Impaired Sprouting and Axonal Atrophy in Cerebellar Climbing Fibres following In Vivo Silencing of the Growth-Associated Protein GAP-43

The adult mammalian central nervous system has a limited ability to establish new connections and to recover from traumatic or degenerative events. The olivo-cerebellar network represents an excellent model to investigate neuroprotection and repair in the brain during adulthood, due to its high plasticity and ordered synaptic organization. To shed light on the molecular mechanisms involved in these events, we focused on the growth-associated protein GAP-43 (also known as B-50 or neuromodulin). During development, this protein plays a crucial role in growth and in branch formation of neurites, while in the adult it is only expressed in a few brain regions, including the inferior olive (IO) where climbing fibres (CFs) originate. Following axotomy GAP-43 is usually up-regulated in association with regeneration. Here we describe an in vivo lentiviral-mediated gene silencing approach, used for the first time in the olivo-cerebellar system, to efficiently and specifically downregulate GAP-43 in rodents CFs. We show that lack of GAP-43 causes an atrophy of the CF in non-traumatic conditions, consisting in a decrease of its length, branching and number of synaptic boutons. We also investigated CF regenerative ability by inducing a subtotal lesion of the IO. Noteworthy, surviving CFs lacking GAP-43 were largely unable to sprout on surrounding Purkinje cells. Collectively, our results demonstrate that GAP-43 is essential both to maintain CFs structure in non-traumatic condition and to promote sprouting after partial lesion of the IO

Structure and properties of molybdenum oxide nitrides as model systems for selective oxidation catalyst

<p>Abstract</p> <p>Molybdenum oxide nitride (denoted as Mo(O,N)₃) was obtained by ammonolysis of α-MoO₃with gaseous ammonia. Electronic and geometric structure, reducibility, and conductivity of Mo(O,N)₃were investigated by XRD, XAS, UV-Vis spectroscopy, and impedance measurements. Catalytic performance in selective propene oxidation was determined by online mass spectrometry und gas chromatography. Upon incorporation of nitrogen, Mo(O,N)₃maintained the characteristic layer structure of α-MoO₃. XRD analysis showed an increased structural disorder in the layers while nitrogen is removed from the lattice of Mo(O,N)₃at temperatures above ~600 K. Compared to regular α-MoO₃, Mo(O,N)₃exhibited a higher electronic and ionic conductivity and an onset of reduction in propene at lower temperatures. Surprisingly, α-MoO₃and Mo(O,N)₃exhibited no detectable differences in onset temperatures of propene oxidation and catalytic selectivity or activity. Apparently, the increased reducibility, oxygen mobility, and conductivity of Mo(O,N)₃compared to α-MoO₃had no effect on the catalytic behavior of the two catalysts. The results presented confirm the suitability of molybdenum oxide nitrides as model systems for studying bulk contributions to selective oxidation.</p