PMID- 24068826 OWN - NLM STAT- MEDLINE DCOM- 20131125 LR - 20220321 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 33 IP - 39 DP - 2013 Sep 25 TI - Early BDNF treatment ameliorates cell loss in the entorhinal cortex of APP transgenic mice. PG - 15596-602 LID - 10.1523/JNEUROSCI.5195-12.2013 [doi] AB - Brain-derived neurotrophic factor (BDNF) improves molecular, cellular, and behavioral measures of neural dysfunction in genetic models of Alzheimer's disease (Blurton-Jones et al., 2009; Nagahara et al., 2009). However, BDNF treatment after disease onset has not been reported to improve neuronal survival in these models. We now report prevention of neuronal loss with early life BDNF treatment in mutant mice expressing two amyloid precursor protein (APP) mutations associated with early-onset familial Alzheimer's disease. APP transgenic mice underwent lentiviral BDNF gene delivery into the entorhinal cortices at age 2 months and were examined 5 months later. BDNF-treated mice exhibited significant improvements in hippocampal-dependent contextual fear conditioning compared with control-treated APP mice (p < 0.05). Stereological analysis of entorhinal cortical cell number demonstrated approximately 20% reductions in neuronal number in layers II-VI of the entorhinal cortex in untreated APP mutant mice compared with wild-type mice (p < 0.0001), and significant amelioration of cell loss by BDNF (p < 0.001). Moreover, BDNF gene delivery improved synaptophysin immunoreactivity in the entorhinal cortex and, through anterograde BDNF transport, in the hippocampus (p < 0.01). Notably, BDNF did not affect amyloid plaque numbers, indicating that direct amyloid reduction is not necessary to achieve significant neuroprotective benefits in mutant amyloid models of Alzheimer's disease. FAU - Nagahara, Alan H AU - Nagahara AH AD - Department of Neurosciences-0626, University of California, San Diego, La Jolla, California 92093, and Veterans Affairs Medical Center, San Diego, California 92161. FAU - Mateling, Michael AU - Mateling M FAU - Kovacs, Imre AU - Kovacs I FAU - Wang, Ling AU - Wang L FAU - Eggert, Simone AU - Eggert S FAU - Rockenstein, Edward AU - Rockenstein E FAU - Koo, Edward H AU - Koo EH FAU - Masliah, Eliezer AU - Masliah E FAU - Tuszynski, Mark H AU - Tuszynski MH LA - eng GR - P01 AG010435/AG/NIA NIH HHS/United States GR - P50 AG005131/AG/NIA NIH HHS/United States GR - U01 AG043416/AG/NIA NIH HHS/United States GR - AG10435/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Synaptophysin) SB - IM MH - Alzheimer Disease/genetics/therapy MH - Amyloid beta-Protein Precursor/*genetics/metabolism MH - Animals MH - Brain-Derived Neurotrophic Factor/*genetics/metabolism MH - Cell Death/genetics MH - Conditioning, Classical MH - Entorhinal Cortex/*pathology MH - Fear MH - Genetic Therapy MH - Hippocampus/pathology MH - Mice MH - Mice, Transgenic MH - Plaque, Amyloid/metabolism MH - Protein Transport MH - Synaptophysin/genetics/metabolism PMC - PMC3782628 EDAT- 2013/09/27 06:00 MHDA- 2013/12/16 06:00 PMCR- 2014/03/25 CRDT- 2013/09/27 06:00 PHST- 2013/09/27 06:00 [entrez] PHST- 2013/09/27 06:00 [pubmed] PHST- 2013/12/16 06:00 [medline] PHST- 2014/03/25 00:00 [pmc-release] AID - 33/39/15596 [pii] AID - 5195-12 [pii] AID - 10.1523/JNEUROSCI.5195-12.2013 [doi] PST - ppublish SO - J Neurosci. 2013 Sep 25;33(39):15596-602. doi: 10.1523/JNEUROSCI.5195-12.2013.