21 Jan 2002

Since it became clear that Alzheimer's disease has features in common with chronic inflammation, much effort has gone into determining whether the various inflammatory response molecules are helping to protect, or to destroy, vulnerable neurons. In the current issue of the Journal of Neuroscience, Paul Sawchenko and colleagues at the Salk Institute and the Scripps Research Institute in La Jolla, California, report that the proinflammatory cytokine interleukin-6 (IL-6) has at least one deleterious effect-it interferes with adult hippocampal neurogenesis.

The continual replacement of granule cells in the adult dentate gyrus of the hippocampus has also drawn the attention of AD researchers because this process appears to be critical for cognitive function. Preservation or therapeutic manipulation of the stem cells that give rise to new neurons could possibly become a strategy for replacing neurons lost in AD. Sawchenko and colleagues were interested in what effect IL-6-which apparently is secreted in the brain only under pathological conditions, including Alzheimer's-might have on hippocampal neurogenesis. Previous evidence pointed in opposite directions: IL-6 enhances the survival of neurons and bone marrow progenitor cells in some culture systems, but also appears to restrain neurogenesis in cell cultures of embryonic cerebral precursors. The researchers decided to examine hippocampal neuroproliferation in transgenic mice that express chronic low levels of IL-6, a model that mimics the IL-6 situation in AD.

They found that the regular presence of IL-6 reduces overall neurogenesis in the young adult dentate gyrus by 63 percent relative to wildtype mice. This was not a general effect on all proliferation in that region, since the number of glial cells born and the distribution of new neural and glial cells was similar in the transgenic and wildtype mice. Similarly, the researchers were able to show that the chronic levels of IL-6 did not have a general negative effect on the survival of adult neurons or glia.

"Assuming that neurogenesis does play a salutary role in learning and memory (Kempermann 1997, 1998; Gould 1999; Nilsson 1999), the present findings would suggest that long-term expression of IL-6 in CNS disorders and infection can interfere with neurogenesis and contribute to impaired cognitive function," write the authors.—Hakon Heimer