67 research outputs found

    Alterations in prefrontal-limbic functional activation and connectivity in chronic stress-induced visceral hyperalgesia.

    Get PDF
    Repeated water avoidance stress (WAS) induces sustained visceral hyperalgesia (VH) in rats measured as enhanced visceromotor response to colorectal distension (CRD). This model incorporates two characteristic features of human irritable bowel syndrome (IBS), VH and a prominent role of stress in the onset and exacerbation of IBS symptoms. Little is known regarding central mechanisms underlying the stress-induced VH. Here, we applied an autoradiographic perfusion method to map regional and network-level neural correlates of VH. Adult male rats were exposed to WAS or sham treatment for 1 hour/day for 10 days. The visceromotor response was measured before and after the treatment. Cerebral blood flow (CBF) mapping was performed by intravenous injection of radiotracer ([(14)C]-iodoantipyrine) while the rat was receiving a 60-mmHg CRD or no distension. Regional CBF-related tissue radioactivity was quantified in autoradiographic images of brain slices and analyzed in 3-dimensionally reconstructed brains with statistical parametric mapping. Compared to sham rats, stressed rats showed VH in association with greater CRD-evoked activation in the insular cortex, amygdala, and hypothalamus, but reduced activation in the prelimbic area (PrL) of prefrontal cortex. We constrained results of seed correlation analysis by known structural connectivity of the PrL to generate structurally linked functional connectivity (SLFC) of the PrL. Dramatic differences in the SLFC of PrL were noted between stressed and sham rats under distension. In particular, sham rats showed negative correlation between the PrL and amygdala, which was absent in stressed rats. The altered pattern of functional brain activation is in general agreement with that observed in IBS patients in human brain imaging studies, providing further support for the face and construct validity of the WAS model for IBS. The absence of prefrontal cortex-amygdala anticorrelation in stressed rats is consistent with the notion that impaired corticolimbic modulation acts as a central mechanism underlying stress-induced VH

    Detection of visual activation in the rat brain using 2-deoxy-2-[18F]fluoro-D-glucose and statistical parametric mapping (SPM)

    Get PDF
    Purpose: This study was designed to assess changes in brain glucose metabolism in rats after visual stimulation. Materials and methods: We sought to determine whether visual activation in the rat brain could be detected using a small-animal positron emission tomography (PET) scanner and 2-deoxy-2- [18F]fluoro-D-glucose (FDG). Eleven rats were divided into two groups: (a) five animals exposed to ambient light and (b) six animals stimulated by stroboscopic light (10 Hz) with one eye covered. Rats were injected with FDG and, after 45 min of visual stimulation, were sacrificed and scanned for 90 min in a dedicated PET tomograph. Images were reconstructed by a threedimensional ordered subset expectation maximization algorithm (1.8 mm full width at half maximum). A region-of-interest (ROI) analysis was performed on 14 brain structures drawn on coronal sections. Statistical parametric mapping (SPM) adapted for small animals was also carried out. Additionally, the brains of three rats were sliced into 20-μm sections for autoradiography. Results: Analysis of ROI data revealed significant differences between groups in the right superior colliculus, right thalamus, and brainstem (p≤0.05). SPM detected the same areas as the ROI approach. Autoradiographs confirmed the existence of hyperactivation in the left superior colliculus and auditory cortex. Conclusions: To our knowledge, this is the first report that uses FDG-PET and SPM analysis to show changes in rat brain glucose metabolism after a visual stimulusThis work was supported by grants from the Ministerio de Ciencia y Tecnología (TEC2004-07052), Ministerio de Sanidad y Consumo (CIBERsam CB07/09/0031 and Plan Nacional sobre Drogas 2007/043), Ministerio de Industria (CDTEAM Project), and Fundación de Investigación Médica Mutua Madrileña. We thank Alexandra de Francisco for her assistance with the PET studies, the Atomic, Molecular, and Nuclear Physics Department of the Universidad Complutense in Madrid for reconstructing the PET images, and the National Institute of Health for facilitating the piPET system.Publicad

    JULIDE: A Software Tool for 3D Reconstruction and Statistical Analysis of Autoradiographic Mouse Brain Sections

    Get PDF
    In this article we introduce JULIDE, a software toolkit developed to perform the 3D reconstruction, intensity normalization, volume standardization by 3D image registration and voxel-wise statistical analysis of autoradiographs of mouse brain sections. This software tool has been developed in the open-source ITK software framework and is freely available under a GPL license. The article presents the complete image processing chain from raw data acquisition to 3D statistical group analysis. Results of the group comparison in the context of a study on spatial learning are shown as an illustration of the data that can be obtained with this tool

    Statistical parametric maps of (18)F-FDG PET and 3-D autoradiography in the rat brain: a cross-validation study

    Get PDF
    PURPOSE: Although specific positron emission tomography (PET) scanners have been developed for small animals, spatial resolution remains one of the most critical technical limitations, particularly in the evaluation of the rodent brain. The purpose of the present study was to examine the reliability of voxel-based statistical analysis (Statistical Parametric Mapping, SPM) applied to (18)F-fluorodeoxyglucose (FDG) PET images of the rat brain, acquired on a small animal PET not specifically designed for rodents. The gold standard for the validation of the PET results was the autoradiography of the same animals acquired under the same physiological conditions, reconstructed as a 3-D volume and analysed using SPM. METHODS: Eleven rats were studied under two different conditions: conscious or under inhalatory anaesthesia during (18)F-FDG uptake. All animals were studied in vivo under both conditions in a dedicated small animal Philips MOSAIC PET scanner and magnetic resonance images were obtained for subsequent spatial processing. Then, rats were randomly assigned to a conscious or anaesthetized group for postmortem autoradiography, and slices from each animal were aligned and stacked to create a 3-D autoradiographic volume. Finally, differences in (18)F-FDG uptake between conscious and anaesthetized states were assessed from PET and autoradiography data by SPM analysis and results were compared. RESULTS: SPM results of PET and 3-D autoradiography are in good agreement and led to the detection of consistent cortical differences between the conscious and anaesthetized groups, particularly in the bilateral somatosensory cortices. However, SPM analysis of 3-D autoradiography also highlighted differences in the thalamus that were not detected with PET. CONCLUSION: This study demonstrates that any difference detected with SPM analysis of MOSAIC PET images of rat brain is detected also by the gold standard autoradiographic technique, confirming that this methodology provides reliable results, although partial volume effects might make it difficult to detect slight differences in small regions

    CANNABINOID RECEPTORS IN THE 3D RECONSTRUCTED MOUSE BRAIN: FUNCTION AND REGULATION

    Get PDF
    CB1 receptors (CB1R) mediate the psychoactive and therapeutic effects of cannabinoids including ∆9-tetrahydrocannabinol (THC), the main psychoactive constituent in marijuana. However, therapeutic use is limited by side effects and tolerance and dependence with chronic administration. Tolerance to cannabinoid-mediated effects is associated with CB1R adaptations, including desensitization (receptor-G-protein uncoupling) and downregulation (receptor degradation). The objectives of this thesis are to investigate the regional-specificity in CB1R function and regulation. Previous studies have investigated CB1Rs in a subset of regions involved in cannabinoid effects, but an inclusive regional comparison of the relative efficacies of different classes of cannabinoids to activate G-proteins has not been conducted. A novel unbiased whole-brain analysis was developed based on Statistical Parametric Mapping (SPM) for 3D-reconstructed mouse brain images derived from agonist-stimulated [35S]GTPgS autoradiography, which has not been described before. SPM demonstrated regional differences in the relative efficacies of cannabinoid agonists methanandamide (M-AEA), CP55,940 (CP), and WIN55,212-2 (WIN) in mouse brains. To assess potential contribution of novel sites, CB1R knockout (KO) mice were used. SPM analysis revealed that WIN, but not CP or M-AEA, stimulated [35S]GTPgS binding in regions that partially overlapped with the expression of CB1Rs. We then examined the role of the regulatory protein Beta-arrestin-2 (βarr2) in CB1R adaptations to chronic THC treatment. Deletion of βarr2 reduced CB1R desensitization/downregulation in the cerebellum, caudal periaqueductal gray (PAG), and spinal cord. However in hippocampus, amygdala and rostral PAG, similar desensitization was present in both genotypes. Interestingly, enhanced desensitization was found in the hypothalamus and cortex in βarr2 KO animals. Intra-regional differences in the magnitude of desensitization were noted in the caudal hippocampus, where βarr2 KO animals exhibited greater desensitization compared to WT. Regional differences in βarr2-mediated CB1R adaptation were associated with differential effects on tolerance, where THC-mediated antinociception, but not catalepsy or hypothermia, was attenuated in βarr2 KO mice. Overall, studies using SPM revealed intra- and inter-regional specificity in the function and regulation of CB1Rs and underscores an advantage of using a whole-brain unbiased approach. Understanding the regulation of CB1R signaling within different anatomical contexts represents an important fundamental prerequisite in the therapeutic exploitation of the cannabinoid system

    Analysis of Area-Specific Expression Patterns of RORbeta, ER81 and Nurr1 mRNAs in Rat Neocortex by Double In Situ Hybridization and Cortical Box Method

    Get PDF
    BACKGROUND: The mammalian neocortex is subdivided into many areas, each of which exhibits distinctive lamina architecture. To investigate such area differences in detail, we chose three genes for comparative analyses, namely, RORbeta, ER81 and Nurr1, mRNAs of which have been reported to be mainly expressed in layers 4, 5 and 6, respectively. To analyze their qualitative and quantitative coexpression profiles in the rat neocortex, we used double in situ hybridization (ISH) histochemistry and cortical box method which we previously developed to integrate the data of different staining and individuals in a standard three-dimensional space. PRINCIPAL FINDINGS: Our new approach resulted in three main observations. First, the three genes showed unique area distribution patterns that are mostly complementary to one another. The patterns revealed by cortical box method matched well with the cytoarchitectonic areas defined by Nissl staining. Second, at single cell level, RORbeta and ER81 mRNAs were coexpressed in a subpopulation of layer 5 neurons, whereas Nurr1 and ER81 mRNAs were not colocalized. Third, principal component analysis showed that the order of hierarchical processing in the cortex correlates well with the expression profiles of these three genes. Based on this analysis, the dysgranular zone (DZ) in the somatosensory area was considered to exhibit a profile of a higher order area, which is consistent with previous proposal. CONCLUSIONS/SIGNIFICANCE: The tight relationship between the expression of the three layer specific genes and functional areas were revealed, demonstrating the usefulness of cortical box method in the study on the cerebral cortex. In particular, it allowed us to perform statistical evaluation and pattern matching, which would become important in interpreting the ever-increasing data of gene expression in the cortex

    Brain anatomy: investigations of the effects of aging, fitness, and arterial stiffness

    Get PDF
    This work explores the mechanisms and lifestyle modifiers of brain anatomy throughout the aging process. First, a thorough review of the mechanisms of fitness on brain anatomy is presented. Next, a study examining the effects of aging and fitness on cortical and subcortical brain anatomy in a group of older adults (55-87 years old) is presented. We examine the degree to which cortical, subcortical, and global volumes are sensitive to both age and fitness. Lastly, the effect of cerebrovascular stiffness on the anatomical difference between and within individual subjects is explored across the lifespan (18-75 years old)

    Aerospace medicine and biology: A continuing bibliography with indexes (supplement 373)

    Get PDF
    This bibliography lists 206 reports, articles and other documents introduced into the NASA Scientific and Technical Information System during Feb. 1993. Subject coverage includes: aerospace medicine and physiology, pharmacology, toxicology, environmental effect, life support systems and man/system technology, protective clothing, exobiology and extraterrestrial life, planetary biology, and flight crew behavior and performance
    corecore