A5004686282- Genetic Neurodegenerative Diseases
- Neurological disorders and treatments
- Memory and Neural Mechanisms
- Stress Responses and Cortisol
- Menopause: Health Impacts and Treatments
- Mitochondrial Function and Pathology
- Estrogen and related hormone effects
- Hormonal and reproductive studies
- Neonatal and fetal brain pathology
- Parkinson's Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Memory Processes and Influences
- Advanced Neuroimaging Techniques and Applications
- Sleep and Wakefulness Research
- Neuroscience and Neuropharmacology Research
- Anesthesia and Neurotoxicity Research
- Neuroendocrine regulation and behavior
- Retinal Diseases and Treatments
- Genetics and Neurodevelopmental Disorders
- Anesthesia and Sedative Agents
- Dysphagia Assessment and Management
- Muscle metabolism and nutrition
- Advanced MRI Techniques and Applications
- Hedgehog Signaling Pathway Studies
- Animal Behavior and Reproduction
Oregon National Primate Research Center
2011-2024
Oregon Health & Science University
2009-2023
Emory University
2014-2020
Reed College
2012
The properties of the cell types that are selectively vulnerable in Huntington's disease (HD) cortex, nature somatic CAG expansions mHTT these cells, and their importance CNS circuitry have not been delineated. Here, we employed serial fluorescence-activated nuclear sorting (sFANS), deep molecular profiling, single-nucleus RNA sequencing (snRNA-seq) motor-cortex samples from thirteen predominantly early stage, clinically diagnosed HD donors selected cingulate, visual, insular, prefrontal...
Abstract Recently, AAV2.retro, a new capsid variant capable of efficient retrograde transport in brain, was generated mice using directed evolution approach. However, it remains unclear to what degree will be recapitulated the substantially larger and more complex nonhuman primate (NHP) brain. Here, we compared biodistribution AAV2.retro with its parent serotype, AAV2, adult macaques following delivery into caudate putamen, brain regions which comprise striatum. While AAV2 transduction...
Inflammation has been linked to the development of nonmotor symptoms in Parkinson's disease (PD), which greatly impact patients' quality life and can often precede motor symptoms. Suitable animal models are critical for our understanding mechanisms underlying associated prodromal disturbances. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkey model is commonly seen as a "gold standard" that closely mimics clinical nigrostriatal dopaminergic loss PD, however...
Background Amyloid beta (Aβ) plaque density was examined in the amygdala of rhesus macaques, to elucidate influence age, diet and hormonal environment. Methods Luminex technology used measure cerebrospinal fluid (CSF) concentrations Aβ 40 42 across three decades, while immunohistochemistry examine amygdala. Results found be predominant isoform CSF, but neither or showed an age-related change, ratio only a marginal increase. Significantly fewer plaques were detected old ovariectomized animals...
Studies of the effect hormone therapy on cognitive function in menopausal women have been equivocal, part due to differences type and timing treatment. Here we cognitively tested aged female rhesus macaques (1) delayed response task spatial working memory, (2) a visuospatial attention that measured spatially temporally cued reaction times, (3) simple time as control for motor speed. After acquisition, animals were ovariectomized (OVX). Their performance was compared with intact controls 2...
We created a new nonhuman primate model of the genetic neurodegenerative disorder Huntington’s disease (HD) by injecting mixture recombinant adeno-associated viral vectors, serotypes AAV2 and AAV2.retro, each expressing fragment human mutant HTT ( mHTT ) into caudate putamen adult rhesus macaques. This modeling strategy results in expression huntingtin protein (mHTT) aggregate formation injected brain regions, as well dozens other cortical subcortical regions affected HD patients. queried...
To investigate the role of perirhinal cortex on development recognition measured by visual paired-comparison (VPC) task, infant monkeys with neonatal lesions and sham-operated controls were tested at 1.5, 6, 18, 48 months age VPC task color stimuli intermixed delays 10 s, 30 60 120 s. Monkeys showed an increase in novelty preference between 1.5 6 similar to controls, although these two ages, performance remained significantly poorer than that control animals. With age, animals deteriorated...
ABSTRACT The properties of the cell types that are selectively vulnerable in Huntington’s disease (HD) cortex, nature somatic CAG expansions mHTT these cells, and their importance CNS circuitry have not been delineated. Here we employed serial fluorescence activated nuclear sorting (sFANS), deep molecular profiling, single nucleus RNA sequencing (snRNAseq) to demonstrate layer 5a pyramidal neurons primary motor cortex other cortical areas HD donors. Extensive -CAG occur Betz 6a, 6b resilient...
Men show an age-related decline in the circulating levels of testosterone (T) and dehydroepiandrosterone sulfate (DHEAS). Consequently, there is interest developing androgen supplementation paradigms for old men that replicate hormone profiles young adults. In present study, we used (21-26 years old) male rhesus monkeys as a model to examine efficacy paradigm comprised oral T administration (12 mg/kg body weight, dissolved sesame oil/chocolate) evening, two DHEA administrations, 3 hr apart...
Macaques are the most common nonhuman primate (NHP) species used in neuroscience research. With advancement of many neuroimaging techniques, new studies beginning to apply multiple types vivo magnetic resonance imaging (MRI), such as structural (sMRI) with T1 and T2 weighted contrasts alongside diffusion weighed (DW) imaging. In involving rhesus macaques, this approach can be better understand micro-structural changes that occur during development, various disease states or normative aging....
Estradiol supplementation has been shown to enhance cognitive performance in old ovariectomized rhesus macaques (Macaca mulatta). To determine if similar benefits could be achieved perimenopausal animals using alternative hormonal supplements, we administered dehydroepiandrosterone (DHEA) ovary-intact female for ∼2.5 months. Using computerized touch screen memory tasks, including delayed response (DR) and matching-to-sample (DMS), observed improved with time all of the but failed detect a...
Huntington disease (HD) is a neurodegenerative disorder caused by an expanded polyglutamine (CAG) trinucleotide expansion in the huntingtin (<i>HTT</i>) gene that encodes mutant protein (mHTT). Visualization and quantification of cerebral mHTT will provide proxy for target engagement means to evaluate therapeutic interventions aimed at lowering brain. Here, we validated novel radioligand <sup>11</sup>C-labeled...
The contribution of the perirhinal cortex (PRh) to recognition memory is well characterized in adults, yet same lesions have limited effect on spatial locations. Here, we assessed whether outcomes will follow when are performed infancy. Monkeys with neonatal (Neo-PRh) and control animals were tested three operant tasks as they reached adulthood: Delayed Nonmatching-to-Sample (DNMS) Object Memory Span (OMS), measuring object recognition, Spatial (SMS), Although Neo-PRh did not impact...
Previous research indicated that monkeys with neonatal perirhinal lesions (Neo-PRh) were impaired on working memory (WM) tasks generated proactive interference, but performed normally devoid of interference (Weiss, Nadji, & Bachevalier, 2016). This finding suggested the early disrupted cognitive processes important for resolving such as behavioral inhibition and flexibility. To distinguish between these possibilities, same Neo-PRh their controls tested using Intradimensional/Extradimensional...
The perirhinal cortex is known to support high-level perceptual abilities as well familiarity judgments that may affect recognition memory. We tested whether poor or a loss of judgment contributed the memory impairments reported earlier in monkeys with PRh lesions received infancy (Neo-PRh) (Weiss and Bachevalier, 2016; Zeamer et al., 2015). Perceptual were assessed using version Visual Paired Comparison task black&white (B&W) stimuli, Constant Negative requiring repeated familiarization...
The lateral prefrontal cortex is known for its contribution to working memory (WM) processes in both humans and animals. Yet, recent studies indicate that the part of a broader network interconnected brain areas involved WM. Within medial temporal lobe (MTL) structures, perirhinal cortex, which has extensive direct interactions with orbital required form active/flexible representations familiar objects. However, participation WM not be fully explored. goal this study was assess effects...
Abstract Background Dopamine system dysfunction and altered glucose metabolism are implicated in Huntington's disease (HD), a neurological caused by mutant huntingtin (mHTT) expression. Objective The aim was to characterize alterations cerebral dopamine D 2 /D 3 receptor density utilization newly developed AAV‐mediated NHP model of HD that expresses mHTT throughout numerous brain regions. Methods Positron emission tomography (PET) imaging performed using [ 18 F]fallypride quantify 2‐[...
Circulating levels of dehydroepiandrosterone, a major adrenal steroid, show marked age-related decrease in both humans and nonhuman primates. Because this has been implicated cognitive decline, we administered supplementary dehydroepiandrosterone to perimenopausal rhesus macaques (Macaca mulatta) test for benefits. Although recognition memory improved, there was no benefit spatial working memory. To address the limitations study developed hormone supplementation regimen aged male that more...
The properties of the cell types that are most vulnerable in Huntington's disease (HD) cortex, nature somatic CAG expansions mHTT these cells, and their importance CNS circuitry have not been delineated. Here we employed serial fluorescence activated nuclear sorting (sFANS), deep molecular profiling, single nucleus RNA sequencing (snRNAseq) to demonstrate layer 5a pyramidal neurons selectively primary motor cortex other cortical areas HD donors. Extensive mHTT-CAG occur Betz 6a, 6b resilient...