Rod bipolar cells in the retina of the capuchin monkey (Cebus apella): Characterization and distribution

Rod bipolar cells in Cebus apella monkey retina were identified by an antibody against the alpha isoform of protein kinase C (PKC alpha). which has been shown to selectively identify rod bipolars in two other primates and various mammals. Vertical sections were used to confirm the identity of these cells by their characteristic morphology of dendrites and axons. Their topographic distribution was assessed in horizontal sections; counts taken along the dorsal, ventral, nasal, and temporal quadrants. The density of rod bipolar cells increased from 500 to 2900 cells/mm(2) at 1 mm from the fovea to reach a peak of 10,000-12,000 cellss/mm(2) at 4 mm, approximately 5 deg of eccentricity, and then gradually decreased toward retinal periphery to values of 5000 cells/mm(2) or less. Rod to rod bipolar density ratio remained between 10 and 20 across most of the retinal extension. The number of rod bipolar cells per retina was 6,360,000 +/- 387,433 (mean +/- S.D., n = 6). The anti-PKC alpha antibody has shown to be a good marker of rod bipolar cells of Cebus, and the cell distribution is similar to that described for other primates. In spite of the difference in the central retina, the density variation of rod bipolar cells in the Cebus and Macaca as well as the convergence from rod to rod bipolar cells are Generally similar, suggesting that both retinae stabilize similar sensitivity (as measured by rod density) and convergence.

Clinical significance of lifetime panic disorder in the course of bipolar disorder type I

Objectives: The aim of the study was to analyze the impact of lifetime panic disorder (PD) diagnosis in a sample of patients with bipolar disorder type I (BPI), evaluating clinical and demographic variables. Methods: Ninety-five outpatients from the Bipolar Disorder Research Program at the Institute of Psychiatry of the University of Sao Paulo Medical School were enrolled. Twenty-seven BPI patients with PD were compared to 68 BPI patients without any anxiety disorders regarding clinical and demographic variables. Results: Compared to BPI patients without any anxiety disorders, patients with BPI + PD presented significantly higher number of mood episodes (18.9 +/- 13.8 vs 8.5 +/- 7.8; P < .001), depressive episodes (10.8 +/- 8.2 vs 4.6 +/- 4,8; P = .001), and manic episodes (7.4 +/- 7.3 vs 3.6 +/- 3.6; P = .008). Patients with BPI + PD had more frequently a depressive episode as their first one compared to BPI patients without anxiety disorders (94.1% vs 57.5%; P = .011). Patients with BPI + PD had more comorbidity with lifetime diagnosis of drug abuse or dependence (33.3% vs 8.8%; P = .010) and eating disorders (29.6% vs 6.0%; P = .004). Conclusions: The higher number of mood episodes in general presented by patients with BPI + PD when compared with BPI patients without any anxiety disorders, along with the higher frequencies of drug misuse and eating disorders, indicates that PD comorbidity is associated with a poorer Course and outcome of BPI. The higher frequency of depression as the onset mood episode and the higher number of manic episodes in the group with PD may have important treatment implications and should be further investigated. (C) 2009 Elsevier Inc. All rights reserved.

Functional and Structural Connectivity Between the Perigenual Anterior Cingulate and Amygdala in Bipolar Disorder

Objective: Abnormalities in the morphology and function of two gray matter structures central to emotional processing, the perigenual anterior cingulate cortex (pACC) and amygdala, have consistently been reported in bipolar disorder (BD). Evidence implicates abnormalities in their connectivity in BD. This study investigates the potential disruptions in pACC-amygdala functional connectivity and associated abnormalities in white matter that provides structural connections between the two brain regions in BD. Methods: Thirty-three individuals with BD and 31 healthy comparison subjects (HC) participated in a scanning session during which functional magnetic resonance imaging (fMRI) during processing of face stimuli and diffusion tensor imaging (DTI) were performed. The strength of pACC-amygdala functional connections was compared between BD and HC groups, and associations between these functional connectivity measures from the fMRI scans and regional fractional anisotropy (FA) from the DTI scans were assessed. Results: Functional connectivity was decreased between the pACC and amygdala in the BD group compared with HC group, during the processing of fearful and happy faces (p < .005). Moreover, a significant positive association between pACC-amygdala functional coupling and FA in ventrofrontal white matter, including the region of the uncinate fasciculus, was identified (p < .005). Conclusion: This study provides evidence for abnormalities in pACC-amygdala functional connectivity during emotional processing in BD. The significant association between pACC-amygdala functional connectivity and the structural integrity of white matter that contains pACC-amygdala connections suggest that disruptions in white matter connectivity may contribute to disturbances in the coordinated responses of the pACC and amygdala during emotional processing in BD.

Abnormal Corpus Callosum Integrity in Bipolar Disorder: A Diffusion Tensor Imaging Study

Objective: Abnormalities in the anterior interhemispheric connections provided by the corpus callosum (CC) have long been implicated in bipolar disorder (BID). In this study, we used complementary diffusion tensor imaging methods to study the structural integrity of the CC and localization of potential abnormalities in BD. Methods: Subjects included 33 participants with BID and 40 healthy comparison participants. Fractional anisotropy (FA) measures were compared between groups with region of interest (ROD methods to investigate the anterior, middle, and posterior CC and voxel-based methods to further localize abnormalities. Results: In ROI-based analyses, FA was significantly decreased in the anterior and middle CC in the BID group (p <.05). Voxel-based analyses similarly localized group differences to the genu, rostral body, and anterior midbody of CC (p <.05, corrected). Conclusion: The findings demonstrate abnormalities in the structural integrity of the anterior CC in BID that might contribute to altered interhemispheric connectivity in this disorder.

Abnormal anterior cingulum integrity in bipolar disorder determined through diffusion tensor imaging

Background Convergent evidence implicates white matter abnormalities in bipolar disorder. The cingulum is an important candidate structure for study in bipolar disorder as it provides substantial white matter connections within the corticolimbic neural system that subserves emotional regulation involved in the disorder. Aims To test the hypothesis that bipolar disorder is associated with abnormal white matter integrity in the cingulum. Method Fractional anisotropy in the anterior and posterior cingulum was compared between 42 participants with bipolar disorder and 42 healthy participants using diffusion tensor imaging. Results Fractional anisotropy was significantly decreased in the anterior cingulum in the bipolar disorder group compared with the healthy group (P=0.003); however, fractional anisotropy in the posterior cingulum did not differ significantly between groups. Conclusions Our findings demonstrate abnormalities in the structural integrity of the anterior cingulum in bipolar disorder. They extend evidence that supports involvement of the neural system comprising the anterior cingulate cortex and its corticolimbic gray matter connection sites in bipolar disorder to implicate abnormalities in the white matter connections within the system provided by the cingulum.

Revisiting 2D numerical models for the 19th century outbursts of eta Carinae

We present here new results of two-dimensional hydrodynamical simulations of the eruptive events of the 1840s (the great) and the 1890s (the minor) eruptions suffered by the massive star eta Carinae (Car). The two bipolar nebulae commonly known as the Homunculus and the little Homunculus (LH) were formed from the interaction of these eruptive events with the underlying stellar wind. We assume here an interacting, non-spherical multiple-phase wind scenario to explain the shape and the kinematics of both Homunculi, but adopt a more realistic parametrization of the phases of the wind. During the 1890s eruptive event, the outflow speed decreased for a short period of time. This fact suggests that the LH is formed when the eruption ends, from the impact of the post-outburst eta Car wind (that follows the 1890s event) with the eruptive flow (rather than by the collision of the eruptive flow with the pre-outburst wind, as claimed in previous models; Gonzalez et al.). Our simulations reproduce quite well the shape and the observed expansion speed of the large Homunculus. The LH (which is embedded within the large Homunculus) becomes Rayleigh-Taylor unstable and develop filamentary structures that resemble the spatial features observed in the polar caps. In addition, we find that the interior cavity between the two Homunculi is partially filled by material that is expelled during the decades following the great eruption. This result may be connected with the observed double-shell structure in the polar lobes of the eta Car nebula. Finally, as in previous work, we find the formation of tenuous, equatorial, high-speed features that seem to be related to the observed equatorial skirt of eta Car.

CHANDRA AND SPITZER IMAGING OF THE INFRARED CLUSTER IN NGC 2071

We present results of a sensitive Chandra X-ray observation and Spitzer mid-infrared (mid-IR) observations of the IR cluster lying north of the NGC 2071 reflection nebula in the Orion B molecular cloud. We focus on the dense cluster core known as NGC 2071-IR, which contains at least nine IR sources within a 40 `` x 40 `` region. This region shows clear signs of active star formation including powerful molecular outflows, Herbig-Haro objects, and both OH and H(2)O masers. We use Spitzer Infrared Array Camera (IRAC) images to aid in X-ray source identification and to determine young stellar object (YSO) classes using mid-IR colors. Spitzer IRAC colors show that the luminous source IRS 1 is a class I protostar. IRS 1 is believed to be driving a powerful bipolar molecular outflow and may be an embedded B-type star or its progenitor. Its X-ray spectrum reveals a fluorescent Fe emission line at 6.4 keV, arising in cold material near the protostar. The line is present even in the absence of large flares, raising questions about the nature of the ionizing mechanism responsible for producing the 6.4 keV fluorescent line. Chandra also detects X-ray sources at or near the positions of IRS 2, IRS 3, IRS 4, and IRS 6 and a variable X-ray source coincident with the radio source VLA 1, located just 2 `` north of IRS 1. No IR data are yet available to determine a YSO classification for VLA 1, but its high X-ray absorption shows that it is even more deeply embedded than IRS 1, suggesting that it could be an even younger, less-evolved protostar.

Connexin36, an Essential Element in the Rod Pathway, Is Highly Expressed in the Essentially Rodless Retina of Gallus gallus

Electrical coupling provided by connexins (Cx) in gap junctions (GJ) plays important roles in both the developing and the mature retina. In mammalian nocturnal species, Cx36 is an essential component in the rod pathway, the retinal circuit specialized for night, scotopic vision. Here, we report the expression of Cx36 in a species (Gallus gallus) that phylogenetic development endows with an essentially rodless retina. Cx36 gene is very highly expressed in comparison with other Cxs previously described in the adult retina, such as Cx43, Cx45, and Cx50. Moreover, real-time PCR, Western blot, and immunofluorescence all revealed that Cx36 expression massively increased over time during development. We thoroughly examined Cx36 in the inner and outer plexiform layers, where this protein was particularly abundant. Cx36 was observed mainly in the off sublamina of the inner plexiform layer rather than in the on sublamina previously described in the mammalian retina. In addition, Cx36 colocalized with specific cell markers, revealing the expression of this protein in distinct amacrine cells. To investigate further the involvement of Cx36 in visual processing, we examined its functional regulation in retinas from dark-adapted animals. Light deprivation markedly up-regulates Cx36 gene expression in the retina, resulting in an increased accumulation of the protein within and between cone synaptic terminals. In summary, the developmental regulation of Cx36 expression results in particular circuitry-related roles in the chick retina. Moreover, this study demonstrated that Cx36 onto- and phylogenesis in the vertebrate retina simultaneously exhibit similarities and particularities. J. Comp. Neurol. 512:651-663, 2009. (C) 2008 Wiley-Liss, Inc.

Lack of photoreceptor signaling alters the expression of specific synaptic proteins in the retina

Synaptic modulation by activity-dependent changes constitutes a cellular mechanism for neuronal plasticity. However, it is not clear how the complete lack of neuronal signaling specifically affects elements involved in the communication between neurons. In the retina, it is now well established that both chemical and electrical synapses are essential to mediate the transmission of visual signaling triggered by the photoreceptors. In this study, we compared the expression of synaptic proteins in the retinas of wild-type (WT) vs. rd/rd mice, an animal model that displays inherited and specific ablation of photoreceptors caused by a mutation in the gene encoding the beta-subunit of rod cGMP-phosphodiesterase (Pde6b(rd1)). We specifically examined the expression of connexins (Cx), the proteins that form the gap junction channels of electrical synapses, in addition to synaptophysin and synapsin 1, which are involved in the release of neurotransmitters at chemical synapses. Our results revealed that Cx36 gene expression levels are lower in the retinas of rd/rd when compared with WT. Confocal analysis indicated that Cx36 immunolabeling almost disappeared in the outer plexiform layer without significant changes in protein distribution within the inner plexiform layer of rd/rd retinas. Likewise, synaptophysin expression remarkably decreased in the outer plexiform layer of rd/rd retinas, and this down-regulation was also associated with diminished transcript levels. Furthermore, we observed down-regulation of Cx57 gene expression in rd/rd retinas when compared with WT and also changes in protein distribution. Interestingly, Cx45 and synapsin I expression in rd/rd retinas showed no noticeable changes when compared with WT. Taken together, our results revealed that the loss of photoreceptors leads to decreased expression of some synaptic proteins. More importantly, this study provides evidence that neuronal activity regulates, but is not essential to maintain, the expression of synaptic elements. (c) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

Connexin-mediated communication controls cell proliferation and is essential in retinal histogenesis

Connexin (Cx) channels and hemichannels are involved in essential processes during nervous system development such as apoptosis, propagation of spontaneous activity and interkinetic nuclear movement. In the first part of this study, we extensively characterized Cx gene and protein expression during retinal histogenesis. We observed distinct spatio-temporal patterns among Studied Cx and an overriding, ubiquitous presence of Cx45 in progenitor cells. The role of Cx-mediated communication was assessed by using broad-spectrum (carbenoxotone, CBX) and Cx36/Cx50 channel-specific (quinine) blockers. In vivo application of CBX, but not quinine, caused remarkable reduction in retinal thickness, suggesting changes in cell proliferation/apoptosis ratio. Indeed, we observed a decreased number of mitotic cells in CBX-injected retinas, with no significant changes in the expression of PCNA, a marker for cells in proliferative state. Taken together, Our results pointed a pivotal role of Cx45 in the developing retina. Moreover, this study revealed that Cx-mediated Communication is essential in retinal histogenesis, particularly in the control of cell proliferation. (C) 2009 ISDN. Published by Elsevier Ltd. All rights reserved.

Proteomic analysis of dorsolateral prefrontal cortex indicates the involvement of cytoskeleton, oligodendrocyte, energy metabolism and new potential markers in schizophrenia

Schizophrenia is likely to be a consequence of serial alterations in a number of genes that, together with environmental factors, will lead to the establishment of the illness. The dorsolateral prefrontal cortex (Brodmann`s Area 46) is implicated in schizophrenia and executes high functions such as working memory, differentiation of conflicting thoughts, determination of right and wrong concepts, correct social behavior and personality expression. We performed a comparative proteome analysis using two-dimensional gel electrophoresis of pools from 9 schizophrenia and 7 healthy control patients` dorsolateral prefrontal cortex aiming to identify, by mass spectrometry, alterations in protein expression that could be related to the disease. In schizophrenia-derived samples, our analysis revealed 10 downregulated and 14 upregulated proteins. These included alterations previously implicated in schizophrenia, such as oligodendrocyte-related proteins (myelin basic protein and transferrin), as well as malate dehydrogenase, aconitase, ATP synthase subunits and cytoskeleton-related proteins. Also, six new putative disease markers were identified, including energy metabolism, cytoskeleton and cell signaling proteins. Our data not only reinforces the involvement of proteins previously implicated in schizophrenia, but also suggests new markers, providing further information to foster the comprehension of this important disease. (C) 2008 Elsevier Ltd. All rights reserved.

Lithium reduces Gsk3b mRNA levels: implications for Alzheimer Disease

There is evidence of increased systemic expression of active GSK3B in Alzheimer`s disease patients, which apparently is associated with the formation of senile plaques and neurofibrillary tangles. Due to its central role in the pathogenesis of AD, GSK3B is currently a promising target of the pharmaceutical industry. Whilst trials with specific GSK inhibitors in AD are under way, major attention has been focused on the neuroprotective effects of lithium. Whereas the direct and indirect inhibitory effects of lithium over GSK3 activity have been documented by several groups, its effects over Gsk3 transcription have not yet been addressed. We used quantitative PCR to evaluate the transcriptional regulation of Gsk3a and Gsk3b in lithium-treated primary cultures of rat cortical and hippocampal neurons. We found a significant and dose-dependent reduction in the expression of Gsk3b, which was specific to hippocampal cells. This same effect was further confirmed in vivo by measuring Gsk3 expression in different brain regions and in peripheral leukocytes of adult rats treated with lithium. Our studies show that LiCl can modulate Gsk3b transcription in vitro and in vivo. This observation suggest new regulatory effects of lithium over Gsk3b, contributing to the better understanding of its mechanisms of action, offering a new and complementary explanation for Gsk3b modulation and reinforcing its potential for the inhibition of key pathological pathways in Alzheimer`s disease.