Voltage-activated current properties of male and female mouse vomeronasal sensory neurons: sexually dichotomous?

The vomeronasal organ, the chemosensory organ of the vomeronasal system, is vital in determining sexual and gender-specific behavior in mice. Here, whole-cell voltage-activated currents of individual mouse vomeronasal sensory neurons of two strains (BALB/c and CBA) were measured and correlated to sex in each strain. The average resting membrane potentials, maximal outward current magnitudes, and kinetics of activation and inactivation, were found to be independent of sex. Maximal inward current magnitudes differed significantly across gender in CBA, whereas they did not significantly differ in male and female BALB/c mice: BALB/c males –347±45 pA (n=51), and females –430±56 pA (n=27); CBA males –308±36 pA (n=56) and females –155±18 pA (n=28). These results suggest that some voltage-activated properties may differ slightly according to gender and to strain.D.M. Dean and A. Mazzatenta contributed equally to this work     

Unraveling the resistance of microbial biofilms: has proteomics been helpful?

Biofilms are surface-attached, matrix-encased, structured microbial communities which display phenotypic features that are dramatically different from those of their free-floating, or planktonic, counterparts. Biofilms seem to be the preferred mode of growth of microorganisms in nature, and at least 65% of all human infections are associated with biofilms. The most notable and clinically relevant property of biofilms is their greater resistance to antimicrobials compared with their planktonic counterparts. Although both bacterial and fungal biofilms display this phenotypic feature, the exact mechanisms underlying their increased drug resistance are yet to be determined. Advances in proteomics techniques during the past decade have facilitated in-depth analysis of the possible mechanisms underpinning increased drug resistance in biofilms. These studies have demonstrated the ability of proteomics techniques to unravel new targets for combating microbial biofilms. In this review, we discuss the putative drug resistance mechanisms of microbial biofilms that have been uncovered by proteomics and critically evaluate the possible contribution of the new knowledge to future development in the field. We also summarize strategic uses of novel proteomics technologies in studies related to drug resistance mechanisms of microbial biofilms.     

Reclassification of the serows and gorals: the end of a neverending story?

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Protein tyrosine phosphatase σ regulates the synapse number of zebrafish olfactory sensory neurons

The formation and refinement of synaptic connections are key steps of neural development to establish elaborate brain networks. To investigate the functional role of protein tyrosine phosphatase (PTP) σ, we employed an olfactory sensory neuron (OSN)-specific gene manipulation system in combination with in vivo imaging of transparent zebrafish embryos. Knockdown of PTPσ enhanced the accumulation of synaptic vesicles in the axon terminals of OSNs. The exaggerated accumulation of synaptic vesicles was restored to the normal level by the OSN-specific expression of PTPσ, indicating that presynaptic PTPσ is responsible for the regulation of synaptic vesicle accumulation. Consistently, transient expression of a dominant-negative form of PTPσ in OSNs enhanced the accumulation of synaptic vesicles. The exaggerated accumulation of synaptic vesicles was reproduced in transgenic zebrafish lines carrying an OSN-specific expression vector of the dominant-negative PTPσ. By electron microscopic analysis of the transgenic line, we found the significant increase of the number of OSN-mitral cell synapses in the central zone of the olfactory bulb. The density of docked vesicles at the active zone was also increased significantly. Our results suggest that presynaptic PTPσ controls the number of OSN-mitral cell synapses by suppressing their excessive increase.     

Pioneer neurons: a basis or bottleneck of diversity of nervous systems of Lophotrochozoa?

In a case study on development of larvae of Trochozoa species of different systematic positions, it was shown that peripheral neurons differentiated firstly. According to the characters of early peripheral neurons, in particular their localization in parts that differed from known zones of appearance of central ganglia, the difficult periphery of processes used as a "frame" by differentiated neurons of definitive nervous system, and transient expression of specific markers, it is reputed that these cells are pioneer. On the one hand, pioneer neurons are the bottleneck of morphogenesis diversity in late stages of development which prepare, in early larvae, the framework of the further central nervous system. On the other hand, navigation and marking using pioneer neurons can be a mechanism of evolutionary lability of definitive neural structures. Functional adaptive significance of pioneer neurons of larvae of Trochozoa animals, probably, is in the maintenance of a fast change from larvae life-form to adult life-form in metamorphosis that decreases the time of animals at intermediate stages of morphogenesis, which are associated with a dramatic fall in adaptation.     

Nitrotyrosine as a marker for peroxynitrite‐induced neurotoxicity: the beginning or the end of the end of dopamine neurons?

This review examines the involvement of nitrotyrosine as a marker for peroxynitrite-mediated damage in the dopamine neuronal system. We propose that the dopamine neuronal phenotype can influence the cytotoxic signature of peroxynitrite. Dopamine and tetrahydrobiopterin are concentrated in dopamine neurons, and both are essential for their proper neurochemical function. It is not well appreciated that dopamine and tetrahydrobiopterin are also powerful blockers of peroxynitrite-induced tyrosine nitration. What is more, the reaction of peroxynitrite with either dopamine or tetrahydrobiopterin forms chemical species (i.e. o-quinones and pterin radicals, respectively) whose cytotoxic effects may be manifested far earlier than nitrotyrosine formation in the course of dopamine neuronal damage. A better understanding of how the dopamine neuronal phenotype modulates the effects of reactive nitrogen species could reveal early steps in drug- and disease-induced damage to the dopamine neuron and form the basis for rational, protective therapies.     

Analyzing the activity of large populations of neurons: how tractable is the problem?

Understanding how the brain performs computations requires understanding neuronal firing patterns at successive levels of processing-a daunting and seemingly intractable task. Two recent studies have made dramatic progress on this problem by showing how its dimensionality can be reduced. Using the retina as a model system, they demonstrated that multineuronal firing patterns can be predicted by pairwise interactions.     

Pioneer neurons: A basis or limiting factor of lophotrochozoa nervous system diversity?

It has been demonstrated by us and other authors that first nervous cells in developing larvae from various trochozoan groups differentiate at the periphery. These pioneer neurons are distinguished by the set of characters. They are located outside the forming central ganglia; outgrowing fibers of central neurons use their processes as a “scaffolding” transmitter expression in these neurons is transient. On the one hand, pioneer neurons mark the “frame” of the adult nervous system and thus play a limiting role. On the other hand, pioneering navigation provides possible mechanisms for evolutional plasticity of the nervous system in adults. In addition, pioneer neurons can underlie functional adaptation of trochophore animals, which minimizes fitness decrease during the transition from the larval to the adult form during metamorphosis.     

Competition or inhibition? Developmental strategies in the establishment of peripheral projections by leech neurons

Leech neurons, like those of other invertebrates and those of vertebrates, undergo specific interactions during development which serve to define their adult morphologies and synaptic connections. We review here several observations and experiments that illustrate these interactions. In particular, we consider how they shape and constrain peripheral arborizations and whether the evidence favors competition or inhibition as their mode of action.     

Up-regulation of Cavβ3 subunit in primary sensory neurons increases voltage-activated Ca2+ channel activity and nociceptive input in neuropathic pain

High voltage-activated calcium channels (HVACCs) are essential for synaptic and nociceptive transmission. Although blocking HVACCs can effectively reduce pain, this treatment strategy is associated with intolerable adverse effects. Neuronal HVACCs are typically composed of α(1), β (Cavβ), and α(2)δ subunits. The Cavβ subunit plays a crucial role in the membrane expression and gating properties of the pore-forming α(1) subunit. However, little is known about how nerve injury affects the expression and function of Cavβ subunits in primary sensory neurons. In this study, we found that Cavβ(3) and Cavβ(4) are the most prominent subtypes expressed in the rat dorsal root ganglion (DRG) and dorsal spinal cord. Spinal nerve ligation (SNL) in rats significantly increased mRNA and protein levels of the Cavβ(3), but not Cavβ(4), subunit in the DRG. SNL also significantly increased HVACC currents in small DRG neurons and monosynaptic excitatory postsynaptic currents of spinal dorsal horn neurons evoked from the dorsal root. Intrathecal injection of Cavβ(3)-specific siRNA significantly reduced HVACC currents in small DRG neurons and the amplitude of monosynaptic excitatory postsynaptic currents of dorsal horn neurons in SNL rats. Furthermore, intrathecal treatment with Cavβ(3)-specific siRNA normalized mechanical hyperalgesia and tactile allodynia caused by SNL but had no significant effect on the normal nociceptive threshold. Our findings provide novel evidence that increased expression of the Cavβ(3) subunit augments HVACC activity in primary sensory neurons and nociceptive input to dorsal horn neurons in neuropathic pain. Targeting the Cavβ(3) subunit at the spinal level represents an effective strategy for treating neuropathic pain.     

Competition or inhibition? Developmental strategies in the establishment of peripheral projections by leech neurons

Leech neurons, like those of other invertebrates and those of vertebrates, undergo specific interactions during development which serve to define their adult morphologies and synaptic connections. We review here several observations and experiments that illustrate these interactions. In particular, we consider how they shape and constrain peripheral arborizations and whether the evidence favors competition or inhibition as their mode of action.     

The unfolding story of the Escherichia coli Hsp70 DnaK: is DnaK a holdase or an unfoldase?

We discuss recent experiments that have illuminated individual steps in the reaction cycle of the Escherichia coli Hsp70 molecular chaperone DnaK. Using this new information, we compare two distinctly different global mechanisms of action--holding versus unfolding--and argue that the available evidence suggests that DnaK is an unfoldase.     

Central projections of the sensory hairs on the gemma of the ant Diacamma: substrate for behavioural modulation?

In the ant genus Diacamma, all workers eclose from their cocoons with little clublike thoracic appendages, called gemmae. Whether these gemmae are mutilated determines individual behaviour, and ultimately reproductive role, in two of the three species examined. The gemmae are covered with sensory hairs, which probably serve a mechanoreceptive function. The sensory afferents arising from these hairs were stained and traced into the central nervous system (CNS). They feature widely distributed collaterals invading all three thoracic ganglia as well as the suboesophageal and the second abdominal ganglia. The multisegmental arborization pattern of the gemma afferents is very similar to that of wing-hair afferents of other ants (queens and males) or other insects in general. This implies that gemmae and wings are homologous structures. We discuss the morphology of the gemma afferents with respect to their possible involvement in the behavioural changes associated with mutilation. The neuronal processing may be modulated by (1) the decrease of sensory input onto interneurons (suggested by the afferents' extensive arborizations); or (2) by the effect of neuromodulatory substances (suggested by the finding that terminals occur within the cell body rind of the ganglion).     

Cell division in the CNS: protective response or lethal event in post-mitotic neurons?

Cell cycle events have been documented to be associated with several human neurodegenerative diseases. This review focuses on two diseases--Alzheimer's disease and ataxia telangiectasia--as well as their mouse models. Cell cycle studies have shown that ectopic expression of cell cycle markers is spatially and regional correlated well with neuronal cell death in both disease conditions. Further evidence of ectopic cell cycling is found in both human diseases and in its mouse models. These findings suggest that loss of cell cycle control represents a common pathological root of disease, which underlies the defects in the affected brain tissues in both human and mouse. Loss of cell cycle control is a unifying hypothesis for inducing neuronal death in CNS. In the disease models we have examined, cell cycle markers appear before the more well-recognized pathological changes and thus could serve as early stress markers--outcome measures for preclinical trials of potential disease therapies. As a marker these events could serve as a new criterion in human pathological diagnosis. The evidence to date is compatible with the requirement for a second "hit" for a neuron to progress cell cycle initiation and DNA replication to death. If this were true, any intervention of blocking 'second' processes might prevent or slow the neuronal cell death in the process of disease. What is not known is whether, in an adult neuron, the cell cycle event is part of the pathology or rather a desperate attempt of a neuron under stress to protect itself.     

Germline imprinting: battle of the sexes or battle of the X's?

The X chromosome is largely inactivated in spermatogenesis of heterogametic males, and in multiple phyla it encodes few genes specifically expressed in the male germline. Writing in Nature Genetics, Bean et al. report a parallel between male germline X inactivation in nematodes and a fungal gene-silencing mechanism that alters the way we view the evolution of both phenomena.