TNF-α preconditioning protects neurons via neuron-specific up-regulation of CREB-binding protein

Ramendra N. Saha, Anamitra Ghosh, Carlos A. Palencia, Eric Y Fung, Serena M. Dudek, Kalipada Pahan

Research output: Contribution to journalArticle

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Abstract

Despite being a proinflammatory cytokine, TNF-α preconditions neurons against various toxic insults. However, underlying molecular mechanisms are poorly understood. The present study identifies the importance of CREB-binding protein (CBP) in facilitating TNF-α-mediated preconditioning in neurons. Treatment of rat primary neurons with fibrillar amyloid β1-42 (Aβ) resulted in the loss of CBP protein. However, this loss was compensated by TNF-α reconditioning as the expression of neuronal CBP was up-regulated in response to TNF-α treatment. The induction of CBP by TNF-α was observed only in neurons, but not in astroglia and microglia, and it was contingent on the activation of transcription factor NF-κB. Interestingly, antisense knockdown of CBP abrogated the TNF-α-mediated preconditioning of neurons against Aβ and glutamate toxicity. Similarly in vivo, preadministration of TNF-α in mouse neocortex prevented Aβ-induced apoptosis and loss of choline acetyltransferase-positive cholinergic neurons. However, coadministration of cbp antisense, but not scrambled oligonucleotides, negated the protective effect of TNF-α gainst Aβ neurotoxicity. This study illustrates a novel biological role of TNF-α in increasing neuron-specific expression of CBP for preconditioning that may have therapeutic potential against neurodegenerative disorders.

Original languageEnglish (US)
Pages (from-to)2068-2078
Number of pages11
JournalJournal of Immunology
Volume183
Issue number3
DOIs
StatePublished - Aug 1 2009

Fingerprint

CREB-Binding Protein
Up-Regulation
Neurons
Cholinergic Neurons
Choline O-Acetyltransferase
Poisons
Neocortex
Microglia
Amyloid
Oligonucleotides
Astrocytes
Neurodegenerative Diseases
Glutamic Acid
Transcription Factors
Apoptosis
Cytokines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Saha, R. N., Ghosh, A., Palencia, C. A., Fung, E. Y., Dudek, S. M., & Pahan, K. (2009). TNF-α preconditioning protects neurons via neuron-specific up-regulation of CREB-binding protein. Journal of Immunology, 183(3), 2068-2078. https://doi.org/10.4049/jimmunol.0801892

TNF-α preconditioning protects neurons via neuron-specific up-regulation of CREB-binding protein. / Saha, Ramendra N.; Ghosh, Anamitra; Palencia, Carlos A.; Fung, Eric Y; Dudek, Serena M.; Pahan, Kalipada.

In: Journal of Immunology, Vol. 183, No. 3, 01.08.2009, p. 2068-2078.

Research output: Contribution to journalArticle

Saha, RN, Ghosh, A, Palencia, CA, Fung, EY, Dudek, SM & Pahan, K 2009, 'TNF-α preconditioning protects neurons via neuron-specific up-regulation of CREB-binding protein', Journal of Immunology, vol. 183, no. 3, pp. 2068-2078. https://doi.org/10.4049/jimmunol.0801892
Saha, Ramendra N. ; Ghosh, Anamitra ; Palencia, Carlos A. ; Fung, Eric Y ; Dudek, Serena M. ; Pahan, Kalipada. / TNF-α preconditioning protects neurons via neuron-specific up-regulation of CREB-binding protein. In: Journal of Immunology. 2009 ; Vol. 183, No. 3. pp. 2068-2078.
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