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Olfactory sexual dimorphism has mainly been described in the vomeronasal system, in relation to reproductive behavior, while evidence of sexual dimorphism in the main olfactory bulb (OB) remains scarce. There are no data indicating sex-related differences in the neurochemistry of intrinsic olfactory elements. Neurocalcin (NC) is a calcium-binding protein that is expressed in specific neuronal populations of the central nervous system. Here we analyzed by immunohistochemistry the NC-containing neurons in the mouse main OB, comparing both their quantities and their locations between male and female animals. NC cell density was higher in males than in females in specific locations of the glomerular layer, the external plexiform layer, the mitral cell layer, and the internal plexiform layer. This divergence in the numbers of NC cells was especially patent in central rostrocaudal levels. The NC-containing neurons exhibiting sexual divergence were identified as both juxtaglomerular and short-axon cells. This is the first description of sexual dimorphism regarding neurons belonging to the mouse main OB. According to their distribution in the OB, neurocalcin-immunoreactive interneurons could reflect a sexually dimorphic regulation of specific odorants. [ABSTRACT FROM AUTHOR]

Nicotine exerts its addictive influence through the meso-cortico-limbic reward system, where the striatum is essential. Nicotine addiction involves different neurotransmitters, nitric oxide (NO) being especially important, since it triggers the release of the others by positive feedback. In the nervous system, NO is mainly produced by nitric oxide synthase 1 (NOS1). However, other subtypes of synthases can also synthesize NO, and little is known about the specific role of each isoform in the process of addiction. In parallel, NOS activity and nicotine addiction are also affected by stress and sexual dimorphism. To determine the specific role of this enzyme, we analyzed both NOS expression and NO synthesis in the striatum of wild-type and NOS1-knocked out (KO) mice of both sexes in situations of nicotine sensitization and stress. Our results demonstrated differences between the caudate-putamen (CP) and nucleus accumbens (NA). With respect to NOS1 expression, the CP is a dimorphic region (27.5% lower cell density in males), but with a stable production of NO, exclusively due to this isoform. Thus, the nitrergic system of CP may not be involved in stress or nicotine addiction. Conversely, the NA is much more variable and strongly involved in both situations: its NO synthesis displays dimorphic variations at both basal (68.5% reduction in females) and stress levels (65.9% reduction in males), which disappear when nicotine is infused. Thus, the KO animals showed an increase in NO production (21.7%) in the NA, probably by NOS3, in an attempt to compensate the lack of NOS1., (Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.)

The periglomerular cells (PG) of the olfactory bulb (OB) are involved in the primary processing and the refinement of sensory information from the olfactory epithelium. The neurochemical composition of these neurons has been studied in depth in many species, and over the last decades such studies have focused mainly on the rat. The increasing use of genetic models for research into olfactory function demands a profound characterization of the mouse olfactory bulb, including the chemical composition of bulbar interneurons. Regarding both their connectivity with the olfactory nerve and their neurochemical fate, recently, two different types of PG have been identified in the mouse. In the present report, we analyze both the synaptology and the chemical composition of specific PG populations in the murine olfactory bulb, in particular, those containing the neuropeptide cholecystokinin. Our results demonstrate the existence in the mouse of non-GABAergic PG and that these establish synaptic contacts with the olfactory nerve within the glomeruli. Based on previous classifications, we propose that this population would constitute a new subtype of type 1 mouse PG. In addition, we demonstrate the partial coexistence of cholecystokinin with the calcium-binding proteins neurocalcin and parvalbumin. All these findings add further data to our knowledge of the synaptology and neurochemistry of mouse PG. The differences observed from other rodents reflect the neurochemical heterogeneity of PG in the mammalian OB., (© 2010 Wiley-Liss, Inc.)

The Pax6 transcription factor is a key element along brain development in both the visual and olfactory systems. The involvement of Pax6 in neural fate is well documented in the visual system, whereas in the olfactory system, and in particular in the olfactory bulb (OB), its expression during adulthood has only begun to be elucidated. In the OB, the modulation of primary sensory information is first performed by periglomerular cells (PG). A considerable body of information has unveiled the neurochemical heterogeneity of these neurons. Thus it is well known that Pax6 coexists with dopaminergic/GABAergic mouse PG. However, the presence of this transcription factor in other mouse PG subpopulations has not been studied. Here, we analyzed whether Pax6 is expressed in PG containing the calcium-binding proteins neurocalcin and parvalbumin, and the neuropeptide cholecystokinin. Our results show that Pax6 is not expressed by these PG subpopulations, suggesting that it is mainly restricted to GABAergic PG populations. These findings provide new data in the chemical characterization of mouse Pax6-positive PG.

Postnatally, the Purkinje cell degeneration mutant mice lose the main projecting neurons of the main olfactory bulb (OB): mitral cells (MC). In adult animals, progenitor cells from the rostral migratory stream (RMS) differentiate into bulbar interneurons that modulate MC activity. In the present work, we studied changes in proliferation, tangential migration, radial migration patterns, and the survival of these newly generated neurons in this neurodegeneration animal model. The animals were injected with bromodeoxyuridine 2 weeks or 2 months before killing in order to label neuroblast incorporation into the OB and to analyze the survival of these cells after differentiation, respectively. Both the organization and cellular composition of the RMS and the differentiation of the newly generated neurons in the OB were studied using specific markers of glial cells, neuroblasts, and mature neurons. No changes were observed in the cell proliferation rate nor in their tangential migration through the RMS, indicating that migrating neuroblasts are only weakly responsive to the alteration in their target region, the OB. However, the absence of MC does elicit differences in the final destination of the newly generated interneurons. Moreover, the loss of MC also produces changes in the survival of the newly generated interneurons, in accordance with the dramatic decrease in the number of synaptic targets available.

The dopaminergic system plays important roles in the modulation of olfactory transmission. The present study examines the distribution of dopaminergic cells and the content of dopamine (DA) and its metabolites in control and deprived olfactory bulbs (OB), focusing on the differences between sexes. The content of DA and of its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were measured by HPLC. The morphology and distribution of dopaminergic neurons were studied using tyrosine hydroxylase (TH) immunohistochemistry. Cells were typified with TH-parvalbumin, TH-cholecystokinin or TH-neurocalcin double-immunofluorescence assays. Biochemical analyses revealed sex differences in the content of DA and of its metabolites. In normal conditions, the OBs of male rats had higher concentrations of DA, DOPAC and HVA than the OBs of females. The immunohistochemical data pointed to sex differences in the number of TH-immunopositive cells (higher in male than in female rats). Colocalization analyses revealed that dopaminergic cells constitute a different cell subpopulation from those labelled after parvalbumin, cholecystokinin or neurocalcin immunostaining. Unilateral olfactory deprivation caused dramatic alterations in the dopaminergic system. The DA content and the density of dopaminergic cells decreased, the contents of DA and DOPAC as well as TH immunoreactivity were similar in deprived males and females and, finally, the metabolite/neurotransmitter ratio increased. Our results show that the dopaminergic modulation of olfactory transmission seems to differ between males and females and that it is regulated by peripheral olfactory activity. A possible role of the dopaminergic system in the sexually different olfactory sensitivity, discrimination and memory is discussed.

The rostral migratory stream is one of the few regions of the adult mammalian central nervous system in which cellular migration and proliferation have been described. Most rostral migratory stream cells divide rapidly and hence different proliferation markers have been employed to identify them. Nitrogen base substitutes, such as tritiated thymidine or 5-bromo-2'-deoxyuridine (BrdU), together with endogenous molecules, such as Proliferating Cell Nuclear Antigen (PCNA), are the cell cycle markers most widely employed. Protocols for BrdU and PCNA localization are both plentiful and diverse, but to date no optimized protocol for obtaining trustworthy double staining of both markers has been described. In this work, we propose optimized protocols for achieving both single staining and the joint detection of BrdU and PCNA in the rodent brain using double-immunofluorescence procedures. The double labeling described allows the discrimination of different cell cycle stages in migratory cells from the mouse brain.