Peripheral Lipopolysaccharide Administration Affects the Olfactory Dopamine System in Mice

Abstract

Peripheral administration of lipopolysaccharide (LPS) in an amount that produces acute stress has been found to affect the catecholamine systems in the brain. Acute peripheral LPS administration activated norepinephrine (NE) metabolism in the locus ceruleus (LC). Approximately 40% of murine LC neurons project to the olfactory bulb (OB) and the anterior olfactory nucleus (AON). Thus, we investigated the effects of a single intra-peritoneal (i.p.) LPS injection on catecholamine biosynthesis in the OB and AON in 8-week-old C3H/HeN male mice. In the AON, the content of dopamine (DA), but not that of NE, was highly increased 6 h after LPS injection. In the OB, the contents of DA and NE did not change; but within 2 h after a single i.p. LPS injection, the mRNA levels of IkappaB, TNF-alpha, and TNF-alpha receptor type 1 were significantly enhanced. Almost all TNF-alpha-immunoreactive cells in the OB of the LPS-injected mice were located in the granule cell layer, and unexpectedly, they were not microglia but astroglia. The number of TUNEL-positive cells identified exclusively in the granule cell layer was significantly increased at 24 h after LPS injection. Therefore, our data suggest that astroglia activated by peripherally injected LPS may release TNF-alpha, which may trigger apoptosis in the granule cell layer in the OB. The increase in DA content in the AON and the production of TNF-alpha and apoptotic cells in the OB by acute peripheral LPS administration are not likely to be related.