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Bate C, Kempster S, Last V, et al. Interferon-gamma increases neuronal death in response to amyloid-beta1-42. J Neuroinflammation. 2006;3:7doi: 10.1186/1742-2094-3-7.
Bate, C., Kempster, S., Last, V., & Williams, A. (2006). Interferon-gamma increases neuronal death in response to amyloid-beta1-42. Journal of neuroinflammation, 37. https://doi.org/10.1186/1742-2094-3-7
Bate, Clive, et al. "Interferon-gamma increases neuronal death in response to amyloid-beta1-42." Journal of neuroinflammation vol. 3 (2006): 7. doi: https://doi.org/10.1186/1742-2094-3-7
Bate C, Kempster S, Last V, Williams A. Interferon-gamma increases neuronal death in response to amyloid-beta1-42. J Neuroinflammation. 2006 Mar 28;3:7. doi: 10.1186/1742-2094-3-7. PMID: 16569229; PMCID: PMC1435873.
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J Neuroinflammation. 2006 Mar 28;3:7. doi: 10.1186/1742-2094-3-7.

Interferon-gamma increases neuronal death in response to amyloid-beta1-42.

Journal of neuroinflammation

Clive Bate, Sarah Kempster, Victoria Last, Alun Williams

Affiliations

  1. Department of Pathology and Infectious Diseases, Royal Veterinary College, Hawkshead Lane, North Mymms, Herts, AL9 7TA, UK. [email protected]

PMID: 16569229 PMCID: PMC1435873 DOI: 10.1186/1742-2094-3-7

Abstract

BACKGROUND: Alzheimer's disease is a neurodegenerative disorder characterized by a progressive cognitive impairment, the consequence of neuronal dysfunction and ultimately the death of neurons. The amyloid hypothesis proposes that neuronal damage results from the accumulation of insoluble, hydrophobic, fibrillar peptides such as amyloid-beta1-42. These peptides activate enzymes resulting in a cascade of second messengers including prostaglandins and platelet-activating factor. Apoptosis of neurons is thought to follow as a consequence of the uncontrolled release of second messengers. Biochemical, histopathological and genetic studies suggest that pro-inflammatory cytokines play a role in neurodegeneration during Alzheimer's disease. In the current study we examined the effects of interferon (IFN)-gamma, tumour necrosis factor (TNF)alpha, interleukin (IL)-1beta and IL-6 on neurons.

METHODS: Primary murine cortical or cerebellar neurons, or human SH-SY5Y neuroblastoma cells, were grown in vitro. Neurons were treated with cytokines prior to incubation with different neuronal insults. Cell survival, caspase-3 activity (a measure of apoptosis) and prostaglandin production were measured. Immunoblots were used to determine the effects of cytokines on the levels of cytoplasmic phospholipase A2 or phospholipase C gamma-1.

RESULTS: While none of the cytokines tested were directly neurotoxic, pre-treatment with IFN-gamma sensitised neurons to the toxic effects of amyloid-beta1-42 or HuPrP82-146 (a neurotoxic peptide found in prion diseases). The effects of IFN-gamma were seen on cortical and cerebellar neurons, and on SH-SY5Y neuroblastoma cells. However, pre-treatment with IFN-gamma did not affect the sensitivity to neurons treated with staurosporine or hydrogen peroxide. Pre-treatment with IFN-gamma increased the levels of cytoplasmic phospholipase A2 in SH-SY5Y cells and increased prostaglandin E2 production in response to amyloid-beta1-42.

CONCLUSION: Treatment of neuronal cells with IFN-gamma increased neuronal death in response to amyloid-beta1-42 or HuPrP82-146. IFN-gamma increased the levels of cytoplasmic phospholipase A2 in cultured neuronal cells and increased expression of cytoplasmic phospholipase A2 was associated with increased production of prostaglandin E2 in response to amyloid-beta1-42 or HuPrP82-146. Such observations suggest that IFN-gamma produced within the brain may increase neuronal loss in Alzheimer's disease.

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