Responses of primate caudal parabrachial nucleus and Kölliker-fuse nucleus neurons to whole body rotation

The caudal aspect of the parabrachial (PBN) and K?lliker-Fuse (KF) nuclei receive vestibular nuclear and visceral afferent information and are connected reciprocally with the spinal cord, hypothalamus, amygdala, and limbic cortex. Hence, they may be important sites of vestibulo-visceral integration, particularly for the development of affective responses to gravitoinertial challenges. Extracellular recordings were made from caudal PBN cells in three alert, adult female Macaca nemestrina through an implanted chamber. Sinusoidal and position trapezoid angular whole body rotation was delivered in yaw, roll, pitch, and vertical semicircular canal planes. Sites were confirmed histologically. Units that responded during rotation were located in lateral and medial PBN and KF caudal to the trochlear nerve at sites that were confirmed anatomically to receive superior vestibular nucleus afferents. Responses to whole-body angular rotation were modeled as a sum of three signals: angular velocity, a leaky integration of angular velocity, and vertical position. All neurons displayed angular velocity and integrated angular velocity sensitivity, but only 60% of the neurons were position-sensitive. These responses to vertical rotation could display symmetric, asymmetric, or fully rectified cosinusoidal spatial tuning about a best orientation in different cells. The spatial properties of velocity and integrated velocity and position responses were independent for all position-sensitive neurons; the angular velocity and integrated angular velocity signals showed independent spatial tuning in the position-insensitive neurons. Individual units showed one of three different orientations of their excitatory axis of velocity rotation sensitivity: vertical-plane-only responses, positive elevation responses (vertical plane plus ipsilateral yaw), and negative elevation axis responses (vertical plane plus negative yaw). The interactions between the velocity and integrated velocity components also produced variations in the temporal pattern of responses as a function of rotation direction. These findings are consistent with the hypothesis that a vestibulorecipient region of the PBN and KF integrates signals from the vestibular nuclei and relay information about changes in whole-body orientation to pathways that produce homeostatic and affective responses.     

Neurotensin: revealing a novel neuromodulator circuit in the nucleus accumbens–parabrachial nucleus projection of the domestic chick

Lower brainstem projections from nucleus accumbens (Ac) subregions to the parabrachial complex (PB), the nucleus of the solitary tract and the vagal motor nuclei have been described previously in the domestic chick by our group. Such projections, particulary those from the core and rostral pole regions of Ac have not been found in mammals or pigeons. Here we report on the presence of neurotensin (NT) in the neurons projecting from different Ac subnuclei, and also from the bed nucleus of stria terminalis, to the PB in the domestic chicken. The study is based upon correlated retrograde tracing (using Fast Blue) and NT immunohistochemistry, supplemented with regional charting and quantitative analysis of double-labeled neurons. The number of retrogradely labeled cells in Ac subdivisions reflects the size of FB tracer deposit, and the degree to which it extends to the medial PB. Of all Ac subregions, the core contained the largest amount of double-labeled cells. The findings demonstrate that the anatomical pathway through which the Ac can directly modulate taste-responsive neurons of the PB employs mainly neurotensin as a neuromodulator. The observed anatomical difference between mammals and birds is either a general taxonomic feature or it reflects feeding strategies specific for the domestic chick. The results are also relevant to a better understanding of the role of NT in food intake and reward-related behaviors in birds.     

Role of complement in host–microbe homeostasis of the periodontium

Complement plays a key role in immunity and inflammation through direct effects on immune cells or via crosstalk and regulation of other host signaling pathways. Deregulation of these finely balanced complement activities can link infection to inflammatory tissue damage. Periodontitis is a polymicrobial community-induced chronic inflammatory disease that can destroy the tooth-supporting tissues. In this review, we summarize and discuss evidence that complement is involved in the dysbiotic transformation of the periodontal microbiota and in the inflammatory process that leads to the destruction of periodontal bone. Recent insights into the mechanisms of complement involvement in periodontitis have additionally provided likely targets for therapeutic intervention against this oral disease.     

Negative regulation of caspase-3 expression in the neonatal cerebral cortex by α<Subscript>2A</Subscript>-adrenoceptors

Antisense oligonucleotide to α_2A-adrenoceptors increased the levels of mRNA (reverse polymerase chain reaction) and protein for a key executioner protease of apoptosis caspase-3 (immunoblotting assay) in the cerebral cortex of newborn rats. The relationship between the observed effect and low expression of α₂-adrenoceptors was confirmed by the possibility of correcting this phenomenon by clonidine (stimulator of α₂-adrenoceptors). __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 3, pp. 244–246, March, 2007     

Role of the cerebellum in movements: control of timing or movement transitions?

Patients with cerebellar damage are impaired on a range of timed tasks. However, recent research has indicated that the impairment on temporal production tasks is limited to discontinuous movements. The present experiments were designed to compare two accounts for the increased temporal variability observed in these patients when producing discontinuous movements. First, the impairment on discontinuous movements may be the result of the requirements associated with transitioning between movement onsets and offsets, requirements unique to discontinuous movement production. Second, the impairment may reflect a requirement to represent the temporal goal in timed, discontinuous movements. Patients with unilateral or bilateral cerebellar lesions and matched control subjects performed a key-pressing task. In one condition, the participants pressed and immediately released the key. The other conditions required the participants to press the key, and after either a 550-ms or 950-ms delay, release the key. Individuals with cerebellar damage were impaired on the two timed conditions. These results do not support the transition hypothesis. Rather, they are consistent with the hypothesis that the cerebellum is essential for tasks requiring precise event-like temporal control.     

The Role of the Calcium Channel α2δ-1 Subunit in Skeletal Muscle

Journal of Muscle Research and Cell Motility -     

Role of hypothalamic 5′-AMP-activated protein kinase in the regulation of food intake and energy homeostasis

Although obesity is an epidemic threat to general health worldwide, an effective treatment has yet to be found. Insights into weight-regulatory pathways will accelerate the identification of new molecular targets for anti-obesity agents. 5-AMP-activated protein kinase (AMPK) is an enzyme activated during low cellular energy charge. In peripheral tissues, the activation of AMPK influences various metabolic pathways, including glucose uptake, glycolysis, and fatty acid oxidation, all of which help to re-establish a normal cellular energy balance. AMPK is also present in the neurons of the hypothalamus, a critical center in the regulation of energy homeostasis. Recent studies from our group and others have shown that many factors (-lipoic acid, leptin, insulin, ghrelin, glucose, 2-deoxyglucose, etc.) cause an alteration in hypothalamic AMPK activity that mediates effects on feeding behavior. Hypothalamic AMPK also appears to play a role in the central regulation of energy expenditure and peripheral glucose metabolism. These data indicate that hypothalamic AMPK is an important signaling molecule that integrates nutritional and hormonal signals and modulates feeding behavior and energy metabolism.     

Role of α2A-Adrenoceptors of Locus Coeruleus in Regulation of Plasma Corticosterone Content in Male Rats

Administration of specific oligonucleotide selectively inhibiting _2A-adrenoceptor gene expression into the locus coeruleus of male rats for 3 days activated the hypothalamic-pituitary-adrenal system, which was manifested in a rise of blood plasma corticosterone content in rats with normal and hypertrophied (after castration) adrenal glands. These data indicate that _2A-adrenoceptors of the locus coeruleus are involved in the regulation of basal plasma corticosterone content.     

Histone demethylase retinoblastoma binding protein 2 regulates the expression of α-smooth muscle actin and vimentin in cirrhotic livers

Liver cirrhosis is one of the most common diseases of Chinese patients. Herein, we report the high expression of a newly identified histone 3 lysine 4 demethylase, retinoblastoma binding protein 2 (RBP2), and its role in liver cirrhosis in humans. The siRNA knockdown of RBP2 expression in hepatic stellate cells (HSCs) reduced levels of α-smooth muscle actin (α-SMA) and vimentin and decreased the proliferation of HSCs; and overexpression of RBP2 increased α-SMA and vimentin levels. Treatment with transforming growth factor β (TGF-β) upregulated the expression of RBP2, α-SMA, and vimentin, and the siRNA knockdown of RBP2 expression attenuated TGF-β-mediated upregulation of α-SMA and vimentin expression and HSC proliferation. Furthermore, RBP2 was highly expressed in cirrhotic rat livers. Therefore, RBP2 may participate in the pathogenesis of liver cirrhosis by regulating the expression of α-SMA and vimentin. RBP2 may be a useful marker for the diagnosis and treatment of liver cirrhosis.     

Distribution of metabotropic glutamate receptors in the parabrachial and Kölliker-Fuse nuclei of the rat

In the present study, we analysed the distribution and cellular localization of metabotropic glutamate receptors (1alpha, 2/3, 5) in parabrachial and K?lliker-Fuse nuclei using subtype-specific antisera. Immunolabelling revealed that different nuclei express different sets of metabotropic glutamate receptors. Metabotropic glutamate receptor la immunoreactivity was found in the K?lliker-Fuse nucleus and in several parabrachial nuclei, including the waist area, lateral crescent, medial, external medial and ventral lateral nuclei. The external lateral and internal lateral parabrachial nuclei were devoid of metabotropic glutamate receptor 1alpha immunoreactivity. Metabotropic glutamate receptor 5 immunoreactivity was observed in the K?lliker-Fuse and in the medial parabrachial nuclei, while in the remaining nuclei the staining was very weak. Again, the external lateral nucleus was devoid of metabotropic glutamate receptor 5 immunoreactivity. The metabotropic glutamate receptor 2/3 antisera stained all lateral parabrachial nuclei as well as the K?lliker-Fuse nucleus, while staining in the medial parabrachial nucleus was weak. Metabotropic glutamate receptor 1alpha immunoreactivity was observed on presumed dendritic profiles, while metabotropic glutamate receptor 5 immunoreactivity was found predominantly on neuronal cell bodies. Metabotropic glutamate receptor 2/3 immunoreactivity was present as a fine, punctate immunostaining in the neuropil. Our data suggest that glutamate release in the parabrachial and K?lliker-Fuse nuclei might induce a variety of second messenger cascades, as indicated by the presence or absence of certain types of metabotropic glutamate receptors.     

β-Radiation of the fetal fluid in man

Summary It was experimentally proved that the activity of -radiation of the fetal fluid is different depending upo the sex of the embryo.Thus, radiation activity of the fluid in which a fetus of the female sex (Table 1) was developing, was found to be significantly higher than that of the fluid in which a fetus of the male sex was developing (Table 2).Submitted by Active Member of the Academy of Medical Sciences USSR Professor L.V. Gromashevsky     

Evidence for the involvement of peripheral β-adrenoceptors in delayed liquid gastric emptying induced by dipyrone, 4-aminoantipyrine,and antipyrine in rats

Dipyrone (Dp), 4-aminoantipyrine (AA), and antipyrine (At) delay liquid gastric emptying (GE) in rats. We evaluated adrenergic participation in this phenomenon in a study in male Wistar rats (250-300 g) pretreated subcutaneously with guanethidine (GUA), 100 mg·kg⁻¹·day⁻¹, or vehicle (V) for 2 days before experimental treatments. Other groups of animals were pretreated intravenously (iv) 15 min before treatment with V, prazosin (PRA; 1 mg/kg), yohimbine (YOH; 3 mg/kg), or propranolol (PRO; 4 mg/kg), or with intracerebroventricular (icv) administration of 25 µg PRO or V. The groups were treated iv with saline or with 240 µmol/kg Dp, AA, or At. GE was determined 10 min later by measuring the percentage of gastric retention (%GR) of saline labeled with phenol red 10 min after gavage. %GR (mean±SE, n=8) indicated that GUA abolished the effect of Dp (GUA vs V=31.7±1.6 vs 47.1±2.3%) and of At (33.2±2.3 vs 54.7±3.6%) on GE and significantly reduced the effect of AA (48.1±3.2 vs 67.2±3.1%). PRA and YOH did not modify the effect of the drugs. %GR (mean±SE, n=8) indicated that iv, but not icv, PRO abolished the effect of Dp (PRO vs V=29.1±1.7 vs 46.9±2.7%) and At (30.5±1.7 vs 49±3.2%) and significantly reduced the effect of AA (48.4±2.6 vs 59.5±3.1%). These data suggest activation of peripheral β-adrenoceptors in the delayed GE induced by phenylpyrazolone derivatives.     

Increased αB-crystallin in hypothalamic paraventricular nucleus of rats with myocardial infarction

The hypothalamus plays an important role in maintaining a homeostasis of the body against stress response. In particular, the paraventricular nucleus of the hypothalamus is a critical region for disorders related to the autonomic nervous system, such as congestive heart failure and hypertension. αB-crystallin is a family of heat shock proteins that are widely expressed in the brain, including in glial cells, astrocytes, oligodendrocytes, and neurons. Many studies have demonstrated that expression level of αB-crystallin is up-regulated and involved in protecting cells from pathological conditions. In the present study, we examined the expression and potential role of αB-crystallin in the paraventricular nucleus (PVN) regions of rats with myocardial infarction (MI). Our results demonstrate that mRNA encoding αB-crystallin and protein for both native and phosphorylate forms (Ser-59) of αB-crystallin was significantly increased in the PVN during MI.     

Changes in taste reactivity to intra-oral hypertonic NaCl after lateral parabrachial injections of an α2-adrenergic receptor agonist

Bilateral injections of moxonidine, an α₂-adrenoceptor and imidazoline receptor agonist, into the lateral parabrachial nuclei (LPBN) enhance sodium appetite induced by extracellular dehydration. In the present study, we examined whether LPBN moxonidine treatments change taste reactivity to hypertonic NaCl solution administered into the mouth by intra-oral (IO) cannula. Male Holtzman rats prepared with IO and bilateral LPBN cannulas received subcutaneous injections of furosemide (FURO; 10 mg/kg) and captopril (CAP; 5 mg/kg) to induce hypovolemia with mild hypotension and an accompanying salt appetite and thirst before testing the taste reactivity to oral infusions of 0.3 M NaCl (1.0 ml/min). In the first experiment 45 min after subcutaneous injections of FURO + CAP or vehicle, moxonidine was bilaterally injected into the LPBN, and then 15 min later both bodily and oral-facial ingestive and rejection responses to 0.3 M NaCl delivered through the IO cannula were assessed. Both LPBN vehicle and moxonidine treated rats showed increased ingestive and decreased rejection responses to the IO hypertonic solution. The IO 0.3 M NaCl infusion-evoked ingestive and rejection taste related behaviors were comparable in the LPBN vehicle- vs. the LPBN moxonidine-injected groups. In a second experiment, rats received the same FURO + CAP treatments and LPBN injections. However, beginning 15 min after the LPBN injections, they were given access to water and 0.3 M NaCl and were allowed to consume the fluids for most of the next 60 min with the free access intake being interrupted only for a few minutes at 15, 30 and 60 min after the fluids became available. During each of these three brief periods, a taste reactivity test was conducted. On the three taste reactivity tests rats that received LPBN vehicle injections showed progressive declines in ingestive responses and gradual increases in rejection responses. However, in contrast to the LPBN vehicle treated rats, animals receiving bilateral injections of LPBN moxonidine maintained a high number of ingestive responses and a low number of rejection responses throughout the test period even in spite of evidencing substantial water and 0.3 M NaCl consumption during the periods of free access. The results suggest that after α₂-adrenoceptor agonist delivery to the LPBN the acceptance of 0.3 M NaCl is sustained and the negative attributes of the solution are minimized. The maintained positive rewarding qualities of 0.3 M NaCl are likely to account for why LPBN moxonidine treated rats show such a remarkable salt appetite when assayed by the volume of hypertonic 0.3 M NaCl consumed.     

Inflammasomes and the microbiota—partners in the preservation of mucosal homeostasis

Seminars in Immunopathology - Inflammasomes are multiprotein complexes that serve as signaling platforms initiating innate immune responses. These structures are assembled upon a large array of...