2C, available atwww

2C, available atwww.jneurosci.orgas supplemental material), whereas the antibody used inChiaramello et al. effect on neuron production from mouse SVZ, while decreasing it in rats. Interestingly, mice and rats also differ in their expression of the neurotrophin receptor p75. Our results indicate that TrkB is not essential for adult SVZ neurogenesis and do not support the current view that delivering BDNF to the SVZ can enhance adult neurogenesis. Keywords:neurotrophin, BDNF, TrkB, subventricular zone, neurogenesis, olfactory bulb, p75 == Introduction == Neurogenesis continues throughout adulthood in vertebrates, because of endogenous progenitor cells which could be useful for brain repair (Lie et al., 2004). In rodents, there are two known adult neurogenic regions: the subventricular zone (SVZ) and the hippocampal dentate gyrus. The SVZ contains GFAP+, astrocytic stem cells (type Benznidazole B cells), which generate highly proliferative transient amplifying cells (type C cells) that differentiate into neuroblasts (type A cells) (Alvarez-Buylla and Garcia-Verdugo, 2002). These neuroblasts migrate in chains through the SVZ (Doetsch and Alvarez-Buylla, 1996) and rostral migratory stream (RMS) to the olfactory bulb (OB) (Luskin, 1993;Lois and Alvarez-Buylla, 1994), where cells migrate radially into the granular (GCL) and glomerular (GL) layers and differentiate into inhibitory interneurons (Carleton et al., 2003). We still know very little about the molecules that regulate the generation of thousands of neuroblasts daily from the SVZ. Growth factors are important components of stem cell niches (Horner and Palmer, 2003). Cells in the SVZ respond to multiple extracellular factors, including EGF, FGF2, PDGF, BMPs, noggin, prolactin and erythropoietin, which influence SVZ proliferation and neurogenesis (Craig et al., 1996;Kuhn et al., 1997;Lim et al., 2000;Shingo et al., 2001,2003;Zheng et al., 2004;Jackson et al., 2006). Recent findings indicate that neurotrophins Benznidazole may also play a fundamental role in adult neurogenesis. Neurotrophins are well known for promoting neuronal survival and for modulating synaptic plasticity (Schinder and Poo, 2000;Huang and Reichardt, 2001;Chao, 2003). Two laboratories have now reported that exposing the SVZ to the neurotrophin brain-derived neurotrophic factor (BDNF) increases production of OB interneurons and, unexpectedly, of striatal neurons normally not generated in adult brains (Zigova et al., 1998;Benraiss et al., 2001;Pencea et al., 2001;Chmielnicki et al., 2004). Another neurotrophin, CNTF, has been suggested to stimulate adult neurogenesis in the hypothalamus (Kokoeva et al., 2005). Although these findings are of significant interest for regenerative therapies, we still do not understand the biological mechanisms underlying these neurotrophins’ effects on adult stem cell niches. Most importantly, we do not know which cells directly respond to these neurotrophins nor the nature of their response. We resolved these questions in the SVZ, focusing on the postulated neurogenic effects of BDNF and its receptors TrkB and p75. TrkB exists in two isoforms: a full-length receptor, activated by intracellular domain name cross-phosphorylation, and a truncated receptor, lacking most of the intracellular region (Klein et al., 1989,1990;Middlemas et al., 1991). p75 binds several neurotrophins and its activation can affect cell survival, proliferation, migration, axonal elongation and synaptic plasticity (Dechant and Barde, 2002;Barker, 2004). p75 seems to affect neurogenesis from SVZ progenitors (Small et al., 2007). We found that truncated TrkB is usually expressed in type B and ependymal cells, but not in neuroblasts, whereas p75 is usually expressed in Benznidazole type C cells and neuroblasts. Our data show that SVZ neurogenesis can continue in the absence of TrkB and that most TrkB-KO and WT OB interneurons display similar survival and differentiation. Importantly, BDNF did not increase SVZ neurogenesis in mice and even decreased neurogenesis CBLL1 in rats. == Materials and Methods == == == == == == Animals. == Mice and rats were maintained in standard conditions with food and water ad libitum. All experimental procedures were approved by the UCSF Committee on Animal Health and Care. All rat experiments.