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n2:pmcid: PMC0
bibo:doi: 10.1371%2Fjournal.pone.0007017
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Subject Item: _:vb6020328
rdf:type: n10:Section
dc:title: introduction
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Subject Item: _:vb6020329
rdf:type: n2:Context
rdf:value: Neurocognitive deficits and olfactory changes are frequently observed after chemotherapy and cranial radiotherapy in adult patients [>>1<<], [2]. These changes may result from damage to the neural stem cell (NSC) populations of the subgranular zone of the dentate gyrus (DG), the hippocampus and the subventricular zone (SVZ) lining the forebrain lateral ventricles [3], [4].
n2:mentions: n3:19019972

Subject Item: _:vb6020330
rdf:type: n2:Context
rdf:value: Neurocognitive deficits and olfactory changes are frequently observed after chemotherapy and cranial radiotherapy in adult patients [1], [>>2<<]. These changes may result from damage to the neural stem cell (NSC) populations of the subgranular zone of the dentate gyrus (DG), the hippocampus and the subventricular zone (SVZ) lining the forebrain lateral ventricles [3], [4].
n2:mentions: n3:19289621

Subject Item: _:vb6020331
rdf:type: n2:Context
rdf:value: These changes may result from damage to the neural stem cell (NSC) populations of the subgranular zone of the dentate gyrus (DG), the hippocampus and the subventricular zone (SVZ) lining the forebrain lateral ventricles [>>3<<], [4]. NSCs continually generate new neurons, which are recruited to the DG and the olfactory bulb (OB) of adult mammals [5]. New neuronal progenitors generated in the SVZ migrate along the rostral migratory stream (RMS) towards the OB.
n2:mentions: n3:5886931

Subject Item: _:vb6020332
rdf:type: n2:Context
rdf:value: Within the OB, they integrate into the granule cell layer (GCL), the external plexiform layer (EPL) or the glomerular layer (GL), giving rise to both gamma-aminobutyric acid (GABA)- and dopamine-containing interneurons [>>6<<]–[10]. This ongoing neurogenesis is essential for maintenance of the integrity of the OB circuitry. The blocking of this process depletes the population of OB interneurons [11].
n2:mentions: n3:11826091

Subject Item: _:vb6020333
rdf:type: n2:Context
rdf:value: Within the OB, they integrate into the granule cell layer (GCL), the external plexiform layer (EPL) or the glomerular layer (GL), giving rise to both gamma-aminobutyric acid (GABA)- and dopamine-containing interneurons [6]–[>>10<<]. This ongoing neurogenesis is essential for maintenance of the integrity of the OB circuitry. The blocking of this process depletes the population of OB interneurons [11].
n2:mentions: n3:18337423

Subject Item: _:vb6020334
rdf:type: n2:Context
rdf:value: This ongoing neurogenesis is essential for maintenance of the integrity of the OB circuitry. The blocking of this process depletes the population of OB interneurons [>>11<<].
n2:mentions: n3:18758458

Subject Item: _:vb6020335
rdf:type: n2:Context
rdf:value: Activity-dependent factors regulate OB neurogenesis, suggesting that adult neurogenesis is not exclusively constitutive [>>12<<]–[15]. The new cells added to the OB and DG circuits undergo functional integration [16], [17], and this process is thought to be important for learning and memory [5].
n2:mentions: n3:11923433

Subject Item: _:vb6020336
rdf:type: n2:Context
rdf:value: Activity-dependent factors regulate OB neurogenesis, suggesting that adult neurogenesis is not exclusively constitutive [12]–[>>15<<]. The new cells added to the OB and DG circuits undergo functional integration [16], [17], and this process is thought to be important for learning and memory [5].
n2:mentions: n3:17229106

Subject Item: _:vb6020337
rdf:type: n2:Context
rdf:value: The new cells added to the OB and DG circuits undergo functional integration [>>16<<], [17], and this process is thought to be important for learning and memory [5].
n2:mentions: n3:15788705

Subject Item: _:vb6020338
rdf:type: n2:Context
rdf:value: The new cells added to the OB and DG circuits undergo functional integration [16], [>>17<<], and this process is thought to be important for learning and memory [5].
n2:mentions: n3:16495940

Subject Item: _:vb6020339
rdf:type: n2:Context
rdf:value: Spatial memory deficits have been observed following the disruption of neurogenesis in transgenic mice [>>11<<], [18], [19].
n2:mentions: n3:18758458

Subject Item: _:vb6020340
rdf:type: n2:Context
rdf:value: Spatial memory deficits have been observed following the disruption of neurogenesis in transgenic mice [11], [>>18<<], [19]. However, the functional relevance of adult neurogenesis in olfaction remains unclear. Some studies have suggested that new neurons are not required for olfaction, whereas others have implicated adult-generated neurons in a number
n2:mentions: n3:18509506

Subject Item: _:vb6020341
rdf:type: n2:Context
rdf:value: Spatial memory deficits have been observed following the disruption of neurogenesis in transgenic mice [11], [18], [>>19<<]. However, the functional relevance of adult neurogenesis in olfaction remains unclear. Some studies have suggested that new neurons are not required for olfaction, whereas others have implicated adult-generated neurons in a number of
n2:mentions: n3:18842068

Subject Item: _:vb6020342
rdf:type: n2:Context
rdf:value: For example, olfaction has been shown to be unaffected in Bax-knockout mice [>>20<<] and in mice producing a neuron-specific enolase-diphtheria toxin [11], despite the significantly lower than normal level of neurogenesis in both transgenic models.
n2:mentions: n3:18160647

Subject Item: _:vb6020343
rdf:type: n2:Context
rdf:value: For example, olfaction has been shown to be unaffected in Bax-knockout mice [20] and in mice producing a neuron-specific enolase-diphtheria toxin [>>11<<], despite the significantly lower than normal level of neurogenesis in both transgenic models.
n2:mentions: n3:18758458

Subject Item: _:vb6020344
rdf:type: n2:Context
rdf:value: By contrast, both mice lacking neural cell-adhesion molecule (NCAM) and mice with the brain-derived neurotrophic factor (BDNF) Val66Met knock-in display impaired OB neurogenesis and odor discrimination [>>21<<], [22]. Olfactory discrimination is also impaired in aging rodents, mice heterozygous for leukemia inhibitory factor receptor (Lifr +/−), and waved-1 mutant mice (a hypermorph of TGF-alpha), in which OB neurogenesis level is reduced [23].
n2:mentions: n3:10677540

Subject Item: _:vb6020345
rdf:type: n2:Context
rdf:value: By contrast, both mice lacking neural cell-adhesion molecule (NCAM) and mice with the brain-derived neurotrophic factor (BDNF) Val66Met knock-in display impaired OB neurogenesis and odor discrimination [21], [>>22<<]. Olfactory discrimination is also impaired in aging rodents, mice heterozygous for leukemia inhibitory factor receptor (Lifr +/−), and waved-1 mutant mice (a hypermorph of TGF-alpha), in which OB neurogenesis level is reduced [23].
n2:mentions: n3:18322085

Subject Item: _:vb6020346
rdf:type: n2:Context
rdf:value: Olfactory discrimination is also impaired in aging rodents, mice heterozygous for leukemia inhibitory factor receptor (Lifr +/−), and waved-1 mutant mice (a hypermorph of TGF-alpha), in which OB neurogenesis level is reduced [>>23<<]. Finally, a correlation has been found between the degree of OB neurogenesis and olfactory memory [24], [25], providing further support for the hypothesis that adult neurogenesis plays an important role in olfaction.
n2:mentions: n3:15385618

Subject Item: _:vb6020347
rdf:type: n2:Context
rdf:value: Finally, a correlation has been found between the degree of OB neurogenesis and olfactory memory [>>24<<], [25], providing further support for the hypothesis that adult neurogenesis plays an important role in olfaction.
n2:mentions: n3:16324121

Subject Item: _:vb6020348
rdf:type: n2:Context
rdf:value: Finally, a correlation has been found between the degree of OB neurogenesis and olfactory memory [24], [>>25<<], providing further support for the hypothesis that adult neurogenesis plays an important role in olfaction.
n2:mentions: n3:14561855

Subject Item: _:vb6020349
rdf:type: n2:Context
rdf:value: Focal irradiation of the SVZ leads to a dose-dependent loss of cell types in this region and repopulation may take several months [>>26<<]. Here, we used focal SVZ irradiation in adult mice to disrupt the production of new OB neurons without affecting the rest of the brain or the body. We examined the functional effects of irradiation on odorant detection, discrimination and
n2:mentions: n3:10630191

Subject Item: _:vb6020350
rdf:type: n10:Section
dc:title: materials and methods
n10:contains: _:vb6020352 _:vb6020353 _:vb6020351

Subject Item: _:vb6020351
rdf:type: n2:Context
rdf:value: For the olfactory discrimination task, we used a slightly modified version of the habituation–dishabituation test described elsewhere [>>21<<]. The test cages were boxes of 36×23.5×13 cm (length×width×height), with two compartments separated by an aluminum partition (holes 0.5 cm diameter).
n2:mentions: n3:10677540

Subject Item: _:vb6020352
rdf:type: n2:Context
rdf:value: Mice were maintained on a 1 ml/day water deprivation diet for 10 days and then trained in a go/no-go discrimination task in Knosys (Bethesda, MD) computer-controlled olfactometers, as previously described [>>50<<]. Mice were trained to respond to the presence of an odorant dissolved in mineral oil (positive stimulus, S+) by licking the water delivery tube situated within the odorant sampling port, and to refrain from responding to the presence of
n2:mentions: n3:10587496

Subject Item: _:vb6020353
rdf:type: n2:Context
rdf:value: We followed the memory test procedure described by Bodyak and Slotnick [>>50<<], with minor modifications. Mice were given four daily training sessions of eight blocks of 20 trials for a two-odorant task (S+ was 1% anisole and S- was 1% cineole).
n2:mentions: n3:10587496

Subject Item: _:vb6020354
rdf:type: n10:Section
dc:title: results
n10:contains: _:vb6020356 _:vb6020357 _:vb6020358 _:vb6020359 _:vb6020355

Subject Item: _:vb6020355
rdf:type: n2:Context
rdf:value: It can therefore be used as a reliable marker for the quantification of adult neurogenesis [>>27<<], [28].
n2:mentions: n3:14725617

Subject Item: _:vb6020356
rdf:type: n2:Context
rdf:value: It can therefore be used as a reliable marker for the quantification of adult neurogenesis [27], [>>28<<].
n2:mentions: n3:14574675

Subject Item: _:vb6020357
rdf:type: n2:Context
rdf:value: This finding is consistent with a previous study showing that SVZ progenitor cells are sensitive to irradiation [>>26<<]. Levels of DCX immunoreactivity were significantly lower in the SVZ of irradiated mice (about 30% those of sham-treated mice, Figure 1D; DCX optical density for sham treatment: 0.096±0.009, for SVZ-irradiation treatment: 0.03±0.003,
n2:mentions: n3:10630191

Subject Item: _:vb6020358
rdf:type: n2:Context
rdf:value: Consistent with previous studies (e.g., [>>29<<]), the number of BrdU+ cells halved between day 11 (D11) and D31 in the control OB (p<0.005).
n2:mentions: n3:18987187

Subject Item: _:vb6020359
rdf:type: n2:Context
rdf:value: As irradiation has transient side effects on the functioning of the mature nervous system due to local inflammation [>>30<<], we carried out all behavioral experiments at least two months after irradiation, when inflammation markers had disappeared (data not shown).
n2:mentions: n3:12161748

Subject Item: _:vb6020360
rdf:type: n10:Section
dc:title: discussion
n10:contains: _:vb6020364 _:vb6020365 _:vb6020366 _:vb6020367 _:vb6020361 _:vb6020362 _:vb6020363 _:vb6020372 _:vb6020373 _:vb6020374 _:vb6020375 _:vb6020368 _:vb6020369 _:vb6020370 _:vb6020371 _:vb6020380 _:vb6020381 _:vb6020382 _:vb6020383 _:vb6020376 _:vb6020377 _:vb6020378 _:vb6020379 _:vb6020384

Subject Item: _:vb6020361
rdf:type: n2:Context
rdf:value: Its conservation across all mammalian species and tight regulation [5], [>>31<<]–[33] suggest that adult neurogenesis may affect behavior.
n2:mentions: n3:10195220

Subject Item: _:vb6020362
rdf:type: n2:Context
rdf:value: Its conservation across all mammalian species and tight regulation [5], [31]–[>>33<<] suggest that adult neurogenesis may affect behavior.
n2:mentions: n3:16797263

Subject Item: _:vb6020363
rdf:type: n2:Context
rdf:value: Consistent with previous studies [>>26<<], [30], DCX staining demonstrated that SVZ irradiation reduced the production of newborn neurons in the SVZ.
n2:mentions: n3:10630191

Subject Item: _:vb6020364
rdf:type: n2:Context
rdf:value: Consistent with previous studies [26], [>>30<<], DCX staining demonstrated that SVZ irradiation reduced the production of newborn neurons in the SVZ.
n2:mentions: n3:12161748

Subject Item: _:vb6020365
rdf:type: n2:Context
rdf:value: Both spontaneous and reinforced discrimination tests were used to investigate potential differences in olfactory functions [>>34<<]. Irradiated mice exposed to synthetic odorants discriminated between these odorants as efficiently as sham-treated mice. This finding is consistent with previous studies showing that neonatal irradiation or the genetic blockade of adult
n2:mentions: n3:12177181

Subject Item: _:vb6020366
rdf:type: n2:Context
rdf:value: This finding is consistent with previous studies showing that neonatal irradiation or the genetic blockade of adult neurogenesis does not impair olfactory discrimination [>>11<<], [35]. However, this result contrasts with previous data obtained in NCAM-knockout mice [21] and BDNF Val66Met knock-in mice [22], both of which displayed disrupted neurogenesis. This discrepancy may be due to the impairment of
n2:mentions: n3:18758458

Subject Item: _:vb6020367
rdf:type: n2:Context
rdf:value: This finding is consistent with previous studies showing that neonatal irradiation or the genetic blockade of adult neurogenesis does not impair olfactory discrimination [11], [>>35<<]. However, this result contrasts with previous data obtained in NCAM-knockout mice [21] and BDNF Val66Met knock-in mice [22], both of which displayed disrupted neurogenesis. This discrepancy may be due to the impairment of neurogenesis
n2:mentions: n3:9182941

Subject Item: _:vb6020368
rdf:type: n2:Context
rdf:value: However, this result contrasts with previous data obtained in NCAM-knockout mice [>>21<<] and BDNF Val66Met knock-in mice [22], both of which displayed disrupted neurogenesis.
n2:mentions: n3:10677540

Subject Item: _:vb6020369
rdf:type: n2:Context
rdf:value: However, this result contrasts with previous data obtained in NCAM-knockout mice [21] and BDNF Val66Met knock-in mice [>>22<<], both of which displayed disrupted neurogenesis.
n2:mentions: n3:18322085

Subject Item: _:vb6020370
rdf:type: n2:Context
rdf:value: Irradiation had no effect on social investigation on the basis of olfactory cues (reviewed in [>>36<<]). By contrast, Iwata et al. [37] observed social interaction deficits in animals subjected to irradiation of the entire forebrain, leading to various undesirable side effects.
n2:mentions: n3:17108955

Subject Item: _:vb6020371
rdf:type: n2:Context
rdf:value: By contrast, Iwata et al. [>>37<<] observed social interaction deficits in animals subjected to irradiation of the entire forebrain, leading to various undesirable side effects.
n2:mentions: n3:18509473

Subject Item: _:vb6020372
rdf:type: n2:Context
rdf:value: Most newly produced neurons remaining in the OB after learning are still present several weeks later and can develop thousands of spines [>>9<<], [14], [15], [29]. New neurons may be specifically involved in formation of the synaptic network serving as the structural basis for long-term synaptic changes (the cell-autonomous hypothesis).
n2:mentions: n3:17369823

Subject Item: _:vb6020373
rdf:type: n2:Context
rdf:value: Most newly produced neurons remaining in the OB after learning are still present several weeks later and can develop thousands of spines [9], [>>14<<], [15], [29]. New neurons may be specifically involved in formation of the synaptic network serving as the structural basis for long-term synaptic changes (the cell-autonomous hypothesis).
n2:mentions: n3:17035535

Subject Item: _:vb6020374
rdf:type: n2:Context
rdf:value: Most newly produced neurons remaining in the OB after learning are still present several weeks later and can develop thousands of spines [9], [14], [>>15<<], [29]. New neurons may be specifically involved in formation of the synaptic network serving as the structural basis for long-term synaptic changes (the cell-autonomous hypothesis).
n2:mentions: n3:17229106

Subject Item: _:vb6020375
rdf:type: n2:Context
rdf:value: Most newly produced neurons remaining in the OB after learning are still present several weeks later and can develop thousands of spines [9], [14], [15], [>>29<<]. New neurons may be specifically involved in formation of the synaptic network serving as the structural basis for long-term synaptic changes (the cell-autonomous hypothesis).
n2:mentions: n3:18987187

Subject Item: _:vb6020376
rdf:type: n2:Context
rdf:value: This hypothesis is supported by previous results demonstrating that newly generated neurons are unique in that 1) they have lower thresholds for synaptic plasticity [>>38<<], [39], 2) they induce “synaptic disquietude” [40], 3) they increase complexity at the ‘gate to long-term memory’ [41], and 4) they trigger unique responses during odorant familiarization [42].
n2:mentions: n3:11387388

Subject Item: _:vb6020377
rdf:type: n2:Context
rdf:value: This hypothesis is supported by previous results demonstrating that newly generated neurons are unique in that 1) they have lower thresholds for synaptic plasticity [38], [>>39<<], 2) they induce “synaptic disquietude” [40], 3) they increase complexity at the ‘gate to long-term memory’ [41], and 4) they trigger unique responses during odorant familiarization [42].
n2:mentions: n3:15107864

Subject Item: _:vb6020378
rdf:type: n2:Context
rdf:value: demonstrating that newly generated neurons are unique in that 1) they have lower thresholds for synaptic plasticity [38], [39], 2) they induce “synaptic disquietude” [40], 3) they increase complexity at the ‘gate to long-term memory’ [>>41<<], and 4) they trigger unique responses during odorant familiarization [42].
n2:mentions: n3:11826092

Subject Item: _:vb6020379
rdf:type: n2:Context
rdf:value: lower thresholds for synaptic plasticity [38], [39], 2) they induce “synaptic disquietude” [40], 3) they increase complexity at the ‘gate to long-term memory’ [41], and 4) they trigger unique responses during odorant familiarization [>>42<<]. Thus, bulbar neurogenesis may increase plasticity in several ways, including the addition of new cells, the structural remodeling of neural circuits, and synaptogenesis, and changes in synaptic strength.
n2:mentions: n3:16291946

Subject Item: _:vb6020380
rdf:type: n2:Context
rdf:value: Similar correlations also emerged from theoretical studies demonstrating the involvement of adult neurogenesis in memory storage, rather than in perception or learning [>>43<<], [44]. Aimone et al. also suggested that young neurons facilitate the formation of temporal association in memory [45], and play key role in the encoding of memory [46]. Computer-based studies have indicated a role for constitutive adult
n2:mentions: n3:15157417

Subject Item: _:vb6020381
rdf:type: n2:Context
rdf:value: Similar correlations also emerged from theoretical studies demonstrating the involvement of adult neurogenesis in memory storage, rather than in perception or learning [43], [>>44<<]. Aimone et al. also suggested that young neurons facilitate the formation of temporal association in memory [45], and play key role in the encoding of memory [46]. Computer-based studies have indicated a role for constitutive adult
n2:mentions: n3:15986407

Subject Item: _:vb6020382
rdf:type: n2:Context
rdf:value: Aimone et al. also suggested that young neurons facilitate the formation of temporal association in memory [>>45<<], and play key role in the encoding of memory [46].
n2:mentions: n3:16732202

Subject Item: _:vb6020383
rdf:type: n2:Context
rdf:value: Aimone et al. also suggested that young neurons facilitate the formation of temporal association in memory [45], and play key role in the encoding of memory [>>46<<]. Computer-based studies have indicated a role for constitutive adult neurogenesis in mnesic function, providing a theoretical background for future experimental approaches.
n2:mentions: n3:19186162

Subject Item: _:vb6020384
rdf:type: n2:Context
rdf:value: Previous studies showing a transient role for the OB in memory storage support this notion [>>47<<]. The natural replacement of bulbar neurons provides a rationale for the transfer of memory traces out of the bulb. The loss of OB neurons may be programmed to occur after the transfer of traces from these neurons to other parts of the
n2:mentions: n3:1821183

Subject Item: _:vb413789792
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n2:RelevantScore: 13
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n2:RelevantScore: 13
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n2:RelevantScore: 11
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rdf:type: n2:RelevantBibliographicResource
n2:RelevantScore: 11
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n2:RelevantScore: 11
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n2:RelevantScore: 10
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n2:RelevantScore: 10
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