The Journal of comparative neurology
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This study investigated the role of prostaglandins (PGs) on the neuronal activity and the transcription of corticotropin-releasing factor (CRF) in the brain of conscious immune-challenged rats. Intravenous (i.v.) administration of indomethacin, an inhibitor of PG synthesis, was performed prior to and after the intraperitoneal (i.p.) injection of different doses [250 microg, 25 microg, and 2.5 microg/100 g body weight (b.w.)] of the immune activator lipopolysaccharide (LPS). Systemic administration of the high and middle doses of LPS caused a robust and widespread induction of both immediate-early genes (IEGs), c-fos and nerve growth factor-inducible gene B (NGFI-B) mRNAs, whereas injection of the low dose selectively triggered c-fos expression within the sensorial circumventricular organs. ⋯ In the hypothalamic PVN, inhibition of both c-fos and NGFI-B transcripts by indomethacin was also associated to an abolished influence of the endotoxin on the transcription of neuroendocrine CRF; induction of CRF primary transcript by the middle dose of LPS was selective to the PVN and was completely blocked by pretreatment with indomethacin. Moreover, a large number of tyrosine hydroxylase (TH)-immunoreactive neurons of the VLM (A1/C1) and the NTS (A2/C2) were positive for c-fos mRNA in immune-challenged rats, an effect that was largely prevented by indomethacin in the VLM but not in the NTS. These results indicate that the role of PGs in mediating the stimulatory influence of the acute-phase response depends on the severity of the systemic stressful situation, the brain regions, and the cell groups as well as the activated target genes.
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An in vitro autoradiographic technique has recently been developed to visualize receptor-activated G-proteins by using agonist-stimulated [35S]guanylyl-5'-O-(gamma-thio)-triphosphate ([35S]GTPgammaS) binding in the presence of excess guanosine 5'-diphosphate. This technique was used to localize opioid-activated G-proteins in guinea pig brain, a species that contains the three major types of opioid receptors. This study used selective mu, delta, and kappa opioid agonists as well as nociceptin or orphanin FQ (N/OFQ) peptide, an endogenous ligand for an orphan opioid receptor-like (ORL1) receptor, to stimulate [35S]GTPgammaS binding in guinea pig brain sections. ⋯ Mu-stimulated [35S]GTPgammaS binding predominated in the hypothalamus, amygdala, and brainstem, whereas kappa-stimulated [35S]GTPgammaS binding was particularly high in the substantia nigra and cortex and was moderate in the cerebellum. N/OFQ-stimulated [35S] GTPgammaS binding was highest in the cortex, hippocampus, and hypothalamus and exhibited a unique anatomical distribution compared with opioid-stimulated [35S]GTPgammaS binding. The present study extends previous reports on opioid and ORL1 receptor localization by anatomically demonstrating functional activity produced by mu, delta, and kappa opioid and ORL1 receptor activation of G-proteins.
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The genetic defect in the Purkinje cell degeneration (PCD) mutant mouse completely disrupts the cerebellar corticonuclear connection through intrinsic action on the final integrating unit of the cerebellar cortex, the Purkinje cell (PC). The postsynaptic target neurons of the PC in the deep cerebellar nuclei (DCN) and the vestibular nuclei (VN) are denervated by this PC loss by more than two-thirds of their total y-aminobutyric acid (GABA)-ergic innervation. This massive disinhibition should be reflected in an increased and thus electrophysiologically detectable activity of the respective neurons. ⋯ Direct double labeling of Parv and GABA and of Parv and glycine reveals that the large majority of Parv + neurons colocalize GABA, glycine, or both inhibitory transmitters. These results show that neurons that are postsynaptic to cerebellar PC develop diverse physiological and biochemical reactions in the course of genetically determined PCD. These mechanisms are likely to contribute to the phenotypically mild motor disturbances observed in PCD mutant mice.
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Axonal connections of the medial magnocellular nucleus of the anterior neostriatum in zebra finches.
The medial magnocellular nucleus of the anterior neostriatum (mMAN) is a small cortical nucleus which was previously identified as a component of the neural circuitry controlling vocal behavior in songbirds based on its efferent connection to the High Vocal Center (HVC), a major song control nucleus (Nottebohm et al. [1982] J. Comp. Neurol. 207:344-357; Bottjer et al. [1989] J. ⋯ The other source of afferent input to DMP is located in the external cellular stratum of the lateral hypothalamus (SCE). This newly delineated SCE-->DMP-->mMAN-->HVC/pHVC pathway is the first report of a hypothalamic brain region neuroanatomically integrated with song control circuitry. Because hypothalamic brain regions are important for homeostasis and regulating behavior, the trans-synaptic circuitry of mMAN may help to integrate information about the bird's internal state, such as sexual maturation, with song learning and production.
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Comparative Study
Connexin43 and astrocytic gap junctions in the rat spinal cord after acute compression injury.
To examine the possible role of interastrocytic gap junctions in the maintenance of tissue homeostasis after spinal cord damage, we initiated studies of the astrocytic gap junctional protein connexin43 (Cx43) in relation to temporal and spatial parameters of neuronal loss, reactive gliosis, and white matter survival in a rat model of traumatic spinal cord injury (SCI). Cx43 immunolocalization in normal and compression-injured spinal cord was compared by using two different sequence-specific anti-Cx43 antibodies that have previously exhibited different immunorecognition properties at lesion sites in brain. At 1- and 3-day survival times, gray matter areas with mild to moderate neuronal depletion exhibited a loss of immunolabeling with one of the two antibodies. ⋯ By 7 days post-SCI, Cx43 again co-localized with GFAP-positive cells in the surviving subpial rim, and with astrocytic processes on radially oriented vascular profiles investing the central borders of the lesion. The results indicate that alterations in Cx43 cellular localization and Cx43 molecular modifications reflected by epitope masking, which were previously correlated with gap junction remodeling following excitotoxin-induced lesions in brain, are not responses limited to exogenously applied excitotoxins; they also occur in damaged spinal cord and are evoked by endogenous mechanisms after traumatic SCI. The GFAP/Cx43 co-localization results suggest that during their transformation to a reactive state, spinal cord astrocytes undergo a transitional phase marked by altered Cx43 localization or expression.