Gene Expression Changes in a Model Neuron Cell Line Exposed to Autoantibodies from Patients with Traumatic Brain Injury and/or Type 2 Diabetes
Abstract
Traumatic brain injury and adult type 2 diabetes mellitus are each associated with the late occurrence of accelerated cognitive decline and Parkinson’s disease through unknown mechanisms. Previously, we reported increased circulating agonist autoantibodies targeting the 5-hydroxytryptamine 2A receptor in plasma from subsets of Parkinson’s disease, dementia, and diabetic patients suffering with microvascular complications. Here, we use a model neuron, mouse neuroblastoma (N2A) cell line, to test messenger RNA expression changes following brief exposure to traumatic brain injury and/or type 2 diabetes mellitus plasma harboring agonist 5-hydroxytryptamine 2A receptor autoantibodies. We now report involvement of the mitochondrial dysfunction pathway and Parkinson’s disease pathways in autoantibody-induced gene expression changes occurring in neuroblastoma cells. Functional gene categories upregulated significantly included cell death, cytoskeleton-microtubule function, actin polymerization or depolymerization, regulation of cell oxidative stress, mitochondrial function, immune function, protein metabolism, and vesicle function. Gene categories significantly downregulated included microtubule function, cell adhesion, neurotransmitter release, dopamine metabolism synaptic plasticity, maintenance of neuronal differentiation, mitochondrial function, and cell signaling. Taken together, these results suggest that agonist 5-hydroxytryptamine receptor autoantibodies (which increase in Parkinson’s disease and other forms of neurodegeneration) mediate a coordinating program of gene expression changes in a model neuron which predispose to neuro-apoptosis and are linked to human neurodegenerative diseases pathways.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 19, 2021
- Source ID
- 10.1007/s12035-021-02428-4
Entities
People
- Bruce A Citron
- Mark B. Zimering
- Vedad Delic
Organizations
- Biomedical Laboratory Research and Development, VA Office of Research and Development
- Congressionally Directed Medical Research Programs
- New Jersey Commission on Brain Injury Research
- Rehabilitation Research and Development Service