title: An electrophysiological study on the effects of BDNF and FGF2 on voltage dependent Ca(2+) currents in developing human striatal primordium.
abstract: Over the past decades, studies in both Huntington's disease animal models and pilot clinical trials have demonstrated that replacement of degenerated striatum and repair of circuitries by grafting fetal striatal primordium is feasible, safe and may counteract disease progression. However, a better comprehension of striatal ontogenesis is required to assess the fetal graft regenerative potential. During neuronal development, neurotrophins exert pleiotropic actions in regulating cell fate and synaptic plasticity. In this regard, brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 2 (FGF2) are crucially implicated in the control of fate choice of striatal progenitor cells. In this study, we intended to refine the functional features of human striatal precursor (HSP) cells isolated from ganglionic eminence of 9-12week old human fetuses, by studying with electrophysiological methods the effect of BDNF and FGF2 on the membrane biophysical properties and the voltage-dependent Ca(2+) currents. These features are particularly relevant to evaluate neuronal cell functioning and can be considered reliable markers of the developmental phenotype of human striatal primordium. Our results have demonstrated that BDNF and FGF2 induced membrane hyperpolarization, increased the membrane capacitance and reduced the resting total and specific conductance values, suggesting a more efficient control of resting ionic fluxes. Moreover, the treatment with both neurotrophins enhanced N-type Ca(2+) current amplitude and reduced L- and T-type ones. Overall, our data indicate that BDNF and FGF2 may help HSP cells to attain a more functionally mature phenotype.
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, viale Morgagni 63, 50134 Florence, Italy. Electronic address: roberta.squecco@unifi.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Squecco
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, viale Morgagni 63, 50134 Florence, Italy.
authors.forename: Eglantina
authors.initials: E
authors.lastname: Idrizaj
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Morelli
authors.affiliation: Department of Surgery and Translational Medicine, University of Florence, Largo Palagi 1, 50139 Florence, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Gallina
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
authors.forename: Gabriella B
authors.initials: GB
authors.lastname: Vannelli
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, viale Morgagni 63, 50134 Florence, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Francini
mesh_terms: D000200:Action Potentials; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology*; D055495:Neurogenesis
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015220:Calcium Channels; D016222:Fibroblast Growth Factor 2
keywords: Electrophysiology; Human striatal primordium; Neurotrophic factor BDNF; Neurotrophic factor FGF2