Publication Date

2014

Journal Title

Mol Med

Abstract

Inflammatory conditions characterized by excessive peripheral immune responses are associated with diverse alterations in brain function, and brain-derived neural pathways regulate peripheral inflammation. Important aspects of this bidirectional peripheral immune - brain communication, including the impact of peripheral inflammation on brain region-specific cytokine responses, and brain cholinergic signaling (which plays a role in controlling peripheral cytokine levels) remain unclear. To provide insight, we studied gene expression of cytokines, immune cell markers and brain cholinergic system components in the cortex, cerebellum, brainstem, hippocampus, hypothalamus, striatum, and thalamus in mice following an intraperitoneal lipopolysaccharide injection. Endotoxemia was accompanied by elevated serum levels of IL-1beta, IL-6 and other cytokines, and brain region-specific increases in Il1b (highest, relative to basal level increase - in cortex, lowest increase- in cerebellum) and Il6 (highest increase - in cerebellum, lowest increase - in striatum) mRNA expression. Gene expression of brain Gfap (astrocyte marker) was also differentially increased. However, Iba1 (microglia marker) mRNA expression was decreased in the cortex, hippocampus and other brain regions in parallel with morphological changes, indicating microglia activation. Brain choline acetyltransferase (Chat) mRNA expression was decreased in the striatum; acetylcholinesterase (Ache) mRNA expression was decreased in the cortex and increased in the hippocampus; and M1 muscarinic acetylcholine receptor (Chrm1) mRNA expression was decreased in the cortex and the brainstem. These results reveal a previously unrecognized regional specificity in brain immunoregulatory and cholinergic system gene expression in the context of peripheral inflammation, and are of interest for designing future anti-inflammatory approaches.

Volume Number

20

Pages

601-611

Document Type

Article

EPub Date

2014/10/10

Status

Faculty, Northwell Researcher

Facility

School of Medicine; Northwell Health

Primary Department

Pathology and Laboratory Medicine

Additional Departments

Molecular Medicine; Obstetrics and Gynecology; Neurosurgery

PMID

25299421

DOI

10.2119/molmed.2014.00147

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