Home About us Contact
|
Home About us Contact | ||
|
|
||
Periaqueductal Gray Matter (periaqueductal + gray_matter)
Selected AbstractsTolerance to non-opioid analgesics in PAG involves unresponsiveness of medullary pain-modulating neurons in male ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2009Victor Tortorici Abstract Opiate analgesia can be hampered by a reduction in pharmacological effectiveness (tolerance), and this crucially depends on the periaqueductal gray matter (PAG). Non-opioids like metamizol (dipyrone) or aspirin also induce PAG-dependent analgesia and tolerance, but the neuronal bases of this tolerance are unknown. Metamizol is a pyrazolon derivative and cyclooxygenase inhibitor with widespread use as an analgesic in Europe and Latin America. Metamizol was microinjected into the PAG of awake male rats, and antinociception was assessed by the tail flick (TF) and hot plate (HP) tests. Microinjection twice daily for 2.5 days caused tolerance to metamizol. The rats were then anesthetized and recordings from pain-facilitating on-cells and pain-inhibiting off-cells of the rostral ventromedial medulla (RVM) were performed. PAG microinjection of morphine or metamizol depresses on-cells, activates off-cells and thus inhibits nociception, including TF and HP. In metamizol-tolerant rats, however, PAG microinjection of metamizol failed to affect on- or off-cells, and this is interpreted as the reason for tolerance. In metamizol-tolerant rats morphine microinjection into PAG also failed to affect RVM neurons or nociception (cross-tolerance). In naïve, non-tolerant rats the antinociceptive effect of PAG-microinjected metamizol or morphine was blocked when CTOP, a ,-opioid antagonist, was previously microinjected into the same PAG site. These results emphasize a close relationship between opioid and non-opioid analgesic mechanisms in the PAG and show that, like morphine, tolerance to metamizol involves a failure of on- and off-cells to, respectively, disfacilitate and inhibit nociception. Cross-tolerance between non-opioid and opioid analgesics should be important in the clinical setting. [source] Comparative study of brain morphology in Mecp2 mutant mouse models of Rett syndromeTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 1 2008Nadia P. Belichenko Abstract Rett syndrome (RTT) is caused by mutations in the X-linked gene MECP2. While patients with RTT show widespread changes in brain function, relatively few studies document changes in brain structure and none examine in detail whether mutations causing more severe clinical phenotypes are linked to more marked changes in brain structure. To study the influence of MeCP2-deficiency on the morphology of brain areas and axonal bundles, we carried out an extensive morphometric study of two Mecp2-mutant mouse models (Mecp2B and Mecp2J) of RTT. Compared to wildtype littermates, striking changes included reduced brain weight (,13% and ,9%) and the volumes of cortex (,11% and ,7%), hippocampus (both by ,8%), and cerebellum (,12% and 8%) in both mutant mice. At 3 weeks of age, most (24 of 47) morphological parameters were significantly altered in Mecp2B mice; fewer (18) were abnormal in Mecp2J mice. In Mecp2B mice, significantly lower values for cortical area were distributed along the rostrocaudal axis, and there was a reduced length of the olfactory bulb (,10%) and periaqueductal gray matter (,16%). In Mecp2J mice, while there was significant reduction in rostrocaudal length of cortex, this parameter was also abnormal in hippocampus (,10%), periaqueductal gray matter (,13%), fimbria (,18%), and anterior commissure (,10%). Our findings define patterns of Mecp2 mutation-induced changes in brain structure that are widespread and show that while some changes are present in both mutants, others are not. These observations provide the underpinning for studies to further define microarchitectural and physiological consequences of MECP2 deficiency. J. Comp. Neurol. 508:184,195, 2008. © 2008 Wiley-Liss, Inc. [source] Cellular and subcellular localization of the GABAB receptor 1a/b subunit in the rat periaqueductal gray matterTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 5 2007Paolo Barbaresi Abstract The inhibitory effects of ,-aminobutyric acid (GABA)ergic neurotransmission in the periaqueductal gray matter (PAG) are mediated, at least partly, by metabotropic GABAB receptor subtypes whose cellular and subcellular localization is still unknown. We performed immunohistochemical experiments with an antibody against GABAB receptor subtype 1a/b (GABABR1a/b) by using light and electron microscopy. On light microscopy, GABABR1a/b immunoreactivity (IR) was in all columns, defined by cytochrome oxidase histochemistry. Neuropil labeling was strongest in the lateral portion of dorsolateral PAG. Labeled neurons, albeit not numerous, were in ventrolateral, dorsal, and medial subdivisions and were sparser in dorsolateral PAG. Labeling was mostly on the soma of PAG neurons. Sometimes GABABR1a/b IR spread along proximal dendrites; in these cases bipolar neurons were the most common type. On electron microscopy, GABABR1a/b IR was mainly on dendrites (54.92% of labeled elements) and axon terminals (21.90%) making synapses with labeled and unlabeled postsynaptic elements. Presynaptic labeling was also on unmyelinated and myelinated axons (overall 8% of all labeled elements). Postsynaptically, GABABR1a/b IR was at extrasynaptic sites on dendritic shafts; spines were always unlabeled. On axon terminals, GABABR1a/b IR was on extrasynaptic membranes and sometimes on presynaptic membrane specializations. Of the labeled elements, 13.03% elements were distal astrocytic processes (dAsPs) surrounding both symmetric and asymmetric synapses whose pre- and postsynaptic elements were often labeled. Immunoreactive dAsPs were around the soma and dendrites of both labeled and unlabeled neurons. These findings provide insights into the intrinsic PAG organization and suggest that presynaptic, postsynaptic, and glial GABAB receptors may play crucial roles in controlling PAG neuronal activity. J. Comp. Neurol. 505:478,492, 2007. © 2007 Wiley-Liss, Inc. [source] Time course and nature of brain atrophy in the MRL mouse model of central nervous system lupusARTHRITIS & RHEUMATISM, Issue 6 2009John G. Sled Objective Similar to patients with systemic lupus erythematosus, autoimmune MRL/lpr mice spontaneously develop behavioral deficits and pathologic changes in the brain. Given that the disease-associated brain atrophy in this model is not well understood, the present study was undertaken to determine the time course of morphometric changes in major brain structures of autoimmune MRL/lpr mice. Methods Computerized planimetry and high-resolution magnetic resonance imaging (MRI) were used to compare the areas and volumes of brain structures in cohorts of mice that differ in severity of lupus-like disease. Results A thinner cerebral cortex and smaller cerebellum were observed in the MRL/lpr substrain, even before severe autoimmunity developed. With progression of the disease, the brain area of coronal sections became smaller and the growth of the hippocampus was retarded, which likely contributed to the increase in the ventricle area:brain area ratio. MRI revealed reduced volume across different brain regions, with the structures in the vicinity of the ventricular system particularly affected. The superior colliculus, periaqueductal gray matter, pons, and midbrain were among the regions most affected, whereas the volumes of the parietal-temporal lobe, parts of the cerebellum, and lateral ventricles in autoimmune MRL/lpr mice were comparable with values in congenic controls. Conclusion These results suggest that morphologic alterations in the brains of MRL/lpr mice are a consequence of several factors, including spontaneous development of lupus-like disease. A periventricular pattern of parenchymal damage is consistent with the cerebrospinal fluid neurotoxicity, limbic system pathologic features, and deficits in emotional reactivity previously documented in this model. [source] | ||||||||||