Unlabelled: Astrocytes can both sense and shape the evolution of neuronal network activity and are known to possess unique ion regulatory mechanisms. Here we explore the relationship between astrocytic intracellular pH dynamics and the synchronous network activity that occurs during seizure-like activity. By combining confocal and two-photon imaging of genetically encoded pH reporters with simultaneous electrophysiological recordings, we perform pH measurements in defined cell populations and relate these to ongoing network activity.
View Article and Find Full Text PDFBackground: Developmental stress has been hypothesised to interact with genetic predisposition to increase the risk of developing substance use disorders. Here we have investigated the effects of maternal separation-induced developmental stress using a behavioural proxy of methamphetamine preference in an animal model of attention-deficit/hyperactivity disorder, the spontaneously hypertensive rat, versus Wistar Kyoto and Sprague-Dawley comparator strains.
Results: Analysis of results obtained using a conditioned place preference paradigm revealed a significant strain × stress interaction with maternal separation inducing preference for the methamphetamine-associated compartment in spontaneously hypertensive rats.
Attention-deficit/hyperactivity disorder (ADHD) and developmental stress are considered risk factors for the development of drug abuse. Though the physiological mechanisms underlying this risk are not yet clear, ADHD, developmental stress and drug abuse are known to share underlying disturbances in dopaminergic neurotransmission. Thus, we hypothesized that clearance of cocaine-induced elevations in striatal dopamine would be prolonged in a rat model of ADHD and that this would be further increased by exposure to developmental stress.
View Article and Find Full Text PDFBackground: Tuberculosis (TB) affects one third of the global population, and TB of the central nervous system (CNS-TB) is the most severe form of tuberculosis which often associates with high mortality. The pro-inflammatory cytokine tumour necrosis factor (TNF) plays a critical role in the initial and long-term host immune protection against Mycobacterium tuberculosis (M. tuberculosis) which involves the activation of innate immune cells and structure maintenance of granulomas.
View Article and Find Full Text PDFMycobacterium tuberculosis infection of the central nervous system is thought to be initiated once the bacilli have breached the blood brain barrier and are phagocytosed, primarily by microglial cells. In this study, the interactions of M. tuberculosis with neurons in vitro and in vivo were investigated.
View Article and Find Full Text PDFPoxviral proteins are known to interact with the immune system of the host. Some of them interact with the transcription factors of the host, whereas others interact with the components of the immune system. Vaccinia virus secretes a 28.
View Article and Find Full Text PDFPoxviruses are one of the most complex of animal viruses and encode for over 150 proteins. The interactions of many of the poxviral-encoded proteins with host proteins, as well as with other proteins, such as transcription complexes, have been well characterized at the qualitative level. Some have also been characterized quantitatively by two hybrid systems and surface plasmon resonance approaches.
View Article and Find Full Text PDFEarly life stress, such as maternal separation, causes adaptive changes in neural mechanisms that have adverse effects on the neuroplasticity of the brain in adulthood. As a consequence, children who are exposed to stress during development may be predisposed to neurodegenerative disorders in adulthood. A possible mechanism for increased vulnerability to neurodegeneration may be dysfunctional mitochondria.
View Article and Find Full Text PDFBackground: Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder characterised by symptoms of inattention, impulsivity and hyperactivity. The spontaneously hypertensive rat (SHR) is a well-characterised model of this disorder and has been shown to exhibit dopamine dysregulation, one of the hypothesised causes of ADHD. Since stress experienced in the early stages of life can have long-lasting effects on behaviour, it was considered that early life stress may alter development of the dopaminergic system and thereby contribute to the behavioural characteristics of SHR.
View Article and Find Full Text PDFInterleukin-(IL)-4 and IL-13 signal through heterodimeric receptors containing a common IL-4 receptor-alpha (IL-4Ralpha) subunit, which is important for protection against helminth infections, including schistosomiasis. Previous studies demonstrated important roles for IL-4Ralpha-responsive hematopoietic cells, including T cells and macrophages in schistosomiasis. In this study, we examined the role of IL-4Ralpha responsiveness by nonhematopoietic smooth muscle cells during experimental acute murine schistosomiasis.
View Article and Find Full Text PDFC3 and C3b, the components central to the complement activation, also play a damaging role in several inflammatory disorders. Vaccinia virus complement control protein (VCP) and curcumin (Cur) are natural compounds with different biological origins reported to regulate complement activation. However, both VCP and Cur have not been investigated for their interaction with the third component (C3) prior to it being converted to its activated form (C3b).
View Article and Find Full Text PDFPrenatal stress has been associated with increased vulnerability to psychiatric disturbances including schizophrenia, depression, attention-deficit hyperactivity disorder and autism. Elevated maternal circulating stress hormones alter development of neural circuits in the fetal brain and cause long-term changes in behaviour. The aim of the present study was to investigate whether mild prenatal stress increases the vulnerability of dopamine neurons in adulthood.
View Article and Find Full Text PDFAdverse life events occurring in early development can result in long-term effects on behavioural, physiological and cognitive processes. In particular, perinatal stressors impair neurogenesis in the hippocampus which consequently impairs memory formation. Exercise has previously been shown to have antidepressant effects and to increase cognitive functioning by increasing neurogenesis and neurotrophins in the hippocampus.
View Article and Find Full Text PDFStress affects the brain differently depending on the timing, duration and intensity of the stressor. Separation from the dam for 3 h per day is a potent stressor for rat pups which causes activation of the hypothalamic-pituitary-adrenal (HPA) axis, evidenced by increased plasma levels of adrenocorticotropin (ACTH) and glucocorticoids. Behaviourally, animals display anxiety-like behaviour while structurally, changes occur in neuronal dendrites and spines in the hippocampus and prefrontal regions involved in emotion and behaviour control.
View Article and Find Full Text PDFOne of the key pro-inflammatory mediators activated by amyloid protein in neurodegenerative disorders of the brain, such as Alzheimer's disease is the complement system. Vaccinia virus complement control protein secreted by vaccinia virus, commonly known as VCP, was found to inhibit amyloid protein mediated up-regulation of complement system in vitro. In the current research investigation, VCP was administered twice (First dose at 3 weeks and the second dose at 6-7 months) intracranially into the parietal cortical area of Mo/Hu APPswe transgenic mice.
View Article and Find Full Text PDFIn the normal ageing cortex of the brain there is a group of dying neurons with shrinking dendritic trees and a group of surviving neurons with expanding dendritic trees. The ageing process affects neurotransmitter systems, including glutamate neurons and NMDA receptors. Calcium is an important signaling molecule.
View Article and Find Full Text PDFParkinson's disease (PD) is a progressive neurodegenerative disease of nigrostriatal dopamine (DA) neurons that project from the substantia nigra pars compacta (SNc) to the striatum. To further understand PD, researchers have developed standardized animal models of PD. In this study, Long Evans (LE) rats were unilaterally lesioned by injection of the neurotoxin, 6-hydroxydopamine (6-OHDA), into the medial forebrain bundle (MFB) of the left hemisphere.
View Article and Find Full Text PDFThis study examined the relationship between voluntary running distance and glutamate- and K+-stimulated dopamine release in the striatum (nucleus accumbens and caudate-putamen) of male Long-Evans rats. Twenty-one rats were housed individually in cages with attached running-wheels for 1 week. There was a 19-fold variability between rats in voluntary running distances over this period (range = 2.
View Article and Find Full Text PDFThe spontaneously hypertensive rat (SHR) is an accepted model for attention-deficit hyperactivity disorder (ADHD) since it displays the major symptoms of ADHD (hyperactivity, impulsivity, and poor performance in tasks that require sustained attention). We have previously shown that glutamate activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors released significantly more norepinephrine from SHR prefrontal cortex slices than control Wistar-Kyoto (WKY) rats. The aim of this study was to determine whether N-methyl-D-aspartate (NMDA) receptor function is disturbed in the prefrontal cortex of SHR.
View Article and Find Full Text PDFExposure to an enriched environment provides animals with informal learning opportunities and is associated with increases in brain size, cortical thickness, neuron size, dendritic branching, spine density, and number of synapses per neuron. The NMDA receptor is involved in synaptic plasticity. This study sought to determine the effect of exposure to an enriched environment on NMDA receptor function in barrel cortex slices of spontaneously hypertensive rats (SHR) and their control Wistar-Kyoto (WKY) rats.
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