St Boniface Hospital Research

Winnipeg, Canada

St Boniface Hospital Research

Winnipeg, Canada
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Snow W.M.,St Boniface Hospital Research | Snow W.M.,University of Manitoba | Stoesz B.M.,University of Manitoba | Anderson J.E.,University of Manitoba
AIMS Neuroscience | Year: 2014

The notion that the cerebellum is a central regulator of motor function is undisputed. There exists, however, considerable literature to document a similarly vital role for the cerebellum in the regulation of various non-motor domains, including emotion. Research from numerous avenues of investigation (i.e., neurophysiological, behavioural, electrophysiological, imagining, lesion, and clinical studies) have documented the importance of the cerebellum, in particular, the vermis, in affective processing that appears preserved across species. The cerebellum possesses a distinct laminar arrangement and highly organized neuronal circuitry. Moreover, the cerebellum forms reciprocal connections with several brain regions implicated in diverse functional domains, including motor, sensory, and emotional processing. It has been argued that these unique neuroanatomical features afford the cerebellum with the capacity to integrate information about an organism, its environment, and its place within the environment such that it can respond in an appropriate, coordinated fashion, with such theories extending to the regulation of emotion. This review puts our current understanding of the cerebellum and its role in behaviour in historical perspective, presents an overview of the neuroanatomical and functional organization of the cerebellum, and reviews the literature describing the involvement of the cerebellum in emotional regulation in both humans and non-human animals. In summary, this review discusses the importance of the functional connectivity of the cerebellum with various brain regions in the ability of the cerebellum to effectively regulate emotional behaviour. © 2014, Snow WM, et al.


Oikawa K.,St Boniface Hospital Research | Odero G.L.,St Boniface Hospital Research | Platt E.,St Boniface Hospital Research | Neuendorff M.,St Boniface Hospital Research | And 5 more authors.
BMC Neuroscience | Year: 2012

Background: Nuclear factor kappa B (NF-κB) is a transcription factor typically expressed with two specific subunits (p50, p65). Investigators have reported that NF-κB is activated during the induction of in vitro long term potentiation (LTP), a paradigm of synaptic plasticity and correlate of memory, suggesting that NF-κB may be necessary for some aspects of memory encoding. Furthermore, NF-κB has been implicated as a potential requirement in behavioral tests of memory. Unfortunately, very little work has been done to explore the effects of deleting specific NF-κB subunits on memory. Studies have shown that NF-κB p50 subunit deletion (p50 -/-) leads to memory deficits, however some recent studies suggest the contrary where p50 -/- mice show enhanced memory in the Morris water maze (MWM). To more critically explore the role of the NF-κB p50 subunit in synaptic plasticity and memory, we assessed long term spatial memory in vivo using the MWM, and synaptic plasticity in vitro utilizing high frequency stimuli capable of eliciting LTP in slices from the hippocampus of NF-κB p50 -/- versus their controls (p50 +/+).Results: We found that the lack of the NF-κB p50 subunit led to significant decreases in late LTP and in selective but significant alterations in MWM tests (i.e., some improvements during acquisition, but deficits during retention).Conclusions: These results support the hypothesis that the NF-κ p50 subunit is required in long term spatial memory in the hippocampus. © 2012 Oikawa et al.; licensee BioMed Central Ltd.


Bilevicius E.,University of Manitoba | Kolesar T.A.,University of Manitoba | Kornelsen J.,University of Manitoba | Kornelsen J.,St Boniface Hospital Research
Brain Sciences | Year: 2016

Objective: To assess the neural activity associated with mindfulness-based alterations of pain perception. Methods: The Cochrane Central, EMBASE, Ovid Medline, PsycINFO, Scopus, and Web of Science databases were searched on 2 February 2016. Titles, abstracts, and full-text articles were independently screened by two reviewers. Data were independently extracted from records that included topics of functional neuroimaging, pain, and mindfulness interventions. Results: The literature search produced 946 total records, of which five met the inclusion criteria. Records reported pain in terms of anticipation (n = 2), unpleasantness (n = 5), and intensity (n = 5), and how mindfulness conditions altered the neural activity during noxious stimulation accordingly. Conclusions: Although the studies were inconsistent in relating pain components to neural activity, in general, mindfulness was able to reduce pain anticipation and unpleasantness ratings, as well as alter the corresponding neural activity. The major neural underpinnings of mindfulness-based pain reduction consisted of altered activity in the anterior cingulate cortex, insula, and dorsolateral prefrontal cortex. © 2016 by the authors; licensee MDPI, Basel, Switzerland.


Cadonic C.,St Boniface Hospital Research | Cadonic C.,University of Manitoba | Sabbir M.G.,St Boniface Hospital Research | Albensi B.C.,St Boniface Hospital Research | Albensi B.C.,University of Manitoba
Molecular Neurobiology | Year: 2016

Mitochondria are the primary source for energy generation in the cell, which manifests itself in the form of the adenosine triphosphate (ATP). Nicotinamide dinucleotide (NADH) molecules are the first to enter the so-called electron transport chain or ETC of the mitochondria. The ETC represents a chain of reducing agents organized into four major protein-metal complexes (I-IV) that utilize the flow of electrons to drive the production of ATP. An additional integral protein that is related to oxidative phosphorylation is ATP synthase, referred to as complex V. Complex V carries out ATP synthesis as a result of the electron flow through the ETC. The coupling of electron flow from NADH to molecular oxygen to the production of ATP represents a process known as oxidative phosphorylation. In this review, we describe mainly the bioenergetic properties of mitochondria, such as those found in the ETC that may be altered in Alzheimer’s disease (AD). Increasing evidence points to several mitochondrial functions that are affected in AD. Furthermore, it is becoming apparent that mitochondria are a potential target for treatment in early-stage AD. With growing interest in the mitochondria as a target for AD, it has been hypothesized that deficit in this organelle may be at the heart of the progression of AD itself. The role of mitochondria in AD may be significant and is emerging as a main area of AD research. © 2015, Springer Science+Business Media New York.


Xu Y.-J.,University of Manitoba | Tappia P.S.,St Boniface Hospital Research | Neki N.S.,University of Manitoba | Dhalla N.S.,University of Manitoba
Heart Failure Reviews | Year: 2014

Oxidative stress is considered to play an important role in the pathogenesis of diabetes-induced cardiovascular disease (CVD), which is invariably associated with abnormal blood lipid profile, insulin resistance and metabolic syndrome. Stress, smoking, high saturated fat intake as well as low fruit and vegetable intakes have been shown to increase oxidative stress and hyperlipidemia, which increase the predisposition of diabetic subjects to atherosclerosis, stroke and coronary heart disease. The oxidation of low-density lipoprotein by oxidative stress is essential for the development of atherosclerosis, and the reduction in oxidative stress as well as blood glucose and cholesterol is considered critical for the prevention of diabetes-induced CVD. Although epidemiological studies have demonstrated that vitamin C and vitamin E decrease the incidence of coronary heart disease, different clinical trials have failed to support the beneficial effect of these antioxidants. Nonetheless, it has been suggested that natural forms of these vitamins may be more efficacious than synthetic vitamins, and this may explain the inconsistencies in results. Antioxidants, N-acetyl-L-cysteine and resveratrol, have also been shown to attenuate the diabetes-induced cardiovascular complications. It has been indicated that the antioxidant therapy may be effective in a prevention strategy rather than as a treatment for CVD. The evidence presented here supports the view that cardiovascular complications in diabetes may be induced by oxidative stress and appropriate antioxidant therapy may be promising for attenuating the progression of diabetes-induced CVD. © Springer Science+Business Media New York 2013.


Tappia P.S.,St Boniface Hospital Research | Xu Y.-J.,University of Manitoba | Rodriguez-Leyva D.,University of Manitoba | Aroutiounova N.,University of Manitoba | Dhalla N.S.,University of Manitoba
Physiological Research | Year: 2013

This study was undertaken to examine the effects of dietary supplementation of cysteine and taurine in rats with diabetes induced with streptozotocin (STZ, 65 mg/kg body weight). Experimental animals were treated orally (by gavage) with cysteine (200 mg/kg) and taurine (400 mg/kg), alone or in combination, daily for 8 weeks. In one group, rats were also pretreated 3 weeks before the induction of diabetes (prevention arm) whereas in the other, the treatment was started 3 days after the induction of diabetes (reversal arm). Diabetes increased heart weight/body weight (HW/BW) ratio, plasma glucose, triglyceride and cholesterol levels as well as depressed heart rate (HR), blood pressure, left ventricular systolic pressure (LVSP), rate of contraction (+dP/dt), rate of relaxation (-dP/dt), fractional shortening (FS) and cardiac output (CO). The left ventricular internal diameter in systole (LViDs) was increased whereas that in diastole (LViDd) was decreased. In the prevention arm, treatment of the diabetic animals with cysteine or taurine decreased HW/BW ratio and improved HR, FS, +dP/dt and -dP/dt, as well as normalized LViDs, without altering the increase in glucose level. Cysteine decreased plasma triglyceride and cholesterol levels and improved LVSP whereas CO was improved by taurine. In the reversal arm, cysteine alone or with taurine did not correct the changes in hemodynamic parameters, FS and plasma triglycerides. Diabetes-induced cardiac dysfunction and increases in plasma triglycerides can be prevented, but not reversed, by dietary cysteine alone or in combination with taurine. © 2013 Institute of Physiology v.v.i., Academy of Sciences of the Czech Republic, Prague, Czech Republic.


Dent M.R.,St Boniface Hospital Research | Tappia P.S.,University of Manitoba | Dhalla N.S.,St Boniface Hospital Research
Journal of Cellular Physiology | Year: 2011

This study was undertaken to determine alterations in the β-adrenoceptor (β-AR) signaling system in male and female rats at 4 weeks after the induction of arteriovenous (AV) fistula or shunt. AV shunt produced a greater degree of cardiac hypertrophy and larger increase in cardiac output in male than in female animals. Increases in plasma levels of norepinephrine and epinephrine (EPI) due to AV shunt were also higher in male than females. While no difference in the β1-AR affinity was seen in males and females, AV shunt induced increase in β1-AR density in female rats was higher than that in males. Furthermore, no changes in basal adenylyl cyclase (AC) V/VI mRNA levels were seen; however, the increase in EPI-stimulated AC activities was greater in AV shunt females than in males. AV shunt decreased myocardial β1-AR mRNA level in male rats and increased β2-AR mRNA level in female hearts; an increase in Gi-protein mRNA was detected only in male hearts. Although GRK2 gene expression was increased in both sexes, an increase in GRK3 mRNA was seen only in AV shunt female rats. β-arrestin1 mRNA was elevated in females whereas β-arrestin 2 gene expression was increased in both male and female AV shunt rats. While these data demonstrate gender associated differences in various components of the β-AR system in cardiac hypertrophy due to AV shunt, only higher levels of plasma catecholamines may account for the greater increase in cardiac output and higher degree of cardiac hypertrophy in males. © 2010 Wiley-Liss, Inc.


Arneja A.S.,University of Manitoba | Tamiji J.,University of Manitoba | Hiebert B.M.,St Boniface Hospital Research | Tappia P.S.,St Boniface Hospital Research | Galimova L.,University of Manitoba
American Journal of Physical Medicine and Rehabilitation | Year: 2015

Objective: The aim of this study was to compare the rehabilitation length of stay and functional outcome of patients with amputation on chronic dialysis with a similar group of patients not on dialysis. Design: This was a retrospective cohort study. Twenty-five patients with amputations on chronic dialysis and 25 nonrenal controls with amputation were included in the two groups. Primary outcome measures were Functional Independence Measure scores through discharge and follow-up, the percentage of patients fitted with a prosthesis, the number of patients able to ambulate independently indoors or outdoors or operate a wheelchair, and acute and rehabilitation length of stay for inpatients. Comorbidities and complications in end-stage renal disease (ESRD) patients with amputation on chronic dialysis vs. those without renal disease were also evaluated. Results: Eleven women and 14 men were included in each group. The study group patients were younger than non-ESRD controls (54 ± 12 and 61 ± 11 yrs, respectively; P = 0.05). No significant differences were found between the groups in sex, race, amputation etiology, or comorbidities, except minor amputations of toes and fingers, which were performed more often in the ESRD group compared with the non-ESRD group (14 and 2, respectively; P = 0.0003). Functional Independence Measure score was higher in the non-ESRD group on discharge (112.1 ± 7.6 vs. 107.5 ± 7.7; P = 0.04) and follow-up (111.3 ± 10.7 vs. 104.4 ± 8.7; P = 0.02). The number of patients able to ambulate indoors and outdoors or operate wheelchair independently on discharge was not statistically different between the groups. Length of stay was higher in the ESRD group (153 ± 67 vs. 105 ± 42 days; P = 0.04). Conclusions: Patients with limb amputations on chronic dialysis had significantly longer length of stay and lower Functional Independence Measure scores compared with the non-ESRD group. It is suggested that current practices may need to be adjusted to accommodate the complex rehabilitation needs of the ESRD patient population. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Babick A.,St Boniface Hospital Research | Chapman D.,St Boniface Hospital Research | Zieroth S.,University of Manitoba | Elimban V.,St Boniface Hospital Research | Dhalla N.S.,St Boniface Hospital Research
Journal of Cellular and Molecular Medicine | Year: 2012

This study tested the reversal of subcellular remodelling in heart failure due to myocardial infarction (MI) upon treatment with losartan, an angiotensin II receptor antagonist. Twelve weeks after inducing MI, rats were treated with or without losartan (20 mg/kg; daily) for 8 weeks and assessed for cardiac function, cardiac remodelling, subcellular alterations and plasma catecholamines. Cardiac hypertrophy and lung congestion in 20 weeks MI-induced heart failure were associated with increases in plasma catecholamine levels. Haemodynamic examination revealed depressed cardiac function, whereas echocardiographic analysis showed impaired cardiac performance and marked increases in left ventricle wall thickness and chamber dilatation at 20 weeks of inducing MI. These changes in cardiac function, cardiac remodelling and plasma dopamine levels in heart failure were partially or fully reversed by losartan. Sarcoplasmic reticular (SR) Ca2+-pump activity and protein expression, protein and gene expression for phospholamban, as well as myofibrillar (MF) Ca2+-stimulated ATPase activity and α-myosin heavy chain mRNA levels were depressed, whereas β-myosin heavy chain expression was increased in failing hearts; these alterations were partially reversed by losartan. Although SR Ca2+-release activity and mRNA levels for SR Ca2+-pump were decreased in failing heart, these changes were not reversed upon losartan treatment; no changes in mRNA levels for SR Ca2+-release channels were observed in untreated or treated heart failure. These results suggest that the partial improvement of cardiac performance in heart failure due to MI by losartan treatment is associated with partial reversal of cardiac remodelling as well as partial recovery of SR and MF functions. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.


Tappia P.S.,St Boniface Hospital Research | Xu Y.-J.,St Boniface Hospital Research | Dhalla N.S.,St Boniface Hospital Research
Clinical Lipidology | Year: 2013

Although synthetic chemicals and pharmacological agents are being used for the treatment of cardiovascular disease in the western world, there now appears to be a cultural and philosophical shift toward Eastern Medicine and many patients are increasingly using alternative approaches for prevention and therapeutic purposes. This brief review summarizes the experimental and clinical evidence of some functional foods, herbal products and medicinal plants for improving plasma HDL cholesterol, LDL cholesterol, triglycerides and glucose levels, as well as reducing oxidative stress. In addition, the potential of acupuncture and Yogic meditation are discussed as emerging approaches for reducing cardiovascular disease risk factors. The available evidence indicates that several functional foods, herbal products and medicinal plants exert lipid-lowering and hypoglycemic actions, as well as exhibit antioxidant properties; however, a great deal of research work and extensive clinical trials are needed to establish their use in medical practice. © 2013 Future Medicine Ltd.

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