Brain-Derived Neurotrophic Factor in Patients with Huntington's Disease

Reduced Brain-Derived Neurotrophic Factor (BDNF) levels have been described in a number of patho-physiological conditions, most notably, in Huntington's disease (HD), a progressive neurodegenerative disorder. Since BDNF is also produced in blood, we have undertaken the measurement of its peripheral levels in the attempt to identify a possible link with HD prognosis and/or its progression. Here we evaluated BDNF level in 398 blood samples including 138 controls, 56 preHD, and 204 HD subjects. We found that BDNF protein levels were not reliably different between groups, whether measured in plasma (52 controls, 26 preHD, 105 HD) or serum (39 controls, 5 preHD, 29 HD). Our experience, and a reanalysis of the literature highlighted that intra-group variability and methodological aspects affect this measurement, especially in serum. We also assessed BDNF mRNA levels in blood samples from 47 controls, 25 preHD, and 70 HD subjects, and found no differences among the groups. We concluded that levels of BDNF in human blood were not informative (mRNA levels or plasma protein level) nor reliable (serum protein levels) as HD biomarkers. We also wish to warn the scientific community in interpreting the significance of changes measured in BDNF protein levels in serum from patients suffering from different conditions

Adenosine A2A receptors modulate BDNF both in normal conditions and in experimental models of Huntington’s disease

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, enhances synaptic transmission and regulates neuronal proliferation and survival. Functional interactions between adenosine A2A receptors (A2ARs) and BDNF have been recently reported. In this article, we report some recent findings from our group showing that A2ARs regulate both BDNF functions and levels in the brain. Whereas BDNF (10 ng/ml) increased the slope of excitatory postsynaptic field potentials (fEPSPs) in hippocampal slices from wild-type (WT) mice, it was completely ineffective in slices taken from A2AR knock-out (KO) mice. Furthermore, enzyme immunoassay studies showed a significant reduction in hippocampal BDNF levels in A2AR KO vs. WT mice. Having found an even marked reduction in the striatum of A2AR KO mice, and as both BDNF and A2ARs have been implicated in the pathogenesis of Huntington’s disease (HD), an inherited striatal neurodegenerative disease, we then evaluated whether the pharmacological blockade of A2ARs could influence striatal levels of BDNF in an experimental model of HD-like striatal degeneration (quinolinic acid-lesioned rats) and in a transgenic mice model of HD (R6/2 mice). In both QA-lesioned rats and early symptomatic R6/2 mice (8 weeks), the systemic administration of the A2AR antagonist SCH58261 significantly reduced striatal BDNF levels. These results indicate that the presence and the tonic activation of A2ARs are necessary to allow BDNF-induced potentiation of synaptic transmission and to sustain a normal BDNF tone. The possible functional consequences of reducing striatal BDNF levels in HD models need further investigation

Le pratiche collaborative per la co-produzione di beni e servizi: quale ruolo per gli Enti locali?

Ormai da qualche anno le pratiche collaborative per la produzione di beni e servizi a livello locale sono oggetto di rinnovato interesse da parte di osservatori e studiosi. A fronte di tale attenzione, tuttavia, il concetto stesso di collaborazione ha progressivamente sub\uecto un processo di dilatazione semantica, con una estensione dei referenti empirici che spazia oggi dalle pratiche di democrazia partecipativa, passando per varie forme di partenariato pubblico-privato, fino ad arrivare alle relazioni peer to peer legate all\u2019economia di piattaforma. Parallelamente, la crescita dell\u2019interesse per questo tipo di pratiche da parte sia delle amministrazioni locali che dei practitioners non ha mancato di generare tendenze isomorfiche ed effetti bandwagon, conducendo talvolta verso l\u2019importazione di modelli che non sempre si rivelano adeguati per i diversi contesti di riferimento. Partendo da queste premesse, e adottando un approccio di analisi delle politiche pubbliche, nel presente lavoro ci proponiamo di mettere ordine nella scatola degli attrezzi a cui gli Enti locali possono attingere per governare \u2013 laddove ne abbiano l\u2019intenzione\u2013 questo tipo di pratiche. A tale scopo si far\ue0 ricorso alla categoria analitica degli strumenti di policy, cercando di individuare eventuali regolarit\ue0 o dissomiglianze nelle strategie adottate dai Comuni, di ragionare sul possibile ruolo che essi possono giocare, e sui limiti che caratterizzano la loro azione

Le pratiche collaborative per la co-produzione di beni e servizi: quale ruolo per gli enti locali?

In last decades the academic and political interest for local collaborative arrangements in the production of goods and services has spread across Italy and abroad. As a consequence, the concept of collaboration has been progressively stretched, hovering amidst social and political practices attributable to diverse empirical objects and theoretical perspectives, such as participatory democracy, public-private partnership, peer to peer relations and sharing economy. Such a success has boosted the appeal of collaborative practices likewise, eventually leading towards institutional isomorphic tendencies and bandwagon effects without taking due account of territorial and administrative contextual features. Drawing upon these premises, and relying on an empirically based public policy approach, the article tries to identify and classify the policy instruments that local governments may use to promote and implement different kinds of collaborative practices, as a starting point to understand the role municipalities may play therein, and to reflect upon the possible shortcomings of their institutional actions