive over negative information, as well as increasingly adaptive regulation in response to negative events with advancing age. These findings imply that older individuals evaluate information differently, resulting in lowered reactivity to, and/or faster recovery from, negative information, while maintaining more positive responding to positive information. We examined this hypothesis in an ongoing study on Midlife in the US (MIDUS II) where emotional reactivity and recovery were assessed in a large number of respondents (N = 159) from a wide age range (36–84 …

Contextual Information And Memory For Unfamiliar Tunes In Older And Younger Adults, Samantha A. Deffler, Andrea R. Halpern

Faculty Journal Articles

We examined age differences in the effectiveness of multiple repetitions and providing associative facts on tune memory. For both tune and fact recognition, three presentations were beneficial. Age was irrelevant in fact recognition, but older adults were less successful than younger in tune recognition. The associative fact did not affect young adults' performance. Among older people, the neutral association harmed performance; the emotional fact mitigated performance back to baseline. Young adults seemed to rely solely on procedural memory, or repetition, to learn tunes. Older adults benefitted by using emotional associative information to counteract memory burdens imposed by neutral associative information.

The Role Of Nogo-A In Memory And Neuronal Plasticity In The Aged Rodent Brain, Rebecca Lynn Gillani

Dissertations

The long-term effects of stroke often include cognitive impairments, but other than cognitive rehabilitation, which is often not fully successful, there is no intervention to treat cognitive impairments in stroke survivors. Our laboratory has previously shown that immunotherapy directed against the Nogo-A protein, which is enriched on oligodendrocytes, improves recovery of skilled forelimb sensorimotor function in adult and aged rats after an ischemic stroke lesion to the sensorimotor cortex. Furthermore, this recovery was correlated with axonal sprouting from intact pathways to denervated areas, as well as dendritic sprouting and increased dendritic spine density in the contralateral sensorimotor cortex. In the …

Changes In The Proliferation Of The Subventricular Zone Neural Stem Cell Pool Throughout Aging In The Murine Brain, Olayinka Edwards

Honors Scholar Theses

Previous studies regarding subventricular zone (SVZ) neural stem cells (NSCs) have either observed global changes in the SVZ niche containing NSCs or an impure NSC population. By imaging wholemount preparations of mouse brains and staining with molecular markers specific for proliferating NSC nuclei, the study was able to give a more accurate depiction of the SVZ NSC population than its predecessors. This study will quantify the percentage of proliferating NSCs at various ages of adult murine brain development in order to elucidate a possible correlation between NSC division kinetics and the declining neurogenic output witnessed with aging.

Dopaminergic Innervation Of The Subventricular Zone In The Murine Brain, Linda Beth Drozdowicz

Honors Scholar Theses

The subventricular zone (SVZ) is one of two areas in the brain that, in a healthy mouse, continually generate neurons throughout adulthood. While it was previously thought that only the A9 neurons of the substantia nigra sent dopaminergic afferents to the SVZ, recent studies suggest that the A10 neurons of the ventral tegmental area may innervate this area. This project has aimed to discover which, if either, model is correct.

Examination of the Aphakia (AK) mouse was used to determine the role of distinct midbrain regions in SVZ regulation. Additionally, intraperitoneal injections of the chemical MPTP were used to deduce …

Aging Influences The Neural Correlates Of Lexical Decision But Not Automatic Semantic Priming, Brian T. Gold, Anders H. Andersen, Greg A. Jicha, Charles D. Smith

Neuroscience Faculty Publications

Human behavioral data indicate that older adults are slower to perform lexical decisions (LDs) than young adults but show similar reaction time gains when these decisions are primed semantically. The present study explored the functional neuroanatomic bases of these frequently observed behavioral findings. Young and older groups completed unprimed and primed LD tasks while functional magnetic resonance imaging (fMRI) was recorded, using a fully randomized trial design paralleling those used in behavioral research. Results from the unprimed task found that age-related slowing of LD was associated with decreased activation in perceptual extrastriate regions and increased activation in regions associated with …

Examining Neurophysiological Evidence Of Age-Related Interactions Of Sensory And Cognitive Processes During Speech Processing, Cady Kristen Block

Psychology Theses & Dissertations

The present study sought to examine the contribution of sensory and cognitive factors on speech processing as evidenced by ERP measures and to find support for the Sensory Cognitive Interaction Theory (SCIT) and the Effortfulness Hypothesis in that older adults. who experience sensory deficits with normal aging. must put forth increased effort during early sensory stages of speech processing that may compromise subsequent semantic performance and recall of information. In the present investigation. younger and older adults performed a sentence verification task at low and high presentation levels (PL). Accuracy and response time to sentence verifications were assessed along with …

The Effects Of Aging And Musical Experience On The Representation Of Tonal Hierarchies, Andrea R. Halpern, Seyeul Kwak, James C. Bartlett, W. Jay Dowling

Faculty Journal Articles

Two experiments explored the representation of the tonal hierarchy in Western music among older (aged 60 to 80) and younger (aged 15 to 22) musicians and nonmusicians. A probe tone technique was used: 4 notes from the major triad were presented, followed by 1 note chosen from the 12 notes of the chromatic scale. Whereas musicians had a better sense of the tonal hierarchy than nonmusicians, older adults were no worse than younger adults in differentiating the notes according to musical principles. However, older adults were more prone than younger adults to classify the notes by frequency proximity (pitch height) …