In the present study, the changes of amino acids release in the spinal cord after the application of angiotensin II (ANG II) in the rostral ventrolateral medulla (RVLM) and the distribution of ANG receptors on neurons of the RVLM were investigated. A microdialysis experiment showed that microinjection of angiotensin II into the RVLM significantly (P < 0.01) increased the release of aspartate and glutamate in the intermediolateral column of the spinal cord. Immunofluorescence technique combined with confocal microscopy demonstrated that most of the glutamatergic and GABAergic neurons in the RVLM of both Wistar and spontaneously hypertensive rats (SHR) were double labeled with ANG type 1 (AT1) receptor. Immunocytochemical studies demonstrated that the mean optic density of AT1 receptor of the cell surface as well as the whole cell was higher (P < 0.05) in SHR than that in Wistar rats, indicating that the higher expression of AT1 receptors in the RVLM may contribute to the higher responsiveness of SHR to ANG II stimulation. Immunogold staining and electronmicroscopic study demonstrated that AT1 receptor in the RVLM was distributed on the rough endoplasmic reticulum, cell membrane, and nerve processes. The results suggest that effects evoked by ANG II in the RVLM are closely related to glutamatergic and GABAergic pathways. These results indirectly support the hypothesis that ANG II in the RVLM may activate vasomotor sympathetic glutamatergic neurons, leading to an increase in sympathetic nerve activity and arterial blood pressure.

Cannabinoid receptor type 2 (CB2) agonists display potential analgesic effects in acute and neuropathic pain. However, its complex cellular and molecular mechanisms in bone cancer pain remain unclear. And less relevant reports concerned its time-dependent effects on the long-lasting modifications of behavior, spinal inflammatory cytokines levels, astrocytes activity induced by bone cancer pain. A rat model of bone cancer pain induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells was utilized. Pain behaviors at different time points were assessed by ambulatory pain scores and paw withdrawal mechanical threshold (PWMT). Pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-18, and tumor necrosis factor alpha (TNF-α), were quantitated by Western blots. Glial activity was assessed by immunohistochemistry. Intra-tibia inoculation of Walker 256 mammary gland carcinoma cells induced progressive bone cancer pain; a long-term up-regulation of IL-1β, IL-6, IL-18, and TNF-α; and the activation of glia in spinal cord. Activation of microglia was first evident on day 4 after surgery and reached to a peak on day 7 while activation of astrocytes was on day 10. A single intrathecal injection of JWH-015 attenuated bone cancer induced spontaneous pain and mechanical allodynia, reduced the expression of pro-inflammatory cytokines, and inhibited the activity of astrocytes. All the modifications were transient and peaked at 24 h after JWH-015 administration. Furthermore, the protective effects of JWH-015 were reversed in the presence of CB2-selective antagonist AM630. Overall, our results provided evidences for the persistent participation of inflammation reaction in the progression of bone cancer pain, and demonstrated that JWH-015 reduced the expression of IL-1β, IL-6, IL-18, and TNF-α and inhibited astrocytes activation in a time-dependent manner, thereby displaying an analgesic effect.

Immune system dysregulation plays a key role in the physiopathology of bipolar disorder (BD) and major depressive disorder (MDD). However, whether interleukins might be biomarkers to distinguish these 2 affective disorders is unclear. Here, we assessed the differences in serum levels of interleukin 6 (IL-6) and interleukin 8 (IL-8) as well as C-reactive protein (CRP) in patients with MDD and BD. In total, we enrolled 21 MDD patients, 26 BD patients, and 20 healthy controls. We collected a total of 35 samples from BD patients in 3 different phases, depression phase, manic phase, and remission stage, and 27 samples from MDD patients in acute and remission phases. Serum IL-6 and IL-8 levels were assessed with solid phase sandwich ELISA-based quantitative arrays, and CRP levels were determined with an automatic analyzer. Both serum IL-6 and IL-8 levels were elevated in BD patients but not MDD patients. Subgroup analysis indicated elevated serum IL-6 in both the depression and manic phases in BD patients. The serum CRP levels did not change in either BD or MDD patients. However, sex differences in CRP concentrations were observed in healthy controls. Furthermore, there were linear correlations between the CRP levels and Bech-Rafaelsen Mania Rating Scale (BRMS) scores in BD patients. IL-6 and IL-8 levels may serve as biomarkers to differentiate between MDD and BD patients, even when the clinical manifestations are atypical. IL-6 may be used for the differential diagnosis of MDD and depressive episodes in BD.

The axon guidance cue receptor DCC (deleted in colorectal cancer) plays a critical role in the organization of mesocorticolimbic pathways in rodents. To investigate whether this occurs in humans, we measured (1) anatomical connectivity between the substantia nigra/ventral tegmental area (SN/VTA) and forebrain targets, (2) striatal and cortical volumes, and (3) putatively associated traits and behaviors. To assess translatability, morphometric data were also collected in -haploinsufficient mice. The human volunteers were 20 mutation carriers, 16 relatives, and 20 unrelated healthy volunteers (UHVs; 28 females). The mice were 11 and 16 wild-type C57BL/6J animals assessed during adolescence and adulthood. Compared with both control groups, the human carriers exhibited the following: (1) reduced anatomical connectivity from the SN/VTA to the ventral striatum [: = 0.0005,() = 0.60; UHV: = 0.0029, = 0.48] and ventral medial prefrontal cortex (: = 0.0031, = 0.53; UHV: = 0.034, = 0.35); (2) lower novelty-seeking scores (: = 0.034, = 0.82; UHV: = 0.019, = 0.84); and (3) reduced striatal volume (: = 0.0009, = 1.37; UHV: = 0.0054, = 0.93). Striatal volumetric reductions were also present in mice, and these were seen during adolescence ( = 0.0058, = 1.09) and adulthood ( = 0.003, = 1.26). Together these findings provide the first evidence in humans that an axon guidance gene is involved in the formation of mesocorticolimbic circuitry and related behavioral traits, providing mechanisms through which mutations might affect susceptibility to diverse neuropsychiatric disorders. Opportunities to study the effects of axon guidance molecules on human brain development have been rare. Here, the identification of a large four-generational family that carries a mutation to the axon guidance molecule receptor gene, , enabled us to demonstrate effects on mesocorticolimbic anatomical connectivity, striatal volumes, and personality traits. Reductions in striatal volumes were replicated in-haploinsufficient mice. Together, these processes might influence mesocorticolimbic function and susceptibility to diverse neuropsychiatric disorders.

Purpose. To survey the species diversity of home dust mites (HDM) in Xishuangbanna, a tropical rainforest region in Southwest China. Methods. From August 2010 to January 2011, mite-allergic patients and healthy controls were invited to participate. Dust samples from the patients' homes were collected, and mites in the samples were isolated. Permanent slides were prepared for morphologically based species determination. Results. In total, 6316 mite specimens of morphologically identifiable species were found in 233 dust samples taken from 41 homes. The result shows that the mite family of Pyroglyphidae occupied the highest percentage of the total amount of mites collected, followed by Cheyletidae family. The most common adult Pyroglyphidae mites were Dermatophagoides (D.) farinae, D. pteronyssinus, and D. siboney. The most common mites found from other families were Blomia tropicalis, Tyrophagus putrescentiae, and Aleuroglyphus ovatus. Four main allergenic dust mite species D. farinae, D. pteronyssinus, D. siboney, and Blomia tropicalis were found to be coinhabiting in 6/41 homes. Conclusion. The HDM population in homes in Xishuangbanna, a tropical rainforest region in Southwest China, has its own characteristics. It has rich dust mite species and the dust mite densities do not show significant variation across seasons.