Biomedical subjects

Tara L Moore

Publications and source records attributed to Tara L Moore.

10 recordsLinked to original sources

PubMed2025

Multicompartment Quantitative Proteomics Revealing Potential Mechanisms Underlying the Treatment Effects of Mesenchymal-Derived Extracellular Vesicles in a Monkey Model of Cortical Injury.

Previous studies have demonstrated that mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) enhance functional recovery after cortical injury in rhesus monkeys by reducing chronic microglial inflammation, neuronal damage, and myelination deficits. However, the signaling pathways underlying these therapeutic effects remain largely unexplored. In this study, employing a reliable quantitative proteomics platform UHR-IonStar, we identified the protein cargo of MSC-EVs infused intravenously to rhesus monkeys 24 h and 2 weeks post-injury to the motor cortex. We then analyzed global protein expression changes across cerebrospinal fluid (CSF), plasma, and brain tissue of MSC-EV-treated versus vehicle-treated female, aged rhesus monkeys. A total of 1241/431/4124 monkey proteins were reliably quantified in CSF/plasma/tissue samples, respectively. Longitudinal analysis of CSF and plasma samples highlighted a shift from MSC-EV modulation of inflammatory and metabolic proteins in plasma at early recovery (2 weeks), toward modulation of plasticity-related proteins in CSF and brain tissue at later stages (4 weeks). Further protein-protein interaction analysis identified potential MSC-EV targets related to complementary signaling, proteolysis, and aminoglycan stability, which aligned with our previous findings. This comprehensive, multicompartment monkey proteomics study advances understanding of MSC-EV contents and treatment effects, paving the way for novel treatment of cortical injury.

Animals↗

PubMed2006

Frontal connections and cognitive changes in normal aging rhesus monkeys: a DTI study.

Recent anatomical studies have found that cortical neurons are mainly preserved during the aging process while myelin damage and even axonal loss is prominent throughout the forebrain. We used diffusion tensor imaging (DT-MRI) to evaluate the hypothesis that during the process of normal aging, white matter changes preferentially affect the integrity of long corticocortical association fiber tracts, specifically the superior longitudinal fasciculus II and the cingulum bundle. This would disrupt communication between the frontal lobes and other forebrain regions leading to cognitive impairments. We analyzed DT-MRI datasets from seven young and seven elderly behaviorally characterized rhesus monkeys, creating fractional anisotropy (FA) maps of the brain. Significant age-related reductions in mean FA values were found for the superior longitudinal fasciculus II and the cingulum bundle, as well as the anterior corpus callosum. Comparison of these FA reductions with behavioral measures demonstrated a statistically significant linear relationship between regional FA and performance on a test of executive function. These findings support the hypothesis that alterations to the integrity of these long association pathways connecting the frontal lobe with other forebrain regions contribute to cognitive impairments in normal aging. To our knowledge this is the first investigation reporting such alterations in the aging monkey.

Aging↗

PubMed2005

Executive system dysfunction occurs as early as middle-age in the rhesus monkey.

As our understanding of age-related cognitive decline advances, studies are now focusing on identification of those areas of cognitive function that undergo the first changes with age. In the present study, in order to determine whether executive function is sensitive to the aging process, we assessed the performance of 16 monkeys of middle-age (12-19 years of age) on the conceptual set-shifting task, an analogue of the Wisconsin Card Sorting Test (WCST). We compared their performance to that of seven young adult (5-9 years of age) and 18 aged monkeys (20-30). The findings showed that middle-aged monkeys, like those of advanced age, were significantly impaired on the conceptual set-shifting task (CSST). These findings parallel those of recent studies in humans demonstrating an increase in perseverative errors on the WCST by middle-aged as well as aged individuals and, in turn, support the notion that disruption of executive function is one of the earliest changes in cognition to occur in normal aging.

Age Factors↗

PubMed2005

A non-human primate test of abstraction and set shifting: an automated adaptation of the Wisconsin Card Sorting Test.

Functional assessment of the prefrontal cortices in the non-human primate began with the seminal work of Jacobsen in the 1930s. However, despite nearly 70 years of research, the precise nature of the cognitive function of this region remains unclear. One factor that has limited progress in this endeavor has been the lack of behavioral tasks that parallel most closely those used with humans. In the present study, we describe a test for the non-human primate that was adapted from the Wisconsin Card Sorting Task (WCST), perhaps the most widely used test of prefrontal cognitive function in humans. Our adaptation of this task, the Conceptual Set-Shifting Task (CSST), uses learning criteria and stimuli nearly identical to those of the WCST. The CSST requires the animal to initially form a concept by establishing a pattern of responding to a given stimulus class, maintain responding to that stimulus class, and then shift to a different stimulus class when the reward contingency changes. The data presented here establishes baseline performance on the CSST for young adult rhesus monkeys and demonstrates that components of prefrontal cognitive function can be effectively assessed in the non-human primate in a manner that parallels the clinical assessment of humans.

Animals↗

PubMed2005

Cognitive impairment in aged rhesus monkeys associated with monoamine receptors in the prefrontal cortex.

The "frontal aging hypothesis" has been proposed by many researchers suggesting that the earliest and most severe age-related changes in the cortex occur in the frontal lobes. Two of these changes include decreases in cognitive functions mediated by the prefrontal cortex (PFC) and significant decreases in norepinephrine (NE) and dopamine (DA). To investigate whether the changes in these neurotransmitter systems are directly related to the cognitive decline seen in aging we utilized the rhesus monkey as a model of normal human aging. Our goal was to determine if age-related changes in cognition is associated with changes in norepinephrine and dopamine receptor binding density in the PFC. Eight young monkeys between five and ten years of age (six males and two female) and eight aged monkeys between 25 and 32 years of age (five males and three females) were behaviorally characterized. Subsequently on-the-slide in vitro binding assays were used to quantify the alpha-1 adrenergic, alpha-2 adrenergic and DA1 receptors as well as the NE and DA uptake receptors. Aged animals as a group demonstrated significant cognitive impairments and aging produced a significant decrease in alpha-1 adrenergic and alpha-2 adrenergic receptor binding in the PFC but no significant change in binding for the DA1 receptor or the NE or DA uptake receptors. Further analysis revealed a significant relationship between monoamine receptor binding and cognitive performance on three tasks: delayed non-matching to sample, delayed recognition span test and the conceptual set-shifting task.

Adrenergic alpha-Agonists↗

PubMed2005

Sex, age, and training modulate spatial memory in the rhesus monkey (Macaca mulatta).

The authors tested 90 rhesus monkeys (Macaca mulatta) on a task of spatial memory, the spatial Delayed Recognition Span Test. The results showed that performance declined significantly with age, males had greater scores than females, and the rate of apparent decline with age was greater in males than in females. Both working and reference memory declined with age, but only working memory showed sex differences. The authors compared these data with that of 22 monkeys who were trained on a simpler version of the task before formal testing. Training had no effect on males but dramatically improved working memory in young females. The results confirm a male advantage in spatial working memory at a young age and confirm a greater decline with age in males than in females. It is important to note that prior training completely reverses the deficits of young females.

Age Factors↗

PubMed2003

Fatigue of bovine trabecular bone.

Fatigue loading of bone, from the activities of daily living in the elderly, or from prolonged exercise in the young, can lead to increased risk of fracture. Elderly patients with osteoporosis are particularly prone to fragility fractures of the vertebrae, where load is carried primarily by trabecular bone. In this study, specimens of bovine trabecular bone were loaded in compressive fatigue at four different normalized stresses to one of six maximum strains. The resulting change in modulus and residual strain accumulation were measured over the life of the fatigue test. The number of cycles to reach a given maximum compressive strain increased with decreasing normalized stress. Modulus reduction and specimen residual strain increased with increasing maximum compressive strain, but few differences were observed between specimens loaded to the same maximum strain at different normalized stresses.

Adaptation, Physiological↗

PubMed2003

Fatigue microdamage in bovine trabecular bone.

Microdamage, in the form of small cracks, may accumulate in trabecular bone loaded in fatigue. Specimens of bovine trabecular bone were loaded in compressive fatigue at one of four normalized stresses and loading was stopped after the specimens reached one of six maximum strains. Microdamage was identified using a fluorochrome staining technique, and microdamage parameters, including the number of damaged trabeculae and the damaged area fraction, were measured. No microdamage was observed during loading to strains below the yield strain; at higher strains, all microdamage parameters increased with increasing maximum compressive strain. Few significant differences were observed in the type or amount of microdamage accumulation between specimens loaded to the same maximum strain at different normalized stresses; however, more trabecular fractures were observed at high numbers of cycles, which corresponded to low normalized stresses.

Adaptation, Physiological↗

PubMed2002

Impairment of executive function induced by hypertension in the rhesus monkey (Macaca mulatta).

The effects of chronic, untreated hypertension on executive function were investigated in a nonhuman primate model of hypertensive cerebrovascular disease. Executive function was assessed with the Conceptual Set-Shifting Task (CSST). a task adapted from the human Wisconsin Card Sorting Test (WCST). Like the WCST, the CSST requires abstraction of a stimulus set, followed by a series of set shifts. Performance on the CSST by 7 young adult monkeys (Macaca mulatta) with surgically induced hypertension was compared with that of 6 normotensive monkeys. The hypertensive group was significantly impaired relative to the normotensive group in abstraction and set shifting. Although the neural basis of this impairment is unclear, evidence from studies with humans and monkeys suggests that the prefrontal cortex may be the locus for this effect of hypertension.

Animals↗

PubMedDate not supplied

Impairment in abstraction and set shifting in aged rhesus monkeys.

Understanding the nature of changes in cognition with aging has increased in importance as the number of individuals over the age of 65 years grows. To date, studies have demonstrated that age-related changes occur most extensively in the cognitive domains of memory and executive function. Whereas a large number of studies have been conducted about the effects of aging on memory, far less have explored the effects of aging on the so called "executive function" which include abilities essential for successful performance of higher level activities of daily living. As part of our ongoing effort to better characterize these changes, we assessed executive function in a non-human primate model of normal human aging using the Conceptual Set Shifting Task (CSST). This recently developed task assesses abstraction, concept formation and set shifting in the monkey in a way analogous to the Wisconsin Card Sorting Test (WCST) in humans. Relative to young adult monkeys, aged monkeys evidenced significant difficulty in both acquisition and performance on this task, and moreover, demonstrated a high degree of perseverative responding. The pattern of performance displayed by the aged monkeys suggests an age-related decline in prefrontal cortex (PFC) functioning.

Aging↗