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Peripheral lipopolysaccharide administration affects the olfactory dopamine system in mice
Akira Ota1, Keiji Mori, Yoko S Kaneko
1Department of Physiology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Annals of the New York Academy of Sciences
|January 6, 2009
Summary
Peripheral lipopolysaccharide (LPS) administration activates stress responses. In mice, LPS triggers dopamine increases in the anterior olfactory nucleus and astroglial release of TNF-alpha in the olfactory bulb, potentially causing apoptosis.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Peripheral administration of lipopolysaccharide (LPS) induces acute stress and affects central catecholamine systems.
- Norepinephrine (NE) metabolism in the locus ceruleus (LC) is activated by acute peripheral LPS.
- LC neurons project to the olfactory bulb (OB) and anterior olfactory nucleus (AON), suggesting potential impacts on these brain regions.
Purpose of the Study:
- To investigate the effects of a single intraperitoneal (i.p.) LPS injection on catecholamine biosynthesis in the OB and AON.
- To examine the cellular and molecular responses in the OB following LPS administration.
Main Methods:
- Mice received a single i.p. injection of LPS.
- Catecholamine content (dopamine and NE) was measured in the OB and AON.
- mRNA levels of IkappaB, TNF-alpha, and TNF-alpha receptor type 1 were assessed in the OB.
- Immunohistochemistry was used to identify TNF-alpha-expressing cells in the OB.
- TUNEL staining was performed to detect apoptotic cells in the OB.
Main Results:
- Dopamine content increased in the AON 6 hours after LPS injection, while NE levels remained unchanged.
- In the OB, DA and NE levels did not change, but mRNA levels of IkappaB, TNF-alpha, and TNF-alpha receptor type 1 were elevated within 2 hours.
- TNF-alpha-immunoreactive cells were identified as astroglia in the OB granule cell layer.
- The number of TUNEL-positive (apoptotic) cells significantly increased in the OB granule cell layer 24 hours after LPS injection.
Conclusions:
- Astroglia in the OB, activated by peripheral LPS, may release TNF-alpha, leading to apoptosis in the granule cell layer.
- The observed increase in AON dopamine and OB TNF-alpha production/apoptosis appear to be independent responses to acute peripheral LPS administration.
