PMID- 29458098 OWN - NLM STAT- MEDLINE DCOM- 20190916 LR - 20190916 IS - 1095-9564 (Electronic) IS - 1074-7427 (Linking) VI - 149 DP - 2018 Mar TI - Spermine protects from LPS-induced memory deficit via BDNF and TrkB activation. PG - 135-143 LID - S1074-7427(18)30032-7 [pii] LID - 10.1016/j.nlm.2018.02.012 [doi] AB - Lipopolysaccharide (LPS) has been long known to promote neuroinflammation and learning and memory deficits. Since spermine, one of the main natural polyamines in the central nervous system, protects from LPS-induced memory deficit by a mechanism that comprises GluN2B receptors, the aim of the present study was to determine whether brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB) receptor and cAMP response element binding (CREB) are involved in this protective effect of spermine. Adult male Swiss albino mice received, immediately after training in the novel object recognition task, saline or LPS (250 mug/kg, i.p.); 5 min later they received saline or spermine (0.3 mg/kg, i.p.) and, when specified, 5 min thereafter saline or the TrkB receptor antagonist ANA-12 (0.5 mg/kg, i.p.) in different flanks. Animals were tested 24 h after training. Spermine protected from LPS-induced memory deficit and this protective effect was reversed by ANA-12. In a subset of animals BDNF, CREB and phospho-CREB immunoreactivity was determined in the hippocampi and cerebral cortex 4 h after spermine injection. Spermine reversed the decrease of mature BDNF levels induced by LPS in both hippocampus and cerebral cortex. Spermine increased phospho-CREB content and phospho-CREB/total CREB ratio in the cerebral cortex of LPS-treated mice. The results support that the protective effect of spermine on LPS-induced memory deficits depends on TrkB receptor activation and is accompanied by restoration of mature BDNF levels in hippocampus and cerebral cortex, as well as increased CREB phosphorylation in the cerebral cortex. CI - Copyright (c) 2018. Published by Elsevier Inc. FAU - Fruhauf-Perez, Pamella K AU - Fruhauf-Perez PK AD - Graduate Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil. FAU - Temp, Fernanda R AU - Temp FR AD - Graduate Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil. FAU - Pillat, Micheli M AU - Pillat MM AD - Biochemistry Department, Chemistry Institute, University of Sao Paulo, 05508-900, Brazil. FAU - Signor, Cristiane AU - Signor C AD - Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, RS, Brazil. FAU - Wendel, Arithane Lorena AU - Wendel AL AD - Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, RS, Brazil. FAU - Ulrich, Henning AU - Ulrich H AD - Biochemistry Department, Chemistry Institute, University of Sao Paulo, 05508-900, Brazil. FAU - Mello, Carlos F AU - Mello CF AD - Graduate Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil. Electronic address: cf.mello@smail.ufsm.br. FAU - Rubin, Maribel A AU - Rubin MA AD - Graduate Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil; Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, RS, Brazil. Electronic address: marubin@smail.ufsm.br. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180216 PL - United States TA - Neurobiol Learn Mem JT - Neurobiology of learning and memory JID - 9508166 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Lipopolysaccharides) RN - 0 (Membrane Glycoproteins) RN - 0 (Neuroprotective Agents) RN - 2FZ7Y3VOQX (Spermine) RN - EC 2.7.10.1 (Ntrk2 protein, mouse) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Hippocampus/*drug effects/metabolism MH - Lipopolysaccharides MH - Male MH - Membrane Glycoproteins/*metabolism MH - Memory Disorders/chemically induced/*metabolism MH - Mice MH - Neuroprotective Agents/*pharmacology MH - Phosphorylation/drug effects MH - Protein-Tyrosine Kinases/*metabolism MH - Signal Transduction/drug effects MH - Spermine/*pharmacology OTO - NOTNLM OT - ANA-12 OT - CREB OT - NMDA receptor OT - Neuroinflammation OT - Object recognition task OT - Polyamines EDAT- 2018/02/20 06:00 MHDA- 2019/09/17 06:00 CRDT- 2018/02/20 06:00 PHST- 2017/08/30 00:00 [received] PHST- 2018/01/18 00:00 [revised] PHST- 2018/02/14 00:00 [accepted] PHST- 2018/02/20 06:00 [pubmed] PHST- 2019/09/17 06:00 [medline] PHST- 2018/02/20 06:00 [entrez] AID - S1074-7427(18)30032-7 [pii] AID - 10.1016/j.nlm.2018.02.012 [doi] PST - ppublish SO - Neurobiol Learn Mem. 2018 Mar;149:135-143. doi: 10.1016/j.nlm.2018.02.012. Epub 2018 Feb 16.