[Movement Control of Striatum Neural Pathway].

Striatum is the central structure controlling movement. It plays a pivotal role in the regulation of voluntary movement, unconscious movement, muscle tone, posture adjustment and fine movement. Dysfunction of striatum causes a variety of movement disorders ranging from the hypokinetic disorders with increased muscle tone, such as Parkinson's disease, to the hyperkinetic disorders with decreased muscle tone, such as Huntington's disease. It is generally recognized that striatum receives the neural movement signals from the motor cortex, and then processes and modifies these signals and subsequently transfers the signals back to the motor cortex via thalamus for execution of the movement through pyramidal system. The movement control function of striatum depends on a complex neural circuit system. In this review, the studies on the movement control function of striatum as well as the striatal neural circuit system are summarized with an emphasis on the progress made during recent years for better understanding the mechanism underlying the movement control function as well as the disease association of striatum.

[Leptin Signalings and Leptin Resistance].

Leptin plays a critical role in the regulation of energy balance and metabolic homeostasis. Impairment of leptin function is closely involved in the pathogenesis of obesity, diabetes mellitus and some other metabolic diseases. Leptin initiates intracellular signal transductions in the leptin-receptor-expressing neurons in the central nervous system to exert its physiological functions. The fact that high circulating levels of leptin partially or completely fail to promote weight loss in obesity has given rise to the notion of "leptin resistance". Recently, the impairment of leptin signalings in the hypothalamus has been regarded as a critical contributor to leptin resistance. In this review, the studies on leptin signaling and leptin resistance are summarized with an emphasis on the progress made during the last five years.

High glucose stimulates TNFα and MCP-1 expression in rat microglia via ROS and NF-κB pathways.

AIM: To investigate whether high glucose stimulates the expression of inflammatory cytokines and the possible mechanisms involved. METHODS: ELISA and real-time PCR were used to determine the expression of the inflammatory factors, and a chemiluminescence assay was used to measure the production of reactive oxygen species (ROS). RESULTS: Compared to low glucose (10 mmol/L), treatment with high glucose (35 mmol/L) increased the secretion of tumor necrosis factor (TNF)α and monocyte chemotactic protein-1 (MCP-1), but not interleukin (IL)-1ß and IL-6, in a time-dependent manner in primary cultured rat microglia. The mRNA expression of TNFα and MCP-1 also increased in response to high glucose. This upregulation was specific to high glucose because it was not observed in the osmotic control. High-glucose treatment stimulated the formation of ROS. Furthermore, treatment with the ROS scavenger NAC significantly reduced the high glucose-induced TNFα and MCP-1 secretion. In addition, the nuclear factor kappa B (NF-κB) inhibitors MG132 and PDTC completely blocked the high glucose-induced TNFα and MCP-1 secretion. CONCLUSION: We found that high glucose induces TNFα and MCP-1 secretion as well as mRNA expression in rat microglia in vitro, and this effect is mediated by the ROS and NF-κB pathways.

Role of the central interleukin-1 in stress responses.

The molecules of interleukin-1 (IL-1) system are widely distributed in central nervous system. As a classical pro-inflammatory factor, central IL-1 has diverse biological functions and plays a pivotal role in a number of important physiological and pathophysiological processes. During the past few years, particular attentions have been directed to the stress mediator actions of central IL-1. This paper reviews some recent findings in the studies of central IL-1 functions in stress responses, including the effects of stress on central IL-1, the roles of IL-1 in the initiation of stress responses, the neural circuitries and intracellular signal transduction pathways involved in the central IL-1 mediated stress responses, as well as the actions of central IL-1 on brain high function and behavior under stressful conditions.

Effects of ghrelin on the proliferation and secretion of splenic T lymphocytes in mice.

Ghrelin, a novel gut--brain peptide predominantly produced by the stomach, displays strong growth hormone (GH)-releasing activity mediated by the hypothalamus-pituitary GH secretagogue receptor (GHS-R). Recently, the ghrelin receptor has also been detected in peripheral systems including immune tissues, suggesting that ghrelin may play an important role in the regulation of immune function. In this paper, we assessed the presence and function of the ghrelin receptor in murine splenic T cells. The enriched T cells express the mRNA of ghrelin and ghrelin receptor mRNA, and there is a significantly positive correlation between them. Moreover, we showed that ghrelin dose-dependently inhibits proliferation of splenic T cells when they are costimulated by anti-CD3. In addition, ghrelin suppressed Th(1) (IL-2 and IFN-gamma) and Th(2) (IL-4 and IL-10) cytokines mRNA expression. These results demonstrate the presence of the ghrelin receptor in murine spleen T lymphocytes and a functional role of ghrelin as a modulator of lymphocyte function. This function of ghrelin may have some relevance to the pathophysiology of immunologic alterations related to metabolism.

[Central interleukin-1beta involved in modulation of motor behavior in novelty stress rats].

OBJECTIVE: To investigate the effect of central interleukin-1beta (IL-1beta) on motor behavioral responses in novelty stress rats. METHODS: The novelty stress was elicited by novel environmental stimuli with novelty stress box. The intracerebrolventricular (ICV) cannula and microinjection were performed with rat brain stereotaxic system. Movement behaviors of rats were monitored by behavioral radio-telemetry system. As behavior index, mean percent immobility (MPI) was used to assess immobility of rats. RESULTS: The decrease of MPI was remarkably elicited by novel environmental stimuli. In non-stressful condition, ICV anti-IL-1beta antibody did not influence the MPI. The decrease of MPI induced by novel environmental stimuli was significantly blocked by ICV pretreatment with anti-IL-1beta antibody. In novel stress, MPI of rats was not affected by ICV injection of non specific IgG. CONCLUSION: Central interleukin-1beta plays an important role in modulation of motor behavioral response to novelty stress.

[Progress in central interleukin-1 system and its signaling pathway].

Central interleukin-1 (IL-1 ) system is a relatively independent system which is composed of IL-1 and other molecules associated with IL-1 in functions or structures. The knowledge of central IL-1 system in the constitution and function have been extended with the discovery of new members and its function, the extensive and intensive research on intracellular signaling pathways, as well as the relationship among those molecules. This paper reviews the recent findings in the study of central IL-1 system, which comprises the new members, new signaling molecules, new biological functions, and the effects in the processes of physiology and pathophysiology.

Kirenol upregulates nuclear annexin-1 which interacts with NF-κB to attenuate synovial inflammation of collagen-induced arthritis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Kirenol is a diterpenoid compound purified from the Chinese Herba Siegesbeckiae. Siegesbeckiae has been employed for the treatment of arthritis for centuries, its safety and efficacy are documented through a long history of human use. AIM OF THE STUDY: To investigate the effects on collagen-induced arthritis (CIA) and anti-inflammatory mechanism of kirenol. MATERIALS AND METHODS: Kirenol was administrated intragastrically in rats after the onset of CIA. Pathological changes were evaluated by paw swelling and histopathology. Concentration of IL-1ß in synovial fluid and adrenal corticotropin (ACTH) in plasma were determined by Elisa. Western blot was performed to detect the expression of annexin-1 and glucocorticoid receptor alpha (GRα) in synovium. NF-κB DNA binding activity was assessed by electrophoretic mobility shift assays (EMSA). RESULTS: Kirenol (1, 2, and 4 mg/kg) and prednisolone depressed paw swelling and reduced IL-1ß of synovial fluid in the CIA rats (p<0.05 or p<0.01). Kirenol and prednisolone upregulated nuclear annexin-1 and inhibited NF-κB activity in synovium of CIA. The inhibitory effect of kirenol and prednisolone on NF-κB activity was enhanced by anti-annexin-1 Ab. Prednisolone, but not kirenol, downregulated plasma ACTH and GRα expression significantly (p<0.01). CONCLUSION: Kirenol and prednisolone can upregulate nuclear annexin-1 which interacts with NF-κB to inhibit NF-κB activity, reduce cytokines expression and thereby attenuate inflammation of CIA joints. Kirenol does not lead to ACTH or GR downregulation, which is in contrast to classic glucocorticoid prednisolone. Kirenol shares with GCs similar anti-inflammatory mechanism but bypass the considerable limitation of GCs treatment.

p38 MAPK mediates cardiovascular and behavioral responses induced by central IL-1 beta and footshock in conscious rats.

AIM: To investigate the roles of p38 mitogen-activated protein kinase (p38 MAPK) in the cardiovascular and behavioral responses induced by intracerebral ventricular injection (i.c.v.) of interleukin-1 beta (IL-1 beta) or footshock. METHODS: We examined the effects of p38 MAPK on mean artery blood pressure (mABP), heart rate (HR), and motor activity (MA) during central administration of IL-1 beta, or footshock after i.c.v. SB203580 (a specific inhibitor of the p38 MAPK) with Cardiovascular and Behavior Telemetry System in conscious SD rats. RESULTS: (1) IL-1 beta (i.c.v.) or footshock remarkably rise the mABP, and the maximal changes are (7.8+/-1.8) and (12.3+/-3.5) mmHg, respectively, which was abrogated by the pretreatment with p38 inhibitor SB203580 intracerebroventricularly. (2) Compared with icv saline group, the motor activity was significantly decreased in SB203580 group with maximal changes (-7.6+/-1.1) counts/min after footshock. CONCLUSION: p38 MAPK plays an important role in the pressor response induced by central administration of IL-1 beta or footshock and change of motor activity after footshock in conscious rats.