Tumor necrosis factor-α elevates neurite outgrowth through an NF-κB-dependent pathway in cultured adult sensory neurons: Diminished expression in diabetes may contribute to sensory neuropathy

Autor: Savitha Balakrishnan, Corina Martens, Paul Fernyhough, Darrell R. Smith, Lori Dunn, Ali Saleh, Christopher W. Tweed
Rok vydání: 2011
Předmět:
Blood Glucose
Male
medicine.medical_specialty
Diabetic neuropathy
Sensory Receptor Cells
Neurite
Sensory system
Biology
Transfection
Gene Expression Regulation
Enzymologic
Diabetes Mellitus
Experimental
Proinflammatory cytokine
Rats
Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Tubulin
Ganglia
Spinal
Internal medicine
Neurites
medicine
Animals
Enzyme Inhibitors
Molecular Biology
Cells
Cultured
030304 developmental biology
Analysis of Variance
0303 health sciences
Dose-Response Relationship
Drug
Tumor Necrosis Factor-alpha
General Neuroscience
Body Weight
Neurodegeneration
Age Factors
NF-kappa B
medicine.disease
Streptozotocin
Sensory neuron
Rats
Disease Models
Animal
medicine.anatomical_structure
Endocrinology
nervous system
Tumor necrosis factor alpha
Neurology (clinical)
Neuroscience
030217 neurology & neurosurgery
Signal Transduction
Developmental Biology
medicine.drug
Zdroj: Brain Research. 1423:87-95
ISSN: 0006-8993
DOI: 10.1016/j.brainres.2011.09.029
Popis: The presence of a proinflammatory environment in the sensory neuron axis in diabetes was tested by measuring levels of proinflammatory cytokines in lumbar dorsal root ganglia (DRG) and peripheral nerve from age matched control and streptozotocin (STZ)-induced diabetic rats. The levels of tumor necrosis factor-α (TNFα) and other cytokines were diminished in lumbar DRG from diabetic animals. Consequently, we tested the hypothesis that TNFα modulated axonal plasticity in adult sensory neurons and posited that impairments in this signal transduction pathway may underlie degeneration in diabetic sensory neuropathy. Cultured adult rat sensory neurons were grown under defined conditions and TNFα caused a dose-dependent 2-fold (P0.05) elevation in neurite outgrowth. Neurons derived from 3 to 5month STZ-induced diabetic rats exhibited significantly reduced levels of neurite outgrowth in response to TNFα. TNFα enhanced NF-κB activity as assessed using Western blotting and plasmid reporter technology. Blockade of TNFα-induction of NF-κB activation caused inhibition of neurite outgrowth in cultured neurons. Immunofluorescent staining for NF-κB subunit p50 within neuronal nuclei revealed that medium to large diameter neurons were most susceptible to NF-κB inhibition and was associated with decreased neurite outgrowth. The results demonstrating reduced cytokine expression in DRG confirm that diabetic sensory neuropathy does not involve a neuroinflammatory component at this stage of the disease in experimental animal models. In addition, it is hypothesized that reduced TNFα expression in the DRG and possibly associated deficits in anterograde transport may contribute to impaired collatoral sprouting and regeneration in target tissue in type 1 diabetes.
Databáze: OpenAIRE
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