Merck
  • Home
  • Search Results
  • Tumor Necrosis Factor α Influences Phenotypic Plasticity and Promotes Epigenetic Changes in Human Basal Forebrain Cholinergic Neuroblasts.

Tumor Necrosis Factor α Influences Phenotypic Plasticity and Promotes Epigenetic Changes in Human Basal Forebrain Cholinergic Neuroblasts.

International journal of molecular sciences (2020-08-29)
Giulia Guarnieri, Erica Sarchielli, Paolo Comeglio, Erika Herrera-Puerta, Irene Piaceri, Benedetta Nacmias, Matteo Benelli, Gavin Kelsey, Mario Maggi, Pasquale Gallina, Gabriella Barbara Vannelli, Annamaria Morelli
ABSTRACT

TNFα is the main proinflammatory cytokine implicated in the pathogenesis of neurodegenerative disorders, but it also modulates physiological functions in both the developing and adult brain. In this study, we investigated a potential direct role of TNFα in determining phenotypic changes of a recently established cellular model of human basal forebrain cholinergic neuroblasts isolated from the nucleus basalis of Meynert (hfNBMs). Exposing hfNBMs to TNFα reduced the expression of immature markers, such as nestin and β-tubulin III, and inhibited primary cilium formation. On the contrary, TNFα increased the expression of TNFα receptor TNFR2 and the mature neuron marker MAP2, also promoting neurite elongation. Moreover, TNFα affected nerve growth factor receptor expression. We also found that TNFα induced the expression of DNA-methylation enzymes and, accordingly, downregulated genes involved in neuronal development through epigenetic mechanisms, as demonstrated by methylome analysis. In summary, TNFα showed a dual role on hfNBMs phenotypic plasticity, exerting a negative influence on neurogenesis despite a positive effect on differentiation, through mechanisms that remain to be elucidated. Our results help to clarify the complexity of TNFα effects in human neurons and suggest that manipulation of TNFα signaling could provide a potential therapeutic approach against neurodegenerative disorders.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Protease Inhibitor Cocktail, for use with mammalian cell and tissue extracts, DMSO solution
Sigma-Aldrich
Triton X-100, laboratory grade
Sigma-Aldrich
牛血清白蛋白 来源于牛血清, lyophilized powder, ≥96% (agarose gel electrophoresis)
Sigma-Aldrich
Triton X-100, for molecular biology
Sigma-Aldrich
多聚甲醛, powder, 95%
Sigma-Aldrich
抗微管相关蛋白2(MAP2)抗体, Chemicon®, from rabbit
Sigma-Aldrich
抗胆碱乙酰基转移酶(ChAT)抗体, serum, Chemicon®
Sigma-Aldrich
抗-VAChT (C末端) 兔抗, IgG fraction of antiserum