Integrating data from several individuals born at different times

Integrating data from several individuals born at different times in relation to the nuclear bomb tests allows estimating the turnover CB-839 solubility dmso dynamics of a cell population (Bergmann et al., 2009 and Spalding et al., 2008). This indicated an annual turnover rate of 2.0%–3.4% in the nonneuronal cell population (see Supplemental Information). This represents an average for all cells negative for the respective

neuronal marker profile, and it is likely that the turnover dynamics vary between specific nonneuronal cell types. We next assessed the 14C concentration in genomic DNA from NeuN+ or HuD+/Sox10− neuronal nuclei. In all cases (n = 15), the 14C concentration in neuronal genomic DNA was very close to that present in the atmosphere at the time of birth of each individual (Figure 4) Selleck R428 and not significantly different from what one would see if there was no postnatal generation of olfactory bulb neurons (p = 0.91; see Supplemental Information). We cannot exclude that there may be low-grade turnover of neurons, but at a constant rate, the annual turnover would be 0.008% ± 0.08% (mean ± SE; see Supplemental

Information). That corresponds to <1% of neurons being exchanged after 100 years. It has been estimated that up to 50% of olfactory bulb neurons are exchanged annually in rodents (Imayoshi et al., 2008), and if there is any postnatal olfactory bulb neurogenesis in humans, its extent is orders of magnitude lower. Neurodegenerative and psychiatric diseases and substance abuse have been suggested to reduce olfactory bulb neurogenesis (Hansson ADP ribosylation factor et al., 2010, Höglinger et al., 2004, Negoias et al., 2010, Turetsky et al., 2000 and Winner

et al., 2011). Some individuals in our study were diagnosed with one or more of these conditions (Table S2). However, as all studied individuals had neuronal 14C concentrations corresponding to the time around birth, we did not find any apparent correlation between these conditions and postnatal olfactory bulb neurogenesis in humans. Anosmia is a common and early symptom in several neurodegenerative diseases, and it has been suggested to be related to reduced adult olfactory bulb neurogenesis (Höglinger et al., 2004 and Winner et al., 2011), but this appears unlikely. Functional studies in rodents have implicated adult neurogenesis in olfactory memory formation, odorant discrimination, and social interactions (Lazarini and Lledo, 2011). The lack of comparable adult olfactory bulb neurogenesis in humans poses the question whether these functions are mediated by conceptually different mechanisms in humans, or whether the more limited dependence on olfaction in humans compared to rodents in part may be due to the lack of one type of plasticity, adult neurogenesis. Tissues were procured from cases admitted during 2005 and 2011 to the Department of Forensic Medicine in Stockholm for autopsy, after informed consent from relatives. Ethical permission for this study was granted by the Regional Ethical Committee in Stockholm.

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