PMID- 17976910 OWN - NLM STAT- MEDLINE DCOM- 20080321 LR - 20071123 IS - 0304-3940 (Print) IS - 0304-3940 (Linking) VI - 429 IP - 1 DP - 2007 Dec 11 TI - Peripheral lipopolysaccharide administration transiently affects expression of brain-derived neurotrophic factor, corticotropin and proopiomelanocortin in mouse brain. PG - 69-73 AB - 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. FAU - Schnydrig, Sabine AU - Schnydrig S AD - Department of Physiology, University of Basel, Pestalozzistrasse 25, CH-4056 Basel, Switzerland. FAU - Korner, Lukas AU - Korner L FAU - Landweer, Svenja AU - Landweer S FAU - Ernst, Beat AU - Ernst B FAU - Walker, Gaby AU - Walker G FAU - Otten, Uwe AU - Otten U FAU - Kunz, Dieter AU - Kunz D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071011 PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Lipopolysaccharides) RN - 0 (RNA, Messenger) RN - 66796-54-1 (Pro-Opiomelanocortin) RN - 9002-60-2 (Adrenocorticotropic Hormone) SB - IM MH - Adrenocorticotropic Hormone/genetics/*metabolism MH - Animals MH - Brain/*drug effects/metabolism MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Drug Administration Routes MH - Gene Expression/*drug effects MH - Lipopolysaccharides/*administration & dosage MH - Mice MH - Mice, Inbred C57BL MH - Pro-Opiomelanocortin/genetics/*metabolism MH - RNA, Messenger/biosynthesis MH - Time Factors EDAT- 2007/11/03 09:00 MHDA- 2008/03/22 09:00 CRDT- 2007/11/03 09:00 PHST- 2007/06/18 00:00 [received] PHST- 2007/09/24 00:00 [revised] PHST- 2007/09/27 00:00 [accepted] PHST- 2007/11/03 09:00 [pubmed] PHST- 2008/03/22 09:00 [medline] PHST- 2007/11/03 09:00 [entrez] AID - S0304-3940(07)01076-2 [pii] AID - 10.1016/j.neulet.2007.09.067 [doi] PST - ppublish SO - Neurosci Lett. 2007 Dec 11;429(1):69-73. doi: 10.1016/j.neulet.2007.09.067. Epub 2007 Oct 11.