Behavioral Consequences of NMDA Antagonist-Induced Neuroapoptosis in the Infant Mouse Brain

Background: Exposure to NMDA glutamate antagonists during the brain growth spurt period causes widespread neuroapoptosis in the rodent brain. This period in rodents occurs during the first two weeks after birth, and corresponds to the third trimester of pregnancy and several years after birth in humans. The developing human brain may be exposed to NMDA antagonists through drug-abusing mothers or through anesthesia. Methodology/Principal Findings: We evaluated the long-term neurobehavioral effects of mice exposed to a single dose of the NMDA antagonist, phencyclidine (PCP), or saline, on postnatal day 2 (P2) or P7, or on both P2 and P7. PCP treatment on P2 + P7 caused more severe cognitive impairments than either single treatment. Histological examination of acute neuroapoptosis resulting from exposure to PCP indicated that the regional pattern of degeneration induced by PCP in P2 pups was different from that in P7 pups. The extent of damage when evaluated quantitatively on P7 was greater for pups previously treated on P2 compared to pups treated only on P7. Conclusions: These findings signify that PCP induces different patterns of neuroapoptosis depending on the developmental age at the time of exposure, and that exposure at two separate developmental ages causes more severe neuropathological and neurobehavioral consequences than a single treatment

When Is a Bulge Not a Bulge? Inner Disks Masquerading as Bulges in NGC 2787 and NGC 3945

We present a detailed morphological, photometric, and kinematic analysis of two barred S0 galaxies with large, luminous inner disks inside their bars. We show that these structures, in addition to being geometrically disk-like, have exponential profiles (scale lengths $\sim$ 300--500 pc) distinct from the central, non-exponential bulges. We also find them to be kinematically disk-like. The inner disk in NGC 2787 has a luminosity roughly twice that of the bulge; but in NGC 3945, the inner disk is almost ten times more luminous than the bulge, which itself is extremely small (half-light radius $\approx$ 100 pc, in a galaxy with an outer ring of radius $\approx$ 14 kpc) and only $\sim$ 5% of the total luminosity -- a bulge/total ratio much more typical of an Sc galaxy. We estimate that at least 20% of (barred) S0 galaxies may have similar structures, which means that their bulge/disk ratios may be significantly overestimated. These inner disks dominate the central light of their galaxies; they are at least an order of magnitude larger than typical ``nuclear disks'' found in ellipticals and early-type spirals. Consequently, they must affect the dynamics of the bars in which they reside.Comment: LaTeX, 37 pages, 14 EPS figures. To appear in The Astrophysical Journal (November 10, 2003 issue). Version with full-resolution figures available at http://www.iac.es/galeria/erwin/research

GEMS: Galaxy Evolution from Morphologies and SEDs

GEMS, Galaxy Evolution from Morphologies and SEDs, is a large-area (800 arcmin2) two-color (F606W and F850LP) imaging survey with the Advanced Camera for Surveys on HST. Centered on the Chandra Deep Field South, it covers an area of ~28'x28', or about 120 Hubble Deep Field areas, to a depth of m_AB(F606W)=28.3 (5sigma and m_AB(F850LP)=27.1 (5sigma) for compact sources. In its central ~1/4, GEMS incorporates ACS imaging from the GOODS project. Focusing on the redshift range 0.2<=z<=1.1, GEMS provides morphologies and structural parameters for nearly 10,000 galaxies where redshift estimates, luminosities and SEDs exist from COMBO-17. At the same time, GEMS contains detectable host galaxy images for several hundred faint AGN. This paper provides an overview of the science goals, the experiment design, the data reduction and the science analysis plan for GEMS.Comment: 24 pages, TeX with 6 eps Figures; to appear in ApJ Supplement. Low resolution figures only. Full resolution at http://zwicky.as.arizona.edu/~rix/Misc/GEMS.ps.g

Bar Evolution Over the Last Eight Billion Years: A Constant Fraction of Strong Bars in GEMS

One third of present-day spirals host optically visible strong bars that drive their dynamical evolution. However, the fundamental question of how bars evolve over cosmological times has yet to be addressed, and even the frequency of bars at intermediate redshifts remains controversial. We investigate the frequency of bars out to z~1.0 drawing on a sample of 1590 galaxies from the GEMS survey, which provides morphologies from HST ACS two-color images, and highly accurate redshifts from the COMBO-17 survey. We identify spiral galaxies using the Sersic index, concentration parameter, and rest-frame color. We characterize bars and disks by fitting ellipses to F606W and F850LP images, taking advantage of the two bands to minimize bandpass shifting. We exclude highly inclined (i>60 deg) galaxies to ensure reliable morphological classifications, and apply completeness cuts of M_v <= -19.3 and -20.6. More than 40% of the bars that we detect have semi major axes a<0.5" and would be easily missed in earlier surveys without the small PSF of ACS. The bars that we can reliably detect are fairly strong (with ellipticities e>=0.4) and have a in the range ~1.2-13 kpc. We find that the optical fraction of such strong bars remains at ~(30% +- 6%) from the present-day out to look-back times of 2-6 Gyr (z~0.2-0.7) and 6-8 Gyr (z~0.7-1.0); it certainly shows no sign of a drastic decline at z>0.7. Our findings of a large and similar bar fraction at these three epochs favor scenarios in which cold gravitationally unstable disks are already in place by z~1, and where on average bars have a long lifetime (well above 2 Gyr). The distributions of structural bar properties in the two slices are, however, not statistically identical and therefore allow for the possibility that the bar strengths and sizes may evolve over time.Comment: Accepted by ApJ Letters, to appear in Nov 2004 issue. Minor revisions,updated reference

The Outer Disks of Early-Type Galaxies. I. Surface-Brightness Profiles of Barred Galaxies

We present a study of 66 barred, early-type (S0-Sb) disk galaxies, focused on the disk surface brightness profile outside the bar region and the nature of Freeman Type I and II profiles, their origins, and their possible relation to disk truncations. This paper discusses the data and their reduction, outlines our classification system, and presents $R$-band profiles and classifications for all galaxies in the sample. The profiles are derived from a variety of different sources, including the Sloan Digital Sky Survey (Data Release 5). For about half of the galaxies, we have profiles derived from more than one telescope; this allows us to check the stability and repeatability of our profile extraction and classification. The vast majority of the profiles are reliable down to levels of mu_R ~ 27 mag arcsec^-2; in exceptional cases, we can trace profiles down to mu_R > 28. We can typically follow disk profiles out to at least 1.5 times the traditional optical radius R_25; for some galaxies, we find light extending to ~ 3 R_25. We classify the profiles into three main groups: Type I (single-exponential), Type II (down-bending), and Type III (up-bending). The frequencies of these types are approximately 27%, 42%, and 24%, respectively, plus another 6% which are combinations of Types II and III. We further classify Type II profiles by where the break falls in relation to the bar length, and in terms of the postulated mechanisms for breaks at large radii ("classical trunction" of star formation versus the influence of the Outer Lindblad Resonance of the bar). We also classify the Type III profiles by the probable morphology of the outer light (disk or spheroid). Illustrations are given for all cases. (Abridged)Comment: 41 pages, 26 PDF figures. To appear in the Astronomical Journal. Version with full-resolution figures available at http://www.mpe.mpg.de/~erwin/research

An antiangiogenic neurokinin-B/thromboxane A2 regulatory axis

Establishment of angiogenic circuits that orchestrate blood vessel development and remodeling requires an exquisite balance between the activities of pro- and antiangiogenic factors. However, the logic that permits complex signal integration by vascular endothelium is poorly understood. We demonstrate that a “neuropeptide,” neurokinin-B (NK-B), reversibly inhibits endothelial cell vascular network assembly and opposes angiogenesis in the chicken chorioallantoic membrane. Disruption of endogenous NK-B signaling promoted angiogenesis. Mechanistic analyses defined a multicomponent pathway in which NK-B signaling converges upon cellular processes essential for angiogenesis. NK-B−mediated ablation of Ca2+ oscillations and elevation of 3′–5′ cyclic adenosine monophosphate (cAMP) reduced cellular proliferation, migration, and vascular endothelial growth factor receptor expression and induced the antiangiogenic protein calreticulin. Whereas NK-B initiated certain responses, other activities required additional stimuli that increase cAMP. Although NK-B is a neurotransmitter/ neuromodulator and NK-B overexpression characterizes the pregnancy-associated disorder preeclampsia, NK-B had not been linked to vascular remodeling. These results establish a conserved mechanism in which NK-B instigates multiple activities that collectively oppose vascular remodeling

Behavioral Consequences of NMDA Antagonist-Induced Neuroapoptosis in the Infant Mouse Brain

Background: Exposure to NMDA glutamate antagonists during the brain growth spurt period causes widespread neuroapoptosis in the rodent brain. This period in rodents occurs during the first two weeks after birth, and corresponds to the third trimester of pregnancy and several years after birth in humans. The developing human brain may be exposed to NMDA antagonists through drug-abusing mothers or through anesthesia. Methodology/Principal Findings: We evaluated the long-term neurobehavioral effects of mice exposed to a single dose of the NMDA antagonist, phencyclidine (PCP), or saline, on postnatal day 2 (P2) or P7, or on both P2 and P7. PCP treatment on P2 + P7 caused more severe cognitive impairments than either single treatment. Histological examination of acute neuroapoptosis resulting from exposure to PCP indicated that the regional pattern of degeneration induced by PCP in P2 pups was different from that in P7 pups. The extent of damage when evaluated quantitatively on P7 was greater for pups previously treated on P2 compared to pups treated only on P7. Conclusions: These findings signify that PCP induces different patterns of neuroapoptosis depending on the developmental age at the time of exposure, and that exposure at two separate developmental ages causes more severe neuropathologica

The Role of TLR4 in the Paclitaxel Effects on Neuronal Growth In Vitro

Paclitaxel (Pac) is an antitumor agent that is widely used for treatment of solid cancers. While being effective as a chemotherapeutic agent, Pac in high doses is neurotoxic, specifically targeting sensory innervations. In view of these toxic effects associated with conventional chemotherapy, decreasing the dose of Pac has been recently suggested as an alternative approach, which might limit neurotoxicity and immunosuppression. However, it remains unclear if low doses of Pac retain its neurotoxic properties or might exhibit unusual effects on neuronal cells. The goal of this study was to analyze the concentration-dependent effect of Pac on isolated and cultured DRG neuronal cells from wild-type and TLR4 knockout mice. Three different morphological parameters were analyzed: the number of neurons which developed neurites, the number of neurites per cell and the total length of neurites per cell. Our data demonstrate that low concentrations of Pac (0.1 nM and 0.5 nM) do not influence the neuronal growth in cultures in both wild type and TLR4 knockout mice. Higher concentrations of Pac (1-100 nM) had a significant effect on DRG neurons from wild type mice, affecting the number of neurons which developed neurites, number of neurites per cell, and the length of neurites. In DRG from TLR4 knockout mice high concentrations of Pac showed a similar effect on the number of neurons which developed neurites and the length of neurites. At the same time, the number of neurites per cell, indicating the process of growth cone initiation, was not affected by high concentrations of Pac. Thus, our data showed that Pac in high concentrations has a significant damaging effect on axonal growth and that this effect is partially mediated through TLR4 pathways. Low doses of Pac are devoid of neuronal toxicity and thus can be safely used in a chemomodulation mode. © 2013 Ustinova et al

Secular Evolution and the Formation of Pseudobulges in Disk Galaxies

We review internal processes of secular evolution in galaxy disks, concentrating on the buildup of dense central features that look like classical, merger-built bulges but that were made slowly out of disk gas. We call these pseudobulges. As an existence proof, we review how bars rearrange disk gas into outer rings, inner rings, and gas dumped into the center. In simulations, this gas reaches high densities that plausibly feed star formation. In the observations, many SB and oval galaxies show central concentrations of gas and star formation. Star formation rates imply plausible pseudobulge growth times of a few billion years. If secular processes built dense central components that masquerade as bulges, can we distinguish them from merger-built bulges? Observations show that pseudobulges retain a memory of their disky origin. They have one or more characteristics of disks: (1) flatter shapes than those of classical bulges, (2) large ratios of ordered to random velocities indicative of disk dynamics, (3) small velocity dispersions, (4) spiral structure or nuclear bars in the bulge part of the light profile, (5) nearly exponential brightness profiles, and (6) starbursts. These structures occur preferentially in barred and oval galaxies in which secular evolution should be rapid. So the cleanest examples of pseudobulges are recognizable. Thus a large variety of observational and theoretical results contribute to a new picture of galaxy evolution that complements hierarchical clustering and merging.Comment: 92 pages, 21 figures in 30 Postscript files; to appear in Annual Review of Astronomy and Astrophysics, Vol. 42, 2004, in press; for a version with full resolution figures, see http://chandra.as.utexas.edu/~kormendy/ar3ss.htm