Effects of fenfluramine, m-chlorophenylpiperazine, and other serotonin-related agonists and antagonists on penile erections in nonhuman primates

Fenfluramine, m-chlorophenylpiperazine (m-CPP), 1-phenylpiperazine, and the buspirone metabolite, 1-(2-pyrimidyl)piperazine given intravenously to adult rhesus monkeys regularly elicited penile erections. In contrast, serotonin (5-HT) agonists with 5-HT1A site specificity (8-OH-DPAT, buspirone) as well as trazodone, ritanserin, and metergoline were no different from saline in producing penile erections. Fenfluramine's effects were blocked by the 5-HT2 antagonists, ritanserin and metergoline, while m-CPP's effects were not blocked by the peripheral 5-HT antagonist, xylamidine, indicating that tumescence can be elicited by serotonergic agents which act at non-5-HT1A sites in the central nervous system.     

Adult Mouse Subventricular Zone Stem and Progenitor Cells Are Sessile and Epidermal Growth Factor Receptor Negatively Regulates Neuroblast Migration

Background

The adult subventricular zone (SVZ) contains stem and progenitor cells that generate neuroblasts throughout life. Although it is well accepted that SVZ neuroblasts are migratory, recent evidence suggests their progenitor cells may also exhibit motility. Since stem and progenitor cells are proliferative and multipotential, if they were also able to move would have important implications for SVZ neurogenesis and its potential for repair.

Methodology/Principal Findings

We studied whether SVZ stem and/or progenitor cells are motile in transgenic GFP+ slices with two photon time lapse microscopy and post hoc immunohistochemistry. We found that stem and progenitor cells; mGFAP-GFP+ cells, bright nestin-GFP+ cells and Mash1+ cells were stationary in the SVZ and rostral migratory stream (RMS). In our search for motile progenitor cells, we uncovered a population of motile βIII-tubulin+ neuroblasts that expressed low levels of epidermal growth factor receptor (EGFr). This was intriguing since EGFr drives proliferation in the SVZ and affects migration in other systems. Thus we examined the potential role of EGFr in modulating SVZ migration. Interestingly, EGFr^low neuroblasts moved slower and in more tortuous patterns than EGFr-negative neuroblasts. We next questioned whether EGFr stimulation affects SVZ cell migration by imaging Gad65-GFP+ neuroblasts in the presence of transforming growth factor alpha (TGF-α), an EGFr-selective agonist. Indeed, acute exposure to TGF-α decreased the percentage of motile cells by approximately 40%.

Conclusions/Significance

In summary, the present study directly shows that SVZ stem and progenitor cells are static, that EGFr is retained on some neuroblasts, and that EGFr stimulation negatively regulates migration. This result suggests an additional role for EGFr signaling in the SVZ.     

NOVOcan: a molecular link among selected glial cells

The nervous system is generated from cells lining the ventricular system. Our understanding of the fate potentials and lineage relationships of these cells is being re-evaluated, both because of recent demonstrations that radial glia can generate neurons and because of the identification of fate-determining genes. A variety of intrinsic and extrinsic molecules, including proteoglycans, regulate embryonic and postnatal brain development. Using probes modeled after species conserved domains of heparan sulfate proteoglycans, we cloned a novel gene called novocan, raised monoclonal antibodies against a segment of the predicted amino acid sequence of the expressed protein (NOVOcan) and used the antibodies to establish the cell and tissue localization of NOVOcan in postnatal rat brains by immunohistochemistry. NOVOcan was expressed in cells lining the ventricles, including a variety of radial glia during early postnatal development. Later, as radial glia disappeared and ependymal cells appeared, NOVOcan was detected in ependymal cells and in tanycytes, a specialized form of ependymal cell resembling radial glia. NOVOcan was absent in two known progeny of radial glia, mature astrocytes and neurons. Whereas NOVOcan was also absent in mature oligodendrocytes (OLGs), it was present in OLG precursors in developing white matter. These studies set the stage for determining the roles of NOVOcan in brain cell lineage patterns as well as in other aspects of development.     

Subventricular zone cytoarchitecture changes in Autism

Autism is thought to be a neurodevelopmental disorder with symptoms developing during neonatal neurogenesis in the subventricular zone (SVZ). Autism associated genes alter SVZ proliferation and cytoarchitecture, yet the response of the human SVZ in autism is unknown. Epilepsy drives neurogenesis in rodents, but it is unclear how epilepsy interacts with autism in SVZ responses. The striatal and septal SVZ derive from separate lineages in rodents and generate different interneuron types. Yet it is unclear if autism unevenly regulates the striatal and septal SVZ. The human SVZ was immunohistochemically examined post‐mortem from individuals with autism (n = 11) and controls (n = 11). Autism showed a lower cell density in the septal, but not striatal, SVZ hypocellular gap only in the absence of epilepsy. There was a decline in septal hypocellular gap cells with age in autism, but no correlation with age in controls. In contrast, PCNA+ cell numbers increased only in autism with epilepsy both in the hypocellular gap and in the ependymal layer on the septal but not striatal side. Ependymal cells also became GFAP immunoreactive in autism irrespective of epilepsy co‐morbidity; however, this only occurred on the striatal side. In examining these questions we also discovered a subset of ependymal, astrocyte ribbon and RMS cells which express PCNA and Ki67, PLP, and α‐tubulin. These results are the first example of a neuropsychiatric disease differentially affecting the septal and striatal SVZ. Altered cell density in the hypocellular gap and proliferation marker expression suggest individuals with autism may follow a different growth‐trajectory. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 74: 25–41, 2014     

Trap type, chirality of alpha-pinene, and geographic region affect sampling efficiency of root and lower stem insects in pine.

Root and lower stem insects cause significant damage to conifers, vector phytopathogenic fungi, and can predispose trees to bark beetle attacks. The development of effective sampling techniques is an important component in managing these cryptic insects. We tested the effects of trap type and stereochemistry of alpha-pinene, in combination with ethanol, on catches of the root colonizing weevils (Coleoptera: Curculionidae) Hylobius spp. [mostly Hylobius pales (Herbst)], and Pachylobius picivorus (Germar), the root colonizing bark beetle (Coleoptera: Scolytidae) Hylastes porculus Erickson, and the lower stem colonizing bark beetle Dendroctonus valens (LeConte). We tested for inter-regional differences by conducting similar field assays in the northern (Wisconsin) and southern (Louisiana) United States. The more effective trap type varied with region. Root weevils were caught primarily in pitfall traps in Wisconsin, whereas they were caught mostly in lower stem flight traps in Louisiana. In Wisconsin, root colonizing bark beetles were also caught primarily in pitfall traps, but lower stem colonizing bark beetles were caught primarily in lower stem flight traps. The root feeding weevils preferred (-) over (+)-alpha-pinene in both regions. Some exceptions relating to trap type or gender occurred in southern populations. The two root and lower stem colonizing bark beetles in Wisconsin showed no preference between (+) and (-)-alpha-pinene in combination with ethanol. No bark beetles were caught in the south. Our results suggest that modifying trap type and enantiomeric ratios of monoterpenes for different insect groups and in different regions can improve sampling efficiency for these important pests.