A5049533183- Gut microbiota and health
- Alzheimer's disease research and treatments
- Tryptophan and brain disorders
- Parkinson's Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurological disorders and treatments
- Pluripotent Stem Cells Research
- Nerve injury and regeneration
- Dysphagia Assessment and Management
- Diet and metabolism studies
- Biochemical Analysis and Sensing Techniques
- HIV Research and Treatment
- Olfactory and Sensory Function Studies
- Immune cells in cancer
- Barrier Structure and Function Studies
- Clostridium difficile and Clostridium perfringens research
- Xenotransplantation and immune response
- Cancer Cells and Metastasis
- CRISPR and Genetic Engineering
- Gastroesophageal reflux and treatments
- Neurogenesis and neuroplasticity mechanisms
- Autoimmune Neurological Disorders and Treatments
- Neuroscience of respiration and sleep
- Ginkgo biloba and Cashew Applications
- Sleep and Wakefulness Research
University of Chicago
2018-2024
Rush University Medical Center
2009-2018
State Street (United States)
2018
Rush University
2011-2017
The pace of nigrostriatal degeneration, both with regards to striatal denervation and loss melanin tyrosine hydroxylase-positive neurons, is poorly understood especially early in the Parkinson's disease process. This study investigated extent degeneration patients at different durations from time diagnosis. Brains (n=28) post-diagnostic intervals 1-27 years normal elderly control subjects (n=9) were examined. Sections post-commissural putamen substantia nigra pars compacta processed for...
Parkinson's disease (PD) is the second most common neurodegenerative disorder of aging. The pathological hallmark PD neuronal inclusions termed Lewy bodies whose main component alpha-synuclein protein. finding these in intestinal enteric nerves led to hypothesis that intestine might be an early site response environmental toxin or pathogen. One potential mechanism for toxin(s) and proinflammatory luminal products gain access mucosal tissue promote oxidative stress compromised barrier...
Abstract The diagnosis of Parkinson's disease rests on motor signs advanced central dopamine deficiency. There is an urgent need for biomarkers. Clinicopathological evidence suggests that α‐synuclein aggregation, the pathological signature disease, can be detected in gastrointestinal tract neurons disease. We studied whether we could demonstrate pathology specimens from unprepped flexible sigmoidoscopy distal sigmoid colon early subjects with also looked 3‐nitrotyrosine, a marker oxidative...
Abstract Background: Despite clinicopathological evidence that Parkinson's disease (PD) may begin in peripheral tissues, identification of premotor is not yet possible. Alpha‐synuclein aggregation underlies pathology, and its presence tissues be a reliable biomarker. Objective: We sought alpha‐synuclein pathology colonic before the development characteristic motor symptoms. Methods: Old colon biopsy samples were available for three subjects with PD. Biopsies obtained 2‐5 years PD onset....
Objective Recent evidence suggesting an important role of gut-derived inflammation in brain disorders has opened up new directions to explore the possible gut-brain axis neurodegenerative diseases. Given prominence dysbiosis and colonic dysfunction patients with Parkinson’s disease (PD), we propose that toll-like receptor 4 (TLR4)-mediated intestinal could contribute central PD-related neurodegeneration. Design To test this hypothesis performed studies both human tissue a murine model PD....
We demonstrated that an antibiotic cocktail (ABX)-perturbed gut microbiome is associated with reduced amyloid-β (Aβ) plaque pathology and astrogliosis in the male amyloid precursor protein (APP)SWE/presenilin 1 (PS1)ΔE9 transgenic model of Aβ amyloidosis. now show independent, aggressive APPSWE/PS1L166P (APPPS1-21) mouse amyloidosis, ABX-perturbed a reduction alterations microglial morphology, thus establishing generality phenomenon. Most importantly, these latter occur only brains mice, not...
Tau-mediated neurodegeneration is a hallmark of Alzheimer's disease. Primary tauopathies are characterized by pathological tau accumulation and neuronal synaptic loss. Apolipoprotein E (ApoE)-mediated neuroinflammation involved in the progression tau-mediated neurodegeneration, emerging evidence suggests that gut microbiota regulates an APOE genotype-dependent manner. However, causal link between lacking. In this study, we genetically engineered mouse model tauopathy expressing human ApoE...
Abstract It has recently become well-established that there is a connection between Alzheimer’s disease pathology and gut microbiome dysbiosis. We have previously demonstrated antibiotic-mediated microbiota perturbations lead to attenuation of Aβ deposition, phosphorylated tau accumulation, disease-associated glial cell phenotypes in sex-dependent manner. In this regard, we were intrigued by the finding marine-derived oligosaccharide, GV-971, was reported alter reduce amyloidosis 5XFAD mouse...
Abstract In preceding efforts, we demonstrated that antibiotic (ABX) cocktail-mediated perturbations of the gut microbiome in two independent transgenic lines, termed APP SWE / PS1 ΔE9 and APPPS1-21, leads to a reduction Aβ deposition male mice. To determine whether these observed reductions cerebral amyloidosis are specific any individual or require synergistic effects several antibiotics, treated APPPS1-21 mice with either ABX an cocktail assessed amyloid deposition. Specifically, were...
We previously demonstrated that lifelong antibiotic (ABX) perturbations of the gut microbiome in male APPPS1-21 mice lead to reductions amyloid β (Aβ) plaque pathology and altered phenotypes plaque-associated microglia. Here, we show a short, 7-d treatment preweaned with high-dose ABX is associated Aβ amyloidosis, plaque-localized microglia morphologies, Aβ-associated degenerative changes at 9 wk age only. More importantly, fecal microbiota transplantation (FMT) from transgenic (Tg) or WT...
Abstract Background Previous studies show that antibiotic-mediated (abx) alteration of the gut microbiome (GMB) results in a reduction amyloid beta (Aβ) plaques and proinflammatory microglial phenotype male APPPS1-21 mice. However, effect GMB perturbation on astrocyte phenotypes microglial-astrocyte communication context amyloidosis has not been examined. Methods To study whether modulates amyloidosis, female mice were treated with broad-spectrum abx leading to perturbation. GFAP +...
Recent investigations have focused on the potential role of gastrointestinal (GI) abnormalities in pathogenesis Parkinson's disease (PD). The 'dual-hit' hypothesis PD speculates that a putative pathogen enters brain via two routes: olfactory system and GI system. Here, we investigated (1) whether local exposures neurotoxin rotenone gut or mice could induce PD-like neurological phenotypes as well characteristic neuropathology accordance with this 'dual-hit hypothesis' (2) effects diet...
The mechanism of neurodegeneration in Parkinson’s disease (PD) remains unknown but it has been hypothesised that the intestinal tract could be an initiating and contributing factor to neurodegenerative processes. In PD patients as well animal models for PD, alpha-synuclein-positive enteric neurons colon evidence colonic inflammation have demonstrated. Moreover, several studies reported pro-inflammatory bacterial dysbiosis patients. Here, we report first time significant changes composition...
Recent evidence suggests that Parkinson's disease (PD) is associated with intestinal microbiota dysbiosis, abnormal permeability, and inflammation.Our study aimed to determine if these gut abnormalities are present in another synucleinopathy, multiple system atrophy (MSA).In six MSA 11 healthy control subjects, we performed immunohistochemistry studies of colonic sigmoid mucosa evaluate the barrier marker Zonula Occludens-1 endotoxin-related inflammation Toll-like-receptor-4 expression. We...
We examined the transduction efficiency of different adeno-associated virus (AAV) capsid serotypes encoding for green fluorescent protein (GFP) flanked by AAV2 inverted terminal repeats in nonhuman primate basal ganglia as a prelude to translational studies, well clinical trials patients with Parkinson's disease (PD). Six intact young adult cynomolgus monkeys received single 10 µl injection AAV2/1-GFP, AAV2/5-GFP, or AAV2/8-GFP pseudotyped vectors into caudate nucleus and putamen bilaterally...
Abstract Blood–brain barrier (BBB) dysfunction is emerging as a key pathogenic factor in the progression of Alzheimer’s disease (AD), where increased microvascular endothelial permeability has been proposed to play an important role. However, molecular mechanisms leading brain AD are not fully understood. We studied female APPswe/PS1∆E9 (APP/PS1) mice which constitute transgenic mouse model amyloid-beta (Aβ) amyloidosis and found that increases with aging areas showing greatest amyloid...
Alzheimer's disease (AD) is characterized by appearance of both extracellular senile plaques and intracellular neurofibrillary tangles, comprised aggregates misfolded amyloid-β (Aβ) hyper-phosphorylated tau, respectively. In a previous study, we demonstrated that g3p, capsid protein from bacteriophage M13, binds to remodels proteins assume an amyloid conformation. We engineered fusion ("NPT088") consisting the active fragment g3p human-IgG1-Fc.Aged Tg2576 mice or rTg4510 received NPT088...
Transplanted multipotent human fetal neural stem cells (hfNSCs) significantly improved the function of parkinsonian monkeys in a prior study primarily by neuroprotection, with only 3%-5% expressing dopamine (DA) phenotype. In this paper, we sought to determine whether further manipulation microenvironment overexpression developmentally critical molecule, glial cell-derived neurotrophic factor (GDNF), host striatum could enhance DA differentiation hfNSCs injected into substantia nigra and...
Alcohol increases intestinal permeability to proinflammatory microbial products that promote liver disease, even after a period of sobriety. We sought test the hypothesis alcohol affects stem cells using an in vivo model and ex organoids generated from jejunum colon mice fed chronic alcohol.Mice were control or diet. Intestinal permeability, steatosis-inflammation, stool short-chain fatty acids (SCFAs) measured. Jejunum colonic tissue stained for cell, cell lineage, apical junction markers...