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Morphine is frequently used for the treatment of chronic pain, while long-term use of the drug leads to analgesic tolerance. At present, the prevention of the side effect remains a big challenge. Bulleyaconitine A, a diterpenoid alkaloid from Aconitum bulleyanum plants, has been used to treat chronic pain in China for more than 30 years. In the present study, we tested the effect of bulleyaconitine A on analgesic tolerance induced by morphine injections (10 mg/kg s.c., b.i.d.) in the lumbar 5 spinal nerve ligation model of neuropathic pain. We found that intragastrical application of bulleyaconitine A (0.4 mg/kg) 30 min before each morphine injection substantially inhibited the decrease in morphine's inhibitory effect on mechanical allodynia and thermal hyperalgesia. Mechanistically, morphine injections further potentiated the lumbar 5 spinal nerve ligation induced long-term potentiation at C-fiber synapses in the spinal dorsal horn, a synaptic model of chronic pain. This effect was completely blocked by intragastrical bulleyaconitine A. It has been well established that activation of protein kinase C gamma and of glial cells in the spinal dorsal horn are critical for the development of opioid tolerance and neuropathic pain. We found that morphine injections exacerbated the upregulation of phospho-protein kinase C gamma (an active form of protein kinase C gamma), and the activation of microglia and astrocytes in the spinal dorsal horn induced by lumbar 5 spinal nerve ligation, and the effects were considerably prohibited by intragastrical bulleyaconitine A. Thus, spinal long-term potentiation at C-fiber synapses may underlie morphine tolerance. Oral administration of bulleyaconitine A may be a novel and simple approach for treating of opioid tolerance. [ABSTRACT FROM AUTHOR]

Abstract: The human brain can be studied as a hierarchy of complex networks on different temporal and spatial scales. On each scale, from gene, protein, synapse, neuron and microcircuit, to area, pathway and the whole brain, many advances have been made with the development of related techniques. Brain network studies on different temporal and spatial scales are booming. However, such studies have focused on single levels, and can only reflect limited aspects of how the brain is formed and how it works. Therefore, it is increasingly urgent to integrate a variety of techniques, methods and models, and to merge fragmented findings into a uniform research framework or platform. To this end, we have proposed the concept of the brainnetome and several related programs/projects have been launched in China. In this paper, we offer a brief review on the methodologies of the brainnetome, which include techniques on different scales, the brainnetome atlas, and methods of brain network analysis. We then take Alzheimer's disease and schizophrenia as examples to show how the brainnetome can be studied in neurological and psychiatric disorders. We also review the studies of how risk genes for brain diseases affect the brain networks. Finally, we summarize the challenges for the brainnetome, and what actions and measures have been taken to address these challenges in China. It is envisioned that the brainnetome will open new avenues and some long-standing issues may be solved by combining the brainnetome with other “omes”. [Copyright &y& Elsevier]

Abstract: Aim of the study: The present study was aimed to explore the effects of Salvia miltorrhiza in inducing rMSCs to differentiate into functional neurons. Materials and methods: rMSCs were isolated and cultured in vitro, then Salvia miltorrhiza was added to induce rMSCs to differentiate repeatedly for 5 times with an optimized protocol, and neurophysiological functions such as action potential, endocytosis and exocytosis of the induced cells were investigated. Results: About 98% of rMSCs expressed markers related to neural stem cells after treatment with preinduction medium, but they remained fibroform, the classical morphological state of MSCs, after exposure to induction medium for 2h, and the induced cells showed a neural shape. Next, fetal bovine serum (FBS) was added into the induction medium, transforming the neuron-like cells into fibroform cells. Finally, after exposure to induction medium, the cells could be transformed into neuron-like cells again. After the procedure was repeated 5 times, the induced cells displayed a classical neural shape and more than 95% of them expressed neural markers, including TUJ-1, NF and synaptophysin. Furthermore, the induced cells displayed neurophysiological functions, as characterized by action potential, endocytosis and exocytosis in response to a solution with a high concentration of potassium (K+). Conclusion: Salvia miltorrhiza can induce rMSCs to differentiate into neurons with neurophysiological functions efficiently by an optimized protocol. [Copyright &y& Elsevier]

Abstract: Depressive symptoms affect 40% to 50% of Parkinson''s disease (PD) patients, and adversely impact their quality of life. The decrease of serotonin (5-HT) in the synaptic cleft is commonly considered as the cause of depression. The reuptake of 5-HT released into the synaptic cleft is mediated by the 5-HT transporter (5-HTT). Many studies have focused on the relationship between the 5-HTT-linked polymorphic region (5-HTTLPR) and depression. The present study is to investigate the association between the polymorphisms in the promoter of the 5-HTT gene (including 5-HTTLPR and rs25531), which determine either a higher or lower 5-HT uptake, and risk for depression of PD. Three hundred six idiopathic PD patients were recruited randomly from hospital clinic and the Center for Epidemiological Studies Depression Scale (CES-D) was used as the diagnosis or rating scale for depression. Polymerase Chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used and the patients’ genotypes were divided as LA, LG, SA, and SG. We found no evidence for an association between variants of 5-HTTLPR and rs25531 alleles, and depressive symptoms in Chinese PD patients. [Copyright &y& Elsevier]

Background and purpose: Prion protein (PrP) predominantly localized at synapses can modulate neuronal excitability. The prion protein gene ( PRNP) has been considered one of the candidate genes that play a role in seizure susceptibility. A recent study demonstrated that the 129V allele in the PRNP gene was associated with susceptibility to temporal lobe epilepsy (TLE) in female patients in an Italian population. We screened variations in the open-reading frame (ORF) of the PRNP gene and also replicated the association of the M129V polymorphism with TLE in a Han Chinese population. Methods: The M129V polymorphism was genotyped in 320 MTLE patients and 558 non-epilepsy controls. All subjects were Han Chinese. Results: No novel polymorphism in the ORF of the PRNP gene was detected. Differences in the genotype distributions and allele frequencies of this polymorphism between cases and controls were insignificant ( P = 0.24). Further analysis with stratification of the results by gender or age and analysis of clinical features in relation to M129V genotypes also yielded negative findings. Conclusions: The present study provides evidence that the M129V polymorphism in the PRNP gene is not associated with MTLE in a Han Chinese population. [ABSTRACT FROM AUTHOR]