scholarly journals Low (Therapeutic) Dose of Warfarin Is Not Associated with Cognitive and Exploratory Behavior Impairment in Rats: Mechanistic Studies (OR15-01-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Guylaine Ferland ◽  
Pierre Allaire ◽  
Bouchra Ouliass
Keyword(s):  
Spatial Memory ◽  
Cell Signaling ◽  
Exploratory Behavior ◽  
Low Dose ◽  
Sphingolipid Metabolism ◽  
Compensatory Mechanisms ◽  
Behavioral Impairment ◽  
Numerous Cell ◽  
Behavior Impairment ◽  
The Impact

Abstract Objectives In addition to its role in hemostasis, vitamin K (VK) is involved in brain function through various proteins and sphingolipid metabolism. Warfarin (W), a widely prescribed anticoagulant drug, exerts its beneficial effect in coagulation by partially blocking the recycling of the vitamin. In previous studies, we provided evidence that, when administered in large doses, W leads to cognitive and exploratory behavior impairment, and alteration in the VK dependent proteins Gas6 and protein S (PS) and their downstream pro-survival extracellular signal-regulated (ERK) and serine-threonine (Akt) kinases pathways. In light of its widespread use as oral anticoagulant, the present study aimed to investigate the impact of W on cognition and behavior, Gas6 and PS and their signaling pathways when administered in doses comparable to those used in the clinical setting. Methods Male Wistar rats (n = 14/gp) were fed an AIN-93 based diet containing 750 mcg phylloquinone/kg/d and were randomly allocated to treatment with 0,1 mg W/kg/d (in drinking water) (W group) or not (C group), for 9 wks. Spatial memory (Morris Water Maze) and exploratory behavior (Open Field) were assessed. Gas6, PS, pAkt, pERK, caspases −3 and −12 (apoptosis), brain-derived neurotrophic factor (BDNF), and microglial CD11b/c protein (a marker of inflammation), were assessed by immunoblotting in hippocampus (HPP), frontal cortex (FC), and striatum (STR), three regions involved in cognition. VK contents were determined in these 3 brain regions by HPLC. Group difference was tested by unpaired Student t-test. Results Low dose W had no impact on brain VK concentrations, spatial memory, and exploratory behavior (all P > 0.05). In contrast, W treatment was associated with numerous cell-signaling modulations, namely increased PS, ERK and Akt activity, and caspase −3 and −12 expression, in HPP; increased BDNF in FC and STR; increased expression of CD11bc in STR, (all P < 0.05). Conclusions This study provides evidence that low dose W is not associated with cognitive and behavioral impairment despite numerous cell-signaling modulations that have the potential to be beneficial or detrimental to the brain. Whether these events represent compensatory mechanisms to maintain homeostasis deserves further investigation. Funding Sources Study funded by CIHR.

scholarly journals Cell migration guided by long-lived spatial memory

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Joseph d’Alessandro ◽  
Alex Barbier--Chebbah ◽  
Victor Cellerin ◽  
Olivier Benichou ◽  
René Marc Mège ◽  
...  
Keyword(s):  
Cell Migration ◽  
Spatial Memory ◽  
Large Scale ◽  
Single Cells ◽  
Environmental Perturbations ◽  
Motile Cells ◽  
Unicellular Organisms ◽  
Biochemical Signals ◽  
The Impact ◽  
Cell Trajectories

AbstractLiving cells actively migrate in their environment to perform key biological functions—from unicellular organisms looking for food to single cells such as fibroblasts, leukocytes or cancer cells that can shape, patrol or invade tissues. Cell migration results from complex intracellular processes that enable cell self-propulsion, and has been shown to also integrate various chemical or physical extracellular signals. While it is established that cells can modify their environment by depositing biochemical signals or mechanically remodelling the extracellular matrix, the impact of such self-induced environmental perturbations on cell trajectories at various scales remains unexplored. Here, we show that cells can retrieve their path: by confining motile cells on 1D and 2D micropatterned surfaces, we demonstrate that they leave long-lived physicochemical footprints along their way, which determine their future path. On this basis, we argue that cell trajectories belong to the general class of self-interacting random walks, and show that self-interactions can rule large scale exploration by inducing long-lived ageing, subdiffusion and anomalous first-passage statistics. Altogether, our joint experimental and theoretical approach points to a generic coupling between motile cells and their environment, which endows cells with a spatial memory of their path and can dramatically change their space exploration.

scholarly journals Vulnerability factors for mephedrone-induced conditioned place preference in rats—the impact of sex differences, social-conditioning and stress

2021 ◽  
Author(s):  
Olga Wronikowska ◽  
Maria Zykubek ◽  
Łukasz Kurach ◽  
Agnieszka Michalak ◽  
Anna Boguszewska-Czubara ◽  
...  
Keyword(s):  
Sex Differences ◽  
Conditioned Place Preference ◽  
Low Dose ◽  
Social Factor ◽  
Place Preference ◽  
Female Rats ◽  
Male Rats ◽  
Social Conditioning ◽  
Male And Female Rats ◽  
The Impact

Abstract Rationale Mephedrone is a frequently overused drug of abuse that belongs to the group of novel psychoactive substances. Although its mechanism of action, as well as toxic and psychoactive effects, has been widely studied, the role of different factors that could contribute to the increased vulnerability to mephedrone abuse is still poorly understood. Objectives The aim of the presented study was to assess the impact of several factors (sex differences, social-conditioning, and chronic mild unpredictable stress — CMUS) on the liability to mephedrone-induced reward in Wistar rats. Methods The rewarding effects of mephedrone in male and female rats were assessed using the conditioned place preference (CPP) procedure. Furthermore, the impact of social factor and stress was evaluated in male rats using social-CPP and CMUS-dependent CPP, respectively. Results Mephedrone induced classic-CPP in female (10 mg/kg), as well as in male (10 and 20 mg/kg) rats. However, the impact of mephedrone treatment during social-CPP was highly dose-dependent as the rewarding effects of low dose of mephedrone (5 mg/kg; non-active in classic-CPP) were potentiated when administered during social-conditioning. Interestingly, social-conditioning with a higher dose of 20 mg/kg (that induced classic-CPP) was able to reverse these effects. Finally, CMUS potentiated rewarding effects of a low dose of mephedrone (5 mg/kg) and increased the level of corticosterone in rats’ prefrontal cortex and hippocampus. Conclusions Altogether, the presented results give new insight into possible factors underlying the vulnerability to mephedrone abuse and can serve as a basis for further studies assessing mechanisms underlying observed effects.

scholarly journals The Impact of Loading Dose on Outcome in Stroke Patients Receiving Low-Dose Tissue Plasminogen Activator Thrombolytic Therapy

2020 ◽  
Vol Volume 14 ◽  
pp. 257-263 ◽  
Author(s):  
Yi-Sin Wong ◽  
Sheng-Feng Sung ◽  
Chi-Shun Wu ◽  
Yung-Chu Hsu ◽  
Yu-Hsiang Su ◽  
...  
Keyword(s):  
Thrombolytic Therapy ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Low Dose ◽  
Loading Dose ◽  
Stroke Patients ◽  
Tissue Plasminogen ◽  
The Impact

scholarly journals Cognitive changes across the menopause transition: A longitudinal evaluation of the impact of age and ovarian status on spatial memory

2017 ◽  
Vol 87 ◽  
pp. 96-114 ◽  
Author(s):  
Stephanie V. Koebele ◽  
Sarah E. Mennenga ◽  
Ryoko Hiroi ◽  
Alicia M. Quihuis ◽  
Lauren T. Hewitt ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Cognitive Changes ◽  
Longitudinal Evaluation ◽  
Ovarian Status ◽  
Menopause Transition ◽  
The Impact

scholarly journals Hypoxia and Hypoxia-Inducible Factor Signaling in Muscular Dystrophies: Cause and Consequences

2021 ◽  
Vol 22 (13) ◽  
pp. 7220
Author(s):  
Thuy-Hang Nguyen ◽  
Stephanie Conotte ◽  
Alexandra Belayew ◽  
Anne-Emilie Declèves ◽  
Alexandre Legrand ◽  
...  
Keyword(s):  
Cell Function ◽  
Current Knowledge ◽  
Genetic Defect ◽  
Hypoxia Inducible Factor ◽  
Muscular Dystrophies ◽  
Compensatory Mechanisms ◽  
Hypoxia Response ◽  
Muscle Disorders ◽  
Almost All ◽  
The Impact

Muscular dystrophies (MDs) are a group of inherited degenerative muscle disorders characterized by a progressive skeletal muscle wasting. Respiratory impairments and subsequent hypoxemia are encountered in a significant subgroup of patients in almost all MD forms. In response to hypoxic stress, compensatory mechanisms are activated especially through Hypoxia-Inducible Factor 1 α (HIF-1α). In healthy muscle, hypoxia and HIF-1α activation are known to affect oxidative stress balance and metabolism. Recent evidence has also highlighted HIF-1α as a regulator of myogenesis and satellite cell function. However, the impact of HIF-1α pathway modifications in MDs remains to be investigated. Multifactorial pathological mechanisms could lead to HIF-1α activation in patient skeletal muscles. In addition to the genetic defect per se, respiratory failure or blood vessel alterations could modify hypoxia response pathways. Here, we will discuss the current knowledge about the hypoxia response pathway alterations in MDs and address whether such changes could influence MD pathophysiology.

scholarly journals Cognitive functions in young adults with generalized anxiety disorder

2018 ◽  
Vol 56 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Kiara Leonard ◽  
Amitai Abramovitch
Keyword(s):  
Anxiety Disorder ◽  
Cognitive Load ◽  
Generalized Anxiety Disorder ◽  
Cognitive Functions ◽  
Theoretical Models ◽  
Generalized Anxiety ◽  
Neuropsychological Battery ◽  
Compensatory Mechanisms ◽  
Neuropsychological Profile ◽  
The Impact

AbstractBackground:Anxiety and worry are central symptoms of Generalized Anxiety Disorder (GAD) that have been theorized to negatively impact cognitive functions. However, most of the research has focused on threat-related or emotionally-charged stimuli, and a surprisingly small number of investigations examined ‘cold’ cognitive functions using classic neuropsychological tests. Such investigations are particularly important given that some theoretical models suggest compensatory mechanisms associated with anxiety that in certain circumstances may result in intact performance. The aim of the present study is to assess the neuropsychological profile associated with GAD, using a comprehensive neuropsychological battery.Methods:A sample of 23 college students meeting criteria for DSM-5 GAD and 20 control participants completed a psychometrically valid comprehensive computerized neuropsychological battery and clinical questionnaires.Results:The GAD sample presented with significantly elevated symptomatic rates of anxiety, worry, depression and stress. However, no significant differences were found on any neuropsychological outcome measures or domain indexes. Effect sizes were small, some of which favored the GAD sample.Conclusion:Despite substantial psychopathological burden, GAD exhibited intact cognitive functioning. These results support the Cognitive Control Theory of Anxiety, suggesting that elevated primary anxiety may not impact ‘cold’ cognitive functions in the absence of threat or substantial cognitive load. Given that this is one of the only studies employing a comprehensive neuropsychological battery in GAD, more research is needed in this population to replicate these results and to examine the impact of anxiety on cognitive functions at varying degrees of cognitive load in this population.

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