PMID- 25852506 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20150408 LR - 20200929 IS - 1662-5153 (Print) IS - 1662-5153 (Electronic) IS - 1662-5153 (Linking) VI - 9 DP - 2015 TI - Impact of an additional chronic BDNF reduction on learning performance in an Alzheimer mouse model. PG - 58 LID - 10.3389/fnbeh.2015.00058 [doi] LID - 58 AB - There is increasing evidence that brain-derived neurotrophic factor (BDNF) plays a crucial role in Alzheimer's disease (AD) pathology. A number of studies demonstrated that AD patients exhibit reduced BDNF levels in the brain and the blood serum, and in addition, several animal-based studies indicated a potential protective effect of BDNF against Abeta-induced neurotoxicity. In order to further investigate the role of BDNF in the etiology of AD, we created a novel mouse model by crossing a well-established AD mouse model (APP/PS1) with a mouse exhibiting a chronic BDNF deficiency (BDNF(+/-)). This new triple transgenic mouse model enabled us to further analyze the role of BDNF in AD in vivo. We reasoned that in case BDNF has a protective effect against AD pathology, an AD-like phenotype in our new mouse model should occur earlier and/or in more severity than in the APP/PS1-mice. Indeed, the behavioral analysis revealed that the APP/PS1-BDNF(+/-)-mice show an earlier onset of learning impairments in a two-way active avoidance task in comparison to APP/PS1- and BDNF(+/-)-mice. However in the Morris water maze (MWM) test, we could not observe an overall aggrevated impairment in spatial learning and also short-term memory in an object recognition task remained intact in all tested mouse lines. In addition to the behavioral experiments, we analyzed the amyloid plaque pathology in the APP/PS1 and APP/PS1-BDNF(+/-)-mice and observed a comparable plaque density in the two genotypes. Moreover, our results revealed a higher plaque density in prefrontal cortical compared to hippocampal brain regions. Our data reveal that higher cognitive tasks requiring the recruitment of cortical networks appear to be more severely affected in our new mouse model than learning tasks requiring mainly sub-cortical networks. Furthermore, our observations of an accelerated impairment in active avoidance learning in APP/PS1-BDNF(+/-)-mice further supports the hypothesis that BDNF deficiency amplifies AD-related cognitive dysfunctions. FAU - Psotta, Laura AU - Psotta L AD - Institute of Physiology, Medical Faculty, Otto-von-Guericke-University Magdeburg Magdeburg, Germany. FAU - Rockahr, Carolin AU - Rockahr C AD - Department of Zoology/Developmental Neurobiology, Institute of Biology, Faculty of Natural Sciences, Otto-von-Guericke University Magdeburg Magdeburg, Germany. FAU - Gruss, Michael AU - Gruss M AD - Department of Zoology/Developmental Neurobiology, Institute of Biology, Faculty of Natural Sciences, Otto-von-Guericke University Magdeburg Magdeburg, Germany. FAU - Kirches, Elmar AU - Kirches E AD - Institute of Neuropathology, Faculty of Medicine, Otto-von-Guericke University Magdeburg Magdeburg, Germany. FAU - Braun, Katharina AU - Braun K AD - Department of Zoology/Developmental Neurobiology, Institute of Biology, Faculty of Natural Sciences, Otto-von-Guericke University Magdeburg Magdeburg, Germany ; Center for Behavioral Brain Sciences (CBBS), Otto-von-Guericke University Magdeburg Magdeburg, Germany. FAU - Lessmann, Volkmar AU - Lessmann V AD - Institute of Physiology, Medical Faculty, Otto-von-Guericke-University Magdeburg Magdeburg, Germany ; Center for Behavioral Brain Sciences (CBBS), Otto-von-Guericke University Magdeburg Magdeburg, Germany. FAU - Bock, Jorg AU - Bock J AD - Department of Zoology/Developmental Neurobiology, Institute of Biology, Faculty of Natural Sciences, Otto-von-Guericke University Magdeburg Magdeburg, Germany ; Center for Behavioral Brain Sciences (CBBS), Otto-von-Guericke University Magdeburg Magdeburg, Germany. FAU - Endres, Thomas AU - Endres T AD - Institute of Physiology, Medical Faculty, Otto-von-Guericke-University Magdeburg Magdeburg, Germany ; Center for Behavioral Brain Sciences (CBBS), Otto-von-Guericke University Magdeburg Magdeburg, Germany. LA - eng PT - Journal Article DEP - 20150320 PL - Switzerland TA - Front Behav Neurosci JT - Frontiers in behavioral neuroscience JID - 101477952 PMC - PMC4367180 OTO - NOTNLM OT - APP/PS1 OT - Alzheimer's disease OT - BDNF OT - active avoidance OT - object recognition OT - water maze EDAT- 2015/04/09 06:00 MHDA- 2015/04/09 06:01 PMCR- 2015/01/01 CRDT- 2015/04/09 06:00 PHST- 2014/10/14 00:00 [received] PHST- 2015/02/18 00:00 [accepted] PHST- 2015/04/09 06:00 [entrez] PHST- 2015/04/09 06:00 [pubmed] PHST- 2015/04/09 06:01 [medline] PHST- 2015/01/01 00:00 [pmc-release] AID - 10.3389/fnbeh.2015.00058 [doi] PST - epublish SO - Front Behav Neurosci. 2015 Mar 20;9:58. doi: 10.3389/fnbeh.2015.00058. eCollection 2015.