Jennifer A. Chalmers
University of Toronto
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Featured researches published by Jennifer A. Chalmers.
Oecologia | 2005
Cesar Rodriguez-Saona; Jennifer A. Chalmers; Sherosha Raj; Jennifer S. Thaler
Herbivore-induced plants responses can affect the preference and performance of herbivores and their natural enemies. These responses may vary depending on the identity and number of herbivore species feeding on the plant so that when herbivores from different guilds feed on plants, the interactions between plants, herbivores, and natural enemies may be disrupted. Tomato plants were damaged either by the caterpillar Spodoptera exigua, or the aphid Macrosiphum euphorbiae, or damaged by both herbivores, or undamaged controls. We measured the preference and performance of S. exigua and its parasitoid Cotesia marginiventris, and activity of proteinase inhibitors (PI) as an indicator of induced resistance. Compared to undamaged plants, caterpillar damage reduced the number of eggs laid by S. exigua adults, reduced growth, consumption, and survival of larval S. exigua and C. marginiventris, and increased activity of PIs 43%; but did not increase attraction of C. marginiventris. While pupal mass of S. exigua was not affected, the pupal mass of C. marginiventris decreased on caterpillar-damaged plants compared to controls. In contrast, plants damaged by aphids were preferred for oviposition by S. exigua, and had increased larval consumption and survival, compared to controls. Aphid feeding did not affect the preference or performance of C. marginiventris, or PI activity, compared to controls. While oviposition was deterred on caterpillar-damaged plants, plants damaged by both herbivores received the same amount of oviposition as controls. The attraction of C. marginiventris to plants damaged by caterpillars and aphids was increased compared to controls. However, plants damaged by both herbivores had similar PI activity, larval growth and survival of S. exigua and C. marginiventris, as plants singly damaged by caterpillars. Overall, the preference component for both the herbivore and parasitoid was more strongly affected by damage due to multiple herbivores than the performance component.
Hypertension | 2007
Tami A. Martino; Nazneen Tata; Denise D. Belsham; Jennifer A. Chalmers; Marty Straume; Paul Lee; Horia Pribiag; Neelam Khaper; Peter Liu; Fayez Dawood; Peter H. Backx; Martin R. Ralph; Michael J. Sole
Day/night rhythms are recognized as important to normal cardiovascular physiology and timing of adverse cardiovascular events; however, their significance in disease has not been determined. We demonstrate that day/night rhythms play a critical role in compensatory remodeling of cardiovascular tissue, and disruption exacerbates disease pathophysiology. We use a murine model of pressure overload cardiac hypertrophy (transverse aortic constriction) in a rhythm-disruptive 20-hour versus 24-hour environment. Echocardiography reveals increased left ventricular end-systolic and -diastolic dimensions and reduced contractility in rhythm-disturbed transverse aortic constriction animals. Furthermore, cardiomyocytes and vascular smooth muscle cells exhibit reduced hypertrophy, despite increased pressure load. Microarray and real-time PCR demonstrate altered gene cycling in transverse aortic constriction myocardium and hypothalamic suprachiasmatic nucleus. With rhythm disturbance, there is a consequent altered cellular clock mechanism (per2 and bmal), whereas key genes in hypertrophic pathways (ANF, BNP, ACE, and collagen) are downregulated paradoxical to the increased pressure. Phenotypic rescue, including reversal/attenuation of abnormal pathology and genes, only occurs when the external rhythm is allowed to correspond with the animals’ innate 24-hour internal rhythm. Our study establishes the importance of diurnal rhythm as a vital determinant in heart disease. Disrupted rhythms contribute to progression of organ dysfunction; restoration of normal diurnal schedules appears to be important for effective treatment of disease.
The FASEB Journal | 2009
Denise D. Belsham; Laura J. Fick; Prasad S. Dalvi; Maria-Luisa Centeno; Jennifer A. Chalmers; Paul Lee; Yangyang Wang; Daniel J. Drucker; Margaret M. Koletar
The distinct lack of cell lines derived from the adult brain is evident. Ciliary neurotrophic factor (CNTF) triggers neurogenesis in primary culture from adult mouse hypothalamus, as detected by bromodeoxyuridine and Ki67 immunostaining. Using SV‐40 T‐antigen, we immortalized dividing neurons and generated clonal cell lines expressing neuropeptides and receptors involved in neuroendocrine function. We hypothesized that proglucagon‐derived peptides may be the mechanistic downstream effectors of CNTF due to documented neuroprotective and proliferative effects. Indeed, proglucagon gene expression was induced by CNTF, and exposure of primary cells to glucagon‐like peptide‐1 receptor (GLP‐1) agonist, exendin‐4, induced cell proliferation. Intracere‐ broventricular injection of CNTF into adult mice caused increased expression of proglucagon peptide in the hypothalamus. Using a specific GLP‐1‐receptor antagonist, we found that neurogenesis was significantly attenuated and primary culture from GLP‐1‐receptor‐knockout mice lacked CNTF‐mediated neuronal proliferation, thus linking the induction of neurogenesis in the hypothalamus to GLP‐1‐receptor signaling.—Belsham, D. D., Fick, L. J., Dalvi, P. S., Centeno, M.‐L., Chalmers, J. A., Lee, P. K. P., Wang, Y., Drucker, D. J., Koletar, M. M. Ciliary neurotro‐ phic factor recruitment of glucagon‐like peptide‐1 mediates neurogenesis allowing immortalization of adult murine hypothalamic neurons. FASEB J. 23, 4256–4265 (2009). www.fasebj.org
Neurobiology of Learning and Memory | 2004
Sean W. Cain; Caroline H. Ko; Jennifer A. Chalmers; Martin R. Ralph
In golden hamsters, the expression of a conditioned place preference (CPP) or avoidance (CPA) is regulated in a circadian pattern such that the preference and avoidance are exhibited strongly at the circadian time of prior training, but not at other circadian times. In the rat, reports are conflicting regarding whether time of day learning is evident. We investigated whether this conflict arises because different strains of rat have been used. In this experiment, Long Evans and Wistar rats were trained at a specific circadian time to discriminate between a context paired with food reward and an unpaired context. Animals were then tested for preference at the same or a different circadian time. Long Evans rats showed preference for the paired context at both times tested, whereas Wistar rats showed preference only when training and testing times matched. The results show that time of day learning can be generalized to rats using the Wistar strain.
American Journal of Physiology-regulatory Integrative and Comparative Physiology | 2008
Jennifer A. Chalmers; Tami A. Martino; Nazneen Tata; Martin R. Ralph; Michael J. Sole; Denise D. Belsham
The circadian system in mammals is a hierarchy of oscillators throughout the organism that are coordinated by the circadian clock in the hypothalamic suprachiasmatic nucleus. Peripheral clocks act to integrate time-of-day information from neural or hormonal signals, regulating gene expression, and, subsequently, organ physiology. However, the mechanisms by which the central clock communicates with peripheral oscillators are not understood and are likely tissue specific. In this study, we establish a mouse vascular cell model suitable for investigations of these mechanisms at a molecular level. Using the immortalized vascular smooth muscle cell line Movas-1, we determined that these cells express the circadian clock machinery with robust rhythms in mRNA expression over a 36-h period after serum shock synchronization. Furthermore, norepinephrine and forskolin were able to synchronize circadian rhythms in bmal1. With synchronization, we observed cycling of specific genes, including the tissue inhibitor of metalloproteinase 1 and 3 (timp1, timp3), collagen 3a1 (col3a1), transgelin 1 (sm22alpha), and calponin 1 (cnn1). Diurnal expression of these genes was also found in vivo in mouse aortic tissue, using microarray and real-time RT-PCR analysis. Both of these revealed ultradian rhythms in genes similar to the cycling observed in Movas-1 in vitro. These findings highlight the cyclical nature of structurally important genes in the vasculature that is similar both in vivo and in vitro. This study establishes the Movas-1 cells as a novel cell model from which to further investigate the molecular mechanisms of clock regulation in the vasculature.
Molecular and Cellular Endocrinology | 2014
Jennifer A. Chalmers; Janet Jinyoung Jang; Denise D. Belsham
Glucose-sensing neurons play a role in energy homeostasis, yet how orexigenic neurons sense glucose remains unclear. As models of glucose-inhibited (GI) neurons, mHypoE-29/1 and mHypoA-NPY/GFP cells express the essential orexigenic neuropeptide AgRP and glucose sensing machinery. Exposure to increasing concentrations of glucose or the glucose analog 2-deoxyglucose (2-DG) results in a decrease in AgRP mRNA levels. Taste receptor, Tas1R2 mRNA expression was reduced by glucose, whereas 2-DG reduced Tas1R3 mRNA levels. Increasing glucose concentrations elicited a rise in Akt and neuronal nitric oxide synthase (nNOS) phosphorylation, CaMKKβ levels, and a reduction of AMP-kinase alpha phosphorylation. Inhibitors of NOS and the cystic fibrosis transmembrane conductance regulator (CFTR) prevented a decrease in AgRP secretion with glucose, suggesting a pivotal role for nNOS and the CFTR in glucose-sensing. These models possess the hallmark characteristics of GI neurons, and can be used to disentangle the mechanisms by which orexigenic neurons sense glucose.
Journal of Molecular Endocrinology | 2008
Jennifer A. Chalmers; Shuo-Yen J. Lin; Tami A. Martino; Sara Arab; Peter Liu; Mansoor Husain; Michael J. Sole; Denise D. Belsham
Neuroendocrine peptides express biologic activity relevant to the cardiovascular system, including regulating heart rate and blood pressure, though little is known about the mechanisms involved. Here, we investigated neuroendocrine gene expression underlying diurnal physiology of the heart. We first used microarray and RT-PCR analysis and demonstrate the simultaneous expression of neuroendocrine genes in normal murine heart, including POMC, GnRH, neuropeptide Y, leptin receptor, GH-releasing hormone, cocaine- and amphetamine-regulated transcript, proglucagon, and galanin. We examined diurnal gene expression profiles, with cosinar bioinformatics to evaluate statistically significant rhythms. The POMC gene exhibits a day/night, circadian or diurnal, pattern of expression in heart, and we postulated that this may be important to cardiac growth and renewal. POMC diurnal gene rhythmicity is altered in pressure-overload cardiac hypertrophy, when compared with control heart, and levels increased at the dark-to-light transition times. These findings are also consistent with the proposal that neuropeptides mediate adverse remodeling processes, such as occur in pathologic hypertrophy. To investigate cellular responses, we screened three cell lines representing fibroblasts, cardiac myocytes, and vascular smooth muscle cells (NIH3T3, heart line 1, and mouse vascular smooth muscle cell line 1 (Movas-1) respectively). POMC mRNA expression is the most notable in Movas-1 cells and, furthermore, exhibits rhythmicity with culture synchronization. Taken together, these results highlight the diverse neuroendocrine mRNA expression profiles in cardiovasculature, and provide a novel model vascular culture system to research the role these neuropeptides play in organ health, integrity, and disease.
Behavioural Brain Research | 2012
Sean W. Cain; Jennifer A. Chalmers; Martin R. Ralph
The expression of passive avoidance (PA) learning in rats displays a daily or circadian rhythm in that optimal performance is displayed when the time of testing matches the time of training. Lesions of the suprachiasmatic nucleus (SCN) were later shown to abolish this rhythm. Using golden hamsters, we have since demonstrated similar rhythms of performance in a conditioned place avoidance (CPA) task but unlike the PA results in rats, the rhythmic expression of CPA was maintained in arrhythmic hamsters with lesions of the SCN. We determined whether PA performance in hamsters is dependent on the SCN (as in the rat) or independent (as in the hamster CPA). Performance on the PA task was rhythmic in intact control animals with optimal performance occurring when training and testing time matched and significantly diminished at both 6h before and 6h after training time. SCN-lesions, verified by the loss of behavioral circadian rhythms, had no effect on the rhythmic expression. Therefore, time of day modulation of PA performance in the hamster does not depend on the SCN circadian clock.
PLOS ONE | 2011
Ginah L. Kim; Xiaomei Wang; Jennifer A. Chalmers; David R. Thompson; Sandeep S. Dhillon; Margaret M. Koletar; Denise D. Belsham
The pituitary is a complex endocrine tissue composed of a number of unique cell types distinguished by the expression and secretion of specific hormones, which in turn control critical components of overall physiology. The basic function of these cells is understood; however, the molecular events involved in their hormonal regulation are not yet fully defined. While previously established cell lines have provided much insight into these regulatory mechanisms, the availability of representative cell lines from each cell lineage is limited, and currently none are derived from adult pituitary. We have therefore used retroviral transfer of SV40 T-antigen to mass immortalize primary pituitary cell culture from an adult mouse. We have generated 19 mixed cell cultures that contain cells from pituitary cell lineages, as determined by RT-PCR analysis and immunocytochemistry for specific hormones. Some lines expressed markers associated with multipotent adult progenitor cells or transit-amplifying cells, including SOX2, nestin, S100, and SOX9. The progenitor lines were exposed to an adenylate cyclase activator, forskolin, over 7 days and were induced to differentiate to a more mature gonadotrope cell, expressing significant levels of α-subunit, LHβ, and FSHβ mRNAs. Additionally, clonal populations of differentiated gonadotropes were exposed to 30 nM gonadotropin-releasing hormone and responded appropriately with a significant increase in α-subunit and LHβ transcription. Further, exposure of the lines to a pulse paradigm of GnRH, in combination with 17β-estradiol and dexamethasone, significantly increased GnRH receptor mRNA levels. This array of adult-derived pituitary cell models will be valuable for both studies of progenitor cell characteristics and modulation, and the molecular analysis of individual pituitary cell lineages.
Molecular Endocrinology | 2016
Leigh Wellhauser; Jennifer A. Chalmers; Denise D. Belsham
The arcuate nucleus of the hypothalamus represents a key center for the control of appetite and feeding through the regulation of 2 key neuronal populations, notably agouti-related peptide/neuropeptide Y and proopimelanocortin (POMC)/cocaine- and amphetamine-regulated transcript neurons. Altered regulation of these neuronal networks, in particular the dysfunction of POMC neurons upon high-fat consumption, is a major pathogenic mechanism involved in the development of obesity and type 2 diabetes mellitus. Efforts are underway to preserve the integrity or enhance the functionality of POMC neurons in order to prevent or treat these metabolic diseases. Here, we report for the first time that the nitric oxide (NO(-)) donor, sodium nitroprusside (SNP) mediates anorexigenic actions in both hypothalamic tissue and hypothalamic-derived cell models by mediating the up-regulation of POMC levels. SNP increased POMC mRNA in a dose-dependent manner and enhanced α-melanocortin-secreting hormone production and secretion in mHypoA-POMC/GFP-2 cells. SNP also enhanced insulin-driven POMC expression likely by inhibiting the deacetylase activity of sirtuin 1. Furthermore, SNP enhanced insulin-dependent POMC expression, likely by reducing the transcriptional repression of Foxo1 on the POMC gene. Prolonged SNP exposure prevented the development of insulin resistance. Taken together, the NO(-) donor SNP enhances the anorexigenic potential of POMC neurons by promoting its transcriptional expression independent and in cooperation with insulin. Thus, increasing cellular NO(-) levels represents a hormone-independent method of promoting anorexigenic output from the existing POMC neuronal populations and may be advantageous in the fight against these prevalent disorders.