PMID- 11724927 OWN - NLM STAT- MEDLINE DCOM- 20020110 LR - 20181113 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 98 IP - 25 DP - 2001 Dec 4 TI - A caged Ab reveals an immediate/instructive effect of BDNF during hippocampal synaptic potentiation. PG - 14702-7 AB - Neurotrophins have been shown to be involved in functional strengthening of central nervous system synapses. Although their general importance in this process is undisputed, it remains unresolved whether neurotrophins are truly mediators of synaptic strengthening or merely important cofactors. To address this question, we have devised a method to inactivate endogenous brain-derived neurotrophic factor (BDNF) with high time resolution by "caging" a function-blocking mAb against BDNF with a photosensitive protecting compound. Different assays were used to show that this inactivation of the Ab is reversible by UV light. Synaptic potentiation after theta-burst [corrected] stimulation in the CA1 region of acute hippocampal slices was significantly less when applying the unmodified Ab compared with the caged Ab. Importantly, photoactivation of the caged Ab during the time of induction of synaptic enhancement led to a marked decrease in potentiation. Our experiments therefore strengthen the view that endogenous BDNF has fast effects during induction of synaptic plasticity. The results additionally show that caged Abs can provide a tool for precise spatiotemporal control over endogenous protein levels. FAU - Kossel, A H AU - Kossel AH AD - Max-Planck-Institut fur Neurobiologie, 82152 Munchen-Martinsried, Germany. FAU - Cambridge, S B AU - Cambridge SB FAU - Wagner, U AU - Wagner U FAU - Bonhoeffer, T AU - Bonhoeffer T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20011127 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Antibodies, Monoclonal) RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM EIN - Proc Natl Acad Sci U S A 2002 Jan 8;99(1):541 MH - Animals MH - Antibodies, Monoclonal/chemistry/radiation effects MH - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/immunology/*physiology MH - Female MH - Hippocampus/*physiology MH - In Vitro Techniques MH - Long-Term Potentiation/physiology MH - Mice MH - Photobiology MH - Time Factors PMC - PMC64745 EDAT- 2001/11/29 10:00 MHDA- 2002/01/11 10:01 PMCR- 2002/06/04 CRDT- 2001/11/29 10:00 PHST- 2001/11/29 10:00 [pubmed] PHST- 2002/01/11 10:01 [medline] PHST- 2001/11/29 10:00 [entrez] PHST- 2002/06/04 00:00 [pmc-release] AID - 251326998 [pii] AID - 3269 [pii] AID - 10.1073/pnas.251326998 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14702-7. doi: 10.1073/pnas.251326998. Epub 2001 Nov 27.