Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The olfactory system continuously incorporates new neurons into functional circuits throughout life. Axons from olfactory sensory neurons (OSNs) in the nasal cavity synapse on mitral, tufted and periglomerular (PG) cells in the main olfactory bulb, and low levels of turnover within the OSN population results in ingrowth of new axons under normal physiological conditions. Subpopulations of bulb interneurons are continually eliminated by apoptosis, and are replaced by new neurons derived from progenitors in the adult forebrain subventricular zone. Integration of new neurons, including PG cells that are contacted by sensory axons, leads to ongoing reorganization of adult olfactory bulb circuits. The mechanisms regulating this adaptive structural plasticity are not all known, but the process is reminiscent of early nervous system development. Neurotrophic factors have well-established roles in controlling neuronal survival and connectivity during development, leading to speculation that trophic interactions between OSNs and their target bulb neurons may mediate some of these same processes in adults. A number of different trophic factors and their cognate receptors are expressed in the adult olfactory pathway. Neurotrophin-3 (NT3) is among these, as reflected by beta-galactosidase expression in transgenic reporter mice expressing lacZ under the NT3 promoter. Using a combination of approaches, including immunocytochemistry, real-time PCR of laser-captured RNA, and adenovirus-mediated gene transfer of NT3 fusion peptides in vivo, we demonstrate that OSNs express and anterogradely transport NT3 to the olfactory bulb. We additionally observe that in mice treated with adenovirus encoding NT3 tagged with hemagglutinin (HA), a subset of bulb neurons expressing the TrkC neurotrophin receptor are immunoreactive for HA, suggesting their acquisition of the fusion peptide from infected sensory neurons. Our results therefore provide evidence that OSNs may serve as an afferent source of trophic signals for the adult mouse olfactory bulb.
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PMID:Anterograde trafficking of neurotrophin-3 in the adult olfactory system in vivo. 2326 63

Trace amine-associated receptors (TAARs) are a class of G-protein-coupled receptors found in mammals. While TAAR1 is expressed in several brain regions, all the other TAARs have been described mainly in the olfactory epithelium and the glomerular layer of the olfactory bulb and are believed to serve as a new class of olfactory receptors sensing innate odors. However, there is evidence that TAAR5 could play a role also in the central nervous system. In this study, we characterized a mouse line lacking TAAR5 (TAAR5 knockout, TAAR5-KO) expressing beta-galactosidase mapping TAAR5 expression. We found that TAAR5 is expressed not only in the glomerular layer in the olfactory bulb but also in deeper layers projecting to the limbic brain olfactory circuitry with prominent expression in numerous limbic brain regions, such as the anterior olfactory nucleus, the olfactory tubercle, the orbitofrontal cortex (OFC), the amygdala, the hippocampus, the piriform cortex, the entorhinal cortex, the nucleus accumbens, and the thalamic and hypothalamic nuclei. TAAR5-KO mice did not show gross developmental abnormalities but demonstrated less anxiety- and depressive-like behavior in several behavioral tests. TAAR5-KO mice also showed significant decreases in the tissue levels of serotonin and its metabolite in several brain areas and were more sensitive to the hypothermic action of serotonin 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propilamino)tetralin (8-OH-DPAT). These observations indicate that TAAR5 is not just innate odor-sensing olfactory receptor but also serves to provide olfactory input into limbic brain areas to regulate emotional behaviors likely via modulation of the serotonin system. Thus, anxiolytic and/or antidepressant action of future TAAR5 antagonists could be predicted. In general, "olfactory" TAAR-mediated brain circuitry may represent a previously unappreciated neurotransmitter system involved in the transmission of innate odors into emotional behavioral responses.
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PMID:Trace Amine-Associated Receptor 5 Provides Olfactory Input Into Limbic Brain Areas and Modulates Emotional Behaviors and Serotonin Transmission. 3219 74

Trace amine-associated receptors (TAARs) are a class of sensory G protein-coupled receptors that detect biogenic amines, products of decarboxylation of amino acids. The majority of TAARs (TAAR2-TAAR9) have been described mainly in the olfactory epithelium and considered to be olfactory receptors sensing innate odors. However, there is recent evidence that one of the members of this family, TAAR5, is expressed also in the limbic brain areas receiving projection from the olfactory system and involved in the regulation of emotions. In this study, we further characterized a mouse line lacking TAAR5 (TAAR5 knockout, TAAR5-KO mice) that express beta-galactosidase mapping TAAR5 expression. We found that in TAAR5-KO mice the number of dopamine neurons, the striatal levels of dopamine and its metabolites, as well as striatal levels of GDNF mRNA, are elevated indicating a potential increase in dopamine neuron proliferation. Furthermore, an analysis of TAAR5 beta-galactosidase expression revealed that TAAR5 is present in the major neurogenic areas of the brain such as the subventricular zone (SVZ), the subgranular zone (SGZ) and the less characterized potentially neurogenic zone surrounding the 3rd ventricle. Direct analysis of neurogenesis by using specific markers doublecortin (DCX) and proliferating cell nuclear antigen (PCNA) revealed at least 2-fold increase in the number of proliferating neurons in the SVZ and SGZ of TAAR5-KO mice, but no such markers were detected in mutant or control mice in the areas surrounding the 3rd ventricle. These observations indicate that TAAR5 involved not only in regulation of emotional status but also adult neurogenesis and dopamine transmission. Thus, future TAAR5 antagonists may exert not only antidepressant and/or anxiolytic action but may also provide new treatment opportunity for neurodegenerative disorders such as Parkinson's disease.
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PMID:Increased dopamine transmission and adult neurogenesis in trace amine-associated receptor 5 (TAAR5) knockout mice. 3313 88


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