Crabtreemelgaard4031

Aim Oxytocin, a peptide hormone synthesized in the hypothalamic paraventricular nucleus, has been reported to participate in the regulation of learning and memory performance. However, no report has demonstrated the effect of oxytocin on the amyloid-beta (Aβ)-induced impairment of synaptic plasticity. In this study, we examined the effects of oxytocin on the Aβ-induced impairment of synaptic plasticity in mice. Methods To investigate the effect of oxytocin on synaptic plasticity, we prepared acute hippocampal slices for extracellular recording and assessed long-term potentiation (LTP) with perfusion of the Aβ active fragment (Aβ25-35) in the absence and presence of oxytocin. Results We found that oxytocin reversed the impairment of LTP induced by Aβ25-35 perfusion in the mouse hippocampus. These effects were blocked by pretreatment with the selective oxytocin receptor antagonist L-368,899. Furthermore, the treatment with the ERK inhibitor U0126 and selective Ca2+-permeable AMPA receptor antagonist NASPM completely antagonized the effects of oxytocin. Conclusion This is the first report to demonstrate that oxytocin could reverse the effects of Aβ on hippocampal LTP in mice. We propose that ERK phosphorylation and Ca2+-permeable AMPA receptors are involved in this effect of oxytocin.Previous studies reported that ginsenoside Rg1 (Rg1) exerts antidepressant-like effect in animal models of depression. However, its effect on post-traumatic stress disorder (PTSD) remains elusive; PTSD is a common and costly psychiatric condition with negative cognitive and affective dysfunctions, such as anxiety and depression. In this study, we evaluated the role of Rg1 in a validated mice model of PTSD induced by single-prolonged stress (SPS). Sertraline, one of the FDA-approved medications for PTSD was used as a positive control. Our results showed that SPS exposure led to increased anxiety-like and despair-like behaviors. SPS exposure also caused enhanced contextual fear memory and overgeneralization of learned fear. Sertraline significantly ameliorated those abnormal behaviors induced by SPS, while Rg1 did not. Meanwhile, we found that sertraline but not Rg1 blocked the suppressive effect of SPS on adult neurogenesis in the hippocampus. Consistently, we found that SPS elevated adrenocorticotropic hormone (ACTH) level in the serum, which was inhibited by sertraline but not Rg1. Our results thus demonstrate that Rg1 at a dose used to treat depression may not be effective to rescue behavioral deficits associated with PTSD.The autophagy, which can be regulated by lysosomal membrane proteins, plays a critical role in maintaining normal podocyte function. TM7SF1 is a novel lysosomal membrane protein, but its effect on autophagy is still unknown. This study aimed to identify the role of TM7SF1 in mouse podocyte (MPC5) autophagy. Prednisolone F Interestingly, we detected an increase in LC3BII and SQSTM1/P62 in MPC5 through inhibiting TM7SF1, and which can be completely corrected after blocking the autolysosome degradation with chloroquine (CQ). Moreover, inhibition of TM7SF1 expression did not increase the mRNA level of SQSTM1/P62. Theses results suggested that inhibition of TM7SF1 led to impaired degradation of autophagy products, which manifest as an abnormal accumulation of LC3BII and SQSTM1/P62. Further studies showed that the downregulation of TM7SF1 resulted in a significant decrease in the number of acid lysosomes, which directly led to decreases in the number and function of autolysosomes. In conclusion, TM7SF1 is therefore essential for autolysosomes degradation pathway at the end of autophagy flow, and for the maintenance of podocyte function.Type-2 diabetes (T2D) is a common metabolic disorder, which causes several physiological and pathological complications. Spleen is regarded as an important organ, which regulates immune system and iron metabolism in the body. Precious few studies have been conducted to explore the pathological and deleterious roles of diabetes on spleen. In our current study, we have explored and confirmed the pathological effects of diabetes on spleen in db/db experimental mice model. In our current study, 0.5 mg/kg fibroblast growth factor 1 (FGF1) dose was intraperitoneally administrated to db/db mice. We found that diabetes evidently induced spleen enlargement and fibrosis progression in the db/db mice. Additionally, our studies demonstrate that iron has hugely deposited in the spleen in db/db mice. Several studies have documented that diabetes largely disrupts the inflammatory cells distribution, immune homeostasis, proliferation and oxidative stress with the down-regulation of anti-inflammatory cytokines and antioxidant activities. Moreover, we have observed that FGF1 administration significantly reversed the deleterious effect of diabetes on spleen enlargement and dysfunction. In summary, these substantial findings clearly demonstrate that diabetes plays deleterious roles in maintaining the spleen structure and functions. Therefore, our investigations suggest that FGF1 can effectively prevent diabetes-mediated splenomegaly progression.Degeneration of the retinal pigment epithelium (RPE) is a hallmark of atrophic age-related macular degeneration (AMD). Microglia mediated inflammatory responses and oxidative stress are critical pathophysiological processes in the onset and progression of RPE degeneration. Given the central role of the RPE, strategies to protect these cells from damage caused by oxidative stress and inflammation present a promising therapeutic approach to mitigate AMD. Ligands for the translocator protein (18 kDa) (TSPO) have been shown to confer protection against retinal inflammatory responses and neurodegeneration by acting primarily through retinal glia. However, despite RPE cells demonstrating strong TSPO expression, it remains unclear whether TSPO ligands could also inhibit inflammatory responses of RPE cells. Here, we investigated the influence of three different TSPO ligands XBD173, PK11195 and Ro5-4864 on inflammatory responses in human ARPE-19 cells triggered by supernatants from reactive human microglial cells and the lysosomal destabilizer, LLOMe. Our findings revealed that TSPO ligands significantly inhibited proinflammatory gene expression, inflammasome-mediated caspase-1 activation, lipid accumulation and intracellular ROS levels in stressed ARPE-19 cells. Notably, TSPO ligands induced activation of Nrf2 pathway and its downstream regulated genes in ARPE-19 cells, with Hmox-1 being the most strongly upregulated gene. Collectively, our study indicates that TSPO ligands can enhance the Nrf2 antioxidant pathway in RPE cells and protect them from cellular damage resulting from inflammation and oxidative stress.Introduction Herein we report a case of a surgical repair of double substance loss along the nasolabial groove by means of a double superior advancement flap from the cheek to the upper lip that we have here called the "double jigsaw puzzle" flap. Observation A 58-year-old man underwent surgery for 2 basal cell carcinomas located in the right white upper lip. The two lesions were first removed and the two defects were then carried over to the cheek symmetrically along the nasolabial groove. Two triangular "lugs" were excised on both sides to allow horizontal advancement of the cheek to the upper lip to fill the 2 gaps from the upper lip excisions like 2 pieces of a puzzle. The nasolabial groove was then recreated by deep anchoring stitches, with suturing comprising superficial stitches. Discussion This surgical flap can be created quickly and easily and yields good aesthetic results in the immediate postoperative period and in the longer term, and the scar is totally masked within the nasolabial fold. The only limitation to a good aesthetic outcome is the presence of a small area of hairless skin within what constitutes an area of hair growth in male subjects.Auditory deviance detection is a function of the auditory system that allows reduction of the processing demand for repetitive stimuli while stressing unpredictable ones, which are potentially more informative. Deviance detection has been extensively studied in humans using the oddball paradigm, which evokes an event-related potential known as mismatch negativity (MMN). The same stimulation paradigms are used in animal studies that aim to elucidate the neuronal mechanisms underlying deviance detection. In order to understand the circuitry responsible for deviance detection in the auditory cortex (AC), it is necessary to determine the properties of excitatory and inhibitory neurons separately. Measuring the spike widths of neurons recorded extracellularly from the anaesthetized rat AC, we classified them as fast spiking or regular spiking units. These two neuron types are generally considered as putative inhibitory or excitatory, respectively. In response to an oddball paradigm, we found that both types of units showed similar amounts of deviance detection overall. When considering each AC field separately, we found that only in A1 fast spiking neurons showed higher deviance detection levels than regular spiking neurons, while in the rest of the fields there was no such distinction. Interpreting these responses in the context of the predictive coding framework, we found that the responses of both types of units reflect mainly prediction error signaling (i.e., genuine deviance detection) rather than repetition suppression.Depression is a leading cause of disability worldwide and a major contributor to the overall global burden of disease, especially for women of childbearing age. Social science scholarship has demonstrated significant relationships between mental health, food insecurity (FI), water insecurity (WI), and HIV. Little is known, however, about the temporal relationships between food and water insecurity or the mechanisms through which these multiple stressors may operate or interact to impact depression. We therefore used syndemic theory to explore the complex relationships between FI, WI, and HIV on depressive symptomatology among Kenyan women of mixed HIV status (n=183, NCT02979418). We sought to 1) understand the temporal relationships between time-variant risk factors for depression, i.e. FI and WI, and 2) assess how these factors potentially interacted with HIV to impact depressive symptomatology. We first assessed the bidirectional relationship between WI and FI using a cross-lagged three-wave, two-variable panel model. Next, we modeled depressive symptomatology at 21 months as a linear function of the potentially syndemic interaction between FI, WI, and HIV status, adjusting for household wealth. WI had a predominant predictive effect on FI (Bayesian posterior predictive p-value=0.13); there was no reverse causality for the influence of FI on WI. The interaction effect of FI, WI, and HIV was significantly associated with greater depressive symptomatology (β=0.06) at 21 months postpartum. These data suggest that water insecurity may be an important determinant of food insecurity. Further, the co-occurrence of FI, WI, and HIV increases the likelihood of maternal depressive symptomatology, i.e. there is a syndemic relationship. These findings suggest that the role of household WI in other adverse health outcomes beyond mental well-being should be examined, and that interventions to improve mental health will be more effective if they also consider concurrent resource insecurities, regardless of HIV status.