Dopamine receptor activation promotes adult neurogenesis in an acute Parkinson model

Cell proliferation of neural progenitors in the subventricular zone (SVZ) of Parkinson disease (PD) patients and animal models is decreased. It was previously demonstrated that the neurotransmitter dopamine modulates cell proliferation in the embryonic brain. The aim of the present study was to analyze whether oral treatment with the dopamine receptor agonist pramipexole (PPX) modulates adult neurogenesis in the SVZ/olfactory bulb system in a dopaminergic lesion model. 6-Hydroxydopamine (6-OHDA) lesioned adult rats received either PPX (1.0 mg/kg) or PBS orally twice daily and bromodeoxyuridine (BrdU, a cell proliferation marker) for 10 days and were perfused immediately after treatment or 4 weeks after PPX withdrawal. Stereological analysis revealed a significant augmentation in SVZ proliferation by PPX. Consecutively, enhanced neuronal differentiation and more new neurons were present in the olfactory bulb 4 weeks after PPX withdrawal. In addition, dopaminergic neurogenesis was increased in the olfactory bulb after PPX treatment. Motor activity as assessed by using an open field paradigm was permanently increased even after long term PPX withdrawal. In addition, we demonstrate that D2 and D3 receptors are present on adult rat SVZ-derived neural progenitors in vitro, and PPX specifically increased mRNA levels of epidermal growth factor receptor (EGF-R) and paired box gene 6 (Pax6).Oral PPX treatment selectively increases adult neurogenesis in the SVZ–olfactory bulb system by increasing proliferation and cell survival of newly generated neurons. Analyzing the neurogenic fate decisions mediated by D2/D3 signaling pathways may lead to new avenues to induce neural repair in the adult brain.     

Fibroblast growth factor 2 is required for maintaining the neural stem cell pool in the mouse brain subventricular zone

Cells within the subventricular zone (SVZ) express basic Fgf (Fgf2) and Fgf receptor proteins. We show that the absence of Fgf2 gene products reduces by 50% the dividing progenitor population of the anterior SVZ (SVZa) without changing their cell cycle time. Every 2-3 cell cycles of the SVZa progenitor cell population, 30,000 newly generated neurons capable of long-term survival are added to the glomerular layer of the olfactory bulb. Fgf2 knockout mice have smaller olfactory bulbs due to decreased output of these newly generated cells into the bulbs. A population of slow-dividing neural stem cells (NSCs) residing in the SVZa is identified by its slow cell cycle kinetics (cell cycle approx. 20 days); these cells, called 'S' cells, are negative for glial fibrillary acidic protein and occasionally express brain-lipid-binding protein, a molecular marker of radial glia. The number of these dividing NSCs is reduced from about 13,000 in wild-type to 8,500 cells in Fgf2 knockout mice. Thus, FGF2 regulates the number of proliferative cells and olfactory bulb neurogenesis by maintaining a slow-dividing stem cell pool within the SVZa.     

Long-term survival and cell death of newly generated neurons in the adult rat olfactory bulb

In the adult rat olfactory bulb, neurons are continually generated from progenitors that reside in the lateral ventricle wall. This study investigates long-term survival and cell death of newly generated cells within the adult olfactory bulb. After injecting rats at 2 months of age with 5-bromodeoxyuridine (BrdU), the newly generated cells were quantified over a period of 19 months. A peak of BrdU-positive cells was reached in the olfactory bulb 1 month after BrdU injection, when all new cells have finished migrating from the ventricle wall. Thereafter, a reduction of BrdU-positive cells to about 50% was observed and it was confirmed by dUTP-nick end-labelling (TUNEL) that progenitors and young neurons undergo programmed cell death. However, cells that survived the first 3 months after BrdU injection persisted for up to 19 months. The majority of the BrdU-positive cells that reach the olfactory bulb differentiate into granule cells, but a small fraction migrate further into the glomerular layer. These newborn cells differentiate more slowly into periglomerular interneurons, with a delay of more than 1 month when compared to the granule cells. The newly generated periglomerular neurons, among them a significant fraction of dopaminergic cells, showed a similar decline in number compared to the granule cell layer and long-term survival for the remaining new neurons of up to 19 months. Rather than replacing old neurons, this data suggests that adult olfactory bulb neurogenesis utilizes the overproduction and turnover of young neurons, which is reminiscent of the cellular dynamics observed during brain development.     

Changes in adult olfactory bulb neurogenesis in mice expressing the A30P mutant form of alpha-synuclein

In familial and sporadic forms of Parkinson's disease (PD), alpha-synuclein pathology is present in the brain stem nuclei and olfactory bulb (OB) long before Lewy bodies are detected in the substantia nigra. The OB is an active region of adult neurogenesis, where newly generated neurons physiologically integrate. While accumulation of wild-type alpha-synuclein is one of the pathogenic hallmarks of non-genetic forms of PD, the A30P alpha-synuclein mutation results in an earlier disease onset and a severe clinical phenotype. Here, we study the regulation of adult neurogenesis in the subventricular zone (SVZ)/OB system in a tetracycline-suppressive (tet-off) transgenic model of synucleinopathies, expressing human mutant A30P alpha-synuclein under the control of the calcium/calmodulin-dependent protein kinase II alpha (CaMK) promoter. In A30P transgenic mice alpha-synuclein was abundant at the site of integration in the glomerular cell layer of the OB. Without changes in proliferation in the SVZ, significantly fewer newly generated neurons were observed in the OB granule cell and glomerular layers of A30P transgenic mice than in controls, most probably due to increased cell death. By tetracycline-dependent abrogation of A30P alpha-synuclein expression, OB neurogenesis and programmed cell death was restored to control levels. Our results indicate that, using A30P conditional (tet-off) mice, A30P alpha-synuclein has a negative impact on olfactory neurogenesis and suppression of A30P alpha-synuclein enhances survival of newly generated neurons. This finding suggests that interfering with alpha-synuclein pathology can rescue newly generated neurons, possibly leading to new targets for therapeutic interventions in synucleinopathies.     

Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice

The generation and maturation of adult neural stem/progenitor cells are impaired in many neurodegenerative diseases, among them is Parkinson's disease (PD). In mammals, including humans, adult neurogenesis is a lifelong feature of cellular brain plasticity in the hippocampal dentate gyrus (DG) and in the subventricular zone (SVZ)/olfactory bulb system. Hyposmia, depression, and anxiety are early non-motor symptoms in PD. There are parallels between brain regions associated with non-motor symptoms in PD and neurogenic regions. In autosomal dominant PD, mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are frequent. LRRK2 homologs in non-vertebrate systems play an important role in chemotaxis, cell polarity, and neurite arborization. We investigated adult neurogenesis and the neurite development of new neurons in the DG and SVZ/olfactory bulb system in bacterial artificial chromosome (BAC) human Lrrk2 G2019S transgenic mice. We report that mutant human Lrrk2 is highly expressed in the hippocampus in the DG and the SVZ of adult Lrrk2 G2019S mice. Proliferation of newly generated cells is significantly decreased and survival of newly generated neurons in the DG and olfactory bulb is also severely impaired. In addition, after stereotactic injection of a GFP retrovirus, newly generated neurons in the DG of Lrrk2 G2019S mice exhibited reduced dendritic arborization and fewer spines. This loss in mature, developed spines might point towards a decrease in synaptic connectivity. Interestingly, physical activity partially reverses the decrease in neuroblasts observed in Lrrk2 G2010S mice. These data further support a role for Lrrk2 in neuronal morphogenesis and provide new insights into the role of Lrrk2 in adult neurogenesis.     

Evidence of newly generated neurons in the human olfactory bulb

The subventricular zone (SVZ) is known to be the major source of neural stem cells in the adult brain. In rodents and nonhuman primates, many neuroblasts generated in the SVZ migrate in chains along the rostral migratory stream (RMS) to populate the olfactory bulb (OB) with new granular and periglomerular interneurons. In order to know if such a phenomenon exists in the adult human brain, we applied single and double immunostaining procedures to olfactory bulbs obtained following brain necropsy in normal adult human subjects. Double immunofluorescence labelling with a confocal microscope served to visualize cells that express markers of proliferation and immature neuronal state as well as markers that are specific to olfactory interneurons. Newborn cells that express cell cycle proteins [Ki-67, proliferating cell nuclear antigen (PCNA)] were detected in the granular and glomerular layers (GLs) of the human olfactory bulb; these cells coexpressed markers of immature neuronal state, such as Doublecortin (DCX), NeuroD and Nestin. Numerous differentiating cells expressed molecular markers of early committed neurons [beta-tubulin class III (TuJ1)] and were also immunoreactive for glutamic acid decarboxylase (GAD), a marker of GABAergic neurons, or tyrosine hydroxylase (TH), a marker of dopaminergic neurons. Other early committed neurons expressed the calcium-binding proteins calretinin (CR) or parvalbumin (PV). These results provide strong evidence for the existence of adult neurogenesis in the human olfactory system. Despite its relatively small size compared to that in rodents and nonhuman primates, the olfactory bulb in humans appears to be populated, throughout life, by new granular and periglomerular neurons that express a wide variety of chemical phenotypes.     

Dopaminergic lesion enhances growth factor-induced striatal neuroblast migration

Adult neurogenesis persists in the subventricular zone and is decreased in Parkinson disease (PD). The therapeutic potential of neurogenesis in PD requires understanding of mechanisms of 1) neural stem cell generation; 2) their guidance to the lesion site; and 3) the environment that enables neuronal differentiation, survival, and functional integration. We examined the combined intraventricular infusion of epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF-2) in a 6-hydroxydopamine-induced rodent model of PD. Epidermal growth factor and FGF-2 induced a massive increase in cell proliferation and in numbers of doublecortin-expressing neuroblasts in the subventricular zone. These growth factors also increased dopaminergic neurogenesis in the olfactory bulb and promoted the migration of newly generated neuroblasts from the subventricular zone into the adjacent striatum. The effects of EGF and FGF-2 were present in unlesioned animals but were dramatically enhanced in 6-hydroxydopamine-lesioned animals.These findings suggest that newly generated neuroblasts may be redirected to the region of dopaminergic deficit, and that EGF and FGF-2 can enhance dopaminergic neurogenesis in the olfactory bulb but not in the striatum. Similar mechanisms may be involved in the increased numbers of dopaminergic neurons observed in the olfactory bulbs of PD patients and their functional olfactory deficits.     

6‐hydroxydopamine‐induced Parkinson's disease‐like degeneration generates acute microgliosis and astrogliosis in the nigrostriatal system but no bioluminescence imaging‐detectable alteration in adult neurogenesis

Parkinson's disease is a slowly progressing neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra (SN), leading to severe impairment in motor and non‐motor functions. Endogenous subventricular zone (SVZ) neural stem cells constantly give birth to new cells that might serve as a possible source for regeneration in the adult brain. However, neurodegeneration is accompanied by neuroinflammation and dopamine depletion, potentially compromising regeneration. We therefore employed in vivo imaging methods to study striatal deafferentation (N‐ω‐fluoropropyl‐2β‐carbomethoxy‐3β‐(4‐[¹²³I]iodophenyl)nortropane single photon emission computed tomography, DaTscan^™) and neuroinflammation in the SN and striatum (N,N‐diethyl‐2‐(2‐(4‐(2‐[¹⁸F]fluoroethoxy)phenyl)‐5,7‐dimethylpyrazolo[1,5‐a]pyrimidin‐3‐yl)acetamide positron emission tomography, [¹⁸F]DPA‐714 PET) in the intranigral 6‐hydroxydopamine Parkinson's disease mouse model. Additionally, we transduced cells in the SVZ with a lentivirus encoding firefly luciferase and followed migration of progenitor cells in the SVZ–olfactory bulb axis via bioluminescence imaging under disease and control conditions. We found that activation of microglia in the SN is an acute process accompanying the degeneration of dopaminergic cell bodies in the SN. Dopaminergic deafferentation of the striatum does not influence the generation of doublecortin‐positive neuroblasts in the SVZ, but generates chronic astrogliosis in the nigrostriatal system.     

Strategies to promote differentiation of newborn neurons into mature functional cells in Alzheimer brain

Adult neurogenesis occurs in the subgranular zone (SGZ) and subventricular zone (SVZ). New SGZ neurons migrate into the granule cell layer of the dentate gyrus (DG). New SVZ neurons seem to enter the association neocortex and entorhinal cortex besides the olfactory bulb. Alzheimer disease (AD) is characterized by neuron loss in the hippocampus (DG and CA1 field), entorhinal cortex, and association neocortex, which underlies the learning and memory deficits. We hypothesized that, if the AD brain can support neurogenesis, strategies to stimulate the neurogenesis process could have therapeutic value in AD. We reviewed the literature on: (a) the functional significance of adult-born neurons; (b) the occurrence of endogenous neurogenesis in AD; and (c) strategies to stimulate the adult neurogenesis process. We found that: (a) new neurons in the adult DG contribute to memory function; (b) new neurons are generated in the SGZ and SVZ of AD brains, but they fail to differentiate into mature neurons in the target regions; and (c) numerous strategies (Lithium, Glatiramer Acetate, nerve growth factor, environmental enrichment) can enhance adult neurogenesis and promote maturation of newly generated neurons. Such strategies might help to compensate for the loss of neurons and improve the memory function in AD.     

Human wild-type alpha-synuclein impairs neurogenesis

Neurodegenerative diseases classified as synucleinopathies are characterized by alpha-synuclein inclusions. In these disorders, alpha-synuclein accumulates within glial or neuronal cells in the brain including regions of adult neurogenesis. We hypothesized a pathophysiological role for alpha-synuclein in newly generated cells of the adult brain and in this study examined regions of neurogenesis in adult mice overexpressing human wild-type alpha-synuclein under the control of the platelet-derived growth factor promoter. The number of proliferating cells and the fate of newly generated cells were analyzed in the olfactory bulb system and in the hippocampal dentate gyrus. There were no effects on proliferation detectable; however, significantly less neurogenesis and fewer neurons were observed in the olfactory bulb as well as in the hippocampus of adult human alpha-synuclein mice compared to control littermates. This effect was almost exclusively due to diminished survival of neuronal precursors in the target regions of neurogenesis. Our data imply that the finely tuned equilibrium of neuronal cell birth and death in neurogenic regions may be altered in human alpha-synuclein-overexpressing mice. We hypothesize that reduced adult neurogenesis in the olfactory bulb may contribute to olfactory deficits in neurodegenerative disorders associated with alpha-synuclein inclusions.     

Hepatocyte growth factor acts as a mitogen and chemoattractant for postnatal subventricular zone-olfactory bulb neurogenesis

Neural progenitor cells persist throughout life in the forebrain subventricular zone (SVZ). They generate neuroblasts that migrate to the olfactory bulb and differentiate into interneurons, but mechanisms underlying these processes are poorly understood. Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic factor that influences cell motility, proliferation and morphogenesis in neural and non-neural tissues. HGF and its receptor, c-Met, are present in the rodent SVZ-olfactory bulb pathway. Using in vitro neurogenesis assays and in vivo studies of partially HGF-deficient mice, we find that HGF promotes SVZ cell proliferation and progenitor cell maintenance, while slowing differentiation and possibly altering cell fate choices. HGF also acts as a chemoattractant for SVZ neuroblasts in co-culture assays. Decreased HGF signaling induces ectopic SVZ neuroblast migration and alters the timing of migration to the olfactory bulb. These results suggest that HGF influences multiple steps in postnatal forebrain neurogenesis. HGF is a mitogen for SVZ neural progenitors, and regulates their differentiation and olfactory bulb migration.     

Role of sensory activity on chemospecific populations of interneurons in the adult olfactory bulb

The olfactory bulb (OB) retains a remarkable capacity to renew its interneuronal populations throughout the lifespan of animals. Neuronal precursors giving rise to the bulbar interneurons are generated in the subventricular zone and have to migrate long distances before reaching the OB. In the adult OB these neuronal precursors differentiate into distinct neuronal types, including GABAergic cells located in the granule cell layer and a diverse set of neurons in the glomerular layer comprising GABAergic and dopaminergic interneurons, as well as other neuronal subtypes expressing calretinin and calbindin. While the role of sensory activity in the integration and/or survival of newly generated cells in the olfactory system is well established, very little is known about how odorant‐induced activity affects fate specification of newborn cells as well as survival and fate maintenance of preexisting neuronal populations generated in adulthood. The present study demonstrates that sensory deprivation diminishes not only the number of newborn cells in the OB, but also reduces the density of granule and periglomerular cells generated before nostril occlusion. It also shows that sensory activity has an important influence on the development and expression of dopaminergic, but not GABAergic, calretinin or calbindin phenotypes. Our data reveal that odorant‐induced activity is important for the survival of both newborn and preexisting OB interneurons generated at adulthood and suggests that these chemospecific populations are differentially affected by sensory deprivation. J. Comp. Neurol. 518:1847–1861, 2010. © 2009 Wiley‐Liss, Inc.     

Morphological bases for a role of nitric oxide in adult neurogenesis

The subventricular zone (SVZ) of the adult mouse brain retains the capacity to generate new neurons from stem cells. The neuronal precursors migrate tangentially along the rostral migratory stream (RMS) towards the olfactory bulb, where they differentiate as periglomerular and granular interneurons. In this study, we have investigated whether nitric oxide (NO), a signaling molecule in the nervous system with a role in embryonic neurogenesis, may be produced in the proximity of the progenitor cells in the adult brain, as a prerequisite to proposing a functional role for NO in adult neurogenesis. Proliferating and immature precursor cells were identified by immunohistochemistry for bromo-deoxyuridine (BrdU) and PSA-NCAM, respectively, and nitrergic neurons by either NADPH-diaphorase staining or immunohistochemical detection of neuronal NO synthase (NOS I). Nitrergic neurons with long varicose processes were found in the SVZ, intermingled with chains of cells expressing PSA-NCAM or containing BrdU. Neurons with similar characteristics surrounded the RMS all along its caudo-rostral extension as far as the core of the olfactory bulb. No expression of NOS I by precursor cells was detected either in the proliferation or in the migration zones. Within the olfactory bulb, many small cells in the granular layer and around the glomeruli expressed either PSA-NCAM or NOS I and, in some cases, both markers. Colocalization was also found in a few isolated cells at a certain distance from the neurogenesis areas. The anatomical disposition shown indicates that NO may be released close enough to the neuronal progenitors to allow a functional influence of this messenger in adult neurogenesis.     

Effect of the Estrous Cycle on Olfactory Bulb Response to Vaginocervical Stimulation in the Rat: Results from Electrophysiology and Fos Immunocytochemistry Experiments

To determine whether the stage of the estrous cycle modified the response of olfactory bulb neurons to vaginocervical stimulation, (1) vaginocervical stimulation was applied to animals in proestrus-estrus and metestrus-diestrus and the extracellular electrophysiological response of units in the mitral cell layer of the main olfactory bulb was compared, and (2) the effect of vaginocervical or sham stimulation and the effect of the estrous cycle on the number of neurons stained immunocytochemically for Fos in the main and accessory olfactory bulb was examined. Animals in proestrus-estrus had basal firing rates of 21.8 ± 1.8 spikes per 5 s and vaginocervical stimulation produced an increase in firing rate. In contrast, animals in metestrus-diestrus had a slower basal firing rate (14.3 ± 2.3 spikes per 5 s) and vaginocervical stimulation produced a decrease in the firing rate. For animals in proestrus-estrus, vaginocervical stimulation increased the number of Fos-stained cells in the granular cell layer of the accessory olfactory bulb, and in the glomerular and in external plexiform layers of the main olfactory bulb. In contrast, the number of Fos-stained cells decreased in the granular cell layer of the main olfactory bulb after stimulation was applied to animals in proestrus-estrus. The number of Fos-stained cells in the granular layer of the accessory olfactory bulb and the granular and glomerular cell layers of the main olfactory bulb was modulated by the estrous cycle. Therefore, olfactory bulb activity, measured both electrophysiologically and by Fos staining, was affected by the estrous cycle and vaginocervical stimulation, and the two variables interacted. It is likely that integration of interoceptive and environmental stimulation is important for the normal expression of sexual behavior in the female rat.     

Induction of tyrosine hydroxylase expression in rat forebrain neurons

Olfactory nerve input is required for the normal expression of tyrosine hydroxylase (TH) by dopaminergic neurons in the glomerular region of the rodent main olfactory bulb. To determine whether the olfactory nerve exerts a similar influence on neurons in other brain regions, we performed unilateral bulbectomies in rat pups on postnatal day 5-7 and examined the brains 2-6 months later, after the regenerated olfactory nerve had penetrated the forebrain. Tissue was stained for TH, dopamine beta-hydroxylase (DBH) and olfactory marker protein immunoreactivity. We observed novel TH-immunoreactivity in neurons located in those areas of the adult forebrain which received olfactory nerve fibers, particularly the rostral extension of the subependymal layer. Many of these neurons resembled the periglomerular cells of the olfactory bulb. No cell staining for DBH was observed in these areas, suggesting the possible dopaminergic phenotype of these neurons. Our data indicate that afferent regulation of neurotransmitter expression by the olfactory nerve is not limited to the cells of the olfactory bulb.     

Pax6 regulates Tbr1 and Tbr2 expressions in olfactory bulb mitral cells

Tracking olfactory bulb mitral cell development with BrdU labeling, we find that mitral cells are generated from Pax6 + radial glial cells in the ventricular zone of the embryonic olfactory bulb. Unlike cortical projection neurons, postmitotic mitral cell precursors express both Tbr1 and Tbr2. Our tracking experiments revealed that down-regulation of Pax6 preceded up-regulation of Tbrs, and that Tbr1 emerged earlier than Tbr2. Using in utero electroporation, we also show that Pax6 negatively regulates the expression of Tbr1 and Tbr2 in postmitotic mitral cell precursors. Exogenous expression of Pax6 in embryonic olfactory bulb postmitotic precursors decreased the number of cells that progressed to a mitral cell fate. In contrast, exogenous expression of Pax6 resulted in an increase of GABAergic and/or dopaminergic interneurons. These results indicate that Pax6 is a regulator of fate determination of precursor cells.     

Transiently impaired neurogenesis in MPTP mouse model of Parkinson's disease

It is still being debated whether neurogenesis in the subventricular zone (SVZ) is enhanced in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injury in the adult mouse brain. Our previous studies provided evidence that MPTP induces apoptosis of migrating neuroblasts (neural progenitor cells, A cells) in the SVZ and rostral migratory stream (RMS). We investigated cellular kinetics in the adult SVZ and olfactory bulb (OB) after MPTP damage. Cells were labeled with bromodeoxyuridine (BrdU), and the effects of MPTP on the survival and fate of migrating and residing neuroblasts were evaluated. Two days after BrdU labeling and MPTP treatment, the number of BrdU-positive cells in the SVZ and OB of MPTP-treated mice was significantly lower than in the SVZ and OB of saline controls. Additionally, fewer BrdU-positive cells migrated to the OB of treated mice than to that of saline controls, and the cells that did migrate diffused radially into the granule cell layer (GCL) when observed at 7, 14, and 28 days. In the OB GCL, the differentiation of BrdU-positive cells into mature neurons significantly attenuated 14 and 28 days after MPTP injury. Moreover, the impaired neurogenesis was followed by a recovery of A cells in the SVZ and OB, suggesting activation of the self-repair process as a result of MPTP-induced depletion of BrdU-positive cells. Our findings clarify the kinetics underlying neurogenesis in MPTP-treated mice and may contribute to the development of an animal model of Parkinson's disease, and the demonstration of cellular kinetics in SVZ may also provide a new insight into assessing neurogenesis in MPTP-treated mouse.     

Effects of thyroid hormone replacement on associative learning and hippocampal synaptic plasticity in adult hypothyroid rats

Newborn neurons generated by proliferative progenitors in the adult subventricular zone (SVZ) integrate into the olfactory bulb circuitry of mammals. Survival of these newly-formed cells is regulated by the olfactory input. The presence of new neurons in the accessory olfactory bulb (AOB) has already been demonstrated in some mammalian species, albeit their neurochemical profile and functional integration into AOB circuits are still to be investigated. To unravel whether the mouse AOB represents a site of adult constitutive neurogenesis and whether this process can be modulated by extrinsic factors, we have used multiple in vivo approaches. These included fate mapping of bromodeoxyuridine-labelled cells, lineage tracing of SVZ-derived enhanced green fluorescent protein-positive engrafted cells and neurogenesis quantification in the AOB, in both sexes, as well as in females alone after exposure to male-soiled bedding or its derived volatiles. Here, we show that a subpopulation of SVZ-derived neuroblasts acquires proper neurochemical profiles of mature AOB interneurons. Moreover, 3D reconstruction of long-term survived engrafted neuroblasts in the AOB confirms these cells show features of fully integrated neurons. Finally, exposure to male-soiled bedding, but not to its volatile compounds, significantly increases the number of new neurons in the AOB, but not in the main olfactory bulb of female mice. These data show SVZ-derived neuroblasts differentiate into new functionally integrated neurons in the AOB of young and adult mice. Survival of these cells seems to be regulated by an experience-specific mechanism mediated by pheromones.