Of note, this is the first time that TA is clearly detected in glial cells although its expression is variable. TA seems to be upregulated in glia cells following stress, suggesting that in physiological conditions its expression level is very low. In adult human brain, where TA expression is more heterogeneous relative to rodent brain, TA was almost undetectable in glia cells. In recent years, different functional roles have been attributed to TA including the involvement in the secretory pathway, synaptic vesicle turnover and release. Both in vitro and in vivo studies have suggested that TA may act as a chaperone, not only at the ER but also at the synapse, by mediating the transport, assembly and disassembly of the molecular complex and consequently affecting SV turnover and neurotransmitter release. Ultrastructural studies of primate and human striatum have shown that TA immunostaining is associated with small clear LOUREIRIN-B vesicles within axons and presynaptic terminals, and it is also found enriched in synaptosomal fractions. Here we provided for the first time a detailed analysis of TA localization in the main synaptic terminals of juvenile cerebellum in correlation to extensive synaptogenesis. We observed a quite homogenous distribution in both glutamatergic and GABA-ergic synapses. As already mentioned a crucial aspect of synaptogenesis is the detection of the target. The selection of a specific synaptic input depends on different events, such as the guidance of axons to their appropriate targets, the release of diffusible factors, and signaling mediated by trans-synaptic adhesion complexes. Curiously, a novel class of secreted synaptic organizers has been identified as crucial player for synapse formation and maintenance. TA interacts with sarcoglycans which are components of the dystrophin-glycoprotein complex involved in GABA-ergic synapse development. In addition, synaptic activity is thought to mediate Amikacin hydrate competition between convergent inputs, leading to the strengthening or elimination of an immature synapse. For example the transition from multiple to single innervation of PCs by CFs is one of the best systems to investigate activity-dependent synaptic competition that underlies the refinement of synaptic circuits in the central nervous system. Recent evidence has provided important information on the activity-dependent mechanisms that regulate the refinement of synaptic circuits and determine connectional specificity in the cerebellum. If TA, by regulating SV transport and turnover, plays a role in the molecular and/or activity-dependent mechanisms that control the spatial specificity of synaptogenesis has to be investigated. The insulin-like growth factor system is comprised of two insulin-like growth factors, type I and II IGF receptors, insulin receptor, a family of IGF binding proteins and IGFBP-degrading proteases. Growth hormone regulates the IGF-I production by the liver, which is the source of the majority of IGF-I found in plasma. On the other hand, IGF-II and IGFBPs found in the serum are most likely sourced from a variety of tissues. IGF signalling through the type I IGF receptor is involved in 
cell proliferation, differentiation, apoptosis and general anabolic cell processes. An absence of IGF leads to growth hormone resistant growth failure, which may be treated using the synthetic IGF mecasermin. A low level of IGF-I has also been shown to be associated with insulin-dependent diabetes in children and cardiovascular disease in adults. Excessive levels of IGFs in the circulation are linked with an increased risk of cancer, and there is some compelling evidence that the IGF/IGF-IR system plays a major role in some types of human neoplasm.