Abstract
Persistent inflammation and successive innate immune reaction have been considered to cause Parkinson's disease (PD). Recently, we have found that peripherally injected lipopolysaccharide (LPS) induced tumor necrosis factor (TNF)-α production in astrocytes in the olfactory bulb (OB) and enhanced the number of apoptotic cells in the OB. This finding could be one of the explanations for the olfactory dysfunction observed frequently and early in the patients suffering from PD. Herein, we attempted to clarify the relative roles of TNF-α playing in the induction of programmed cell death after peripheral LPS injection, in which TNF receptor-deficient mice (TNFR−/−) were used. The intraperitoneal injection of 50 μg LPS into wild-type mice induced the successive increases in mRNA expression levels in the OB of the genes encoding TNF-α and caspase-8. The number of TUNEL-positive cells in the OB increased to a significant level in LPS-injected wild-type mice at 24 h after the LPS injection. On the contrary, LPS (50 μg)-injected TNFR−/− mice did not reveal any increase in caspase-8 mRNA expression level and the number of apoptotic cells in the OB, despite the significant increase in the TNF-α mRNA expression level at the site. These findings suggest the fact that a crucial role should be assigned to TNF-α in the induction of programmed cell death triggered by peripheral LPS injection. [J Physiol Sci. 2006;56 Suppl:S212]
