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Andrew J. Roebuck

Other affiliations: Yukon College
Bio: Andrew J. Roebuck is an academic researcher from University of Saskatchewan. The author has contributed to research in topics: Working memory & Epilepsy. The author has an hindex of 5, co-authored 16 publications receiving 92 citations. Previous affiliations of Andrew J. Roebuck include Yukon College.

Papers
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Journal ArticleDOI
01 Jul 2018
TL;DR: Overall, while the offspring of polyI:C-treated rats displayed behavior abnormalities, maternal serum cytokines were not related to the long-term behavior changes in the offspring.
Abstract: Influenza during pregnancy is associated with the development of psychopathology in the offspring. We sought to determine whether maternal cytokines produced following administration of viral mimetic polyinosinic-polycytidylic acid (polyI:C) to pregnant rats were predictive of behavioral abnormalities in the adult offspring. Timed-pregnant Sprague Dawley rats received a single intravenous injection of 4-mg/kg polyI:C or saline on gestational day (GD)15. Blood was collected 3 h later for serum analysis of cytokine levels with ELISA. Male offspring were tested in a battery of behavioral tests during adulthood and behavior was correlated with maternal cytokine levels. Maternal serum levels of CXCL1 and interleukin (IL)-6, but not tumor necrosis factor (TNF)-α or CXCL2, were elevated in polyI:C-treated dams. PolyI:C-treated dams experienced post-treatment weight loss and polyI:C pups were smaller than controls at postnatal day (PND)1. Various behavior alterations were seen in the polyI:C-treated offspring. Male polyI:C offspring had enhanced MK-801-induced locomotion, and reduced sociability. PolyI:C offspring failed to display crossmodal and visual memory, and oddity preference was also impaired. Set-shifting, assessed with a lever-based operant conditioning task, was facilitated while touchscreen-based reversal learning was impaired. Correlations were found between maternal serum concentrations of CXCL1, acute maternal temperature and body weight changes, neonatal pup mass, and odd object discrimination and social behavior. Overall, while the offspring of polyI:C-treated rats displayed behavior abnormalities, maternal serum cytokines were not related to the long-term behavior changes in the offspring. Maternal sickness effects and neonatal pup size may be better indicators of later effects of maternal inflammation in the offspring.

49 citations

Journal ArticleDOI
TL;DR: In this article, the authors characterized aspects of the endocannabinoid system in brain areas relevant to seizures in GAERS and tested whether positive allosteric modulators (PAMs) of CB1R reduced SWDs.

20 citations

Journal ArticleDOI
01 Mar 2019
TL;DR: In this article, neural recordings were obtained from the medial prefrontal cortex (mPFC) of awake, behaving rats performing an odor span task of WM capacity, which revealed that distinct mPFC activity states underlie the delay, foraging, and reward epochs of the odour span task.
Abstract: Medial prefrontal cortex (mPFC) activity is fundamental for working memory (WM), attention, and behavioral inhibition; however, a comprehensive understanding of the neural computations underlying these processes is still forthcoming. Toward this goal, neural recordings were obtained from the mPFC of awake, behaving rats performing an odor span task of WM capacity. Neural populations were observed to encode distinct task epochs and the transitions between epochs were accompanied by abrupt shifts in neural activity patterns. Putative pyramidal neuron activity increased earlier in the delay for sessions where rats achieved higher spans. Furthermore, increased putative interneuron activity was only observed at the termination of the delay thus indicating that local processing in inhibitory networks was a unique feature to initiate foraging. During foraging, changes in neural activity patterns associated with the approach to a novel odor, but not familiar odors, were robust. Collectively, these data suggest that distinct mPFC activity states underlie the delay, foraging, and reward epochs of the odor span task. Transitions between these states likely enables adaptive behavior in dynamic environments that place strong demands on the substrates of working memory.

17 citations

Journal ArticleDOI
TL;DR: It is suggested that while acute stress enhances the acquisition of PAL, CORT alone does not, and this dissociation may be due to differences between these treatments and their ability to produce sufficient catecholamine release in the amygdala, a requirement for stress effects on memory.

15 citations

Journal ArticleDOI
TL;DR: The data suggest that GAERS have impaired behavioral flexibility and identify some sex-dependent differences, which may make it suitable for assessing the potential benefit of antiepileptic drugs on comorbid behavioral and cognitive deficits.

14 citations


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Journal Article
TL;DR: In this paper, a homozygous, missense, single nucleotide (G to C) mutation in the Cav3.2 T-type Ca2+ channel gene (Cacna1h) in the genetic absence epilepsy rats from Strasbourg (GAERS) model was described.
Abstract: Low-voltage-activated, or T-type, calcium (Ca2+) channels are believed to play an essential role in the generation of absence seizures in the idiopathic generalized epilepsies (IGEs). We describe a homozygous, missense, single nucleotide (G to C) mutation in the Cav3.2 T-type Ca2+ channel gene (Cacna1h) in the genetic absence epilepsy rats from Strasbourg (GAERS) model of IGE. The GAERS Cav3.2 mutation (gcm) produces an arginine to proline (R1584P) substitution in exon 24 of Cacna1h, encoding a portion of the III–IV linker region in Cav3.2. gcm segregates codominantly with the number of seizures and time in seizure activity in progeny of an F1 intercross. We have further identified two major thalamic Cacna1h splice variants, either with or without exon 25. gcm introduced into the splice variants acts “epistatically,” requiring the presence of exon 25 to produce significantly faster recovery from channel inactivation and greater charge transference during high-frequency bursts. This gain-of-function mutation, the first reported in the GAERS polygenic animal model, has a novel mechanism of action, being dependent on exonic splicing for its functional consequences to be expressed.

158 citations

Journal ArticleDOI
TL;DR: Empirical evidence for the effects of maternal infection and immune activation, as well as major findings in different poly I:C MIA models with a focus on polyI:C exposure timing, behavioural and molecular changes in the offspring, are reviewed.

92 citations

Journal ArticleDOI
TL;DR: It is pivotal that researchers working with poly(I:C)-based MIA models ascertain and consider the precise molecular composition and immunogenicity of the product in use, as different poly( I:C) products can induce varying immune responses and can differentially affect maternal physiology and pregnancy outcomes.
Abstract: Maternal immune activation (MIA) models that are based on administration of the viral mimetic, poly(I:C), are widely used as experimental tools to study neuronal and behavioral dysfunctions in relation to immune-mediated neurodevelopmental disorders and mental illnesses. Evidence from investigations in non-pregnant rodents suggests that different poly(I:C) products can vary in terms of their immunogenicity, even if they are obtained from the same vendor. The present study aimed at extending these findings to pregnant mice, while also controlling various poly(I:C) products for potential contamination with lipopolysaccharide (LPS). We found significant variability between different batches of poly(I:C) potassium salt obtained from the same vendor (Sigma-Aldrich) in terms of the relative amount of dsRNA fragments in the high molecular weight range (1000-6000 nucleotides long) and with regards to their effects on maternal thermoregulation and immune responses in maternal plasma, placenta and fetal brain. Batches of poly(I:C) potassium salt containing larger amounts of high molecular weight fragments induced more extensive effects on thermoregulation and immune responses compared to batches with minimal amounts of high molecular weight fragments. Consistent with these findings, poly(I:C) enriched for high molecular weight dsRNA (HMW) caused larger maternal and placental immune responses compared to low molecular weight (LMW) poly(I:C). These variable effects were unrelated to possible LPS contamination. Finally, we found marked variability between different batches of the poly(I:C) potassium salt in terms of their effects on spontaneous abortion rates. This batch-to-batch variability was confirmed by three independent research groups using distinct poly(I:C) administration protocols in mice. Taken together, the present data confirm that different poly(I:C) products can induce varying immune responses and can differentially affect maternal physiology and pregnancy outcomes. It is therefore pivotal that researchers working with poly(I:C)-based MIA models ascertain and consider the precise molecular composition and immunogenicity of the product in use. We recommend the establishment of reference databases that combine phenotype data with empirically acquired quality information, which can aid the design, implementation and interpretation of poly(I:C)-based MIA models.

81 citations

Journal ArticleDOI
TL;DR: In this article, the potential of the ECS in the treatment of various diseases, and the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.
Abstract: The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems. In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development. The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development. The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases. This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “C. sativa L.” or “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.

58 citations

Journal ArticleDOI
TL;DR: In this article, game-based data from commercial off-the-shelf games have been used as a digital biomarker to assess and model mental health and health decline, which can be used for population screening or prevalence estimations.
Abstract: Background: Assessment for mental health is performed by experts using interview techniques, questionnaires, and test batteries and following standardized manuals; however, there would be myriad benefits if behavioral correlates could predict mental health and be used for population screening or prevalence estimations. A variety of digital sources of data (eg, online search data and social media posts) have been previously proposed as candidates for digital biomarkers in the context of mental health. Playing games on computers, gaming consoles, or mobile devices (ie, digital gaming) has become a leading leisure activity of choice and yields rich data from a variety of sources. Objective: In this paper, we argue that game-based data from commercial off-the-shelf games have the potential to be used as a digital biomarker to assess and model mental health and health decline. Although there is great potential in games developed specifically for mental health assessment (eg, Sea Hero Quest), we focus on data gathered “in-the-wild” from playing commercial off-the-shelf games designed primarily for entertainment. Methods: We argue that the activity traces left behind by natural interactions with digital games can be modeled using computational approaches for big data. To support our argument, we present an investigation of existing data sources, a categorization of observable traits from game data, and examples of potentially useful game-based digital biomarkers derived from activity traces. Results: Our investigation reveals different types of data that are generated from play and the sources from which these data can be accessed. Based on these insights, we describe five categories of digital biomarkers that can be derived from game-based data, including behavior, cognitive performance, motor performance, social behavior, and affect. For each type of biomarker, we describe the data type, the game-based sources from which it can be derived, its importance for mental health modeling, and any existing statistical associations with mental health that have been demonstrated in prior work. We end with a discussion on the limitations and potential of data from commercial off-the-shelf games for use as a digital biomarker of mental health. Conclusions: When people play commercial digital games, they produce significant volumes of high-resolution data that are not only related to play frequency, but also include performance data reflecting low-level cognitive and motor processing; text-based data that are indicative of the affective state; social data that reveal networks of relationships; content choice data that imply preferred genres; and contextual data that divulge where, when, and with whom the players are playing. These data provide a source for digital biomarkers that may indicate mental health. Produced by engaged human behavior, game data have the potential to be leveraged for population screening or prevalence estimations, leading to at-scale, nonintrusive assessment of mental health.

43 citations