PMID- 11810035 OWN - NLM STAT- MEDLINE DCOM- 20020326 LR - 20180213 IS - 0028-3835 (Print) IS - 0028-3835 (Linking) VI - 75 IP - 1 DP - 2002 Jan TI - The neurotrophins NT3 and BDNF induce selective specification of neuropeptide coexpression and neuronal connectivity in arcuate and periventricular hypothalamic neurons in vitro. PG - 55-69 AB - Little is known on the influence of epigenetic factors in the developing hypothalamus, a region particularly involved in neuroendocrine regulation and rich in neuropeptides. The present study evaluated the effects of neurotrophins and neuronal activity on neuronal differentiation in hypothalamic cultures sampled from either arcuate or anterior periventricular regions of 17-day-old Sprague-Dawley fetuses. Expression of neuropeptides, tyrosine hydroxylase, neurotrophins and neurotrophin receptors was tested on young (6 days in vitro, DIV) and more mature (14 DIV) cultured neurons by multiple reverse transcription polymerase chain reaction on single cells. In parallel, spontaneous postsynaptic currents were recorded as an index of neuronal connectivity. Neurotrophin-3 (NT3) was expressed in a much larger population of neurons than brain-derived neurotrophic factor (BDNF) at both culture times. At 6 DIV, synaptic currents were scarce and expression of the neurotrophin receptors trkB and trkC was found in a small proportion of neurons only. These parameters increased markedly between 6 and 14 DIV, and also upon addition of neurotrophins. The most striking consequence of arcuate neuron maturation in vitro between 6 and 14 DIV was a marked phenotypic specification affecting somatostatin, neuropeptide Y and pro-opiomelanocortin, the three major neuropeptides expressed in the cultures. NT3, but not BDNF, was able to reproduce maturation-related phenotypic specification in 6 DIV arcuate cultures. Maturation-dependent phenotypic specification was less marked in periventricular cultures; in that case BDNF, not NT3 had a slight effect on phenotype specification. It is concluded that NT3 plays a selective role in phenotypic specification of neuropeptides in the arcuate region, whereas other maturation parameters (neurotrophin receptor expression and/or synaptogenesis) can be potentiated by either neurotrophin in both structures. CI - Copyright 2002 S. Karger AG, Basel FAU - Petit, Florence AU - Petit F AD - INSERM U159, Paris, France. FAU - Huicq, Severina AU - Huicq S FAU - Gardette, Robert AU - Gardette R FAU - Epelbaum, Jacques AU - Epelbaum J FAU - Loudes, Catherine AU - Loudes C FAU - Kordon, Claude AU - Kordon C FAU - Faivre-Bauman, Annie AU - Faivre-Bauman A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Switzerland TA - Neuroendocrinology JT - Neuroendocrinology JID - 0035665 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (DNA Primers) RN - 0 (Neuropeptide Y) RN - 0 (Neurotrophin 3) RN - 51110-01-1 (Somatostatin) RN - 66796-54-1 (Pro-Opiomelanocortin) RN - 88813-36-9 (Galanin) RN - 9034-39-3 (Growth Hormone-Releasing Hormone) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.10.1 (Receptor, trkC) SB - IM MH - Animals MH - Arcuate Nucleus of Hypothalamus/cytology/*physiology MH - Brain-Derived Neurotrophic Factor/*genetics MH - Cells, Cultured MH - DNA Primers MH - Galanin/genetics MH - Gene Expression/physiology MH - Growth Hormone-Releasing Hormone/genetics MH - In Vitro Techniques MH - Neural Pathways/physiology MH - Neurons/cytology/*physiology MH - Neuropeptide Y/genetics MH - Neurotrophin 3/*genetics MH - Paraventricular Hypothalamic Nucleus/cytology/*physiology MH - Patch-Clamp Techniques MH - Phenotype MH - Pro-Opiomelanocortin/genetics MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, trkB/genetics MH - Receptor, trkC/genetics MH - Somatostatin/genetics MH - Tyrosine 3-Monooxygenase/genetics EDAT- 2002/01/26 10:00 MHDA- 2002/03/27 10:01 CRDT- 2002/01/26 10:00 PHST- 2002/01/26 10:00 [pubmed] PHST- 2002/03/27 10:01 [medline] PHST- 2002/01/26 10:00 [entrez] AID - nen75055 [pii] AID - 10.1159/000048221 [doi] PST - ppublish SO - Neuroendocrinology. 2002 Jan;75(1):55-69. doi: 10.1159/000048221.