PMID- 12960034 OWN - NLM STAT- MEDLINE DCOM- 20031203 LR - 20091119 IS - 0013-7227 (Print) IS - 0013-7227 (Linking) VI - 144 IP - 11 DP - 2003 Nov TI - Estrogen enhances retrograde transport of brain-derived neurotrophic factor in the rodent forebrain. PG - 5022-9 AB - The neurotrophins and their receptors activate signaling molecules to regulate neural function in development and adulthood. Neurons in the septum-diagonal band complex (or basal forebrain) derive neurotrophins through retrograde transport of these peptides from their forebrain targets. The present study tests the hypothesis that the gonadal hormone estrogen enhances retrograde transport of the neurotrophin brain-derived neurotrophic factor (BDNF). Estrogen increases BDNF expression in the horizontal limb of the diagonal band of Broca (hlDBB) and its forebrain target the olfactory bulb. In the present study, rhodamine-labeled (Rho-) BDNF injected into the olfactory bulb was rapidly transferred to neurons in the hlDBB. Significantly greater numbers of hlDBB neurons were retrogradely labeled with Rho-BDNF in animals pretreated with estrogen, compared with placebo-replaced controls. Anti-tyrosine kinase (trk) B antibodies injected into the olfactory bulb attenuated retrograde transport of Rho-BDNF in a dose-dependent manner, suggesting that estrogen may enhance BDNF transport in this circuit through regulation of its trk receptor. Anti-trkB antibodies also reduced cAMP response element binding protein phosphorylation in the hlDBB and combined injections of anti-trkA and trkB in the olfactory bulb reduced estrogen-induced increases in basal forebrain choline acetyltransferase. These studies support the hypothesis that estrogen facilitates neurotrophin transport in forebrain circuits. FAU - Jezierski, Melinda K AU - Jezierski MK AD - Department of Human Anatomy and Medical Neurobiology, Texas A&M University System Health Science Center, College Station, Texas 77843, USA. FAU - Sohrabji, Farida AU - Sohrabji F LA - eng GR - AG19515/AG/NIA NIH HHS/United States GR - NS36297/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. DEP - 20030731 PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (Antibodies) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Drug Combinations) RN - 0 (Estrogens) RN - 0 (Rhodamines) RN - EC 2.3.1.6 (Choline O-Acetyltransferase) RN - EC 2.7.10.1 (Receptor, trkA) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Antibodies/administration & dosage MH - Biological Transport, Active/drug effects MH - Brain-Derived Neurotrophic Factor/*pharmacokinetics MH - Choline O-Acetyltransferase/antagonists & inhibitors MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Diagonal Band of Broca/cytology/metabolism MH - Dose-Response Relationship, Drug MH - Drug Combinations MH - Estrogens/*pharmacology MH - Female MH - Neurons/metabolism MH - Olfactory Bulb/metabolism MH - Phosphorylation/drug effects MH - Prosencephalon/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, trkA/immunology MH - Receptor, trkB/immunology MH - Rhodamines EDAT- 2003/09/10 05:00 MHDA- 2003/12/04 05:00 CRDT- 2003/09/10 05:00 PHST- 2003/09/10 05:00 [pubmed] PHST- 2003/12/04 05:00 [medline] PHST- 2003/09/10 05:00 [entrez] AID - en.2003-0724 [pii] AID - 10.1210/en.2003-0724 [doi] PST - ppublish SO - Endocrinology. 2003 Nov;144(11):5022-9. doi: 10.1210/en.2003-0724. Epub 2003 Jul 31.