, 2008). Notably, XBP1 exerts neuroprotective effects against amyloid-β induced neuronal death in a Drosophila model, although here XBP1 overexpression does not affect ER stress per se, but rather the regulation of cytosolic Ca2+ levels upon downregulation of ryanodine receptors ( Casas-Tinto et al., 2011). Likewise, XBP1 Temozolomide molecular weight is upregulated in chemical mouse models of PD, and AAV-mediated XBP1 overexpression in the substantia nigra is neuroprotective in this condition ( Sado et al., 2009). As a

word of caution, however, XBP1 knockdown can also result in decreased load of misfolded proteins and neuroprotection ( Hetz et al., 2009), and CHOP upregulation may not always lead to apoptosis ( Halterman et al., 2010). Accordingly, the outcome of IRE-XBP1 and CHOP pathway activation may

depend on the identity of the affected neurons, on context, and on the specific triggers that induce the UPR. Clearly, the issues raised by the results of this elegant study have important potential implications for our understanding of how axonal dysfunction influences neuronal function, repair, and death under acute and chronic conditions. “
“The evolutionarily preserved neuropeptide oxytocin (OT) is perhaps best known for its role as an important hormonal regulator of mammalian reproductive processes such as cervical softening, uterine contraction, and milk ejection. In addition to these peripheral effects, OT is involved in functions of the central find protocol nervous system. From enhancing

social recognition, pair bonding, and maternal behavior found to reducing stress effects and pain sensitivity, central effects of OT have been demonstrated in many mammalian species (Landgraf and Neumann, 2004). OT strengthens pair bonding in monogamous female prairie voles, whereas blocking OT receptors prevents pair bonding. OT can induce maternal behavior in virgin rats whereas rats selectively bred for strong maternal behavior start to neglect their pups when central OT receptors are pharmacologically blocked. In humans, intranasally applied OT attenuates the stress response induced by public speaking, and OT release during breast-feeding lowers stress hormone levels and elevates mood in mothers (Lee et al., 2009). Interestingly, these anxiolytic effects of OT have been associated with reduced neuronal activation in the amygdala, a key brain structure for anxiety and fear (LeDoux, 2000). The central nucleus of the amygdala (CeA), comprising lateral (CeL) and medial (CeM) subdivisions, mediates acquisition and expression of behavioral as well as autonomic fear responses (Maren and Quirk, 2004). Strong OT receptor expression within the CeL has been reported, and in mice, local application of OT in the CeA results in attenuation of conditioned fear responses (Viviani et al., 2011). However, the way by which OT reaches the CeA to affect fear has remained unclear (Neumann, 2007).