Establishment and evaluation of a stress depression model induced by light and dampness on mice / 中华行为医学与脑科学杂志

Objective@#To establish a novel stress-induced depression model by changing the lighting conditions and continuously damping cushion (L-D).@*Methods@#The L-D stress depression animal model was established in C57BL / 6 mice with body weight of 18-22 g. Seventy-five mice with the horizontal and vertical scores higher than 30 and less than 120 in open field test were employed.In the research of model construction, mice were randomly divided into three groups: control group (n=9), chronic unpredictable mild stress(CUMS) model group (n=10) and L-D model group (n=9). In the drug intervention experiments, mice were randomly divided into five groups: control group (n=9), chronic unpredictable mild stress(CUMS) model group (n=10), L-D model group (n=9), CUMS+ fluoxetine group (n=10) and L-D model+ fluoxetine group (n=9). Open field test, forced swimming test and sucrose preference test were used to evaluate the degree of depression in animals.@*Results@#(1) In the open field test, the horizontal score of CUMS model group (67.20±5.81) and the L-D model group (52.56±19.05) were significantly lower than that of the control group (76.44±9.22) (t=2.645, t=3.387, both P<0.05). And horizontal score of the L-D model was significantly lower than that of the CUMS model (t=2.321, both P<0.05). In forced swimming experiment, compared with the control group ((39.67±21.12)s), the immobility time of the CUMS model group ((60.90±10.34)s) and the L-D model group ((74.89±16.10)s) were significantly prolonged (t=2.831, 3.979, both P<0.05). The immobility time of the L-D model group was also significantly higher than that of the CUMS model group (t=2.278, P<0.05). In the sucrose preference experiment, the percentage of sucrose preference in CUMS model group ((72±7)%) and L-D model group ((65±5)%) was lower than that in the control group ((81±12)%) (t=2.195, 3.875, both P<0.05). The percentage of sucrose preference of L-D model group was significantly higher than that of CUMS model group (t=2.286, P<0.05). (2) After intervention with antidepressants, the horizontal scores of the CUMS model group (65.60±6.43) and the L-D model group (54.33±14.67) were significantly lower than that of the control group (75.78±8.27) in open field test (t=3.011, t=3.861, both P<0.05), and the score of L-D group was lower than that of CUMS group(t=2.235, P<0.05). The vertical score of the L-D model group (33.44±4.54) was significantly lower than that of the control group (39.22±5.56) (t=2.553, P<0.05). There was significant increase in the level score and vertical score of CUMS model and L-D model after fluoxetine intervention (t=3.090, t=2.692, both P<0.05), and significant twist in the vertical score of CUMS model and L-D model (t=2.681, t=2.354; both P<0.05). In the forced swimming experiment, the immobility time of the L-D model((64.11±13.06)s) was significantly longer than that of the control group ((42.00±13.77)s) (t=3.494, P<0.05). The immobility time of CUMS model and L-D model mice was significantly longer than that of non-intervention group (t=2.137, 2.940, both P<0.05). After the intervention of fluoxetine, there was no significant difference between the CUMS group, L-D group, the control group(all P>0.05).@*Conclusion@#Changing the lighting conditions and continuously damping cushion is a new method to establish mice model with depression behavior.Shorter modeling duration and simple operation are the main advantages of this model.

Scorpion toxin BmK I directly activates Nav1.8 in primary sensory neurons to induce neuronal hyperexcitability in rats

Voltage-gated sodium channels (VGSCs) in primary sensory neurons play a key role in transmitting pain signals to the central nervous system. BmK I, a site-3 sodium channel-specific toxin from scorpion Buthus martensi Karsch, induces pain behaviors in rats. However, the subtypes of VGSCs targeted by BmK I were not entirely clear. We therefore investigated the effects of BmK I on the current amplitude, gating and kinetic properties of Nav1.8, which is associated with neuronal hyperexcitability in DRG neurons. It was found that BmK I dose-dependently increased Nav1.8 current in small-sized (<25 μm) acutely dissociated DRG neurons, which correlated with its inhibition on both fast and slow inactivation. Moreover, voltage-dependent activation and steady-state inactivation curves of Nav1.8 were shifted in a hyperpolarized direction. Thus, BmK I reduced the threshold of neuronal excitability and increased action potential firing in DRG neurons. In conclusion, our data clearly demonstrated that BmK I modulated Nav1.8 remarkably, suggesting BmK I as a valuable probe for studying Nav1.8. And Nav1.8 is an important target related to BmK I-evoked pain.

Structural Classification and Functional Characterization ofShort-Chain Scorpion Toxic Peptides / 生物化学与生物物理进展

Recent research has revealed that scorpion venom contains short-chain peptides with the specificity on K+or C1-channels, in addition to the knowledge of many kinds of long-chain peptides with the specificity on Na+ channels. According to the similarity of molecular structure and/or function, they have been classified into several groups. These short-chain scorpion peptides are playing more and more important role in studying the structure and function of K+ or C1- channels. The advance of structure and function of short-chain scorpion peptides in recent years was briefly introduced.