PMID- 12749020 OWN - NLM STAT- MEDLINE DCOM- 20030716 LR - 20151119 IS - 0360-4012 (Print) IS - 0360-4012 (Linking) VI - 72 IP - 5 DP - 2003 Jun 1 TI - EGF and NGF injected into the brain of old mice enhance BDNF and ChAT in proliferating subventricular zone. PG - 557-64 AB - The response of cells localized in the brain subventricular zone (SVZ) to growth factor stimulation has been largely described for development and adult life, whereas no information on their behavior during aging is available. To address the question of whether the cells in the SVZ of old mice respond to the intracerebroventricular administration of epidermal growth factor (EGF) and nerve growth factor (NGF), we studied the distribution of proliferating cells and the effects on ChAT and brain-derived neurotrophic factor (BDNF) synthesis in forebrain and SVZ. It was found that the conjoint administration of EGF + NGF produced a major increase in ChAT expression in both forebrain and SVZ. The ChAT mRNA levels and the number of ChAT positive cells localized in the ventricular border and in the parenchyma of SVZ area were also increased significantly in the mice receiving EGF + NGF. Enhanced numbers of SVZ cells expressing proliferative markers were also discovered in EGF + NGF treated mice and some of these cells expressed cholinergic markers, as demonstrated by double immunostaining. In addition, EGF and NGF treatments significantly upregulate BDNF protein and mRNA levels in this brain region. The present study demonstrates that cells localized in SVZ of aged mouse brain retain the capacity to respond to EGF and NGF and that after stimulation with these two growth factors, the synthesis of ChAT and BDNF also increases. The implication that cells of the SVZ remain a reservoir of cholinergic and BDNF-positive neurons in aged brain opens a new perspective for understanding the role of growth factors during neurodegenerative disorders associated with aging. CI - Copyright 2003 Wiley-Liss, Inc. FAU - Tirassa, Paola AU - Tirassa P AD - Istituto di Neurobiologia e Medicina Molecolare, Rome, Italy. FAU - Triaca, Viviana AU - Triaca V FAU - Amendola, Tiziana AU - Amendola T FAU - Fiore, Marco AU - Fiore M FAU - Aloe, Luigi AU - Aloe L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Ki-67 Antigen) RN - 0 (RNA, Messenger) RN - 62229-50-9 (Epidermal Growth Factor) RN - 9061-61-4 (Nerve Growth Factor) RN - EC 2.3.1.6 (Choline O-Acetyltransferase) RN - G34N38R2N1 (Bromodeoxyuridine) RN - N9YNS0M02X (Acetylcholine) SB - IM MH - Acetylcholine/biosynthesis MH - Aging/*metabolism MH - Animals MH - Brain/cytology/*drug effects/*growth & development MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Bromodeoxyuridine MH - Cell Division/drug effects/genetics MH - Choline O-Acetyltransferase/genetics/*metabolism MH - Drug Interactions/physiology MH - Drug Therapy, Combination MH - Epidermal Growth Factor/*pharmacology MH - Immunohistochemistry MH - Ki-67 Antigen/metabolism MH - Male MH - Mice MH - Nerve Growth Factor/*pharmacology MH - Neurons/cytology/*drug effects/metabolism MH - RNA, Messenger/drug effects/metabolism MH - Stem Cells/cytology/*drug effects/metabolism MH - Up-Regulation/drug effects/genetics EDAT- 2003/05/16 05:00 MHDA- 2003/07/17 05:00 CRDT- 2003/05/16 05:00 PHST- 2003/05/16 05:00 [pubmed] PHST- 2003/07/17 05:00 [medline] PHST- 2003/05/16 05:00 [entrez] AID - 10.1002/jnr.10614 [doi] PST - ppublish SO - J Neurosci Res. 2003 Jun 1;72(5):557-64. doi: 10.1002/jnr.10614.