Significance: Change in the nervous system occurs in response to diverse inputs, both normal and pathological. Defining such changes is required for understanding normal nervous-system functions and pathologies—e.g., from learning and memory to intractable disease. A unique combination pharmacology strategy allows identification of distinct neuronal subclasses through their constant functional expression of a specific subset of signaling proteins. Phenotypic alterations in signaling for one specific neuronal subclass were tracked as a function of development. These alterations provide proof-of-principle that changes in individual types of neurons can be monitored as a function of learning, disease, or aging. Developing biomarkers and therapeutic interventions for intractable nervous-system pathologies will require simultaneously monitoring different neuronal subclasses for such changes early during disease progression.
1 January 2013 in Frontiers in Cellular Neuroscience
We investigated the functional expression of nicotinic acetylcholine receptors (nAChRs) in heterogeneous populations of dissociated rat and mouse lumbar dorsal root ganglion (DRG) neurons by calcium imaging. By this experimental approach, it is possible to investigate the functional expression of multiple receptor and ion-channel subtypes across more than 100 neuronal and glial cells simultaneously. Based on nAChR expression, DRG neurons could be divided into four subclasses: 1) neurons that express predominantly alpha3beta4 and alpha6beta4 nAChRs; 2) neurons that express predominantly alpha7 nAChRs; 3) neurons that express a combination of alpha3beta4/alpha6beta4 and alpha7 nAChRs; and 4) neurons that do not express nAChRs. In this comparative study, the same four neuronal subclasses were observed in mouse and rat DRG. However, the expression frequency differed between species: substantially more rat DRG neurons were in the first three subclasses than mouse DRG neurons, at all developmental time points tested in our study. Approximately 70-80% of rat DRG neurons expressed functional nAChRs, in contrast to only ~15-30% of mouse DRG neurons. Our study also demonstrated functional coupling between nAChRs, voltage-gated calcium channels and mitochondrial Ca2+ transport in discrete subsets of DRG neurons. In contrast to the expression of nAChRs in DRG neurons, we demonstrated that a subset of non-neuronal DRG cells expressed muscarinic acetylcholine receptors (mAChRs) and not nAChRs. The general approach to comparative cellular neurobiology outlined in this paper has the potential to better integrate molecular and systems neuroscience by uncovering the spectrum of neuronal subclasses present in a given cell population and the functionally integrated signaling components expressed in each subclass.
Transient receptor potential (TRP) cation channels are molecular targets of various natural products. TRPA1 is specifically activated by natural products like allyl isothiocyanate (mustard oil), cinnamaldehyde (cinnamon), and allicin (garlic). In this study, we demonstrate that TRPA1 is also a target of trans-anethole in Fennel Oil (FO) and fennel seed extract. Similar to FO, trans-anethole selectively elicited calcium influx in TRPA1-expressing mouse sensory neurons of the dorsal root and trigeminal ganglia. These FO- and anethole-induced calcium responses were blocked by a selective TRPA1-channel antagonist, HC-030031. Moreover, both FO and trans-anethole induced calcium influx and transmembrane currents in HEK293 cells stably overexpressing human TRPA1 channels, but not in regular HEK293 cells. Mutation of the "ST" binding site of human TRPA1 significantly attenuated channel activation by trans-anethole, whereas pretreating with glutathione (GSH), a nucleophile, did not. Conversely, activation of TRPA1 by the electrophile allyl isothiocyanate was abolished by glutathione, but was ostensibly unaffected by mutation of the "ST" binding site. Finally, it was found that trans-anethole, was capable of desensitizing TRPA1 and unlike allyl isothiocyanate, it failed to induce nocifensive behaviors in mice. We conclude that trans-anethole is a selective, non-electrophilic, and seemingly less-irritating agonist of TRPA1.
Effects of gamma irradiation on photoluminescent properties of colloidal quantum dots are reported. Optical degradation is evaluated by tracking the dependence of photoluminescence intensity on irradiation dose. quantum dots show poor radiation hardness, and severely degrade after less than exposure to gamma photons.
We report on the successful preparation and characterization of fluorescent magnetic core/shell Fe3O4/ZnSe nanoparticles (NPs) with a spherical shape by organometallic synthesis. The 7 nm core/3 nm shell NPs show good magnetic and photoluminescence (PL) responses. The observed PL emission/excitation spectra are shifted to shorter wavelengths, compared to a reference ZnSe NP sample. A dramatic reduction of PL quantum yield is also observed. The temperature dependence of the magnetization for the core/shell NPs shows the characteristic features of two coexisting and interacting magnetic (Fe3O4) and nonmagnetic (ZnSe) phases. Compared to a reference Fe3O4 NP sample, the room-temperature Néel relaxation time in core/shell NPs is three times longer.