PMID- 29156571 OWN - NLM STAT- MEDLINE DCOM- 20180702 LR - 20181207 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 22 IP - 11 DP - 2017 Nov 18 TI - Studies for Improving a Rat Model of Alzheimer's Disease: Icv Administration of Well-Characterized beta-Amyloid 1-42 Oligomers Induce Dysfunction in Spatial Memory. LID - 10.3390/molecules22112007 [doi] LID - 2007 AB - During the past 15 years, several genetically altered mouse models of human Alzheimer's disease (AD) have been developed. These costly models have greatly facilitated the evaluation of novel therapeutic approaches. Injecting synthetic beta-amyloid (Abeta) 1-42 species into different parts of the brain of non-transgenic rodents frequently provided unreliable results, owing to a lack of a genuine characterization of the administered Abeta aggregates. Previously, we have published a new rat AD-model in which protofibrillar-fibrillar Abeta1-42 was administered into rat entorhinal cortex (Sipos 2007). In order to develop a more reliable model, we have injected well-characterized toxic soluble Abeta1-42 species (oligomers, protofibrils and fibrils) intracerebroventricularly (icv) into rat brain. Studies of the distribution of fluorescent-labeled Abeta1-42 in the brain showed that soluble Abeta-species diffused into all parts of the rat brain. After seven days, the Abeta-treated animals showed a significant decrease of spatial memory in Morris water maze test and impairment of synaptic plasticity (LTP) measured in acute hippocampal slices. The results of histological studies (decreased number of viable neurons, increased tau levels and decreased number of dendritic spines) also supported that icv administration of well-characterized toxic soluble Abeta species into rat brain provides a reliable rat AD-model. FAU - Kasza, Agnes AU - Kasza A AD - Department of Medical Chemistry, University of Szeged, Dome square 8, Szeged H-6720, Hungary. kaszagi@gmail.com. FAU - Penke, Botond AU - Penke B AD - Department of Medical Chemistry, University of Szeged, Dome square 8, Szeged H-6720, Hungary. penke.botond@med.u-szeged.hu. FAU - Frank, Zsuzsanna AU - Frank Z AD - Department of Medical Chemistry, University of Szeged, Dome square 8, Szeged H-6720, Hungary. frankzsu@gmail.com. FAU - Bozso, Zsolt AU - Bozso Z AD - Department of Medical Chemistry, University of Szeged, Dome square 8, Szeged H-6720, Hungary. bozso.zsolt@med.u-szeged.hu. FAU - Szegedi, Viktor AU - Szegedi V AUID- ORCID: 0000-0003-4191-379X AD - Department of Medical Chemistry, University of Szeged, Dome square 8, Szeged H-6720, Hungary. szegv@yahoo.com. FAU - Hunya, Akos AU - Hunya A AD - LipidArt Research and Development Ltd., Temesvari krt. 62, Szeged H-6726, Hungary. akos.hunya@lipidart.com. FAU - Nemeth, Klaudia AU - Nemeth K AD - Department of Medical Chemistry, University of Szeged, Dome square 8, Szeged H-6720, Hungary. klausz20@gmail.com. FAU - Kozma, Gabor AU - Kozma G AD - Department of Applied and Environmental Chemistry, University of Szeged, Rerrich Bela square 1, Szeged H-6720, Hungary. kozmag@chem.u-szeged.hu. FAU - Fulop, Livia AU - Fulop L AD - Department of Medical Chemistry, University of Szeged, Dome square 8, Szeged H-6720, Hungary. fulop.livia@med.u-szeged.hu. LA - eng PT - Journal Article DEP - 20171118 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 0 (Amyloid beta-Peptides) SB - IM MH - Alzheimer Disease/*drug therapy/physiopathology MH - Amyloid beta-Peptides/administration & dosage/*therapeutic use MH - Animals MH - Disease Models, Animal MH - Male MH - Maze Learning/drug effects MH - Rats MH - Spatial Memory/*drug effects PMC - PMC6150403 OTO - NOTNLM OT - AD rat model OT - Golgi staining OT - Morris water maze OT - amyloid beta OT - hippocampus OT - icv administration OT - long-term potentiation OT - spatial memory COIS- The authors declare no conflict of interest. EDAT- 2017/11/22 06:00 MHDA- 2018/07/03 06:00 PMCR- 2017/11/18 CRDT- 2017/11/22 06:00 PHST- 2017/10/09 00:00 [received] PHST- 2017/11/07 00:00 [revised] PHST- 2017/11/13 00:00 [accepted] PHST- 2017/11/22 06:00 [entrez] PHST- 2017/11/22 06:00 [pubmed] PHST- 2018/07/03 06:00 [medline] PHST- 2017/11/18 00:00 [pmc-release] AID - molecules22112007 [pii] AID - molecules-22-02007 [pii] AID - 10.3390/molecules22112007 [doi] PST - epublish SO - Molecules. 2017 Nov 18;22(11):2007. doi: 10.3390/molecules22112007.