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Open AccessJournal ArticleDOI

Progressive decline in avoidance learning paralleled by inflammatory neurodegeneration in transgenic mice expressing interleukin 6 in the brain

TLDR
A critical role for a proinflammatory cytokine is suggested in the cognitive deficits and associated neuroinflammatory changes that have been documented in neurodegenerative diseases such as Alzheimer disease and AIDS.
Abstract
Inflammation with expression of interleukin 6 (IL-6) in the brain occurs in many neurodegenerative disorders. To better understand the role of IL-6 in such disorders, we examined performance in a learning task in conjunction with molecular and cellular neuropathology in transgenic mice that express IL-6 chronically from astrocytes in the brain. Transgenic mice exhibited dose- and age-related deficits in avoidance learning that closely corresponded with specific progressive neuropathological changes. These results establish a link between the central nervous system expression of IL-6, inflammatory neurodegeneration, and a learning impairment in transgenic mice. They suggest a critical role for a proinflammatory cytokine in the cognitive deficits and associated neuroinflammatory changes that have been documented in neurodegenerative diseases such as Alzheimer disease and AIDS.

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The induction of pain: an integrative review

TL;DR: A global account of mechanisms involved in the induction of pain is provided, including neuronal pathways for the transmission of nociceptive information from peripheral nerve terminals to the dorsal horn, and therefrom to higher centres.
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Immune modulation of learning, memory, neural plasticity and neurogenesis

TL;DR: These effects are mediated by inflammation-induced neuronal hyper-excitability and adrenocortical stimulation, followed by reduced production of neurotrophins and other plasticity-related molecules, facilitating many forms of neuropathology associated with normal aging as well as neurodegenerative and neuropsychiatric diseases.
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Irradiation induces neural precursor-cell dysfunction

TL;DR: It is shown that the deficit in neurogenesis reflects alterations in the microenvironment that regulates progenitor-cell fate, as well as a defect in the proliferative capacity of the neural progenitors in the irradiated hippocampus.
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Inflammatory processes in Alzheimer's disease.

TL;DR: While inflammation has been thought to arise secondary to degeneration, recent experiments demonstrated that inflammatory mediators may stimulate APP processing by upregulation of beta secretase 1 and therefore are able to establish a vicious cycle.
References
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Journal ArticleDOI

Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF).

TL;DR: With IL 6 transgenic mice, deregulation of the IL 6 expression was suggested to be involved in the generation of plasmacytoma/myeloma and mesangium proliferative glomerulonephritis and the findings suggest the presence of a positive regulatory loop in acute‐phase reaction.
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Impaired Long-Term Potentiation, Spatial Learning, and Hippocampal Development in fyn Mutant Mice

TL;DR: A common tyrosine kinase pathway may regulate the growth of neurons in the developing hippocampus and the strength of synaptic plasticity in the mature hippocampus.
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Cytotoxicity of microglia

TL;DR: Interference with the microglial activation or the productions of cytotoxic metabolites by microglia may offer new therapeutic opportunities for the prevention of neuronal cell death in CNS disease.
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Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6.

TL;DR: Transgenic mice generated in which the cytokine interleukin 6 (IL-6), under the regulatory control of the glial fibrillary acidic protein gene promoter, was overexpressed in the CNS exhibited a neurologic syndrome the severity of which correlated with the levels of cerebral IL-6 expression.
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Parvalbumin in most gamma-aminobutyric acid-containing neurons of the rat cerebral cortex.

TL;DR: With semithin frozen sections, it is possible to demonstrate that most GABA neurons in the rat somatosensory cortex contain the calcium-binding protein parValbumin and that parvalbumin is found virtually only in GABA neurons.
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