[Pathogenesis of ferroptosis on chronic kidney disease and traditional Chinese medicine intervention: a review].

Chronic kidney disease(CKD) is an insidious disease that has become a significant global public health issue due to its high incidence rate, low awareness, low diagnostic rate, poor prognosis, and high medical costs. Recent studies have shown that CKD development is associated with varying degrees of ferroptosis features. Traditional Chinese medicine(TCM) can regulate iron metabolism, lipid peroxidation, antioxidant systems to inhibit ferroptosis and delay the progression of CKD. Consequently, the intervention mechanism of ferroptosis has become one of the focuses of CKD research. TCM has thousands of years of traditional experience and wisdom. It focuses on the overall regulation of human body functions and can stimulate the body's disease resistance and recovery capabilities, which has certain advantages in treating CKD. However, there is currently a lack of comprehensive articles on the application of TCM in intervening ferroptosis to treat CKD and the pathogenesis of ferroptosis in CKD. Therefore, this article summarizes the latest research progress both domestically and internationally, briefly introduces the main mechanisms of ferroptosis, and systematically reviews the relationship between ferroptosis and CKD. The article integrates TCM theories related to ferroptosis in CKD, including "deficiency" "stasis" "phlegm turbidity" and "toxins" and summarizes the research status of active ingredients and herbal formulas in intervening ferroptosis to treat CKD. By considering ferroptosis from a new perspective, this article aims to provide new targets and directions for the application of TCM in treating CKD.

FoxG1 as a Potential Therapeutic Target for Alzheimer's Disease: Modulating NLRP3 Inflammasome via AMPK/mTOR Autophagy Pathway.

An increasing body of research suggests that promoting microglial autophagy hinders the neuroinflammation initiated though the NLRP3 inflammasome activation in Alzheimer's disease (AD). The function of FoxG1, a crucial transcription factor involved in cell survival by regulating mitochondrial function, remains unknown during the AD process and neuroinflammation occurs. In the present study, we firstly found that Aß peptides induced AD-like neuroinflammation upregulation and downregulated the level of autophagy. Following low-dose Aß25-35 stimulation, FoxG1 expression and autophagy exhibited a gradual increase. Nevertheless, with high-concentration Aß25-35 treatment, progressive decrease in FoxG1 expression and autophagy levels as the concentration of Aß25-35 escalated. In addition, FoxG1 has a positive effect on cell viability and autophagy in the nervous system. In parallel with the Aß25-35 stimulation, we employed siRNA to decrease the expression of FoxG1 in N2A cells. A substantial reduction in autophagy level (Beclin1, LC3II, SQSTM1/P62) and a notable growth in inflammatory response (NLRP3, TNF-α, and IL-6) were observed. In addition, we found FoxG1 overexpression owned the effect on the activation of AMPK/mTOR autophagy pathway and siRNA-FoxG1 successfully abolished this effect. Lastly, FoxG1 suppressed the NLRP3 inflammasome and enhanced the cognitive function in AD-like mouse model induced by Aß25-35. Confirmed by cellular and animal experiments, FoxG1 suppressed NLRP3-mediated neuroinflammation, which was strongly linked to autophagy regulated by AMPK/mTOR. Taken together, FoxG1 may be a critical node in the pathologic progression of AD and has the potential to serve as therapeutic target.

The impact of ulinastatin on wound infection and healing in patients with burn wounds: A meta-analysis.

Burn injuries result in localised tissue damage and precipitate systemic responses; routine clinical treatments, which typically include metabolic nutritional support and anti-infection therapies, do not yield optimal outcomes. Therefore, we aimed to systematically evaluate the effects of ulinastatin on wound infection and healing in patients with burns to provide reliable evidence-based recommendations for burn treatment. An electronic search of the Web of Science, PubMed, Cochrane Library, Embase, Wanfang, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure databases, supplemented by manual searches, was conducted from database inception to October 2023 to collect randomised controlled trials (RCTs) assessing the efficacy of ulinastatin for the treatment of burns. Two researchers screened all retrieved articles according to the inclusion and exclusion criteria; the included studies were evaluated for quality, and the relevant data were extracted. Stata 17.0 software was employed for data analysis. Overall, 8 RCTs with 803 patients were included, with 404 and 399 in the ulinastatin and conventional treatment groups, respectively. The analysis revealed that wound infections (odds ratio [OR] = 0.08, 95% CI: 0.02-0.35, p = 0.001) and complications (OR = 0.21, 95% CI: 0.10-0.42, p < 0.001) were significantly lower, and wound healing time (standardised mean differences [SMD] = -1.31, 95% CI: -2.05 to -0.57, p = 0.001) was significantly shorter, in the ulinastatin groups than in the control group. This meta-analysis revealed that ulinastatin can effectively reduce the incidence of wound infections and complications and significantly shorten the duration of wound healing in patients with burns, thereby promoting early recovery in these patients.

The Spectrum of Low-pTJ/ψ in Heavy-Ion Collisions in a Statistical Two-Body Fractal Model.

We establish a statistical two-body fractal (STF) model to study the spectrum of J/ψ. J/ψ serves as a reliable probe in heavy-ion collisions. The distribution of J/ψ in hadron gas is influenced by flow, quantum and strong interaction effects. Previous models have predominantly focused on one or two of these effects while neglecting the others, resulting in the inclusion of unconsidered effects in the fitted parameters. Here, we study the issue from a new point of view by analyzing the fact that all three effects induce a self-similarity structure, involving a J/ψ-π two-meson state and a J/ψ, π two-quark state, respectively. We introduce modification factor qTBS and q2 into the probability and entropy of charmonium. qTBS denotes the modification of self-similarity on J/ψ, q2 denotes that of self-similarity and strong interaction between c and c¯ on quarks. By solving the probability and entropy equations, we derive the values of qTBS and q2 at various collision energies and centralities. Substituting the value of qTBS into distribution function, we successfully obtain the transverse momentum spectrum of low-pT J/ψ, which demonstrates good agreement with experimental data. The STF model can be employed to investigate other mesons and resonance states.

PGC-1α regulates critical period onset/closure, mediating cortical plasticity.

Peroxisome proliferator-activated receptor PPARγ coactivator-α (PGC-1α) is concentrated in inhibitory interneurons and plays a vital role in neuropsychiatric diseases. We previously reported some characteristic features of schizophrenia (SZ) in GABAergic neuron-specific Pgc-1alpha knockout (KO) mice (Dlx5/6-Cre: Pgc-1alphaf/f). However, there is a fundamental gap in the molecular mechanism by which the Pgc-1alpha gene is involved in the neurobehavioral abnormalities of SZ. The loss of critical period (CP) triggers-maturations of parvalbumin interneurons (PVIs) and brakes-and the formation of perineuronal nets (PNNs) implicates mistimed trajectories during adult brain development. In this study, using the Pgc-1alpha KO mouse line, we investigated the association of Pgc-1alpha gene deletion with SZ-like behavioral deficits, PVI maturation, PNN integrity and synaptic ultrastructure. These findings suggest that Pgc-1alpha gene deletion resulted in a failure of CP onset and closure, thereby prolonging cortical plasticity timing. To determine whether the manipulation of the PNN structure is a potential method of altering neuronal plasticity, GM6001, a broad-spectrum matrix metalloproteinase (MMP)-inhibitor was applied. Here we confirmed that the treatment could effectively correct the CP plasticity window and ameliorate the synaptic ultrastructure in the Pgc-1alpha KO brain. Moreover, the intervention effect on neuronal plasticity was followed by the rescue of short-term habituation deficits and the mitigation of aberrant salience, which are some characteristic features of SZ. Taken collectively, these findings suggest that the role of PGC-1α in regulating cortical plasticity is mediated, at least partially, through the regulation of CP onset/closure. Strategically introduced reinforcement of molecular brakes may be a novel preventive therapy for psychiatric disorders associated with PGC-1α dysregulation.

Mutation of the attractin gene impairs working memory in rats.

OBJECTIVE: Attractin (ATRN) is a widely expressed member of the cell adhesion and guidance protein family in humans that is closely related to cellular immunity and neurodevelopment. However, while previous studies in our laboratory have confirmed the effect of ATRN mutations on long-term memory, its specific role and the molecular mechanism by which it influences spatial cognition are poorly understood. METHODS: This study aimed to examine the effect of ATRN mutations on working memory in water maze with a novel ATRN-mutant rat generated by the CRISPR/Cas9 system; the mutation involved the substitution of the 505th amino acid, glycine (G), with cysteine (C), namely, a mutation from GGC to TGC. The changes in myelin basic protein (MBP) expression in rats were also analyzed with the western blot. RESULTS: The ATRN-G505C(KI/KI) rats exhibited significant increases in the required latency and distance traveled to locate the escape platform in a Morris water maze test of working memory. In addition, the expression of MBP was reduced in ATRN-mutant rats, as shown in the western blot analysis. CONCLUSION: Our results indicate that ATRN gene mutations may directly lead to the impairment of working memory in the water maze; this impairment may be due to the inhibition of MBP expression, which in turn affects the spatial cognition.

FOXG1 Contributes Adult Hippocampal Neurogenesis in Mice.

Strategies to enhance hippocampal precursor cells efficiently differentiate into neurons could be crucial for structural repair after neurodegenerative damage. FOXG1 has been shown to play an important role in pattern formation, cell proliferation, and cell specification during embryonic and early postnatal neurogenesis. Thus far, the role of FOXG1 in adult hippocampal neurogenesis is largely unknown. Utilizing CAG-loxp-stop-loxp-Foxg1-IRES-EGFP (Foxg1fl/fl), a specific mouse line combined with CreAAV infusion, we successfully forced FOXG1 overexpressed in the hippocampal dentate gyrus (DG) of the genotype mice. Thereafter, we explored the function of FOXG1 on neuronal lineage progression and hippocampal neurogenesis in adult mice. By inhibiting p21cip1 expression, FOXG1-regulated activities enable the expansion of the precursor cell population. Besides, FOXG1 induced quiescent radial-glia like type I neural progenitor, giving rise to intermediate progenitor cells, neuroblasts in the hippocampal DG. Through increasing the length of G1 phase, FOXG1 promoted lineage-committed cells to exit the cell cycle and differentiate into mature neurons. The present results suggest that FOXG1 likely promotes neuronal lineage progression and thereby contributes to adult hippocampal neurogenesis. Elevating FOXG1 levels either pharmacologically or through other means could present a therapeutic strategy for disease related with neuronal loss.

A Role for PGC-1a in the Control of Abnormal Mitochondrial Dynamics in Alzheimer's Disease.

Emerging evidence suggests that the proper control of mitochondrial dynamics provides a window for therapeutic intervention for Alzheimer's disease (AD) progression. The transcriptional coactivator peroxisome proliferator activated receptor gamma coactivator 1 (PGC-1a) has been shown to regulate mitochondrial biogenesis in neurons. Thus far, the roles of PGC-1a in Alzheimer's disease and its potential value for restoring mitochondrial dysfunction remain largely unknown. In the present study, we explored the impacts of PGC-1a on AD pathology and neurobehavioral dysfunction and its potential mechanisms with a particular focus on mitochondrial dynamics. Paralleling AD-related pathological deposits, neuronal apoptosis, abnormal mitochondrial dynamics and lowered membrane potential, a remarkable reduction in the expression of PGC-1a was shown in the cortex of APP/PS1 mice at 6 months of age. By infusing AAV-Ppargc1α into the lateral parietal association (LPtA) cortex of the APP/PS1 brain, we found that PGC-1a ameliorated AD-like behavioral abnormalities, such as deficits in spatial reference memory, working memory and sensorimotor gating. Notably, overexpressed PGC-1a in LPtA rescued mitochondrial swelling and damage in neurons, likely through correcting the altered balance in mitochondrial fission-fusion and its abnormal distribution. Our findings support the notion that abnormal mitochondrial dynamics is likely an important mechanism that leading to mitochondrial dysfunction and AD-related pathological and cognitive impairments, and they indicate the potential value of PGC-1a for restoring mitochondrial dynamics as an innovative therapeutic target for AD.

GABAB receptors constrain glutamate presynaptic release and postsynaptic actions in substantia gelatinosa of rat spinal cord.

The substantia gelatinosa (SG, lamina II of spinal cord gray matter) is pivotal for modulating nociceptive information from the peripheral to the central nervous system. γ-Aminobutyric acid type B receptors (GABABRs), the metabotropic GABA receptor subtype, are widely expressed in pre- and postsynaptic structures of the SG. Activation of GABABRs by exogenous agonists induces both pre- and postsynaptic inhibition. However, the actions of endogenous GABA via presynaptic GABABRs on glutamatergic synapses, and the postsynaptic GABABRs interaction with glutamate, remain elusive. In the present study, first, using in vitro whole-cell recordings and taking minimal stimulation strategies, we found that in rat spinal cord glutamatergic synapses, blockade of presynaptic GABABRs switched "silent" synapses into active ones and increased the probability of glutamate release onto SG neurons; increasing ambient GABA concentration mimicked GABABRs activation on glutamatergic terminals. Next, using holographic photostimulation to uncage glutamate on postsynaptic SG neurons, we found that postsynaptic GABABRs modified glutamate-induced postsynaptic potentials. Taken together, our data identify that endogenous GABA heterosynaptically constrains glutamate release via persistently activating presynaptic GABABRs; and postsynaptically, GABABRs modulate glutamate responses. The results give new clues for endogenous GABA in modulating the nociception circuit of the spinal dorsal horn and shed fresh light on the postsynaptic interaction of glutamate and GABA.

FOXG1 as a Potential Therapeutic Target for Alzheimer's Disease with a Particular Focus on Cell Cycle Regulation.

BACKGROUND: Several recent findings have revealed that targeting of cell cycle reentry and (or) progression may provide an opportunity for the therapeutic intervention of Alzheimer's disease (AD). FOXG1 has been shown to play important roles in pattern formation, cell proliferation, and cell specification. Thus far, the roles of FoxG1 and its involvement in AD are largely unknown. OBJECTIVE: Our study aimed to explore the intervention effect of FOXG1 on AD pathology and its potential mechanism with a particular focus on cell cycle regulation. METHODS: We investigated the association of Foxg1 gene variants with AD-like behavioral deficits, p21 expression, neuronal apoptosis, and amyloid-ß (Aß) aggregate formation; we further determined whether targeting FOXG1-regulated cell cycle has therapeutic potential in AD. RESULTS: Paralleling AD-like behavioral abnormalities, neuronal apoptosis, and Aß deposits, a significant reduction in the expression of FOXG1 was observed in APP/PS1 mice at 6 months of age. Using the APP/PS1;Foxg1fl/fl-CreAAV mouse line, we found that FOXG1 potentially antagonized cell cycle reentry by negatively regulating the levels of p21-activated kinase (PAK3). By reducing p21cip1-mediated arrest at the G2 stage and regulating cyclin A1- and cyclin B-dependent progression patterns of the cell cycle, FOXG1 blocked neuronal apoptosis and Aß deposition. CONCLUSION: These results indicate that FOXG1 contributes to the regulation of the neuronal cell cycle, thereby affecting brain abnormalities in AD. An elevation of the FOXG1 level, either pharmacologically or through other means, could present a therapeutic strategy for AD.

Presynaptic GABAB receptors differentially modulate GABA release from cholecystokinin and parvalbumin interneurons onto CA1 pyramidal neurons: A cell type-specific labeling and activating study.

Combining cell type-specific optogenetics and whole cell recordings on mouse acute hippocampal slices, we compared GABA release from cholecystokinin-expressing (CCK) and parvalbumin-expressing (PV) interneurons onto CA1 pyramidal neurons. Baclofen, a selective GABAB receptor agonist, inhibited GABAergic synaptic transmission greater from CCK terminals, compared to that from PV terminals. The N-type calcium channels on CCK and P/Q-type calcium channels on PV terminals contributed to the GABAB receptor-mediated inhibition, respectively. Our data thus provide direct evidence that GABAB receptors differentially modulate GABA release from CCK and PV interneurons, adding to an increasing list of differences between these two interneuron subtypes in modulating hippocampal pyramidal neurons.

Ameliorative effect of SIRT1 in postpartum depression mediated by upregulation of the glucocorticoid receptor.

Recent evidence has confirmed the association of glucocorticoid receptor (GR) gene variants with the "stress" endocrine axis in postpartum depression (PPD). Sirtuin 1(SIRT1) is an NAD+-dependent histone deacetylase and transcriptional enhancer of GR. However, to date, the function of the SIRT1 gene in the regulation of GR expression in PPD remains to be fully determined. A hormone-stimulated pregnancy (HSP) and subsequent "postpartum" withdrawal of estrogen was employed to mimic the fluctuations in estradiol associated with pregnancy and postpartum. We confirmed that estradiol benzoate withdrawal (EW)-rats displayed depression- and anxiety-like behaviors. These behavioral dysfunctions are associated with attenuated expression of SIRT1 and GR in the hippocampus. To assess the role of SIRT1, as well as its regulatory target directly, a selective SIRT1 activator (SRT2104) was infused into the hippocampus of EW-rats. We found that pharmacological activation of hippocampal SIRT1 blocks the development of depression-related, but not anxiety-related, phenotypes of PPD. In addition, the activation of SIRT1 leads to an increase in hippocampal GR expression in EW-rats. We further confirmed that SIRT1 physically interacts with GR in a glucocorticoid-dependent manner. Taken together, our results suggest that neuropathology in PPD is caused, at least in part, by the inhibition of the SIRT1-GR signaling pathway. Elevating SIRT1 levels, either pharmacologically or through other means, could represent a therapeutic strategy for PPD.

Attractin Gene Deficiency in Rats Leads to Impairments in Both Activity and Spatial Learning and Memory.

Attractin (ATRN), an autosomal recessive gene that is widely distributed in the brain, is involved in the execution of a variety of brain functions and associated with certain neuropsychiatric disorders. Here, we introduce a novel rat strain harboring a mutation in ATRN that was generated by knocking in ATRN-G505C via the CRISPR/Cas9 system. We assessed the behavioral performance of these mutant ATRN knock-in rats. The G505C mutation was introduced into exon 9, and a synthetic primer was inserted into introns 8-9 for genotyping. The 505th amino acid, a Gly (G) residue, was mutated to a Cys (C) residue, i.e., GGC was mutated to TGC. Behavioral experiments showed that homozygous ATRN rats spent significantly more time searching for the escape platform in the acquisition trial and significantly less time in the target area in the probe trial in the Morris water maze (MWM) test and traveled a significantly shorter distance in the open field test (OFT) than wild-type rats. In addition, Western blot analysis and immunohistochemistry showed that rats with the mutant ATRN gene exhibited significantly reduced expression of brain-derived neurotrophic factor (BDNF). In summary, our results indicate that mutations in the ATRN gene directly lead to learning and memory impairments and slight motor deficits. These findings provide new clues for the mechanism by which mutant ATRN induces neurodegenerative changes.

LncRNA PCAT1 Interacts with DKC1 to Regulate Proliferation, Invasion and Apoptosis in NSCLC Cells via the VEGF/AKT/Bcl2/Caspase9 Pathway.

Long noncoding RNAs (lncRNAs) are increasingly recognized as indispensable components of the regulatory network in the progression of various cancers, including nonsmall cell lung cancer (NSCLC). The lncRNA prostate cancer associated transcript 1 (PCAT1) has been involved in tumorigenesis of multiple malignant solid tumors, but it is largely unknown that what is the role of lncRNA-PCAT1 and how it functions in the progression of lung cancer. Herein, we observed that lncRNA PCAT1 expression was upregulated in both human NSCLC tissues and cell lines, which was determined by qualitative polymerase chain reaction analysis. Then, gain-and loss-of-function manipulations were performed in A549 cells by transfection with a specific short interfering RNA against PCAT1 or a pcDNA-PCAT1 expression vector. The results showed that PCAT1 not only promoted NSCLC cell proliferation and invasion but also inhibited cell apoptosis. Bioinformatics and expression correlation analyses revealed that there was a potential interaction between PCAT1 and the dyskerin pseudouridine synthase 1 (DKC1) protein, an RNA-binding protein. Then, RNA pull-down assays with biotinylated probes and transcripts both confirmed that PCAT1 directly bounds with DKC1 that could also promote NSCLC cell proliferation and invasion and inhibit cell apoptosis. Moreover, the effects of PCAT1 and DKC1 on NSCLC functions are synergistic. Furthermore, PCAT1 and DKC1 activated the vascular endothelial growth factor (VEGF)/protein kinase B (AKT)/Bcl-2/caspase9 pathway in NSCLC cells, and inhibition of epidermal growth factor receptor, AKT, or Bcl-2 could eliminate the effect of PCAT1/DKC1 co-overexpression on NSCLC cell behaviors. In conclusion, lncRNA PCAT1 interacts with DKC1 to regulate proliferation, invasion, and apoptosis in NSCLC cells via the VEGF/AKT/Bcl-2/caspase9 pathway.

PGC-1α reduces Amyloid-ß deposition in Alzheimer's disease: Effect of increased VDR expression.

Amyloid-ß (Aß) is the core component of amyloid plaques of Alzheimer's disease (AD). Recent evidence has confirmed that Aß triggers neurodegeneration by dramatically suppressing vitamin D receptor (VDR) expression. Thus far, the onset mechanisms and means of preventing AD are largely unknown. Perioxisome proliferator-activated receptor-γ coactivator (PGC-1α), as a transcriptional coactivator of VDR could protect cells against oxidative stress. Thus, upregulation of PGC-1α is a candidate therapeutic strategy for AD. To investigate the effect of PGC-1α in AD, and to illuminate the precise involvement of VDR in the neuroprotective strategy, the varies of molecular of PGC-1α and VDR were studied in APP/PS-1 double transgenic (2xTg-AD) mice at 6 months of age, significant reduction in the expression of PGC-1α and VDR was found in their hippocampus and the cortex. Besides, a specific mouse line, Dlx5/6-Cre:PGC-1αfl/fl in which the PGC-1α deficiency was limited to the hippocampus and the cortex, was used to study the target intervention of PGC-1α, decreased expression of VDR and increased oxidative damage were observed in AD-related brain regions by PGC-1α deficiency. To explore the function and therapeutic strategy of PGC-1α in AD, an adeno-associated virus (AAV) was used to induce PGC-1α overexpressed in the hippocampus of 2xTg-AD mice. Overexpressed PGC-1α results in a remarkable increase in the levels of VDR associated with a significant reduction in the expression of Aß plaques and of 8-oxo-dG in 2xTg-AD mice. These data may have ramifications for neuroprotective strategies targeting overexpression of PGC-1α in Alzheimer's disease.

Enhancing excitatory projections from the ventral subiculum to the nucleus accumbens shell contribute to the MK-801-induced impairment of prepulse inhibition.

Prepulse inhibition (PPI), a measure of sensorimotor gating, has been shown to be disrupted in several animal models of neuropsychiatric disorders, such as schizophrenia. The neural circuits involving the hippocampus and nucleus accumbens (NAC) have been studied in rats to uncover the neurochemical and neuroanatomical substrates that regulate PPI. Majority of the studies of the hippocampus on PPI to date have been focused on CA1, CA2, and dentate gyrus (DG) area. Little is known about the role of the subiculum, which maintains the hippocampal formation intact, on the sensorimotor gating. In this study, the PPI disruption was induced by intraperitoneal injection of MK-801 in rats, and the neuronal activity in the dorsal and ventral subiculum by c-Fos immunostaining was examined. The projections from the subiculum to the nucleus accumbens (NAC) were detected by retrograde tracing of cholera toxin B subunit, in the PPI dysfunctional animals. The results showed an increase in neuronal activity in the ventral subiculum (vSub) while remaining constant in the dorsal subiculum during PPI disruption. The excitatory projections from the vSub to the NAC shell were significantly enhanced when PPI was disrupted. Muscimol Inhibition of vSub could significantly ameliorate the MK801-induced PPI deficit. This data suggests that the enhancement of neuronal activity in the vSub was associated with the PPI impairment, possibly due to the enhanced excitatory output from vSub the NAC shell.

Adult conditional knockout of PGC-1α in GABAergic neurons causes exaggerated startle reactivity, impaired short-term habituation and hyperactivity.

Interneurons not only contribute to the global balance of activity in cortical networks but also mediate the precise gating of information through specific proteins. Accumulating evidence demonstrates that peroxisome-proliferator-activated receptor-gamma co-activator 1 alpha (PGC-1α) is concentrated in inhibitory interneurons and that it plays an important role in neuropsychiatric diseases. However, the functions of the transcriptional coactivator PGC-1α in sensorimotor gating, short-term habituation and spatial reference memory are still not entirely clear. To investigate the precise involvement of PGC-1α in the progression of psychiatric disorders, we first generated PGC-1α conditional knockout mice through transgenic expression of Cre recombinase under the control of dlx5/6 promoter, Cre-mediated excision events occurred specifically in γ-amino-butyric-acid-(GABA)ergic neurons. Short-term habituation and spatial reference memory in Dlx5/6-Cre::PGC-1αfl/fl mice were evaluated using the novel object recognition test and the Morris water maze test, and sensorimotor gating was measured by prepulse inhibition of the acoustic startle reflex. Protein expression of parvalbumin (PV) in specific brain regions was studied by western blotting, immunofluorescence and immunohistochemistry. Here, we show that mice lacking the PGC-1α gene in GABAergic neurons exhibit deficits in short-term habituation, hyperactivity, reduced prepulse inhibition and exaggerated startle reactivity but normal associative spatial reference memory. In particular, these mice display aberrant salience, whereby more attention is paid to a further copy of the original object (now familiar) (relative to the first presentation of the original object, and relative to the presentation of the novel object). These behavioral dysfunctions were associated with decreased PV expression in the cortex (including somatosensory and motor cortex) as well as in the hippocampus, especially in its CA1 and CA3 regions. Together, these findings draw attention to a hyper-response phenotype of PGC-1α conditional knockout mice and indicate that PGC-1α is a novel regulator of gene expression and function in PV-positive interneurons and a potential therapeutic target for psychiatric disorders associated with PGC-1α dysregulation.

Mu opioid receptors inhibit GABA release from parvalbumin interneuron terminals onto CA1 pyramidal cells.

Selectively activating (by optogenetics) parvalbumin-expressing (PV) interneurons induces GABA release onto CA1 pyramidal cells. Here we report that this release was attenuated by presynaptic mu opioid receptors (MORs) activation. On the other hand, conventional electric shock, presumably activating non-selectively presynaptic GABAergic terminals, also induced GABA release; however, this release showed relatively limited depression by MORs activation. The data suggest that MORs specifically inhibit GABA release from PV terminals and therefore, further support the idea that MORs contribute to homeostasis in CA1 neuro-circuit.

Inhibition of expression of glucocorticoids receptors may contribute to postpartum depression.

Although postpartum depression (PPD) is the leading cause of disability worldwide, its molecular mechanisms are poorly understood. Recent evidence has suggested that impaired glucocorticoid receptor (GR), the signaling of key molecules of the HPA axis, plays a key role in the behavioral and neuroendorcrine alterations of major depression. However, the role of GR in postpartum period, which following with the abrupt withdrawal of placental corticotropin releasing hormone (CRH) and resulting in a re-equilibration of the maternal HPA axis in the days of post-delivery, is still not entirely clear. Previously, a hormone-simulated pregnancy (HSP), and the subsequent 'postpartum' withdrawal in estrogen has been employed to mimic the fluctuations in estradiol associated with pregnancy and postpartum. Using the HSP model, we investigated here the effect of 'postpartum' withdrawal in estrogen as well as depression- and anxiety-like behavior by intra-hippocampal infusion with GR inhibitor-RU486. Following the successful acquisition of PPD model by withdrawal in estrogen, reduced GR expression was observed in hippocampus. Further, HSP-rats suffered intra-hippocampal RU486 infusion presented depression- and anxiety-like behavior as postpartum depression. Together, these results suggest an important, though complex, role for GR in the behavioral regulation of postpartum depression.

Creation of superposition of arbitrary states encoded in two high-Q cavities.

The principle of superposition is a key ingredient for quantum mechanics. A recent work [Phys. Rev. Lett.116, 110403 (2016)10.1103/PhysRevLett.116.110403] has shown that a quantum adder that deterministically generates a superposition of two unknown states is forbidden. Here we consider the implementation of the probabilistic quantum adder in the 3D cavity-transmon system. Our implementation is based on a three-level superconducting transmon qubit dispersively coupled to two cavities. Numerical simulations show that high-fidelity generation of the superposition of two coherent states is feasible with current circuit QED technology. Our method also works for other physical systems such as two optical cavities coupled to a three-level atom or two nitrogen-vacancy center ensembles interacted with one three-level superconducting flux qubit.