An enhanced olfactory marker protein immunoreactivity in individual olfactory receptor neurons following olfactory bulbectomy may be related to increased neurogenesis

Olfactory marker protein (OMP) is a 19-kD acidic protein found throughout the cytoplasm of mature olfactory receptor neurons (ORNs). Its function remains unknown. Following olfactory bulbectomy, the proportion of ORNs mature enough to express OMP declines greatly. However, in the few remaining mature ORNs, it has been observed that the intensity of OMP immunoreactivity (IR) appears to increase over that of ORNs on the unoperated side. We have now investigated this phenomenon quantitatively in rats subjected to unilateral olfactory bulbectomy. Results show that at all postbulbectomy survival periods examined quantitatively (3 days to 6 months), a significant decrease (19–37%) occurs in the transmission of incident light through OMP(+)-ORNs in bulbectomized versus unoperated olfactory epithelium (OE). Further, we also observed a consistent side-to-side difference in OMP IR in control unoperated animals. Possible explanations for these observations and their relation to the still unknown function of OMP are discussed. To test the possibility that OMP might serve a mitogenic role in the OE, recombinant OMP was added to organotypic explant cultures of fetal olfactory mucosa. Addition of OMP resulted in a dose-dependent increase in the density of bromodeoxyuridine-positive cells in the cultures, with a 50% increase occurring at the plateau OMP concentration of 25 nM. © 1998 John Wiley & Sons, Inc. J Neurobiol 34: 377–390, 1998     

Notch2 Signaling Maintains NSC Quiescence in the Murine Ventricular-Subventricular Zone

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Novel functions of GABA signaling in adult neurogenesis

Neurotransmitter gamma-aminobutiric acid （GABA） through ionotropic GABAA and metabotropic GABAB receptors plays key roles in modulating the development, plasticity and function of neuronal networks. GABA is inhibitory in mature neurons but excitatory in immature neurons, neuroblasts and neural stem/progenitor cells （NSCs/ NPCs）. The switch from excitatory to inhibitory occurs following the development of glutamatergic synaptic input and results from the dynamic changes in the expression of Na＋/K＋/2CF co-transporter NKCC1 driving CF influx and neuron-specific K＋/Cl co-transporter KCC2 driving Cl efflux. The developmental transition of KCC2 expression is regulated by Disrupted-in-Schizophrenia 1 （DISC1） and brain-derived neurotrophic factor （BDNF） signaling. The excitatory GABA signaling during early neurogenesis is important to the activity/experience-induced regulation of NSC quiescence, NPC proliferation, neuroblast migration and new-born neuronal maturation/functional integration. The inhibitory GABA signaling allows for the sparse and static functional networking essential for learning/memory development and maintenance.     

TRIM32-dependent transcription in adult neural progenitor cells regulates neuronal differentiation

In the adult mammalian brain, neural stem cells in the subventricular zone continuously generate new neurons for the olfactory bulb. Cell fate commitment in these adult neural stem cells is regulated by cell fate-determining proteins. Here, we show that the cell fate-determinant TRIM32 is upregulated during differentiation of adult neural stem cells into olfactory bulb neurons. We further demonstrate that TRIM32 is necessary for the correct induction of neuronal differentiation in these cells. In the absence of TRIM32, neuroblasts differentiate slower and show gene expression profiles that are characteristic of immature cells. Interestingly, TRIM32 deficiency induces more neural progenitor cell proliferation and less cell death. Both effects accumulate in an overproduction of adult-generated olfactory bulb neurons of TRIM32 knockout mice. These results highlight the function of the cell fate-determinant TRIM32 for a balanced activity of the adult neurogenesis process.     

The aging neurogenic subventricular zone

In the adult mouse brain, the subventricular zone (SVZ) is a neurogenic stem cell niche only 4-5 cell diameters thick. Within this narrow zone, a unique microenvironment supports stem cell self-renewal, gliogenesis or neurogenesis lineage decisions and tangential migration of newly generated neurons out of the SVZ and into the olfactory bulb. However, with aging, SVZ neurogenesis declines. Here, we examine the dynamic interplay between SVZ cytoarchitecture and neurogenesis through aging. Assembly of high-resolution electron microscopy images of corresponding coronal sections from 2-, 10- and 22-month-old mice into photomontages reveal a thinning of the SVZ with age. Following a 2-h BrdU pulse, we detect a significant decrease in cell proliferation from 2 to 22 months. Neuroblast numbers decrease with age, as do transitory amplifying progenitor cells, while both SVZ astrocytes and adjacent ependymal cells remain relatively constant. At 22 months, only residual pockets of neurogenesis remain and neuroblasts become restricted to the anterior dorsolateral horn of the SVZ. Within this dorsolateral zone many key components of the younger neurogenic niche are maintained; however, in the aged SVZ, increased numbers of SVZ astrocytes are found interposed within the ependyma. These astrocytes co-label with markers to ependymal cells and astrocytes, form intercellular adherens junctions with neighboring ependymal cells, and some possess multiple basal bodies of cilia within their cytoplasm. Together, these data reveal an age-related, progressive restriction of SVZ neurogenesis to the dorsolateral aspect of the lateral ventricle with increased numbers of SVZ astrocytes interpolated within the ependyma.     

Encoding of plant odour information in insects: peripheral and central mechanisms

Insects are suitable model organisms for studying mechanisms underlying olfactory coding and olfactory learning, by their unique adaptation to host plants in which the chemical senses are essential. Recent molecular biological studies have shown that a large number of genes in insects and other organisms are coding for olfactory receptor proteins. In general, one receptor type seems to be expressed in each neurone. The functional characterisations of olfactory receptor neurones have been extensive in certain insect species, demonstrating a fine-tuning of single neurones to biologically relevant odourants; both insect and plant produced volatiles. Stained neurones of the same functional type have been shown to project in one and the same glomerular unit in the primary olfactory centre, the antennal lobe. This corresponds to molecular biological studies, showing projections in one glomerulus by neurones expressing the same receptor type. Comparison of these findings with physiological and morphological characterisations of antennal lobe neurones has indicated correspondence between input and output of the glomerular units. Examples are presented from studies of heliothine moths. From the antennal lobe, the olfactory information is further conveyed to the mushroom bodies, particularly important for learning, and the lateral protocerebrum, a premotoric area. The three brain areas are regions of synaptic plasticity important in learning of odours, which is well studied in the honeybee but also in species of moths.     

腺苷酸环化酶3缺失下调小鼠嗅觉受体基因表达

主要嗅觉表皮组织（MOE）是哺乳动物感知气味分子的重要器官,气味诱导是嗅觉受体神经元（ORN）活动的起点,嗅觉受体（OR）结合气味分子后通过环腺苷酸（cAMP）信号通路向下游传递信号。腺苷酸环化酶3（AC3）是此通路中的重要分子。为了探讨AC3缺失对小鼠MOE内ORs基因表达的影响,本文以AC3敲除型小鼠(AC3-/-)和野生型小鼠(AC3+/+)为材料,采用荧光定量PCR（qRT-PCR）、荧光原位杂交（FISH）技术分析了部分ORs基因及与其相关因子在MOE中的表达。qRT-PCR表明,3月龄AC3-/-小鼠MOE中嗅觉受体 Olfr15、Olfr16、Olfr533、Olfr536、Olfr1507和Olfr642的表达量均显著下降。出生后PND7、PND30和PND90 三个不同发育时期的AC3-/-小鼠MOE原位杂交显示,嗅觉受体Olfr15、Olfr536和Olfr1507表达的细胞数目均减少。进一步qRT-PCR分析发现,3月龄AC3-/-小鼠嗅觉受体相关因子Rtp1、Rtp2、Reep1、Lhx2、Emx2和Ric-8b的表达也均发生显著下调。由此推测,AC3缺失导致的ORs及其相关因子的表达下调可能是嗅觉行为障碍的原因之一。     

PRDM12 Is Required for Initiation of the Nociceptive Neuron Lineage during Neurogenesis

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Resistance of glia-like central and peripheral neural stem cells to genetically induced mitochondrial dysfunction—differential effects on neurogenesis

Mitochondria play a central role in stem cell homeostasis. Reversible switching between aerobic and anaerobic metabolism is critical for stem cell quiescence, multipotency, and differentiation, as well as for cell reprogramming. However, the effect of mitochondrial dysfunction on neural stem cell (NSC) function is unstudied. We have generated an animal model with homozygous deletion of the succinate dehydrogenase subunit D gene restricted to cells of glial fibrillary acidic protein lineage (hGFAP-SDHD mouse). Genetic mitochondrial damage did not alter the generation, maintenance, or multipotency of glia-like central NSCs. However, differentiation to neurons and oligodendrocytes (but not to astrocytes) was impaired and, hence, hGFAP-SDHD mice showed extensive brain atrophy. Peripheral neuronal populations were normal in hGFAP-SDHD mice, thus highlighting their non-glial (non hGFAP⁺) lineage. An exception to this was the carotid body, an arterial chemoreceptor organ atrophied in hGFAP-SDHD mice. The carotid body contains glia-like adult stem cells, which, as for brain NSCs, are resistant to genetic mitochondrial damage.     

Cellular organization of adult neurogenesis in the Common Marmoset

Adult neurogenesis within the subgranular zone (SGZ) of the hippocampal dentate gyrus and the subventricular zone (SVZ) of the lateral ventricle (LV) has been most intensely studied within the brains of rodents such as mice and rats. However, little is known about the cell types and processes involved in adult neurogenesis within primates such as the common marmoset (Callithrix jacchus). Moreover, substantial differences seem to exist between the neurogenic niche of the LV between rodents and humans. Here, we set out to use immunohistochemical and autogradiographic analysis to characterize the anatomy of the neurogenic niches and the expression of cell type-specific markers in those niches in the adult common marmoset brain. Moreover, we demonstrate significant differences in the activity of neurogenesis in the adult marmoset brain compared to the adult mouse brain. Finally, we provide evidence for ongoing proliferation of neuroblasts within both the SGZ and SVZ of the adult brain and further show that the age-dependent decline of neurogenesis in the hippocampus is associated with a decrease in neuroblast cells.     

昆虫嗅觉受体功能的研究进展

嗅觉对昆虫的生存和繁殖至关重要。近年来对昆虫嗅觉识别的分子机制研究表明,嗅觉受体主要包括气味受体和离子型受体,它们在气味分子的识别过程中发挥关键和核心作用。为系统了解昆虫嗅觉受体功能的研究现状,本文综述了气味受体和离子型受体的发现历程、结构特征、表达定位,重点描述了气味受体和离子型受体的功能研究及其研究方法,力求为嗅觉受体研究和昆虫行为调控研究提供基础和参考。