Editing Brain-derived neurotrophic factor (section)

==== Synapse stability ====

In addition to mediating transient effects on NMDAR activation to promote memory-related molecular changes, BDNF should also initiate more stable effects that could be maintained in its absence and not depend on its expression for long term synaptic support.<ref name="pmid14706865">{{cite journal | vauthors = Briones TL, Suh E, Jozsa L, Hattar H, Chai J, Wadowska M | title = Behaviorally-induced ultrastructural plasticity in the hippocampal region after cerebral ischemia | journal = Brain Research | volume = 997 | issue = 2 | pages = 137–46 | date = February 2004 | pmid = 14706865 | doi = 10.1016/j.brainres.2003.10.030 | s2cid = 34763792 }}</ref>
It was previously mentioned that [[AMPA]] receptor expression is essential to learning and memory formation, as these are the components of the synapse that will communicate regularly and maintain the synapse structure and function long after the initial activation of NMDA channels.  BDNF is capable of increasing the mRNA expression of GluR1 and GluR2 through its interaction with the TrkB receptor and promoting the synaptic localization of [[GluR1]] via PKC- and CaMKII-mediated Ser-831 phosphorylation.<ref name="pmid17337442">{{cite journal | vauthors = Caldeira MV, Melo CV, Pereira DB, Carvalho R, Correia SS, Backos DS, Carvalho AL, Esteban JA, Duarte CB | title = Brain-derived neurotrophic factor regulates the expression and synaptic delivery of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunits in hippocampal neurons | journal = The Journal of Biological Chemistry | volume = 282 | issue = 17 | pages = 12619–28 | date = April 2007 | pmid = 17337442 | doi = 10.1074/jbc.M700607200 | doi-access = free }}</ref>  It also appears that BDNF is able to influence [[Gl1]] activity through its effects on NMDA receptor activity.<ref name="Wu_2004">{{cite journal | vauthors = Wu K, Len GW, McAuliffe G, Ma C, Tai JP, Xu F, Black IB | title = Brain-derived neurotrophic factor acutely enhances tyrosine phosphorylation of the AMPA receptor subunit GluR1 via NMDA receptor-dependent mechanisms | journal = Brain Research. Molecular Brain Research | volume = 130 | issue = 1–2 | pages = 178–86 | date = November 2004 | pmid = 15519688 | doi = 10.1016/j.molbrainres.2004.07.019 }}</ref>  BDNF significantly enhanced the activation of GluR1 through phosphorylation of tyrosine830, an effect that was abolished in either the presence of a specific [[NR2B]] antagonist or a trk receptor tyrosine kinase inhibitor.<ref name="Wu_2004"/> Thus, it appears BDNF can upregulate the expression and synaptic localization of AMPA receptors, as well as enhance their activity through its postsynaptic interactions with the NR2B subunit. Further, BDNF can regulate the nanoscale architecture of adhesion proteins such as [[Neogenin]] which are essential for spine enlargement and activity.<ref name="pmid39228790">{{cite journal | vauthors = Shohayeb B, Sempert K, Wallis TP, Meunier FA, Durisic N, O'Brien EA, Flores C, Cooper HM | title = BDNF-dependent nano-organization of Neogenin and the WAVE regulatory complex promotes actin remodeling in dendritic spines | journal = iScience | volume = 27 | issue = 9 | pages = 2589-0042 | date = September 2024 | pmid = 39228790| doi = 10.1016/j.isci.2024.110621 | pmc = 11369513 }}</ref> This suggests BDNF is not only capable of initiating synapse formation through its effects on NMDA receptor activity, but it can also support the regular every-day signaling necessary for stable memory function.