Histone Deacetylases 1 and 2 Regulate Microglia Function during Development,Homeostasis, and Neurodegeneration in a Context-Dependent Manner

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Dorsal subcoeruleus nucleus (SubCD) involvement in context-associated fear memory consolidation

The neurobiological mechanisms of emotional memory processing can be investigated using classical fear conditioning as a model system, and evidence from multiple lines of research suggests that sleep influences consolidation of emotional memory. In rodents, some of this evidence comes from a common finding that sleep deprivation from 0 to 6 h after fear conditioning training impairs processing of conditioned fear memory. Here, we show that during a 6-h session of sleep–wake (S–W) recording, immediately after a session of context-associated fear conditioning training, rats spent more time in wakefulness (W) and less time in slow-wave sleep (SWS) and rapid eye movement (REM) sleep. This context-associated fear conditioning training-induced reduction in SWS lasts for 2 h, and the REM sleep reduction lasts throughout the entire 6-h post-training S–W recording period. Interestingly, these reductions in SWS and REM sleep during this 6-h period did not impair memory consolidation for context-associated fear conditioning. The results of this study show, for the first time, that lesions within the dorsal part of the subcoeruleus nucleus (SubCD), which were unintentionally caused by the implantation of bipolar recording electrodes, impair consolidation of context-associated fear conditioning memory. Together, the results of these experiments suggest that emotional memory processing associated with fear conditioning can be completed successfully within less than a normal amount of sleep, but it requires a structurally and functionally intact SubCD, an area in the brain stem where phasic pontine wave (P-wave) generating cells are located.     

Dendritic cell activating peptides induce distinct cytokine profiles

High-mobility group box 1 protein (HMGB1), a DNA-binding nuclear and cytosolic protein, is a pro-inflammatory cytokine released by monocytes and macrophages. HMGB1 as well as its B box domain induce maturation of human dendritic cells (DCs). This report demonstrates that the B box domain induces phenotypic maturation of murine bone marrow-derived dendritic cells (BM-DCs) as evidenced by increased CD86, CD40 and MHC-II expression. The B box domain enhanced secretion of pro-inflammatory cytokines and chemokines: IL-1beta, IL-2, IL-5, IL-8, IL-12 and tumor necrosis factor (TNF)-alpha, but not IL-6 and IL-10. Furthermore, four peptides whose sequences correspond to different regions of HMGB1 induced production of IL-1beta, IL-2 and IL-12 (p70), but not IL-10 and IL-6 in mouse BM-DCs. Interestingly, these peptides differed in their capacity to induce TNF-alpha, IL-5, IL-18 and IL-8. B box domain as well as peptide-activated DCs acted as potent stimulators of allogeneic T cells in a mixed leukocyte reaction. DCs exposed to HMGB1 peptides induced proliferation of ovalbumin-specific syngeneic T cells. These DC-activating peptides could serve as an adjuvant in immunotherapeutic or vaccine context and the selective activity of these different peptides suggests a means to customize the functional properties of DCs.     

Differential diagnoses of nocturnal fear and movement paroxysm: a case report

Recurrent nocturnal behavioural and movement paroxysms are a diagnostic challenge for the clinical pediatrician. We report on an adolescent girl who presents recurrent stereotypical nightmare-like episodes occurring during non-REM sleep stages 1-2 (N1 and N2). We discuss the differential diagnoses between epileptic and nonepileptic events and between nocturnal frontal and temporal seizures. The pathophysiological and unusual electroencephalographical features are discussed with respect to clinical features and results of interictal FDG-PET. Conclusion In case of stereotypical nightmare-like episodes in children or adolescents, an epileptic origin has to be ruled out before a parasomnia is diagnosed. In addition, a normal awake EEG or interictal sleep EEG in the diagnostic workup may not exclude an epileptic disorder. In case of nightly stereotypic motor or affective events, an epileptic disorder should be discussed.     

Regulation of rapid eye movement sleep in the freely moving rat: local microinjection of serotonin,norepinephrine, and adenosine into the brainstem

STUDY OBJECTIVES: Considerable evidence suggests that rapid eye movement (REM) sleep is induced by glutamatergic activation of cholinergic cells within the pedunculopontine tegmentum (PPT). The aim of this study is to test a popular hypothesis that serotonin, norepinephrine, and adenosine act on PPT cells to regulate REM sleep. This study also tests an alternate hypothesis that serotonin may inhibit REM sleep signs by direct action on the individual REM sleep sign generators. DESIGN: Serotonin, norepinephrine, and adenosine were locally microinjected into the PPT and serotonin was microinjected into the pontine-wave (P-wave) generator (dorsal part of the locus subcoeruleus nucleus) while quantifying the effects on REM sleep and P-wave activity in freely moving rats. SETTING: N/A. PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Local microinjections of serotonin, norepinephrine, and adenosine into the PPT did not change REM sleep. Microinjection of serotonin into the P-wave generator suppressed P-wave activity but not REM sleep. CONCLUSIONS: The present findings provide direct evidence that serotonin, norepinephrine, and adenosine-induced REM sleep suppression in the behaving rat are not mediated by the PPT. The results also provide direct evidence, for the first time, that serotonin suppresses P-wave activity by acting directly on the P-wave generator. These results suggest that the serotonin-induced inhibition of REM sleep in the freely moving rat is probably not mediated through the mesopontine cholinergic cell compartment but, rather, through individual REM sleep sign generators.     

Galactose residues on the lipooligosaccharide of Moraxella catarrhalis 26404 form the epitope recognized by the bactericidal antiserum from conjugate vaccination

Lipooligosaccharide (LOS) from Moraxella catarrhalis has the potential to elicit bactericidal antibodies against the pathogen. We generated LOS-based conjugate vaccines that elicited bactericidal antibodies in animal models. However, epitopes on the LOS recognized by the functional anti-LOS antibodies remain unidentified. In this study, a mutant strain, D4, which lost the recognition by a bactericidal anti-LOS rabbit serum in Western blotting was generated from a serotype C strain 26404 by random transposon mutagenesis. Sequence analysis revealed there was an insertion of a kanamycin resistance gene in the lgt2 gene of D4, which encodes beta(1-4)-galactosyltransferase. An isogenic lgt2 mutant, 26404lgt2, was constructed. Structural analysis indicated that the mutant strain produced a truncated LOS lacking terminal galactoses from 4- and 6-linked oligosaccharide chains of strain 26404. Further studies showed that the antiserum lost the recognition of both mutant cells and LOSs in Western blotting, an enzyme-linked immunosorbent assay (ELISA), or a flow cytometry assay. The antiserum also lost the ability to kill the mutant strain in a bactericidal assay, whereas it showed a bactericidal titer of 1:80 to strain 26404. In an inhibition ELISA, d-(+)-galactose or 26404lgt2 LOS showed no inhibition. However, the 26404 LOS and a serotype A O35E LOS with terminal galactoses on its 6-linked oligosaccharide chain showed >90% inhibition, while a serotype B 26397 LOS showed >60% inhibition. These studies suggest that the terminal alpha-Gal-(1-->4)-beta-Gal on the 6-linked oligosaccharide chain of 26404 LOS plays a critical role in forming the epitope recognized by the bactericidal antiserum induced by immunization with our conjugate vaccine.     

Epidemiological profile of outbreaks of cholera in India during 1975-1989

Cholera has been present in India since antiquity. Six pandemics originated in Indian subcontinent. The present seventh pandemic caused by El Tor Vibrio cholerae started from Indonesia (Sulawesi) in 1961 and entered India in 1964. By the end of 1965 it has replaced the age old classical V. cholerae. Many of the States which never had cholera or were free from it for a long time got infected and became endemic foci of El Tor infection. This article reviews the epidemiological features of important outbreaks reported after 1975 in India.     

Amylin and amylin-amide lack an acute effect on blood glucose and insulin

Amylin-amide has been implicated in the pathogenesis of type II diabetes due to its proposed inhibitory effect on insulin release from beta cells of the pancreatic islets, and on glucose uptake by the skeletal muscle. In experiments with rats and rabbits we failed to demonstrate these anti-insulin actions of amylin and amylin-amide. A single bolus dose of the two peptides (500 pmol) administered i.v. failed to suppress plasma insulin levels or to elevate blood glucose levels. The continuous infusion of amylin-amide into rabbits also failed to suppress the release of insulin in response to hyperglycaemia produced by an i.v. bolus injection of glucose. These in vivo observations imply that the amylin peptides may not have a primary physiological role in carbohydrate metabolism, but in view of our previous findings, we speculate that the peptide has a more prominent role in calcium homeostasis.     

Rare association of central pontine myelinolysis with infantile tremor syndrome

Central pontine myelinolysis (CPM) is an acute demyelination within the central basis pontis. Though exact mechanism is not known it is seen commonly with rapid correction of hyponatremia and also with pontine ischemia or infarction, demyelinating diseases, pontine neoplasm and different metabolic diseases. We report a rare association of CPM in a patient of Infantile Tremor Syndrom (ITS). ITS is a syndrome of tremor, mental and physical retardation, pigmentary changes of hair and skin and anemia in malnourished children. Though first reported in Indian subcontinent many identical cases were reported from around the world. Our case is a 15 month old child with generalized tremor, mild hepatosplenomegaly with features of grade II malnutrition including skin and hair changes. All the signs and symtoms of tremor improved after treatment with the World Health Organization (WHO) protocol for protein energy malnutrition (PEM) and administration of propranolol without any side effects.