Interleukin 18 (IL-18) participates in the inflammatory immune response of lymphocytes. Delay in learning or memory are common in the IL-18 knockout mouse. Many IL-18-immunoreactive neurons are found in the retrosplenial cortex (RSC) and the subiculum. These neurons also contain the IL-18 receptor. We determined the location and the ultrastructure of the IL-18 receptor-immunoreactive neurons in the RSC and observed changes in the IL-18 receptor-immunoreactive neurons of the IL-18 knockout mouse. The IL-18 receptor-immunoreactive neurons were found specifically in layer V of the granular RSC. They were medium-sized neurons with a light oval nucleus and had little cytoplasm with many free ribosomes, rough endoplasmic reticulum and many mitochondria, but no Nissl bodies. The number of axosomatic terminals was about six per section. The IL-18 receptor-immunoreactive neurons were not found in the RSC in the IL-18 knockout mouse at 5 or 9 weeks of age. However, many small electron-dense neurons were found in layer V. Both the nucleus and cytoplasm were electron-dense, but not necrotic. The mitochondria and rough endoplasmic reticulum were swollen. The IL-18 receptor-immunoreactive neurons were presumed to be degenerating. The degeneration of the IL18-receptor-immunoreactive neurons in the RSC may cause the abnormal behaviors of the IL-18 knockout mice.
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