Prevention of Glaucoma-Induced Retinal Ganglion Cell Loss Using Alpha7 nAChR Agonists

In this study, the neuroprotective effect of various nicotinic alpha7 acetylcholine receptor agonists in an in-vivo model of glaucoma using adult Long Evans rats was analyzed. Glaucoma-like conditions were induced in the eyes of Long Evans rats after injection of hypertonic saline into episcleral veins to create scar tissue and increase the animal’s intraocular pressure. This procedure produced significant loss of retinal ganglion cells within one month and was associated with an increase of intraocular pressure. Using this model system, various alpha7 nicotinic acetylcholine receptor (a7 nAChR) agonists were applied at different doses as eye drops to the right eye of adult Long Evans rats while the left eye was left as an internal control. The a7 nAChR agonists used in this study prevented loss of RGCs in a dose dependent manner after the procedure to induce glaucoma-like conditions. PHA-543613 and PNU- 282987 provided the largest degree of RGC survival after inducing glaucomalike conditions, followed by nicotine, SEN 12333, tropisetron, 3-Bromocytisine and DMAB. To provide evidence that neuroprotection of RGCs was mediated through activation of a7 nAChR, in some studies different concentrations of the a7 nAChR antagonist, MLA, was intravitreally injected into experimentally treated eyes before initiation of eye drops and the procedure to induce glaucoma-like conditions. In the presence of MLA, RGC neuroprotection was blocked. Results from these studies suggest that selective a7 nAChR agonists may be used in future therapeutic treatments for glaucoma or other CNS diseases associated with a7 nAChRs

A Nicotinic Acetylcholine Receptor Agonist Prevents Loss of Retinal Ganglion Cells in a Glaucoma Model

Purpose.: The purpose of this study was to analyze the neuroprotective effect of an α7 nAChR agonist, PNU-282987, using an in vivo model of glaucoma in Long Evans rats. Methods.: One eye in each animal was surgically manipulated to induce glaucoma in control untreated animals and in animals that were treated with intravitreal injections of PNU-282987. To induce glaucoma-like conditions, 0.05 mL of 2 M NaCl was injected into the episcleral veins of right eyes in each rat to create scar tissue and increase intraocular pressure. The left eye in each rat acted as an internal control. One month following NaCl injection, rats were euthanized, retinas were removed, flatmounted, fixed, and nuclei were stained with cresyl violet or RGCs were immunostained with an antibody against Thy 1.1 or against Brn3a. Stained nuclei in the RGC layer and labeled RGCs in NaCl-injected retinas were counted and compared with cell counts from untreated retinas in the same animal. Results.: NaCl injections into the episcleral veins caused a significant loss of cells by an average of 27.35% (±2.12 SEM) in the RGC layer within 1 month after NaCl injection, which corresponded to a significant loss of RGCs. This loss of RGCs was eliminated if 5 μL of 100 μM PNU-282987 was injected into the right eye an hour before NaCl injection. Conclusions.: The results from this study support the hypothesis that the α7 agonist, PNU-282987, has a neuroprotective effect in the rat retina. PNU-282987 may be a viable candidate for future therapeutic treatments of glaucoma

Stability of small amplitude normal modes of a Bose-Einstein condensate with a singly quantized vortex confined in an optical lattice

We study the dynamics of a BEC with a singly quantized vortex, placed in the combined potential of a 1-D (2-D) optical lattice and an axi-symmetric harmonic trap. A time-dependent variational Lagrangian analysis shows that an optical lattice helps to stabilize the vortex which in absence of the optical lattice is unstable. We find that the normal modes are stable only if the depth of the optical potential is more than a certain critical value. This critical value of the optical potential depends on the interaction parameter.In general higher the interaction parameter,lower the value of the optical potential required to stabilize the vortex. The BEC with the singly quantized vortex is found to be relatively more unstable in a 2-D optical lattice compared to a 1-D optical lattice.Comment: Revised version with 11 pages including 1 figur

Vortex stabilization in a small rotating asymmetric Bose-Einstein condensate

We use a variational method to investigate the ground-state phase diagram of a small, asymmetric Bose-Einstein condensate with respect to the dimensionless interparticle interaction strength $\gamma$ and the applied external rotation speed $\Omega$. For a given $\gamma$, the transition lines between no-vortex and vortex states are shifted toward higher $\Omega$ relative to those for the symmetric case. We also find a re-entrant behavior, where the number of vortex cores can decrease for large $\Omega$. In addition, stabilizing a vortex in a rotating asymmetric trap requires a minimum interaction strength. For a given asymmetry, the evolution of the variational parameters with increasing $\Omega$ shows two different types of transitions (sharp or continuous), depending on the strength of the interaction. We also investigate transitions to states with higher vorticity; the corresponding angular momentum increases continuously as a function of $\Omega$

Small-amplitude normal modes of a vortex in a trapped Bose-Einstein condensate

We consider a cylindrically symmetric trap containing a small Bose-Einstein condensate with a singly quantized vortex on the axis of symmetry. A time-dependent variational Lagrangian analysis yields the small-amplitude dynamics of the vortex and the condensate, directly determining the equations of motion of the coupled normal modes. As found previously from the Bogoliubov equations, there are two rigid dipole modes and one anomalous mode with a negative frequency when seen in the laboratory frame.Comment: 4 pages, no figures, Revte

The alpha1 subunit of the GABA(A) receptor modulates fear learning and plasticity in the lateral amygdala.

Synaptic plasticity in the amygdala is essential for emotional learning. Fear conditioning, for example, depends on changes in excitatory transmission that occur following NMDA receptor activation and AMPA receptor modification in this region. The role of these and other glutamatergic mechanisms have been studied extensively in this circuit while relatively little is known about the contribution of inhibitory transmission. The current experiments addressed this issue by examining the role of the GABA(A) receptor subunit alpha1 in fear learning and plasticity. We first confirmed previous findings that the alpha1 subunit is highly expressed in the lateral nucleus of the amygdala. Consistent with this observation, genetic deletion of this subunit selectively enhanced plasticity in the lateral amygdala and increased auditory fear conditioning. Mice with selective deletion of alpha1 in excitatory cells did not exhibit enhanced learning. Finally, infusion of a alpha1 receptor antagonist into the lateral amygdala selectively impaired auditory fear learning. Together, these results suggest that inhibitory transmission mediated by alpha1-containing GABA(A) receptors plays a critical role in amygdala plasticity and fear learning

Health Risk of Obesity in Native American Adolescents

Recent reports demonstrate the need to improve methods for identifying obesity among adolescent minority populations, especially among Native American adolescents. Our study examined several anthropometric measures to see which one was the best indicator of obesity for Native American adolescents. We compared our data with that provided by the Centers for Disease Control and Prevention (CDC), and the National Health and Nutrition Examination Surveys (NHANESIII). We examined which measures diï¬ered signiï¬cantly from the NHANESIII, and which were most eï¬ective for measuring obesity in Native American adolescents. Our study population represented a cross-sectional, epidemiological population (N=183) of Native American students (ages 14-18) from diverse tribal backgrounds at an urban residential high school. We obtained baseline anthropometric measurements of height, weight, waist, triceps skin-fold, and calf skin-fold measures from the Native American students and compared this information with reference data to assess weight classiï¬cation by body mass indices for our population. Under the conditions of our study, we found the calf skin-fold measure to be the best indicator of normal weight in male Native American adolescents, and the triceps skin-fold measure to be the best indicator of obesity in male Native American adolescents. The assessment of health risk by anthropometric measures we obtained appears appropriate for predicting obesity and developing eï¬ective interventions for Native American adolescents in general. Correlations between anthropometric measures and obesity in our study population may prove of signiï¬cant interest for monitoring obesity prevention initiatives for Native American adolescents

Stability of rotating states in a weakly-interacting Bose-Einstein condensate

We investigate the lowest state of a rotating, weakly-interacting Bose-Einstein condensate trapped in a harmonic confining potential that is driven by an infinitesimally asymmetric perturbation. Although in an axially-symmetric confining potential the gas has an axially-symmetric single-particle density distribution, we show that in the presence of the small asymmetric perturbation its lowest state is the one given by the mean-field approximation, which is a broken-symmetric state. We also estimate the rate of relaxation of angular momentum when the gas is no longer driven by the asymmetric perturbation and identify two regimes of "slow" and "fast" relaxation. States of certain symmetry are found to be more robust.Comment: 6 pages, RevTe