Peripheral lipopolysaccharide administration transiently affects expression of brain-derived neurotrophic factor, corticotropin and proopiomelanocortin in mouse brain.
Peripheral inflammation induced by intraperitoneal (i.p.) injection of Lipopolysaccharide (LPS) is known to cause functional impairments in the brain affecting memory and learning. One of mechanisms may be the interference with neurotrophin (NT) expression and function. In the current study we administered a single, high dose of LPS (3mg/kg, i.p.) into mice and investigated changes in brain-derived neurotrophic factor (BDNF) gene expression within 1-6 days after LPS injection. Crude synaptosomes were isolated from brain tissue and subjected to Western-blot analyses. We found transient reductions in synaptosomal proBDNF- and BDNF protein expression, with a maximal decrease at day 3 as compared to saline injected controls. The time course of reduction of BDNF mRNA in whole brain extracts parallels the decrease in protein levels in synaptosomes. LPS effects in the central nervous system (CNS) are known to crucially involve the activation of the hypothalamic-pituitary-adrenal (HPA) axis. We analysed the time course of corticotropin releasing hormone (CRH)- and proopiomelanocortin (POMC) mRNA expression. As observed for BDNF-, CRH- and POMC mRNA levels are also significantly reduced on day 3 indicating a comparable time course. These results suggest that peripheral inflammation causes a reduction of trophic supply in the brain, including BDNF at synaptic sites. The mechanisms involved could be a negative feedback of the activated HPA axis.
Schnydrig
Sabine
S
Department of Physiology, University of Basel, Pestalozzistrasse 25, CH-4056 Basel, Switzerland.
Korner
Lukas
L
Landweer
Svenja
S
Ernst
Beat
B
Walker
Gaby
G
Otten
Uwe
U
Kunz
Dieter
D
D000324:Adrenocorticotropic Hormone / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D004333:Drug Administration Routes; D015870:Gene Expression / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone