Cerebrospinal fluid from Alzheimer patients affects cell-mediated nerve growth factor production and cell survival in vitro
| Autor: | Maria Eriksdotter, Sumonto Mitra, Lars Wahlberg, Lars O. Tjernberg, Bengt Linderoth, Homira Behbahani, Manuel Navarro-Oviedo |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Lewy Body Disease
0301 basic medicine medicine.medical_specialty Cell Survival Interleukin-1beta Cell Inflammation Retinal Pigment Epithelium Nerve growth factor production Biology 03 medical and health sciences 0302 clinical medicine Alzheimer Disease Internal medicine Nerve Growth Factor medicine Humans Cognitive Dysfunction Viability assay Cholinergic neuron Cell Line Transformed Cerebrospinal Fluid Basal forebrain Amyloid beta-Peptides Lewy body Epithelial Cells Cell Biology Staurosporine medicine.disease Peptide Fragments 030104 developmental biology Nerve growth factor medicine.anatomical_structure Endocrinology Gene Expression Regulation nervous system medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Experimental Cell Research. 371:175-184 |
| ISSN: | 0014-4827 |
| Popis: | Alzheimer's disease (AD) is characterized by early degeneration of cholinergic neurons and decreased levels of nerve growth factor (NGF). Thus, increasing the NGF levels by for instance encapsulated cell bio-delivery (ECB) is a potential treatment strategy. The results from our previous first-in-human studies on ECB of NGF to the basal forebrain cholinergic neurons were promising, but indicated some variability of long-term viability of the encapsulated cells and associated reduced NGF-release. Here we studied the effect of amyloid beta-peptides (Aβ), interleukin 1-beta (IL-1β), and CSF from AD, Lewy body dementia (LBD) or subjective cognitive impairment (SCI) patients on the NGF overproducing cell line NGC-0295. At physiological concentrations, neither Aβ40 nor Aβ42 had any major impact on cell viability or NGF-production. In contrast, IL-1β dose-dependently affected NGF-production over time. Exposure of NGF-producing cells to CSF from AD patients showed significantly reduced NGF-release as compared to CSF from LBD or SCI patients. By mass spectrometry we found 3 proteins involved in inflammatory pathways to have an altered expression in AD CSF compared to LBD and SCI. Cell survival and NGF-release were not affected by Aβ. NGF-release was affected by IL-1β, suggesting that inflammation has a negative effect on ECB cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect