title: Brain region-specific alterations in the gene expression of cytokines, immune cell markers and cholinergic system components during peripheral endotoxin-induced inflammation.
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 after an intraperitoneal lipopolysaccharide injection. Endotoxemia was accompanied by elevated serum levels of interleukin (IL)-1β, IL-6 and other cytokines and brain region-specific increases in Il1b (the highest increase, relative to basal level, was in cortex; the lowest increase was 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 antiinflammatory approaches.
authors.affiliation: Laboratory of Biomedical Science, Center for Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.|Hofstra North Shore-LIJ School of Medicine at Hofstra University, Hempstead, New York, United States of America.
authors.forename: Harold A
authors.initials: HA
authors.lastname: Silverman
authors.affiliation: Laboratory of Biomedical Science, Center for Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Meghan
authors.initials: M
authors.lastname: Dancho
authors.affiliation: Pediatrics-Neurology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Angelique
authors.initials: A
authors.lastname: Regnier-Golanov
authors.affiliation: Neuropathology-Anatomic Pathology, North Shore-LIJ Health System, New Hyde Park, New York, United States of America.
authors.forename: Mansoor
authors.initials: M
authors.lastname: Nasim
authors.affiliation: Laboratory of Biomedical Science, Center for Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Mahendar
authors.initials: M
authors.lastname: Ochani
authors.affiliation: Laboratory of Biomedical Science, Center for Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Peder S
authors.initials: PS
authors.lastname: Olofsson
authors.affiliation: Cohen Children's Medical Center, North Shore-LIJ Health System, New Hyde Park, New York, United States of America.|Center for Heart and Lung Research, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ahmed
authors.affiliation: Hofstra North Shore-LIJ School of Medicine at Hofstra University, Hempstead, New York, United States of America.|Center for Heart and Lung Research, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Edmund J
authors.initials: EJ
authors.lastname: Miller
authors.affiliation: Laboratory of Biomedical Science, Center for Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Sangeeta S
authors.initials: SS
authors.lastname: Chavan
authors.affiliation: The Houston Methodist Research Institute, Houston, Texas, United States of America.
authors.forename: Eugene
authors.initials: E
authors.lastname: Golanov
authors.affiliation: Hofstra North Shore-LIJ School of Medicine at Hofstra University, Hempstead, New York, United States of America.|Laboratory of Medicinal Biochemistry, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Christine N
authors.initials: CN
authors.lastname: Metz
authors.affiliation: Laboratory of Biomedical Science, Center for Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.|Hofstra North Shore-LIJ School of Medicine at Hofstra University, Hempstead, New York, United States of America.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Tracey
authors.affiliation: Laboratory of Biomedical Science, Center for Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.|Hofstra North Shore-LIJ School of Medicine at Hofstra University, Hempstead, New York, United States of America.
authors.forename: Valentin A
authors.initials: VA
authors.lastname: Pavlov
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics; D016207:Cytokines / Q000097:blood / Q000235:genetics; D058851:GPI-Linked Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein; D007249:Inflammation / Q000097:blood / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008807:Mice, Inbred BALB C; D008840:Microfilament Proteins / Q000235:genetics; D009414:Nerve Growth Factors / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000235:genetics
chemical_list: C491049:Aif1 protein, mouse; C072167:CAT development factor; D002135:Calcium-Binding Proteins; D016207:Cytokines; D058851:GPI-Linked Proteins; D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; D008840:Microfilament Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; C528900:glial fibrillary astrocytic protein, mouse; D000110:Acetylcholinesterase; C548245:Ache protein, mouse