PRISM :: Browsing by Author "Pittman, Quentin J."

Browsing by Author "Pittman, Quentin J."

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Open Access
Adaptability and Function of the Placental Endocrine System
(2020-06-08) Eaton, Malcolm Ellis; Cross, James C.; Hallgrímsson, Benedikt; De Bruyn, Raylene; Pittman, Quentin J.; Slater, Donna M.; Davidge, Sandra Thomas
The placenta acts as the arbitrator for the exchange of nutrients and gases across the feto-maternal interface, ensuring that the fetus can grow, and the mother can remain healthy to deliver and nurture her offspring. The placenta achieves this by changing its structure and function throughout gestation. Failure to undergo these changes is a major cause of obstetric syndromes, intrauterine growth restriction and pre-term birth. These complications result in deleterious long-term outcomes for both fetus and mother and understanding the complex aetiology of these complications is fundamental to impacting lifelong health. One of the less well-studied ways that the placenta adapts is by secreting hormones that regulate maternal adaptations to pregnancy. Previous work in the Cross lab established that a family of 22 Prolactin-related hormone genes, termed the placenta Prolactin-related hormones (PPRH), that are specifically expressed from the mouse placenta regulate maternal adaptations to pregnancy. The mouse provided a model to study how the placenta adapted its structure and function to changes in the maternal environmental and PPRH levels. We first established the normal course of cell growth in the placenta to understand the timing of changes in trophoblast cells number and found evidence of cell hypertrophy and endoreduplication in addition to hyperplasia. We then challenged pregnancies with a maternal diet low in protein. We found that the normal course of cellular differentiation and growth was altered, but that these changes were adapting to preserve fetal growth. Interestingly, we found that male and female fetuses used different strategies. We then created a model that was haplo-deficient in PPRH genes and, to our surprise, fetuses were overgrown while mothers failed to gain weight late-term. Interpreting the expression patterns of individual hormone genes in the context of other placental knockouts helped us identify putative roles for several hormones and demonstrated that this locus is highly adaptable. Distinguishing the targets and functions of these hormones and separating between primary and secondary effects remains a topic of interest. In examining PPRH null mutants, we found that the size of the maternal liver, spleen and gut were altered, along with the gut microbiota. These results indicate that the placenta is a highly adaptable organ that changes in normal pregnancy and has mechanisms built in to mitigate impacts of environmental changes. By studying the changes over time, we reveal insights into how placenta-specific hormones regulate maternal physiology, placental function and fetal growth outcomes. There is still a great deal to learn about the placenta but increasing our understanding of this fascinating organ will contribute to the interpretation and treatment of obstetric syndromes.
Open Access
Cardiovascular regulation by the paraventricular nucleus
(1991) Bagdan, Bonnie; Pittman, Quentin J.
Open Access
Depressive and anxiety-like behaviour in the eae model of multiple sclerosis
(2012) Nayani, Nausheen; Pittman, Quentin J.
Multiple Sclerosis (MS) is a debilitating and devastating neurodegenerative disease affecting thousands of Canadians. Accumulating evidence indicates depression and anxiety are co-morbidities affecting a large proportion of MS patients. This thesis tests the hypothesis that, independent of motor deficits, animals with experimental MS will display cognitive behavioural alterations that are associated with inflammatory changes in areas such as the amygdala and hippocampus. Experimental Autoimmune Encephalomyelitis (EAE) was elicited in mice, and, 7-8 days later, before any motor deficits were observed, mice with EAE displayed increased anxiety-like symptoms in the elevated plus maze and open field, increased depressive-like symptoms in the Porsolt swim and tail suspension tests and decreased sociability. Quantitative RT- PCR indicated that TNF-a and IL-1?? mRNA was generally insignificant in the amygdala and hippocampus of EAE animals compared to controls; thus further studies are required to elucidate if neuroinflammatory changes in the brain are associated with the behavioural alterations.
Open Access
Development of the febrile response to pyrogens in the foetal and newborn lamb
(1976) Pittman, Quentin J.; Cooper, Keith E.
Open Access
Early life antibiotic and prebiotic exposure: impact on gut microbiota, metabolism and obesity risk
(2019-09-18) Klančič, Teja; Reimer, Raylene A.; Pittman, Quentin J.; Shearer, Jane
Background: Obesity is a complex disease with multiple contributing factors including the gut microbiota. Antibiotics, when administered early in life, disrupt gut microbiota development and thereby increase the risk of obesity, whereas dietary agents such as prebiotics, reduce obesity risk via several pathways including microbiota-dependent mechanisms. Objective: This dissertation examines how antibiotics when administered with/without prebiotics, alter metabolic, microbial and anthropometric outcomes in rodents and humans. Specifically, the objectives were to: 1) assess the impact of indirect (maternal) antibiotic exposure with prebiotic co-administration on obesity risk in dams and their offspring; 2) determine the impact of direct antibiotic/prebiotic exposure in young rat pups on obesity risk and other metabolic parameters; 3) analyze available human birth cohort data from the All Our Families (AOF) study and explore the association between maternal antibiotic exposure and infant BMI z scores. Methods: 1) Sprague-Dawley rats consumed antibiotic and/or prebiotic during their 3rd week of pregnancy and lactation and their offspring were challenged with a high-fat high-sugar (HFS) diet from 9-17 weeks of age; 2) Rat pups were administered three pulses of azithromycin with/without prebiotic diet and weaned onto a HFS diet; 3) Using the AOF dataset, the association between infant BMI z score and maternal antibiotic use during pregnancy or during birth was examined. In the animal studies, body composition, gut microbiota composition, and metabolic outcomes were examined in dams and their offspring. In the human cohort, the association between antibiotic use during birth (intrapartum, n=1303)/during pregnancy (n=1943) and infant BMI z-score was investigated. Results: 1) Maternal antibiotic use during pregnancy/lactation impairs metabolism and postpartum weight loss in dams and increases obesity risk in their offspring, which was prevented with prebiotic co-administration; 2) Direct administration of azithromycin increased body weight and impaired insulin production/sensitivity. Prebiotic co-administration normalized the impairments; 3) Intrapartum antibiotic exposure might contribute to the development of child overweight/obesity at 1 year of age. Conclusion: Our results provide evidence for the ability of prebiotic co-administration with antibiotics to prevent metabolic impairments and obesity in rats. Future clinical trials should investigate whether this is also possible in humans.
Open Access
Early-Life Inflammation Affects Amygdala Function and Associated Behaviours in Adolescence and Adulthood
(2018-01-23) Doenni, Vienna Maria; Pittman, Quentin J.; Hill, Matthew N
Inflammation is one of the most common results of viral and bacterial infections. While inflammation is a normal mechanism to clear pathogens, there is now emerging evidence that it can have profound effects on brain and behaviour. We discovered a susceptible window around postnatal day (P) 14, when a single exposure to an immune challenge with lipopolysaccharide (LPS - a bacterial, inflammatory compound) can cause changes in physiological and behavioural processes that persist into adulthood. In this research, I addressed the hypothesis that a single postnatal immune challenge on P14 causes long lasting alterations in amygdala function and associated behaviours. I investigated reciprocal social behaviour, anxiety, startle and fear behaviour in both male and female rats, and found that an immune challenge on P14 decreased sociability and delayed the extinction of a fearful memory of a cue but not context. The effects of P14 LPS were present in both males and females. Acutely at P14, LPS activated cells in the amygdala and decreased concentrations of the endocannabinoid anandamide. In adolescence endocannabinoid concentration, receptor binding and degradative enzyme activity were altered in males and females. When the activity of the anandamide degrading enzyme FAAH was normalized by an inhibitor (oral or intra amygdala), before a social encounter, behavioural changes caused by P14 LPS were normalized to control levels. This lead us to believe that the amygdaloid cannabinoid system is a substantial contributor to changes seen in response to early-life inflammation. Early-life inflammation may substantially shape adolescent social and fear behaviour and contribute to related disorders. I further investigated amygdala-mediated schizophrenia-like behaviours and found that –unlike maternal immune activation- sensorimotor gating and reactions to stressors are unaffected by postnatal inflammation on P14. Lastly, I investigated alcohol drinking as another amygdala related behaviour and found that P14 LPS leads to increased alcohol drinking in the adult, when pre-exposed to alcohol during adolescence. Taken together, my work strongly suggests that inflammation on P14 alters amygdala signalling and behaviour, and could help us understand differences in susceptibility for fear and anxiety disorders, schizophrenia and alcohol disorders.
Open Access
Effect of Cafeteria Diet Induced Obesity on Neuroinflammation in the Orbitofrontal Cortex
(2016) Kaur, Manpreet; Borgland, Stephanie; Pittman, Quentin J.; Trang, Tuan
Palatable food consumption is associated with obesity and induce inflammation in brain. The orbitofrontal cortex is implicated in compulsive behavior. Glial changes lead to synaptic remodeling and altered behavior. However it is not clear if metabolic changes associated with cafeteria diet consumption lead to glial changes in OFC. My study addressed this important question whether intake of cafeteria diet leads to glial changes in OFC. I observed that rats with extended access to cafeteria diet become obese, exhibited inflexible behaviour and increased GFAP and IBA1 expression in the hippocampus and the hypothalamus. Further, there was an increase observed in several proinflammatory cytokines in the hypothalamus. My work has shown that extended intake of cafeteria diet is associated with increased GFAP expression in OFC without any changes in IBA1 expression, proliferation and the levels of proinflammatory cytokines. This is the first study reporting astrocytic activation in OFC associated with compulsive food intake.
Open Access
The Effects of Anabolic-Androgenic Steroids on Repetitive Mild Traumatic Brain Injury Outcomes
(2019-08-16) Tabor, Jason Benjamin; Mychasiuk, Richelle; Yeates, Keith Owen; Spanswick, Simon C.; Shultz, Sandy R.; Debert, Chantel Teresa; Pittman, Quentin J.
Given the considerable prevalence of AAS abuse and RmTBI incidence in adolescents and their overlapping symptomology, the goal of this research was to characterize any cumulative behavioural and neuropathological outcomes of AAS on the concussed brain in adolescent Sprague Dawley rats. Although there were minimal effects of AAS on RmTBI outcomes, we identified cumulative effects of RmTBI and abrupt AAS and exercise cessation on measures of anxiety, working memory, in addition to altered gene expression in the neural circuitry involved in the innate stress response. Additionally, we identified alarming effects of AAS on the developing brain; prefrontal cortex atrophy, amygdala hypertrophy, and damaged white matter in the corpus callosum were identified which were associated with changes in gene expression and subsequent behavioural impairments. The findings from this investigation provide valuable insight into the effects of AAS exposure on the developing brain in the context of RmTBI.
Open Access
Experimental febrile convulsions in the rat
(2005) Heida, James George; Pittman, Quentin J.
Open Access
Galanin modulates neurotransmission in electrophysiologically identified supraoptic oxytocin and vasopressin neurons
(2003) Kozoriz, Michael Gregory; Pittman, Quentin J.
Open Access
Neonatal exposure to lipopolysaccharide alters the febrile response, nociceptive threshold, and predisposition to inflammation in adulthood
(2002) Boisse, Lysa; Pittman, Quentin J.
Open Access
Neonatal programming of the adult neuroimmune response
(2006) Ellis, Shaun L.; Pittman, Quentin J.
Open Access
Neural plasticity after a prolonged experimental febrile seizure
(2010) Reid, Aylin Yasmin; Pittman, Quentin J.; Teskey, G. Campbell
Open Access
Postnatal inflammation alters CNS excitability in the rat
(2009) Galic, Michael A.; Pittman, Quentin J.
Open Access
Recruitment of α4β7 monocytes and neutrophils to the brain in experimental colitis is associated with elevated cytokines and anxiety-like behavior
(2022-04-04) Cluny, Nina L.; Nyuyki, Kewir D.; Almishri, Wagdi; Griffin, Lateece; Lee, Benjamin H.; Hirota, Simon A.; Pittman, Quentin J.; Swain, Mark G.; Sharkey, Keith A.
Abstract Background Behavioral comorbidities, such as anxiety and depression, are a prominent feature of IBD. The signals from the inflamed gut that cause changes in the brain leading to these behavioral comorbidities remain to be fully elucidated. We tested the hypothesis that enhanced leukocyte–cerebral endothelial cell interactions occur in the brain in experimental colitis, mediated by α4β7 integrin, to initiate neuroimmune activation and anxiety-like behavior. Methods Female mice treated with dextran sodium sulfate were studied at the peak of acute colitis. Circulating leukocyte populations were determined using flow cytometry. Leukocyte–cerebral endothelial cell interactions were examined using intravital microscopy in mice treated with anti-integrin antibodies. Brain cytokine and chemokines were assessed using a multiplex assay in animals treated with anti-α4β7 integrin. Anxiety-like behavior was assessed using an elevated plus maze in animals after treatment with an intracerebroventricular injection of interleukin 1 receptor antagonist. Results The proportion of classical monocytes expressing α4β7 integrin was increased in peripheral blood of mice with colitis. An increase in the number of rolling and adherent leukocytes on cerebral endothelial cells was observed, the majority of which were neutrophils. Treatment with anti-α4β7 integrin significantly reduced the number of rolling leukocytes. After anti-Ly6C treatment to deplete monocytes, the number of rolling and adhering neutrophils was significantly reduced in mice with colitis. Interleukin-1β and CCL2 levels were elevated in the brain and treatment with anti-α4β7 significantly reduced them. Enhanced anxiety-like behavior in mice with colitis was reversed by treatment with interleukin 1 receptor antagonist. Conclusions In experimental colitis, α4β7 integrin-expressing monocytes direct the recruitment of neutrophils to the cerebral vasculature, leading to elevated cytokine levels. Increased interleukin-1β mediates anxiety-like behavior.
Open Access
Regulation of arginine vasopressin receptors
(1991) Poulin, Paule; Pittman, Quentin J.
Open Access
Role of neurohypophyseal peptides in motor control in the neonatal mouse spinal cord
(2004) Pearson, Selina Antonia; Pittman, Quentin J.; Whelan, Patrick
Open Access
Synaptic modulation of ionic currents in the melanotroph
(1989) Williams, Peter J. (Peter John), 1952-; Pittman, Quentin J.
Open Access
The Behavioural, Neuroanatomical, and Molecular Effects of Chronic Social Stress on Mice That Lack Zinc Transporter 3 and Vesicular Zinc
(2018-12-04) McAllister, Brendan Barrymore; Dyck, Richard H.; Antle, Michael C.; Trang, Tuan; Pittman, Quentin J.; Tzounopoulos, Thanos
In certain neurons, zinc ions are stored in synaptic vesicles by a dedicated vesicular zinc transporter, called zinc transporter 3 (ZnT3). Vesicular zinc can then be released synaptically, in an activity-dependent fashion, to transmit signals by modulating a plethora of targets. To understand the function of vesicular zinc in the central nervous system, a useful tool is the ZnT3 knockout (KO) mouse, which lacks ZnT3 and, as a result, lacks vesicular zinc. Behavioural characterization of these mice has revealed subtle abnormalities in cognition and sensory processing. In addition, a pattern is becoming apparent, wherein ZnT3 KO mice behave normally under standard laboratory conditions but fail to exhibit neural plasticity and behavioural adaptation in response to certain treatments or experiences. The experiments described in this thesis were designed to assess how ZnT3 KO mice would respond to the experience of repeated social defeat (RSD) stress, a method of modelling depression-like behaviour in rodents, and to test the hypothesis that ZnT3 KO mice would fail to exhibit stress-induced neural plasticity, resulting in an altered behavioural response to stress. The primary finding was that, compared to wild type (WT) mice, ZnT3 KO mice exhibited reduced social avoidance of a novel conspecific following RSD, suggesting reduced susceptibility to the depression-like behaviour of social withdrawal. Both genotypes were equally susceptible to anxiety-like behaviour following RSD, however. To investigate the mechanisms behind the seemingly protective effect of eliminating vesicular zinc on stress-induced social avoidance, several neuroanatomical parameters were examined. No evidence was found that microglial activation, hippocampal neurogenesis, or hippocampal brain-derived neurotrophic factor (BDNF) levels could account for the difference in behavioural outcome. However, some evidence was found that altered structure of the corpus callosum or reduced BDNF levels in the nucleus accumbens may contribute to the protection against social avoidance in ZnT3 KO mice. Further work will be required to validate and extend these findings, in order to more fully understand the mechanisms behind the altered behavioural response to chronic stress – and the altered capacity for experience-dependent neuroplasticity – in mice that lack vesicular zinc.
Open Access
The effect of prenatal maternal inflammation on cerebeller stripe organization of offspring
(2011) Aavani, Tooka; Pittman, Quentin J.; Hawkes, Richard