An Efficient and Versatile System for Visualization and Genetic Modification of Dopaminergic Neurons in Transgenic Mice.

BACKGROUND & AIMS: The brain dopaminergic (DA) system is involved in fine tuning many behaviors and several human diseases are associated with pathological alterations of the DA system such as Parkinson's disease (PD) and drug addiction. Because of its complex network integration, detailed analyses of physiological and pathophysiological conditions are only possible in a whole organism with a sophisticated tool box for visualization and functional modification. METHODS & RESULTS: Here, we have generated transgenic mice expressing the tetracycline-regulated transactivator (tTA) or the reverse tetracycline-regulated transactivator (rtTA) under control of the tyrosine hydroxylase (TH) promoter, TH-tTA (tet-OFF) and TH-rtTA (tet-ON) mice, to visualize and genetically modify DA neurons. We show their tight regulation and efficient use to overexpress proteins under the control of tet-responsive elements or to delete genes of interest with tet-responsive Cre. In combination with mice encoding tet-responsive luciferase, we visualized the DA system in living mice progressively over time. CONCLUSION: These experiments establish TH-tTA and TH-rtTA mice as a powerful tool to generate and monitor mouse models for DA system diseases

I linguaggi dell'organizzare

I linguaggi dell’organizzare contiene otto scritti molto diversi tra loro, che hanno in comune un percorso di ricerca fortemente strutturato e condiviso. I linguaggi dell’organizzare è una ricerca che coinvolge studiosi di differente scaturigine teorico-disciplare: economisti, fisici, filosofi, neuroscienziati, storici. I linguaggi dell’organizzare pone al centro dell’azione di ricerca i musicisti nella triplice veste di ricercatori e studiosi, compositori e interpreti. I linguaggi dell’organizzare affida ai musicisti una potenzialità deliberante, nei processi di produzione del sapere, che consente a ciasuno studioso di discostarsi dal proprio modello intradisciplinare, in nome del “senso del dono” e di uno scambio interdisciplinare. I linguaggi dell’organizzare si connota come una “impresa”: da impresum, participio passato di imprendere, prendere su di sé. Quindi prefiggersi che nel mondo antico ha a che fare con il riconoscimento di un precetto che è anche intento morale, quindi norma. Perché fare impresa significa con-tenere esperienze, che processano apprendimento, per generare nuove esperienze. I linguaggi dell’organizzare mette in circolazione saperi eterogenei che possono stare insieme, e confrontarsi, e crescere attraverso una capacità riproduttiva, che e mimesis, imitazione, fonte di pensiero critico, quindi contaminazione per la creazione di nuove imprese. Per fare reale innovazione: di prodotto, di processo

BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra

Brain-derived neurotrophic factor (BDNF), present in minute amounts in the adult central nervous system, is a member of the nerve growth factor (NGF) family, which includes neurotrophin-3 (NT-3). NGF, BDNF and NT-3 all support survival of subpopulations of neural crest-derived sensory neurons; most sympathetic neurons are responsive to NGF, but not to BDNF; NT-3 and BDNF, but not NGF, promote survival of sensory neurons of the nodose ganglion. BDNF, but not NGF, supports the survival of cultured retinal ganglion cells but both NGF and BDNF promote the survival of septal cholinergic neurons in vitro. However, knowledge of their precise physiological role in development and maintenance of the nervous system neurons is still limited. The BDNF gene is expressed in many regions of the adult CNS, including the striatum. A protein partially purified from bovine striatum, a target of nigral dopaminergic neurons, with characteristics apparently similar to those of BDNF, can enhance the survival of dopaminergic neurons in mesencephalic cultures. BDNF seems to be a trophic factor for mesencephalic dopaminergic neurons, increasing their survival, including that of neuronal cells which degenerate in Parkinson's disease. Here we report the effects of BDNF on the survival of dopaminergic neurons of the developing substantia nigra