A5103177177- Nerve injury and regeneration
- Parkinson's Disease Mechanisms and Treatments
- Neurogenesis and neuroplasticity mechanisms
- Neurological disorders and treatments
- Genetic Neurodegenerative Diseases
- Neuroscience and Neuropharmacology Research
- Nuclear Receptors and Signaling
- Cholinesterase and Neurodegenerative Diseases
- Autism Spectrum Disorder Research
- RNA Interference and Gene Delivery
- Neuropeptides and Animal Physiology
- Pluripotent Stem Cells Research
- Virus-based gene therapy research
- Memory and Neural Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Nicotinic Acetylcholine Receptors Study
- RNA regulation and disease
- Mitochondrial Function and Pathology
- Stress Responses and Cortisol
- Neuroscience and Neural Engineering
- Estrogen and related hormone effects
- Neuroendocrine regulation and behavior
- Botulinum Toxin and Related Neurological Disorders
- CRISPR and Genetic Engineering
Arizona State University
2021-2025
Research Network (United States)
2023
Rush University Medical Center
2010-2022
Krembil Research Institute
2020
Toronto Western Hospital
2020
McGill University
2020
Rush University
1992-2018
Lund University
2012
Presbyterian St. Luke's Medical Center
1992-2009
Texas Health Dallas
1992-2006
Lentiviral delivery of glial cell line–derived neurotrophic factor (lenti-GDNF) was tested for its trophic effects upon degenerating nigrostriatal neurons in nonhuman primate models Parkinson's disease (PD). We injected lenti-GDNF into the striatum and substantia nigra nonlesioned aged rhesus monkeys or young adult treated 1 week prior with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Extensive GDNF expression anterograde retrograde transport seen all animals. In monkeys, augmented...
Parkinson's disease (PD) is the second most common neurodegenerative disorder. Despite intense investigations, no effective therapy available to stop its onset or halt progression. The present study evaluates ability of peptide corresponding NF-kappaB essential modifier-binding domain (NBD) IkappaB kinase alpha (IKKalpha) IKKbeta prevent nigrostriatal degeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model PD and establish a role for human parkinsonism. First, we...
As part of a safety and tolerability study, 65-year-old man with Parkinson's disease (PD) received monthly intracerebroventricular injections glial-derived neurotrophic factor (GDNF). His parkinsonism continued to worsen following GDNF treatment. Side effects included nausea, loss appetite, tingling, L'hermitte's sign, intermittent hallucinations, depression, inappropriate sexual conduct. There was no evidence significant regeneration nigrostriatal neurons or intraparenchymal diffusion the...
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....
Objective A 12‐month double‐blind sham‐surgery–controlled trial assessing adeno‐associated virus type 2 (AAV2)‐neurturin injected into the putamen bilaterally failed to meet its primary endpoint, but showed positive results for endpoint in subgroup of subjects followed 18 months and several secondary endpoints. Analysis postmortem tissue suggested impaired axonal transport neurturin from substantia nigra. In present study, we tested safety efficacy AAV2‐neurturin delivered Methods We...
Abstract While Parkinson’s disease remains clinically defined by cardinal motor symptoms resulting from nigrostriatal degeneration, it is now appreciated that the commonly consists of multiple pathologies, but unclear where these co-pathologies occur early in and whether they are responsible for degeneration. For past number years, we have been studying a well-characterized cohort subjects with impairment termed mild deficits. Motor deficits were determined on modified validated Unified...
Abstract The present investigation used an antibody directed against the extracellular domain of signal transducing nerve growth factor recepto, trkA, to reveal immunoreactive perikarya or fibers within olfactory bulb and tubercle, cingulate cortex, nucleus accumbens, striatum, endopiriform nucleus, septal/diagonal band complex, basalis, hippocampal thalamic paraventricular reuniens nuclei, periventricular hypothalamus, interpeduncular mesencephalic fifth nerve, dorsal lateral lemniscus,...
Abstract Objective We tested the hypothesis that gene delivery of trophic factor neurturin could preserve motor function and protect nigrostriatal circuitry in hemiparkinsonian monkeys. Methods An adeno‐associated virus–based vector encoding human (AAV2‐NTN; also called CERE‐120) was injected into striatum substantia nigra monkeys 4 days after a unilateral intracarotid injection N ‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) rendered them hemiparkinsonian. Control received either AAV2...
Abstract The present study investigated the neuroanatomical and behavioral effects of human stem cell transplants into striatum quinolinic acid (QA)‐lesioned rats. Twenty‐four rats received unilateral QA (200 nM/μl) injections striatum. One week later, were transplanted with cells derived from fetal cortex (12 weeks postconception) that either 1) pretreated in culture media differentiating cytokine ciliary neurotrophic factor (CNTF; n = 9) or 2) allowed to grow alone (n 7). Each rat was...
NGF immunohistochemistry was combined with quantitative optical densitometry to evaluate whether retrogradely transported is altered within cholinergic basal forebrain (CBF) neurons in Alzheimer's disease (AD). In normal aged humans, almost all CBF stained for NGF. Although fewer total number, remaining perikarya AD displayed diminished (32%) or undetectable immunoreactivity. Based upon these data we hypothesize that there a defect retrograde transport of which may be due abnormal production...
Abstract It is well documented that estrogen increases dendritic spine density in CA1 pyramidal cells of young female rats. However, this effect attenuated aged We report here a quantitative analysis effects on hippocampal number as visualized with antispinophilin (6–8 years old) and (19–23 rhesus monkeys, species pattern endocrine senescence comparable to humans. Monkeys were ovariectomized administered either vehicle or estradiol cypionate 3 months postovariectomy, followed by an...
Abstract Baby hamster kidney (BHK) cells were genetically modified to secrete high levels of human nerve growth factor (BHK‐hNGF). Following polymer encapsulation, these implanted into the lateral ventricle four cynomolgus monkeys immediately following a unilateral transection/aspiration fornix. Three control received identical implants, with exception that BHK not hNGF and thus differed only by construct. One monkey fornix transection only. All displayed complete transections as revealed...
Six Rhesus monkeys between 24 and 29 years of age received unilateral transections the fornix. Three then intraventricular transplants polymer-encapsulated baby hamster kidney (BHK) fibroblasts that had been genetically modified to secrete human nerve growth factor (hNGF). The remaining three identical grafts except cells were not hNGF. Monkeys receiving fornix transection control displayed extensive reductions in number choline acetyltransferase- (57-75%) p75 NGF receptor- (53%)...
A monoclonal antibody raised against the receptor for nerve growth factor (NGF) was used to examine distribution and morphology of NGF receptor-containing neurons within central nervous system Cebus apella monkeys. Most somata demonstrating positive immunoreactivity were localized Ch1-4 regions basal forebrain. Neurons in Ch1 region displayed morphological features typical cholinergic medial septal neurons. These perikarya primarily vertically oriented (40-50 micron along vertical axis) with...
Background: Conflicting results from studies of Lewy-type α−synucleinopathy (LTS) in colonic biopsies subjects with Parkinson's disease (PD) prompted a two-part multicenter assessment. The first assessment, now published (Acta Neuropathol Commun 4 : 35, 2016), examined archived and found that none the tested methods was adequately sensitive or specific. Objective: As amount nervous tissue typical may be insufficient, clinical diagnosis PD not completely accurate, objective current study to...
Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by abnormal accumulation of alpha-synuclein (α-syn) in oligodendrocytes accompanied inflammation, demyelination, and subsequent synapse neuronal loss. Little known about the mechanisms neurodegeneration MSA. However, recent work has highlighted important role immune to pathophysiology other synuclein-related diseases such as Parkinson's disease. In this study, we investigated postmortem brain tissue from...
Multiple system atrophy (MSA) is a rare and fatal synucleinopathy characterized by insoluble alpha-synuclein (α-syn) cytoplasmic inclusions located within oligodendroglia. Neuroinflammation, demyelination, neurodegeneration are correlated with areas of glia (GCI) pathology, however it not known what specifically drives disease pathogenesis. Recent studies have shown that pathologies found in post-mortem tissue from MSA patients can be modeled rodents via modified AAV overexpressing α-syn,...
Abstract Galanin‐immunoreactive profiles were localized within the monkey and human central nervous system. In telencephalon, galanin‐immunoreactive perikarya seen anterior olfactory nucleus, basal forebrain, endopiriform hippocampus, bed nucleus of stria terminalis. The caudate putamen contained whereas accumbens displayed only fibers. diencephalon, medial preoptic area, periventricular, suprachiasmatic, paraventricular, arcuate nuclei as well lateral hypothalamic area. Within thalamus,...