PMID- 22446058 OWN - NLM STAT- MEDLINE DCOM- 20120820 LR - 20211203 IS - 1872-7549 (Electronic) IS - 0166-4328 (Linking) VI - 231 IP - 1 DP - 2012 May 16 TI - Infusion of BDNF into the nucleus accumbens of aged rats improves cognition and structural synaptic plasticity through PI3K-ILK-Akt signaling. PG - 146-53 LID - 10.1016/j.bbr.2012.03.010 [doi] AB - To investigate the involvement of the nucleus accumbens (NAc) in cognitive impairment and the therapeutic effects of brain-derived neurotrophic factor (BDNF) in an animal model of cognitive deficit, we infused BDNF into the NAc of cognitively impaired aged rats. Cognition was evaluated by Morris water maze test. Structural synaptic plasticity was measured by Golgi staining. Brain tissue homogenization was used to measure the changes in signal molecules. Cultured PC-12 cells expressing tyrosine kinase receptor (Trk) B/p75 neurotrophin receptor (p75(NTR)), p75(NTR) or TrkA/p75(NTR) receptors were used for BDNF stimulation assays. Significant decreases in the levels of BDNF, phosphatidylinositol-3-kinase (PI3K) and integrin-linked kinase (ILK) activity, protein kinase B (Akt) Ser(4)(7)(3) phosphorylation, dendritic branching, and density of dendritic spines on medium spiny neurons were observed in the NAc. Importantly, infusion of BDNF restored cognition, synaptic plasticity, and cell signaling. In cultured PC-12 cells, BDNF activated PI3K/Akt signaling through the TrkB receptor, whereas stimulation of ILK/Akt occurred through TrkA/p75(NTR) heteroreceptor. Our study suggested that the decreased BDNF level and its downstream signaling as well as loss of synaptic plasticity in the NAc are associated with cognitive impairments in aged rats. The BDNF-activated PI3K-Akt and ILK-Akt signaling play a key role in structural synaptic plasticity. Our study also suggested that BDNF could be a mechanism-based treatment for dementia. CI - Copyright (c) 2012 Elsevier B.V. All rights reserved. FAU - Li, Min AU - Li M AD - Department of Neurology, Xiangya Hospital, Central South University, Changsha 410078, PR China. FAU - Dai, Fu-Rong AU - Dai FR FAU - Du, Xiao-Ping AU - Du XP FAU - Yang, Qi-Dong AU - Yang QD FAU - Zhang, Xiuwu AU - Zhang X FAU - Chen, Yuxiang AU - Chen Y LA - eng PT - Journal Article DEP - 20120315 PL - Netherlands TA - Behav Brain Res JT - Behavioural brain research JID - 8004872 RN - 0 (Brain-Derived Neurotrophic Factor) RN - EC 2.7.1.- (integrin-linked kinase) RN - EC 2.7.10.1 (Receptor, trkA) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Cognition/*drug effects MH - Dendrites/drug effects/metabolism MH - Neuronal Plasticity/*drug effects MH - Neurons/drug effects/metabolism MH - Nucleus Accumbens/*drug effects/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphorylation/drug effects MH - Protein Serine-Threonine Kinases/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, trkA/metabolism MH - Receptor, trkB/metabolism MH - Signal Transduction/*drug effects MH - Synapses/*drug effects/metabolism EDAT- 2012/03/27 06:00 MHDA- 2012/08/21 06:00 CRDT- 2012/03/27 06:00 PHST- 2012/01/05 00:00 [received] PHST- 2012/03/04 00:00 [revised] PHST- 2012/03/07 00:00 [accepted] PHST- 2012/03/27 06:00 [entrez] PHST- 2012/03/27 06:00 [pubmed] PHST- 2012/08/21 06:00 [medline] AID - S0166-4328(12)00189-1 [pii] AID - 10.1016/j.bbr.2012.03.010 [doi] PST - ppublish SO - Behav Brain Res. 2012 May 16;231(1):146-53. doi: 10.1016/j.bbr.2012.03.010. Epub 2012 Mar 15.