PMID- 16856871 OWN - NLM STAT- MEDLINE DCOM- 20060914 LR - 20060721 IS - 0300-5127 (Print) IS - 0300-5127 (Linking) VI - 34 IP - Pt 4 DP - 2006 Aug TI - Brain-derived neurotrophic factor and control of synaptic consolidation in the adult brain. PG - 600-4 AB - Interest in BDNF (brain-derived neurotrophic factor) as an activity-dependent modulator of neuronal structure and function in the adult brain has intensified in recent years. Localization of BDNF and its receptor tyrosine kinase TrkB (tropomyosin receptor kinase B) to glutamate synapses makes this system attractive as a dynamic, activity-dependent regulator of excitatory transmission and synaptic plasticity in the adult brain. Development of stable LTP (long-term potentiation) in response to high-frequency stimulation requires new gene expression and protein synthesis, a process referred to as synaptic consolidation. Several lines of evidence have implicated endogenous BDNF-TrkB signalling in synaptic consolidation. This mini-review emphasizes new insights into the molecular mechanisms underlying this process. The immediate early gene Arc (activity-regulated cytoskeleton-associated protein) is strongly induced and transported to dendritic processes after LTP induction in the dentate gyrus in live rats. Recent work suggests that sustained synthesis of Arc during a surprisingly protracted time-window is required for hyperphosphorylation of actin-depolymerizing factor/cofilin and local expansion of the actin cytoskeleton in vivo. Moreover, this process of Arc-dependent synaptic consolidation is activated in response to brief infusion of BDNF. Microarray expression profiling has also revealed a panel of BDNF-regulated genes that may co-operate with Arc during LTP maintenance. In addition to regulating gene expression, BDNF signalling modulates the fine localization and biochemical activation of the translation machinery. By modulating the spatial and temporal translation of newly induced (Arc) and constitutively expressed mRNA in neuronal dendrites, BDNF may effectively control the window of synaptic consolidation. These findings have implications for mechanisms of memory storage and mood control. FAU - Soule, J AU - Soule J AD - Department of Biomedicine and Bergen Mental Health Research Center, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway. FAU - Messaoudi, E AU - Messaoudi E FAU - Bramham, C R AU - Bramham CR LA - eng PT - Journal Article PT - Review PL - England TA - Biochem Soc Trans JT - Biochemical Society transactions JID - 7506897 RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Aging/*physiology MH - Animals MH - Brain/*metabolism MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Models, Neurological MH - Protein Transport MH - Synapses/*metabolism RF - 50 EDAT- 2006/07/22 09:00 MHDA- 2006/09/15 09:00 CRDT- 2006/07/22 09:00 PHST- 2006/07/22 09:00 [pubmed] PHST- 2006/09/15 09:00 [medline] PHST- 2006/07/22 09:00 [entrez] AID - BST0340600 [pii] AID - 10.1042/BST0340600 [doi] PST - ppublish SO - Biochem Soc Trans. 2006 Aug;34(Pt 4):600-4. doi: 10.1042/BST0340600.