Differential responses of primary neuron-secreted MCP-1 and IL-9 to type 2 diabetes and Alzheimer’s disease-associated metabolites
Year: 2024
Type: article
Abstract: Type 2 diabetes (T2D) is implicated as a risk factor for Alzheimer's disease (AD), the most common form of dementia. In this work, we investigated neuroinflammatory responses of primary neurons to potentially circulating, blood-brain barrier (BBB) permeable metabolites associated with AD, T2D, or both. We identified nine metabolites associated with protective or detrimental properties of AD and T2D in literature (lauric acid, asparagine, fructose, arachidonic acid, aminoadipic acid, sorbitol, retinol, tryptophan, niacinamide) and stimulated primary mouse neuron cultures with each metabolite before quantifying cytokine secretion via Luminex. We employed unsupervised clustering, inferential statistics, and partial least squares discriminant analysis to identify relationships between cytokine concentration and disease-associations of metabolites. We identified MCP-1, a cytokine associated with monocyte recruitment, as differentially abundant between neurons stimulated by metabolites associated with protective and detrimental properties of AD and T2D. We also identified IL-9, a cytokine that promotes mast cell growth, to be differentially associated with T2D. Indeed, cytokines, such as MCP-1 and IL-9, released from neurons in response to BBB-permeable metabolites associated with T2D may contribute to AD development by downstream effects of neuroinflammation.
Source: Scientific Reports
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,590
Funders: National Science Foundation, Purdue University, Case Western Reserve University, Open Philanthropy Project, Good Ventures Foundation, National Institutes of Health, National Institute on Aging, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke
Awards: Graduate Research Fellowship Program(GRFP), Coupling and spread of molecular and functional pathology of Alzheimer's disease, Interdisciplinary Bioengineering Training in Diabetes Research, APOE4 Increases Astrocytic Tau Internalization to Promote Alzheimer’s-Related Neuronal Pathology, Cross-Disciplinary Neural Engineering (CDNE) Training Program
OpenAlex ID: W4399281724