Neuroprotective effects of Lycium barbarum polysaccharides against rat hippocampal apoptosis induced by chronic intermittent hypoxia

Poster presentationWe have shown neuronal apoptosis in the hippocampus of rats exposed to chronic intermittent hypoxia mimicking severe conditions of obstructive sleep apnea (OSA) syndrome in patients [1]. Lycium barbarum polysaccharides (LBP), active biological ingredients of traditional Chinese herbal medicine Goji, have been shown to possess cytoprotective properties [2]. The aim of this study was to examine the protective effects of LBP against neuronal apoptosis in the hippocampus in a severe OSA rodent model. We hypothesized that oral administration of LBP ameliorates neuronal apoptosis in the rat hippocampus induced by chronic intermittent hypoxia. Adult SD rats were randomly divided into 4 experimental groups, namely: (i) normoxic control (Nx); (ii) Nx treated with LBP; hypoxic groups treated with either (iii) LBP or (iv) vehicle. The hypoxic groups were kept in a normobaric chamber with inspired oxygen alternating from 21 to 5 ± 0.5% oxygen per minute for 8 hr/day for 7 days, whereas Nx groups was maintained in room air for 7 days. LBP (1mg/kg) were orally fed to the rats 2 hours prior the daily hypoxic treatment. Rats were sacrificed and the hippocampus was harvested for measurements of oxidative marker, malondialdehyde (MDA), apoptotic cell death using TUNEL assay, protein expression levels of antioxidant enzymes, and inflammatory cytokines by Western blot. There were significantly more TUNEL positive –labeling cells in the CA regions and dentate gyrus of the hippocampus in the vehicle-treated hypoxic group than those of the Nx control and LBP-treated groups. In addition, levels of MDA and the protein expressions of cleaved caspase 3 and inflammatory cytokines were increased in the vehicle-treated hypoxic group when compared to the Nx groups and were lowered by the LBP treatment. Intriguingly, there were significantly more PCNA-labeling cells in the dentate gyrus of the hippocampus in the LBP-treated hypoxic groups than those of the other groups. Also, the protein expression of cyclin D1 was increased in the hypoxic groups when compared to the Nx groups. In conclusion, oral administration of LBP significantly ameliorates oxidative stress, inflammation and neuronal apoptosis with enhanced proliferative activities in the hippocampus of rats exposed to chronic intermittent hypoxia. Thus, LBP may be proposed as a health supplement to mitigate neurological deficits in OSA patients, for which awaits future studies to delineate the neuroprotective mechanism of LBP. [Studies supported by research grants (HKU 7510/06M, HKU 766110M) from RGC and funding (201007176007, SFPBR 200911159072) from HKU] [1] Hung, M.W., et al. (2008) J Pineal Res 44: 214-221. [2] Chang, R.C., et al. (2008). Cell Mol Neurobiol 28: 643-652.published_or_final_versio

Upregulation of erythropoietin and its receptor expression in the rat carotid body during chronic and intermittent hypoxia

Proceeding of the XVIIth ISAC Meeting (International Society for Arterial Chemoreception Meeting), School of Medicine of Valladolid, Valladolid, Spain, July 1–5, 2008The carotid body (CB) plays important roles in cardiorespiratory changes in intermittent hypoxia (IH). Erythropoietin (EPO), a hypoxia-inducible factor (HIF)-1 target gene, is present in the chemoreceptive type-I cells in the CB but its expression and role in IH resembling sleep apnoeic conditions are not known. We hypothesized that IH upregulates the expression of EPO and its receptor (EPOr) in the rat CB. The CB expressions of EPO and EPOr were examined in rats breathing 10% O 2 (in isobaric chamber for CH, 24 hour/day) or in IH (cyclic between air and 5% O 2 per minute, 8 hour/day) for 3-28 days. Immunohistochemical studies revealed that the EPO and EPOr proteins were localized in CB glomic clusters. The proportional amount of cells with positive staining of EPO immunoreactivities was significantly increased in both IH and CH groups when compared with the normoxic control. The EPO expression was more markedly increased in the CH than that of the IH groups throughout the time course, reaching a peak level at day 14. The positive EPOr immunostaining was increased significantly in the 3-day CH group. By day 14, the EPOr expression elevated considerably at peak levels in both IH and CH rats, whereas the elevation was greater in the CH rats. These results suggest an upregulation of EPO and its receptor expression in the rat CB under IH and CH conditions, presumably mediated by the activation of HIF-1 pathway. The increased EPO binding to its receptor might play a role in the enhancement of CB excitability during the early pathogenesis in patients with sleep-disordered breathing. © Springer Science+Business Media B.V. 2009.postprin

Long-term average spectral characteristics of Cantonese alaryngeal speech

Objective: In Hong Kong, esophageal (SE), tracheoesophageal (TE), electrolaryngeal (EL), and pneumatic artificial laryngeal (PA) speech are commonly used by laryngectomees as a means to regain verbal communication after total laryngectomy. While SE and TE speech has been studied to some extent, little is known regarding the EL and PA sound quality. The present study examined the sound quality associated with SE, TE, EL, and PA speech, and compared with that associated with laryngeal (NL) speech by using long-term average speech spectra (LTAS). Methods: Continuous speech samples of reading a 136-word passage were obtained from NL, SE, TE, EL, and PA speakers of Cantonese. The alaryngeal speakers were all superior speakers selected from the New Voice Club of Hong Kong, which is a self-help organization for the laryngectomees in Hong Kong. TE speakers were fitted with Provox valve, and EL speakers used Servox-type electrolarynx. Speech samples were digitized at 20 kHz and 16 bits/sample by using Praat, based on which LTAS contours were developed. First spectral peak (FSP), mean spectral energy (MSE), and spectral tilt (ST) derived from the LTAS contours associated with different speaker groups were compared. Results: Data revealed all speakers generally exhibited similar LTA contours. However, PA speakers exhibited the lowest average FSP value and the greatest average MSE value. NL phonation was associated with a significantly greater ST value than alaryngeal speech of Cantonese. Conclusion: The differences in FSP, MSE, and ST values in different speaker groups may be related to the different sound sources being used by the laryngectomees, and the difference in the way the sound source is coupled with the vocal tract system. © 2009 Elsevier Ireland Ltd. All rights reserved.postprin

Extensive use of mesopelagic waters by a Scalloped hammerhead shark (Sphyrna lewini) in the Red Sea

Background: Despite being frequently landed in fish markets along the Saudi Arabian Red Sea coast, information regarding fundamental biology of the Scalloped hammerhead shark (Sphyrna lewini) in this region is scarce. Satellite telemetry studies can generate important data on life history, describe critical habitats, and ultimately redefine management strategies for sharks. To better understand the horizontal and vertical habitat use of S. lewini in the Red Sea and to aid with potential future development of zoning and management plans for key habitats, we deployed a pop-up satellite archival transmitting tag to track a single female specimen (240 cm total length) for a tracking period of 182 days. Results: The tag was physically recovered after a deployment period of 6 months, thus providing the complete archived dataset of more than one million depth and temperature records. Based on a reconstructed, most probable track, the shark travelled a circular distance of approximately 1000 km from the central Saudi Arabian Red Sea southeastward into Sudanese waters, returning to the tagging location toward the end of the tracking period. Mesopelagic excursions to depths between 650 and 971 m occurred on 174 of the 182 days of the tracking period. Intervals between such excursions were characterized by constant oscillatory diving in the upper 100 m of the water column. Conclusions: This study provides evidence that mesopelagic habitats might be more commonly used by S. lewini than previously suggested. We identified deep diving behavior throughout the 24-h cycle over the entire 6-month tracking period. In addition to expected nightly vertical habitat use, the shark exhibited frequent mesopelagic excursions during daytime. Deep diving throughout the diel cycle has not been reported before and, while dive functionality remains unconfirmed, our study suggests that mesopelagic excursions may represent foraging events within and below deep scattering layers. Additional research aimed at resolving potential ecological, physiological and behavioral mechanisms underpinning vertical movement patterns of S. lewini will help to determine if the single individual reported here is representative of S. lewini populations in the Red Sea

A robust computational algorithm for inverse photomask synthesis in optical projection lithography

Inverse lithography technology formulates the photomask synthesis as an inverse mathematical problem. To solve this, we propose a variational functional and develop a robust computational algorithm, where the proposed functional takes into account the process variations and incorporates several regularization terms that can control the mask complexity. We establish the existence of the minimizer of the functional, and in order to optimize it effectively, we adopt an alternating minimization procedure with Chambolle's fast duality projection algorithm. Experimental results show that our proposed algorithm is effective in synthesizing high quality photomasks as compared with existing methods.published_or_final_versio

M30 Antagonizes Indoleamine 2,3-Dioxygenase Activation and Neurodegeneration Induced by Corticosterone in the Hippocampus

Monoamine oxidases (MAO), downstream targets of glucocorticoid, maintain the turnover and homeostasis of monoamine neurotransmitters; yet, its pathophysiological role in monoamine deficiency, oxidative stress and neuroinflammation remains controversial. Protective effects of M30, a brain selective MAO inhibitor with iron-chelating antioxidant properties, have been shown in models of neurodegenerative diseases. This study aims to examine the neuroprotective mechanism of M30 against depressive-like behavior induced by corticosterone (CORT). Sprague-Dawley rats were given CORT subcutaneous injections with or without concomitant M30 administration for two weeks. CORT-treated rats exhibited depressive-like behavior with significant elevated levels of MAO activities, serotonin turnover, oxidative stress, neuroinflammation and apoptosis in the hippocampus with significant losses of synaptic proteins when compared to the control. The expression and activity of cytokine-responsive indoleamine 2,3-dioxygenase (IDO-1), a catabolic enzyme of serotonin and tryptophan, was significantly increased in the CORT-treated group with lowered levels of serotonin. Besides, CORT markedly reduced dendritic length and spine density. Remarkably, M30 administration neutralized the aberrant changes in the hippocampus and prevented the induction of depressive-like behavior induced by CORT. Our results suggest that M30 is neuroprotective against CORT-induced depression targeting elevated MAO activities that cause oxidative stress and neuroinflammation, resulting in IDO-1 activation, serotonin deficiency and neurodegeneration.published_or_final_versio

Monoamine oxidase A upregulated by chronic intermittent hypoxia activates indoleamine 2,3-dioxygenase and neurodegeneration

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Neuroprotective Mechanism of Lycium barbarum Polysaccharides against Hippocampal-Dependent Spatial Memory Deficits in a Rat Model of Obstructive Sleep Apnea

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Drawing-Based Automatic Dementia Screening Using Gaussian Process Markov Chains

Screening tests play an important role for early detection of dementia. Among those widely used screening tests, drawing tests have gained much attention in clinical psychology. Traditional evaluation of drawing tests totally relies on the appearance of drawn picture, but does not consider any time-dependent behaviour. We demonstrated that the processing speed and direction can reflect the decline of cognitive function, and thus may be useful for disease screening. We proposed a model of Gaussian process Markov chains (GPMC) to study the complex associations within the drawing data. Specifically, we modeled the process of drawing in a state-space form, where a drawing state is composed of drawing direction and velocity with consideration of the processing time. For temporal modeling, our scope focused more on discrete-time Markov chains on continuous state space. Because of the short processing time of picture drawing, we applied higher-order of Markov chains to model long-term temporal correlation across drawing states. Gaussian process regression was used for universal function approximation to flexibly infer the state transition function. With Gaussian process prior to the distribution of function space, we could encode high-level function properties such as noisiness, smoothness and periodicity. We also derived an efficient training mechanism for complex Gaussian process regression on bivariate Markov chains. With GPMC, we present an optimal decision rule based on Bayesian decision theory. We applied our proposed method to a drawing test for dementia screening, i.e. interlocking pentagon-drawing test. We tested our models with 256 subjects who are aged from 65 to 95. Finally, comparing to the traditional methods, our models showed remarkable improvement in drawing test for dementia screening