Brain Body Institute

Hamilton, Canada

Brain Body Institute

Hamilton, Canada
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Sidor M.M.,McMaster University | Sidor M.M.,Brain Body Institute | Amath A.,McMaster University | Amath A.,Brain Body Institute | And 4 more authors.
Neuroscience | Year: 2010

An immunogenic challenge during early postnatal development leads to long-term changes in behavioural and physiological measures reflecting enhanced emotionality and anxiety. Altered CNS serotonin (5-HT) signalling during the third postnatal week is thought to modify the developing neurocircuitry governing anxiety-like behaviour. Changes in 5-HT signalling during this time window may underlie increased emotionality reported in early immune challenge rodents. Here we examine both the spatial and temporal profile of 5-HT related gene expression, including 5HT1A, 2A, 2C receptors, the 5-HT transporter (5HTT), and tryptophan hydroxylase 2 (TPH2) during early development (postnatal day [P]14, P17, P21, P28) in mice challenged with lipopolysaccharide (LPS) during the first postnatal week. Expression levels were measured using in situ hybridization in regions associated with mediating emotive behaviours: the dorsal raphe (DR), hippocampus, amygdala, and prefrontal cortex (PFC). Increased TPH2 and 5HTT expression in the ventrolateral region of the DR of LPS-mice accompanied decreased expression of ventral DR 5HT1A and dorsal DR 5HTT. In the forebrain, 5HT1A and 2A receptors were increased, whereas 5HT2C receptors were decreased in the hippocampus. Decreased mRNA expression of 5HT2C was detected in the amygdala and PFC of LPS-treated pups; 5HT1A was increased in the PFC. The majority of these changes were restricted to P14-21. These transient changes in 5-HT expression coincide with the critical time window in which 5-HT disturbance leads to permanent modification of anxiety-related behaviours. This suggests that alterations in CNS 5-HT during development may underlie the enhanced emotionality associated with an early immune challenge. © 2010 IBRO.

Lai J.K.Y.,McMaster University | Lai J.K.Y.,Brain Body Institute | Doering L.C.,McMaster University | Foster J.A.,McMaster University | Foster J.A.,Brain Body Institute
Journal of Comparative Neurology | Year: 2016

Neuroligins and neurexins are transsynaptic proteins involved in the maturation of glutamatergic and GABAergic synapses. Research has identified synaptic proteins and function as primary contributors to the development of fragile X syndrome. Fragile X mental retardation protein (FMRP), the protein that is lacking in fragile X syndrome, binds neuroligin-1 and -3 mRNA. Using in situ hybridization, we examined temporal and spatial expression patterns of neuroligin (NLGN) and neurexin (NRXN) mRNAs in the somatosensory (S1) cortex and hippocampus in wild-type (WT) and fragile X knockout (FMR1-KO) mice during the first 5 weeks of postnatal life. Genotype-based differences in expression included increased NLGN1 mRNA in CA1 and S1 cortex, decreased NLGN2 mRNA in CA1 and dentate gyrus (DG) regions of the hippocampus, and increased NRXN3 mRNA in CA1, DG, and S1 cortex between female WT and FMR1-KO mice. In male mice, decreased expression of NRXN3 mRNA was observed in CA1 and DG regions of FMR1-KO mice. Sex differences in hippocampal expression of NLGN2, NRXN1, NRXN2, and NRXN3 mRNAs and in S1 cortex expression of NRXN3 mRNAs were observed WT mice, whereas sex differences in NLGN3, NRXN1, NRXN2, and NRXN3 mRNA expression in the hippocampus and in NLGN1, NRXN2 and NRXN3 mRNA expression in S1 cortex were detected in FMR1-KO mice. These results provide a neuroanatomical map of NLGN and NRXN expression patterns over postnatal development in WT and FMR1-KO mice. The differences in developmental trajectory of these synaptic proteins could contribute to long-term differences in CNS wiring and synaptic function. J. Comp. Neurol. 524:807-828, 2016. © 2015 Wiley Periodicals, Inc.

Hall G.B.C.,McMaster University | Hall G.B.C.,Brain Body Institute | Kamath M.V.,McMaster University | Collins S.,McMaster University | And 10 more authors.
Neurogastroenterology and Motility | Year: 2010

Background Typically, conventional functional imaging methods involve repeated exposures to sensory stimulation. In rectal distension (RD) studies that involve multiple distensions, however, it is difficult to disambiguate the central response to RD from pathological alterations in peripheral neural responses associated with relaxation and accommodation of the rectum. Methods This study addressed potential confounders found in previous imaging studies by collecting functional magnetic resonance imaging studies (fMRI) data during a single slow ramp-tonic distension paradigm and analysing fMRI signal changes using independent component analysis. Key Results Compared with controls, IBS participants showed increased activation of the anterior cingulate cortices, insula and ventral medial prefrontal regions suggesting heightened affective responses to painful visceral stimuli. In addition, the failure by IBS patients to down-regulate activity within ventral medial prefrontal and the posterior cingulate/precuneus regions was suggestive of reduced sensitivity to somatic changes and delayed shifts away from rest in 'default network' activity patterns. Controls showed heightened activation of the thalamus, striatal regions and dorsolateral prefrontal cortex suggesting greater arousal and salience-driven sustained attention reactions and greater modulation of affective responses to discomfort and pain. Conclusion&Inferences This work points to alterations in the central response to visceral pain and discomfort in IBS, highlighting diminished modulation and heightened internalization of affective reactions. © 2009 Blackwell Publishing Ltd.

Warsi M.A.,McMaster University | Warsi M.A.,Brain Body Institute | Molloy W.,St Peters Center For Studies In Aging | Molloy W.,University College Cork | And 3 more authors.
Magnetic Resonance Materials in Physics, Biology and Medicine | Year: 2012

Objectives To correlate temporal fractal structure of resting state blood oxygen level dependent (rsBOLD) functional magnetic resonance imaging (fMRI) with in vivo proton magnetic resonance spectroscopy (1H-MRS), in Alzheimer's disease (AD) and healthy age-matched normal controls (NC). Materials and methods High temporal resolution (4 Hz) rsBOLD signal and single voxel (left putamen) magnetic resonance spectroscopy data was acquired in 33 AD patients and 13 NC. The rsBOLD data was analyzed using two types of fractal dimension (FD) analysis based on relative dispersion and frequency power spectrum. Comparisons in FD were performed between AD and NC, and FD measures were correlated with 1H-MRS findings. Results Temporal fractal analysis of rsBOLD, was able to differentiate AD from NC subjects (P = 0.03). Low FD correlated with markers of AD severity including decreased concentrations of N-acetyl aspartate (R = 0.44, P = 0.015) and increased myoinositol (mI) (R = -0.45, P = 0.012). Conclusion Based on these results we suggest fractal analysis of rsBOLD could provide an early marker of AD. © ESMRMB 2012.

Lokuge S.,Womens Health Concerns Clinic | Frey B.N.,Womens Health Concerns Clinic | Frey B.N.,McMaster University | Foster J.A.,Brain Body Institute | And 7 more authors.
Behavioural Pharmacology | Year: 2010

Estrogen is regulated through two intracellular receptors, estrogen receptor α and estrogen receptor β, through a classic nuclear-initiated response. Recently, estrogen has also been shown to act more rapidly and it is proposed that these fast effects may be the consequence of membrane localized estrogen receptors that act through the second messengers. Although the identification of these receptors remains to be elucidated, the possible role that they play in female-specific mood disorders is of particular interest, especially in times of major hormonal fluctuation. The purpose of this mini-review is to outline the recent literature regarding the rapid effects of estrogen, to explore the intracellular signaling pathways that may be involved in this regulation as well as the connection between estrogen and serotonin neurotransmission and finally, to look into the antidepressant role that estrogen may have, with particular emphasis on female-specific mood disorders. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Rilett K.C.,McMaster University | Friedel M.,Mouse Imaging Ctr. | Ellegood J.,Mouse Imaging Ctr. | MacKenzie R.N.,McMaster University | And 4 more authors.
Brain, Behavior, and Immunity | Year: 2015

Clinical and animal studies demonstrate that immune-brain communication influences behavior and brain function. Mice lacking T cell receptor β and δ chains were tested in the elevated plus maze, open field, and light-dark test and showed reduced anxiety-like behavior compared to wild type. Interestingly sex differences were observed in the behavioural phenotype of TCRβ-/-δ- mice. Specifically, female TCRβ-/-δ- mice spent more time in the light chamber compared to wild type females, whereas male TCRβ-/-δ- spent more time in the center of the open field compared to wild type males. In addition, TCRβ-/-δ- mice did not show sex differences in activity-related behaviors observed in WT mice. Ex vivo brain imaging (7 Tesla MRI) revealed volume changes in hippocampus, hypothalamus, amygdala, periaqueductal gray, and dorsal raphe and other brain regions between wild type and T cell receptor knockout mice. There was also a loss of sexual dimorphism in brain volume in the bed nucleus of the stria terminalis, normally the most sexually dimorphic region in the brain, in immune compromised mice. These data demonstrate the presence of T cells is important in the development of sex differences in CNS circuitry and behavior. © 2015 Elsevier Inc.

Zhou L.,McMaster University | Foster J.A.,McMaster University | Foster J.A.,Brain Body Institute
Neuropsychiatric Disease and Treatment | Year: 2015

The human intestine houses an astounding number and species of microorganisms, estimated at more than 1014 gut microbiota and composed of over a thousand species. An individual’s profile of microbiota is continually influenced by a variety of factors including but not limited to genetics, age, sex, diet, and lifestyle. Although each person’s microbial profile is distinct, the relative abundance and distribution of bacterial species is similar among healthy individuals, aiding in the maintenance of one’s overall health. Consequently, the ability of gut microbiota to bidirectionally communicate with the brain, known as the gut–brain axis, in the modulation of human health is at the forefront of current research. At a basic level, the gut microbiota interacts with the human host in a mutualistic relationship – the host intestine provides the bacteria with an environment to grow and the bacterium aids in governing homeostasis within the host. Therefore, it is reasonable to think that the lack of healthy gut microbiota may also lead to a deterioration of these relationships and ultimately disease. Indeed, a dysfunction in the gut–brain axis has been elucidated by a multitude of studies linked to neuropsychological, metabolic, and gastrointestinal disorders. For instance, altered microbiota has been linked to neuropsychological disorders including depression and autism spectrum disorder, metabolic disorders such as obesity, and gastrointestinal disorders including inflammatory bowel disease and irritable bowel syndrome. Fortunately, studies have also indicated that gut microbiota may be modulated with the use of probiotics, antibiotics, and fecal microbiota transplants as a prospect for therapy in microbiota-associated diseases. This modulation of gut microbiota is currently a growing area of research as it just might hold the key to treatment. © 2015 Zhou and Foster.

Neufeld K.M.,Brain Body Institute | Neufeld K.M.,McMaster University | Kang N.,Brain Body Institute | Kang N.,McMaster University | And 4 more authors.
Neurogastroenterology and Motility | Year: 2011

Background There is increasing interest in the gut-brain axis and the role intestinal microbiota may play in communication between these two systems. Acquisition of intestinal microbiota in the immediate postnatal period has a defining impact on the development and function of the gastrointestinal, immune, neuroendocrine and metabolic systems. For example, the presence of gut microbiota regulates the set point for hypothalamic-pituitary-adrenal (HPA) axis activity. Methods We investigated basal behavior of adult germ-free (GF), Swiss Webster female mice in the elevated plus maze (EPM) and compared this to conventionally reared specific pathogen free (SPF) mice. Additionally, we measured brain mRNA expression of genes implicated in anxiety and stress-reactivity. Key Results Germ-free mice, compared to SPF mice, exhibited basal behavior in the EPM that can be interpreted as anxiolytic. Altered GF behavior was accompanied by a decrease in the N-methyl-D-aspartate receptor subunit NR2B mRNA expression in the central amygdala, increased brain-derived neurotrophic factor expression and decreased serotonin receptor 1A (5HT1A) expression in the dentate granule layer of the hippocampus. Conclusions & Inferences We conclude that the presence or absence of conventional intestinal microbiota influences the development of behavior, and is accompanied by neurochemical changes in the brain. © 2010 Blackwell Publishing Ltd.

Luna R.A.,Baylor College of Medicine | Luna R.A.,Texas Childrens Hospital | Foster J.A.,McMaster University | Foster J.A.,Brain Body Institute
Current Opinion in Biotechnology | Year: 2015

The human gut microbiome is composed of an enormous number of microorganisms, generally regarded as commensal bacteria. Without this inherent microbial community, we would be unable to digest plant polysaccharides and would have trouble extracting lipids from our diet. Resident gut bacteria are an important contributor to healthy metabolism and there is significant evidence linking gut microbiota and metabolic disorders such as obesity and diabetes. In the past few years, neuroscience research has demonstrated the importance of microbiota in the development of brain systems that are vital to both stress reactivity and stress-related behaviours. Here we review recent literature that examines the impact of diet-induced changes in the microbiota on stress-related behaviours including anxiety and depression. © 2014 Elsevier Ltd.

Noseworthy M.D.,McMaster University | Noseworthy M.D.,Brain Body Institute | Noseworthy M.D.,Diagnostic Healthcare | Davis A.D.,Brain Body Institute | And 5 more authors.
Seminars in Musculoskeletal Radiology | Year: 2010

Diagnostic imaging procedures for muscle evaluation have typically provided basic information concerning gross anatomical change resulting from pathology. Up until recently the musculoskeletal radiologist has been fairly limited to using simple proton-density weighted fat-saturated and short tau inversion recovery magnetic resonance imaging scans for assessment of skeletal muscle. Recent advances, however, have resulted in development of newer scans and postprocessing methods that provide much more than gross muscle structure. Scans providing fine structure, muscle function, and metabolism can easily be done using clinical scanners. Here we describe how diffusion tensor imaging (DTI) and blood oxygenation level-dependent (BOLD) imaging together can provide detailed information on muscle structural and functional changes. DTI is useful for visualizing muscle tears, and BOLD can be used for vascular insufficiency (e.g., compartment syndrome). In clinical sites that are gaining experience using these techniques, imaging of muscle pathology is becoming increasingly thorough. In the future, these methods will reduce the need for invasive approaches to study muscle pathology. © 2010 Thieme Medical Publishers, Inc.

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