, 2002). On the other hand, various

paradigms of chronic stress lead to decreased cell proliferation in the adult SGZ, whereas FK228 order the effect of acute stress on cell proliferation and new neuron survival depends on paradigms and species/sex of animals (reviewed by Mirescu and Gould, 2006). The effect of neurodegeneration on adult neurogenesis is also very complex (reviewed by Winner et al., 2011). During neurodegeneration, activation of resident microglia, astrocytes, and infiltrating peripheral macrophages release a plethora of cytokines, chemokines, neurotransmitters, and reactive oxygen species, which in turn affect various aspects of adult neurogenesis. For example, in animal models of Alzheimer’s disease, aberrant GABA signaling affects fate specification of neural progenitors and dendritic growth of newborn neurons in the aged SGZ (Li et al., 2009 and Sun et al., 2009). In both insulin-deficient rats and insulin-resistant mice, diabetes impairs

cell proliferation in the adult SGZ through a glucocorticoid-mediated mechanism (Stranahan et al., 2008). Another major negative regulator of http://www.selleckchem.com/screening/protease-inhibitor-library.html adult neurogenesis is inflammation, induced by injuries, degenerative neurological diseases, and irradiation (reviewed by Carpentier and Palmer, 2009). Inflammation induced by irradiation not only diminishes the proliferative capacity and neuronal fate commitment of neural progenitors in the adult SGZ but also disrupts the local niche with aberrant angiogenesis and increasing number of reactivated microglia cells, resulting in sustained inhibition of neurogenesis from both endogenous and transplanted neural progenitors (Monje et al., 2003). It is clear that every single phase of adult neurogenesis can be regulated by different stimuli and each stimulus can have multiple targets. Furthermore, different stimuli interact with each other and impact the final outcome Parvulin of adult neurogenesis. In general, regulation of adult neurogenesis by external stimuli is complex and the effect depends on timing,

dose/duration, specific paradigms, animal models (age, sex, genetic background), and methods of analysis. The major challenge is to identify cellular and molecular mechanisms underlying different means of adult neurogenesis regulation. What are targets of a particular stimulation-quiescent putative stem cells, their specific progeny (cell-autonomous effect), or mature cell types from the niche (non-cell-autonomous effect)? Are subregions of SGZ and SVZ/olfactory bulb differentially regulated by the same stimuli? Identification of new markers that divide the neurogenic process into multiple stages and the availability of genetically modified mice for cell type-specific gain- and loss-of-function analysis will significantly accelerate these efforts (Figure 2 and Figure 3).