PMID- 8600296 OWN - NLM STAT- MEDLINE DCOM- 19960430 LR - 20071114 IS - 0360-4012 (Print) IS - 0360-4012 (Linking) VI - 42 IP - 5 DP - 1995 Dec TI - Brain-derived neurotrophic factor induces functional expression and phenotypic differentiation of cultured fetal neuropeptide Y-producing neurons. PG - 638-47 AB - A series of studies from our laboratory has established an aggregate culture system of fetal rat brain cells that can serve as a model for studying regulatory processes of the developing neuropeptide Y (NPY)-producing neurons. Using aggregate cultures derived from 17-day-old fetal rat cortex, we addressed these questions: 1) Does brain-derived neurotrophic factor (BDNF) stimulate NPY production, and if so, is stimulation a function of the developmental state of the cultured NPY neuron? 2) Does BDNF induce phenotypic differentiation of NPY neurons? BDNF led to an increase in NPY production and the accumulation of NPY-mRNA in a dose dependent manner. BDNF did not alter the stability of NPY-mRNA, judged by the disappearance rate of NPY-mRNA after blockade of RNA synthesis (estimated t1/2 was 6-8 hr). BDNF stimulation of NPY production was dependent on length of exposure to BDNF and on culture-age. A continuous 8-day exposure to BDNF resulted in a significantly higher level of NPY production than a pulse of 2 days (comparing BDNF exposure on days 0-8 vs. 6-8, or days 8-17 vs. 15-17). Moreover, older neurons (age 17 days) produced twice as much NPY as younger (age 8 days) neurons in response to a 2-day pulse of BDNF (50 ng/ml). BDNF was significantly more effective than NT-3 in inducing NPY production, and NGF was ineffective. Immunocytochemical analysis of 8-day NPY neurons revealed that a 2-day pulse of BDNF induced the appearance of an abundance of morphologically well-defined neurons bearing an elaborate network of neurites. This was in contrast to the control-treated NPY neurons, which were morphologically undefined. In summary, the age-dependent effect of BDNF on NPY production is consistent with induction of functional expression, rather than promotion of survival, of cultured NPY neurons. The neurotrophin specificity for stimulation of NPY production, and the lack of effect of BDNF on the stability of NPY-mRNA, implicate the TrkB receptor in mediating transcriptional activation of the NPY gene. Thus, BDNF exerts a dual effect on developing cultured NPY neurons: induction of functional expression, and phenotypic differentiation of immature neurons into mature neurite-bearing neurons. FAU - Barnea, A AU - Barnea A AD - Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas 75235-9032, USA. FAU - Cho, G AU - Cho G FAU - Lu, G AU - Lu G FAU - Mathis, M AU - Mathis M LA - eng GR - NS32207/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Iodine Radioisotopes) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neuropeptide Y) RN - 0 (Neurotrophin 3) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Blotting, Northern MH - Brain-Derived Neurotrophic Factor MH - Cell Differentiation/drug effects MH - Cell Survival/drug effects MH - Cells, Cultured MH - Immunohistochemistry MH - Iodine Radioisotopes MH - Nerve Growth Factors/*pharmacology MH - Nerve Tissue Proteins/*pharmacology MH - Neurons/cytology/drug effects/*metabolism MH - Neuropeptide Y/*biosynthesis/genetics MH - Neurotrophin 3 MH - Phenotype MH - RNA, Messenger/genetics/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Time Factors MH - Transcription, Genetic/drug effects EDAT- 1995/12/01 00:00 MHDA- 1995/12/01 00:01 CRDT- 1995/12/01 00:00 PHST- 1995/12/01 00:00 [pubmed] PHST- 1995/12/01 00:01 [medline] PHST- 1995/12/01 00:00 [entrez] AID - 10.1002/jnr.490420506 [doi] PST - ppublish SO - J Neurosci Res. 1995 Dec;42(5):638-47. doi: 10.1002/jnr.490420506.