Light plays a pivotal role in the regulation of affective behaviors. However, the precise circuits that mediate the impact of light on depressivelike behaviors are not well understood. Here, we show that light influences depressive-like behaviors through a disynaptic circuit linking the retina and the lateral habenula (LHb). Specifically, M4type melanopsin-expressing retinal ganglion cells (RGCs) innervate GABA neurons in the thalamic ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL), which in turn inhibit CaMKIIa neurons in the LHb. Specific activation of vLGN/IGL-projecting RGCs, activation of LHbprojecting vLGN/IGL neurons, or inhibition of postsynaptic LHb neurons is sufficient to decrease the depressive-like behaviors evoked by longterm exposure to aversive stimuli or chronic social defeat stress. Furthermore, we demonstrate that the antidepressive effects of light therapy require activation of the retina-vLGN/IGL-LHb pathway. These results reveal a dedicated retina-vLGN/ IGL-LHb circuit that regulates depressive-like behaviors and provide a potential mechanistic explanation for light treatment of depression.

Epidural analgesia in the latent phase of labor at cervical dilation of 1.0 cm or more does not prolong the progression of labor and does not increase the rate of Cesarean in nulliparous women compared with the delayed analgesia at the cervical dilation of 4.0 cm or more.

No abstract

Embryo quality is strongly dependent on the in-vitro culture environment. Conventionally, IVF/intracytoplasmic sperm injection (ICSI) embryos are examined microscopically every morning (from day 1 to day 6) to assess fertilization, cleavage and embryo quality. Consequently, the frequent exposure to non-optimal conditions outside the incubator may adversely affect embryonic viability and quality. Hence, this study investigated whether reduction of observation frequency outside the incubator can enhance blastocyst formation rate. A total of 285 IVF/ICSI cycles were divided into two groups. Embryos in the control group (103 cycles) were assessed out-of-incubator every day after insemination (day 1 to day 6; six times). In the experimental group (182 cycles), embryos were assessed four times, on days 1, 3, 5 and 6. The total blastocyst formation rate, day-5 blastocyst formation rate, proportion of good blastocysts and number of cryopreserved blastocysts per patient were significantly lower for the control group compared with the experimental group (42.5%, 31.4%, 50.7%, 1.72+/-1.55 versus 52.6%, 40.7%, 60.1%, 2.64+/-2.59, respectively, P<0.05); although there were no significant differences in the proportions of good embryos on day 3, blastocyst formation rate on day 6, clinical pregnancy rate and implantation rate. Hence, reduction of the observation frequency of embryos outside the incubator can enhance embryo quality and blastocyst formation rate.

No abstract

MIF-associated extracellular signal-regulated kinase 1/2-N-methyl-D-aspartic acid receptor or prostaglandin E(2) cascade accounts for the changes in peripheral nerve injury-induced nociceptive responses.

Pro-inflammatory cytokine production after nociceptive stimuli is pivotal for hyperalgesia. As macrophage migration inhibitory factor (MIF), a pleiotropic cytokine produced mainly by nonneuronal tissue, has been involved in the regulation of neuronal functions, herein we examined the role for MIF in formalin-induced inflammatory pain model. MIF critically contributed to nociceptive behaviors following formalin injection. Specifically, spinal administration of a MIF inhibitor (ISO-1) prevented and reversed flinching responses in rats. Further examination showed that levels of both MIF and the MIF receptor CD74 were substantially increased within the ipsilateral spinal cord dorsal horn after formalin administration. Mechanistic studies revealed that MIF upregulated the expression of the spinal NMDA receptor subunit NR2B via the MAPK signaling pathway. Moreover, microglial cells were found to be the major source of spinal MIF after formalin administration by fluorescence colocalization. These data highlight spinal MIF plays a critical role in the pathogenesis of formalin-induced inflammatory pain and suggest MIF may be a potential target for therapy of such pathological condition.

Purpose The objective of this study was to investigate the effects of vitrification on the preimplantation developmental competence of mouse 2-cell, 4-cell and 8-cell stage embryos. Methods Mouse 2-cell, 4-cell and 8-cell stage embryos were cryopreserved using the cryotop vitrification method and subsequently warmed on a later date. The embryos were then assessed by their morphology, blastocyst formation and hatching rates. Additionally, trophectoderm (TE) and inner cell mass (ICM) cell numbers were compared in hatched blastocysts from the control and experimental groups. Results Vitrified embryos at the 2-cell, 4-cell and 8-cell stages appeared morphologically normal after warming. The overall survival rate of vitrified embryos at various stages after warming was 96.7% and there were no significant differences among 2-cell stage (96.0%), 4-cell stage (96.8%) and 8-cell stage (97.1%) embryos (P>0.05). The blastocyst formation rate (69.4%) and hatching rate (52.6%) of vitrified 2-cell embryos were significantly lower than that from the control group and vitrified 8-cell embryos (P<0.05). In the vitrified 4-cell embryo group, the blastocyst formation rate (90.3%) was similar to the 8-cell group (91.2%), but the hatching rate (60.0%) was significantly lower than that of the non-vitrified control ( 84.1%) and vitrified 8-cell embryo (78.4%) groups (P<0.05). When further development to the fully hatched blastocyst stage was compared, hatched blastocysts derived from vitrified 2-cell, 4-cell and 8-cell embryos had significantly lower cell counts both in the ICM and TE, as compared to fresh blastocysts (P<0.05). Among the vitrified 2-cell, 4-cell and 8-cell embryo groups, there were no significant differences in the cell counts of ICM and TE (P>0.05). Conclusions Although cryotop vitrification was suitable for the cryopreservation of mouse embryos from the 2-cell stage, 4-cell stage and 8-cell stage without significant loss of survival, vitrification had an adverse effect on the development of 2-cell embryos. Mouse embryos at the 8-cell stage had the best tolerance for vitrification and would yield the highest level of post-vitrification developmental competence among early cleavage stage embryos. Nevertheless, it is unclear how these findings can be extrapolated to human embryos.