A5080392411- Parkinson's Disease Mechanisms and Treatments
- Nerve injury and regeneration
- Neurological disorders and treatments
- Neurogenesis and neuroplasticity mechanisms
- Nuclear Receptors and Signaling
- Botulinum Toxin and Related Neurological Disorders
- Neuroscience and Neuropharmacology Research
- Autism Spectrum Disorder Research
- Neuroscience and Neural Engineering
- Alzheimer's disease research and treatments
- RNA regulation and disease
- Neurotransmitter Receptor Influence on Behavior
- Virus-based gene therapy research
- Pluripotent Stem Cells Research
- RNA Interference and Gene Delivery
- Neuroinflammation and Neurodegeneration Mechanisms
- SARS-CoV-2 detection and testing
- Receptor Mechanisms and Signaling
- Neurological diseases and metabolism
- Transcranial Magnetic Stimulation Studies
- Genetic Neurodegenerative Diseases
- CRISPR and Genetic Engineering
- Biosensors and Analytical Detection
- Calpain Protease Function and Regulation
- Neurological and metabolic disorders
Trinity Health Grand Rapids
2016-2025
Michigan State University
2016-2025
Mercy Health
2019-2021
University of Cincinnati
2005-2014
Michigan United
2013
Van Andel Institute
2010-2011
Sabin Vaccine Institute
2008
Rush University Medical Center
1998-2007
Millennium Engineering and Integration (United States)
2006
Presbyterian St. Luke's Medical Center
2000-2003
Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting approximately one-percent of population over age sixty. Although many animal models have been developed to study this each model presents its own advantages and caveats. A unique has arisen role alpha-synuclein (aSyn) in pathogenesis PD. This involves conversion recombinant monomeric aSyn protein a fibrillar form-the pre-formed fibril (aSyn PFF)-which then injected into brain or introduced media culture....
Converging evidence suggests a role for microglia-mediated neuroinflammation in Parkinson's disease (PD). Animal models of PD can serve as platform to investigate the degeneration PD. However, due features previously available models, interpretations contributor or consequence neurodegeneration have remained elusive. In present study, we investigated temporal relationship model synucleinopathy following intrastriatal injection pre-formed alpha-synuclein fibrils (α-syn PFFS). Male Fischer 344...
Parkinson's disease (PD) is a prevalent neurodegenerative with no approved disease-modifying therapies. Multiplications, mutations, and single nucleotide polymorphisms in the SNCA gene, encoding α-synuclein (aSyn) protein, either cause or increase risk for PD. Intracellular accumulations of aSyn are pathological hallmarks Taken together, reduction production may provide therapy We show that antisense oligonucleotides (ASOs) reduce rodent preformed fibril (PFF) models Reduced leads to...
Human studies and preclinical models of Parkinson's disease implicate the involvement both innate adaptive immune systems in progression. Further, pro-inflammatory markers are highly enriched near neurons containing pathological forms alpha synuclein (-syn), -syn overexpression recapitulates neuroinflammatory changes disease. These data suggest that may initiate a inflammatory response, however mechanism by which initiates neuroinflammation is poorly understood. Silencing endogenous...
Animal models that accurately recapitulate the accumulation of alpha-synuclein (α-syn) inclusions, progressive neurodegeneration nigrostriatal system and motor deficits can be useful tools for Parkinson's disease (PD) research. The preformed fibril (PFF) synucleinopathy model in rodents generally displays these PD-relevant features, however, magnitude predictability events is far from established. We therefore sought to optimize α-syn degeneration, understand time course both. Rats were...
The mechanisms underlying the effects of long-term deep brain stimulation subthalamic nucleus (STN DBS) as a therapy for Parkinson's disease (PD) remain poorly understood. present study examined whether functionally effective, ST
The discovery of the involvement alpha-synuclein (α-syn) in Parkinson's disease (PD) pathogenesis has resulted development and use viral vector-mediated α-syn overexpression rodent models. goal these series experiments was to characterize neurodegeneration functional deficits resulting from injection recombinant adeno-associated virus (rAAV) serotype 2/5-expressing human wildtype rat substantia nigra (SN). Rats were unilaterally injected into two sites SN with either rAAV2/5-expressing green...
Examination of early phases synucleinopathy when inclusions are present, but long before neurodegeneration occurs, is critical to both understanding disease progression and the development modifying therapies. The rat alpha-synuclein (α-syn) preformed fibril (PFF) model induces synchronized that recapitulates pathological features Parkinson's (PD) can be used study progression. In this model, phosphorylated α-syn (pSyn) inclusion-containing neurons reactive microglia (major...
The striatum is essential for many aspects of mammalian behavior, including motivation and movement, dysfunctional in motor disorders such as Parkinson's disease. vesicular glutamate transporter 3 (VGLUT3) expressed by striatal cholinergic interneurons (CINs) thus well positioned to regulate dopamine (DA) signaling locomotor activity, a canonical measure basal ganglia output. We now report that VGLUT3 knock-out (KO) mice show circadian-dependent hyperlocomotor activity restricted the waking...
Adeno-associated virus (AAV) is the most common vector for clinical gene therapy of CNS. This popularity originates from a high safety record and longevity transgene expression in neurons. Nevertheless, efficacy CNS indications lacking, one reason this relatively limited spread transduction large regions human brain. Using rationally designed modifications capsid, novel AAV capsids have been generated that improve intracellular processing result increased expression. Here, we sought to...
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is most common neurosurgical treatment for Parkinson's disease motor symptoms. In preclinical models, STN DBS provides neuroprotection substantia nigra (SN) dopamine neurons and increases BDNF in nigrostriatal system primary cortex. However, whether signaling SN participates neuroprotective effects remains unknown. We demonstrate that male rats activates downstream tropomyosin receptor kinase type B (trkB), namely, phosphorylation...
Use of the in vivo alpha-synuclein preformed fibril (α-syn PFF) model synucleinopathy is gaining popularity among researchers aiming to Parkinson's disease and nigrostriatal degeneration. The standardization α-syn PFF generation application critical order ensure consistent, robust pathology. Here, we present a detailed protocol for fibrils from monomeric α-syn, post-fibrilization quality control steps, suggested parameters successful neurosurgical injection PFFs into rats or mice. Starting...
Abstract The common brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with reduced activity-dependent BDNF release and increased risk for anxiety disorders PTSD. Here we behaviorally phenotyped a novel rat model an equivalent valine to methionine substitution in the Bdnf gene (Val68Met). In three-day fear conditioning protocol of learning extinction, adult rats Met/Met genotype demonstrated impaired memory compared Val/Met Val/Val controls, no differences or...