Neuroimmune Cell Coculture Model to Study Parkinson’s Disease Inflamma- tion and Effects of Gut Metabolites

Authors:

Baochan Fan, Joanna Korecka-Roet, Vikram Khurana

Date Created:

2025-01-01

Course Title:

Professor:

Not specified

About Paper:

Parkinson’s Disease (PD) is an incurable neurodegenerative blood mononuclear cells (PBMCs) treated with supernatant from disease pheno-characterized by debilitating motor symptoms and microbiome bacterial isolates upregulated in the PD dysbiotic gut, cognitive deficits. Neuroinflammation constitutes a central and compared to PBS, LPS, and CD3+/CD28+ T cell activation- pathology,withreactivemicrogliaearlyindiseaseprogressionand, inducing Dynabeads. Microbiome metabolites have previously interestingly, increased peripheral immune cell infiltration into theen found to induce a pro-inflammatory phenotype in microglia brain. Immune mechanisms could be involved in the heterogeneity differentiated from iPSCs reprogrammed from the same E46K of symptoms and variable disease penetrance displayed by PD patient. Corticalneuronviabilityinthecocultureswillbemeasured mutations. via live cell imaging assays over 72 hours. T cell activation, cytotoxicity, inflammation, and expansion states in response to Here, we seek to study the cellular interactions between peripheraltreatment and post-culture are evaluated via qPCR for NF-κB and immune cells and cortical neurons in vitro by developing neuron-T cell coculture models. Cortical neurons have been differentiated T cell subpopulation markers. However, gene expression profiling from reprogrammed induced-pluripotent stem cells (iPSCs) of a of these cells proved to be challenging; therefore, we are now severe PD-dementia patient with the rare autosomal dominant optimizing a FACS-based method for analysis. E46K SNCA-linked mutation, cross-compared to isogenic gene Our model can be extended from the E46K patient from whom we corrected iPSCs. The mutation displays variable penetrance have accessible iPSCs to other family members in the lineage to despite similar familial inheritance patterns, rendering it an further study the potential link of variable mutational penetrance interesting focus to study immune effects on neuronal sensitivity to peripheral immune cell activation and neurodegeneration. to the mutation. T cells are isolated from human peripheral Variability of Freshwater and Heat Transport in the East Greenland Coastal

Abstract:

Parkinson’s Disease (PD) is an incurable neurodegenerative blood mononuclear cells (PBMCs) treated with supernatant from disease pheno-characterized by debilitating motor symptoms and microbiome bacterial isolates upregulated in the PD dysbiotic gut, cognitive deficits. Neuroinflammation constitutes a central and compared to PBS, LPS, and CD3+/CD28+ T cell activation- pathology,withreactivemicrogliaearlyindiseaseprogressionand, inducing Dynabeads. Microbiome metabolites have previously interestingly, increased peripheral immune cell infiltration into theen found to induce a pro-inflammatory phenotype in microglia brain. Immune mechanisms could be involved in the heterogeneity differentiated from iPSCs reprogrammed from the same E46K of symptoms and variable disease penetrance displayed by PD patient. Corticalneuronviabilityinthecocultureswillbemeasured mutations. via live cell imaging assays over 72 hours. T cell activation, cytotoxicity, inflammation, and expansion states in response to Here, we seek to study the cellular interactions between peripheraltreatment and post-culture are evaluated via qPCR for NF-κB and immune cells and cortical neurons in vitro by developing neuron-T cell coculture models. Cortical neurons have been differentiated T cell subpopulation markers. However, gene expression profiling from reprogrammed induced-pluripotent stem cells (iPSCs) of a of these cells proved to be challenging; therefore, we are now severe PD-dementia patient with the rare autosomal dominant optimizing a FACS-based method for analysis. E46K SNCA-linked mutation, cross-compared to isogenic gene Our model can be extended from the E46K patient from whom we corrected iPSCs. The mutation displays variable penetrance have accessible iPSCs to other family members in the lineage to despite similar familial inheritance patterns, rendering it an further study the potential link of variable mutational penetrance interesting focus to study immune effects on neuronal sensitivity to peripheral immune cell activation and neurodegeneration. to the mutation. T cells are isolated from human peripheral Variability of Freshwater and Heat Transport in the East Greenland Coastal

Source:

Harvard / Brooke DeJong, Rachelle Gaudet / 2025

Topics:

cell, immune, disease, ipsc, mutation, model, activation, peripheral, e46k, variable, penetrance, patient

Co-authors:

@baochanfan271 , @joannakoreckaroet272 , @vikramkhurana273