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Hippocampal circuitry stimulation is sufficient to regulate adult hippocampal neurogenesis and ameliorate depressive-like behavior, but its underlying mechanism remains unclear. Here, it is shown that inhibition of medial septum (MS)-dentate gyrus (DG) circuit reverses the chronic social defeat stress (CSDS)-induced depression-like behavior. Further analysis exhibits that inhibition of gamma-aminobutyric acidergic neurons in MS projecting to the DG (MSGABA+ -DG) increases the expression of platelet-derived growth factor-BB (PDGF-BB) in somatostatin (SOM) positive interneurons of DG, which contributes to the antidepressant-like effects. Overexpression of the PDGF-BB or exogenous administration of PDGF-BB in DG rescues the effect of chronic stress on the inhibition of neural stem cells (NSCs) proliferation and dendritic growth of adult-born hippocampal neurons, as well as on depressive-like behaviors. Conversely, knockdown of PDGF-BB facilitates CSDS-induced deficit of hippocampal neurogenesis and promotes the susceptibility to chronic stress in mice. Finally, conditional knockdown platelet-derived growth factor receptor beta (PDGFRß) in NSCs blocks an increase in NSCs proliferation and the antidepressant effects of PDGF-BB. These results delineate a previously unidentified PDGF-BB/PDGFRß signaling in regulating depressive-like behaviors and identify a novel mechanism by which the MSGABA+ -DG pathway regulates the expression of PDGF-BB in SOM-positive interneurons.
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Neurogénesis , Ácido gamma-Aminobutírico , Ratones , Animales , Becaplermina/farmacología , Neurogénesis/fisiología , Ácido gamma-Aminobutírico/farmacología , Antidepresivos/farmacología , Giro Dentado/fisiologíaRESUMEN
The aryl-to-vinyl nickel 1,4-migration (1,4-Ni migration) reaction has been reported for the first time. The generated alkenyl Ni species undergo a reductive coupling reaction with unactivated brominated alkanes affording a series of trisubstituted olefins. This tandem reaction exhibits mild conditions, a broad substrate scope, high regioselectivity, and excellent Z/E stereoselectivity. A series of controlled experiments have shown that the critical 1,4-Ni migration process is reversible. In addition, the alkenyl nickel intermediates obtained after migration are highly Z/E stereoselective and do not undergo Z/E isomerization. The obtained trace isomerization products are caused by the instability of the product.
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Recent studies based on animal models of various neurological disorders have indicated that mitophagy, a selective autophagy that eliminates damaged and superfluous mitochondria through autophagic degradation, may be involved in various neurological diseases. As an important mechanism of cellular stress response, much less is known about the role of mitophagy in stress-related mood disorders. Here, we found that tumor necrosis factor-α (TNF-α), an inflammation cytokine that plays a particular role in stress responses, impaired the mitophagy in the medial prefrontal cortex (mPFC) via triggering degradation of an outer mitochondrial membrane protein, NIP3-like protein X (NIX). The deficits in the NIX-mediated mitophagy by TNF-α led to the accumulation of damaged mitochondria, which triggered synaptic defects and behavioral abnormalities. Genetic ablation of NIX in the excitatory neurons of mPFC caused passive coping behaviors to stress, and overexpression of NIX in the mPFC improved TNF-α-induced synaptic and behavioral abnormalities. Notably, ketamine, a rapid on-set and long-lasting antidepressant, reversed the TNF-α-induced behavioral abnormalities through activation of NIX-mediated mitophagy. Furthermore, the downregulation of NIX level was also observed in the blood of major depressive disorder patients and the mPFC tissue of animal models. Infliximab, a clinically used TNF-α antagonist, alleviated both chronic stress- and inflammation-induced behavioral abnormalities via restoring NIX level. Taken together, these results suggest that NIX-mediated mitophagy links inflammation signaling to passive coping behaviors to stress, which underlies the pathophysiology of stress-related emotional disorders.
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Parvalbumin-positive neurons (PVs) are the main class of inhibitory neurons in the mammalian central nervous system. By examining diurnal changes in synaptic and neuronal activity of PVs in the supragranular layer of the mouse primary visual cortex (V1), we found that both PV input and output are modulated in a time- and sleep-dependent manner throughout the 24-h day. We first show that PV-evoked inhibition is stronger by the end of the light cycle (ZT12) relative to the end of the dark cycle (ZT0), which is in line with the lower inhibitory input of PV neurons at ZT12 than at ZT0. Interestingly, PV inhibitory and excitatory synaptic transmission slowly oscillate in opposite directions during the light/dark cycle. Although excitatory synapses are predominantly regulated by experience, inhibitory synapses are regulated by sleep, via acetylcholine activating M1 receptors. Consistent with synaptic regulation of PVs, we further show in vivo that spontaneous PV activity displays daily rhythm mainly determined by visual experience, which negatively correlates with the activity cycle of surrounding pyramidal neurons and the dorsal lateral geniculate nucleus-evoked responses in V1. These findings underscore the physiological significance of PV's daily modulation.
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Neuronas , Parvalbúminas , Animales , Ratones , Parvalbúminas/metabolismo , Neuronas/metabolismo , Células Piramidales/metabolismo , Transmisión Sináptica , Sueño , MamíferosRESUMEN
Long noncoding RNAs (lncRNAs) are involved in various biological processes and implicated in the regulation of neuronal activity, but the potential role of lncRNAs in depression remains largely unknown. Here, we identified that lncRNA Gm2694 was increased in the medial prefrontal cortex (mPFC) of male mice subjected to chronic social defeat stress (CSDS). The down-regulation of Gm2694 in the mPFC alleviated CSDS-induced depressive-like behaviors through enhanced excitatory synaptic transmission. Furthermore, we found that Gm2694 preferentially interacted with the carboxyl-terminal domain of 78-kilodalton glucose-regulated protein (GRP78), which abrogated GRP78 function and disrupted endoplasmic reticulum homeostasis, resulting in a reduction of the surface expression of AMPA receptors (AMPARs). Overexpression of GRP78 in the mPFC promoted the surface expression of AMPARs and attenuated the CSDS-induced depressive-like behaviors of mice. Together, our results unraveled a previously unknown role of Gm2694 in regulating endoplasmic reticulum homeostasis and excitatory synaptic transmission in depression.
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Enfermedad Injerto contra Huésped , ARN Largo no Codificante , Masculino , Ratones , Animales , Chaperón BiP del Retículo Endoplásmico , ARN Largo no Codificante/genética , Retículo Endoplásmico , Homeostasis , Regulación hacia Abajo , Receptores AMPA/genéticaRESUMEN
As a double-stranded DNA (dsDNA) sensor, the PYHIN family member absent in melanoma 2 (AIM2) is an essential component of the inflammasome families. Activation of AIM2 by dsDNA leads to the assembly of cytosolic multimolecular complexes termed the AIM2 inflammasome, resulting in activation of caspase-1, the maturation and secretion of pro-inflammatory cytokines interleukin (IL)-1ß and IL-18, and pyroptosis. Multiple central nervous system (CNS) diseases are accompanied by immune responses and inflammatory cascade. As the resident macrophage cells, microglia cells act as the first and main form of active immune defense in the CNS. AIM2 is highly expressed in microglia as well as astrocytes and neurons and is essential in neurodevelopment. In this review, we highlight the recent progress on the role of AIM2 inflammasome in CNS disorders, including cerebral stroke, brain injury, neuropsychiatric disease, neurodegenerative diseases, and glioblastoma.
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Enfermedades del Sistema Nervioso Central/metabolismo , Proteínas de Unión al ADN/metabolismo , Mediadores de Inflamación/antagonistas & inhibidores , Mediadores de Inflamación/metabolismo , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Caspasa 1/metabolismo , Inhibidores de Caspasas/farmacología , Inhibidores de Caspasas/uso terapéutico , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Enfermedades del Sistema Nervioso Central/patología , ADN/metabolismo , Humanos , Piroptosis/efectos de los fármacos , Piroptosis/fisiologíaRESUMEN
We examined the physical properties of the quasi-one-dimensional superconductor Ta4Pd3Te16 in the normal state by detailed measurements of susceptibility, in-plane anisotropic resistivity, magnetoresistance, Hall resistivity, and Seebeck coefficient. The large Wilson ratio, as inferred from normal-state susceptibility, indicates strong electron-electron interaction. The Hall and Seebeck coefficients show not only significant temperature-dependent behavior, indicating the multiband effect, but also an obvious anomaly around T 1 = 40 K. Analyses of both the Hall resistivity and thermopower using a two-band model indicate that the electrons dominate the electrical transport at low temperatures. Our results imply that it is the quantum fluctuations of the charge order taking place in the temperature range 30-50 K that may result in the abnormal normal-state properties of Ta4Pd3Te16.
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ThFeAsN1-x O x ([Formula: see text]) system with heavy electron doping has been studied by the measurements of x-ray diffraction, electrical resistivity, magnetic susceptibility and specific heat. The non-doped compound exhibits superconductivity at [Formula: see text] K, which is possibly due to an internal uniaxial chemical pressure that is manifested by the extremely small value of As height with respect to the Fe plane. With the oxygen substitution, the T c value decreases rapidly to below 2 K for [Formula: see text], and surprisingly, superconductivity re-appears in the range of [Formula: see text] with a maximum [Formula: see text] of 17.5 K at x = 0.3. For the normal-state resistivity, while the samples in intermediate non-superconducting interval exhibit Fermi liquid behavior, those in other regions show a non-Fermi-liquid behavior. The specific heat jump for the superconducting sample of x = 0.4 is [Formula: see text], which is discussed in terms of anisotropic superconducting gap. The peculiar phase diagram in ThFeAsN1-x O x presents additional ingredients for understanding the superconducting mechanism in iron-based superconductors.
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We report a new quasi-one-dimensional compound KMn6Bi5 composed of parallel nanowires crystallizing in a monoclinic space group C2/ m with a = 22.994(2) Å, b = 4.6128(3) Å, c = 13.3830(13) Å and ß = 124.578(6)°. The nanowires are infinite [Mn6Bi5]- columns each of which is composed of a nanotube of Bi atoms acting as the cladding with a nanorod of Mn atoms located in the central axis of the nanotubes. The nanorods of Mn atoms inside the Bi cladding are stabilized by Mn-Mn bonding and are defined by distorted Mn-centered cluster icosahedra of Mn13 sharing their vertices along the b axis. The [Mn6Bi5]- nanowires are linked with weak internanowire Bi-Bi bonds and charge balanced with K+ ions. The [Mn6Bi5]- nanowires were directly imaged by high-resolution transmission electron microscopy and scanning transmission electron microscopy. Magnetic susceptibility studies show one-dimensional characteristics with an antiferromagnetic transition at â¼75 K and a small average effective magnetic moment (1.56 µB/Mn for H ⥠b and 1.37 µB/Mn for H ⥠b) of Mn from Curie-Weiss fits above 150 K. Specific heat measurements reveal an electronic specific heat coefficient γ of 6.5(2) mJ K-2(mol-Mn)-1 and a small magnetic entropy change Δ Smag ≈ 1.6 J K-1 (mol-Mn)-1 across the antiferromagnetic transition. In contrast to a metallic resistivity along the column, the resistivity perpendicular to the column shows a change from a semiconducting behavior at high temperatures to a metallic one at low temperatures, indicating an incoherent-to-coherent crossover of the intercolumn tunneling of electrons.
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We investigate the electronic structure of group VI-B transition metal di-arsenides (TAs2, T = Mo, W). By comparing the formation energies, the centrosymmetric di-arsenides compounds are energetically more stable, in contrast to the di-phosphorides (MoP2/WP2). Both compounds can be well described by a two-band model with a pair of well-separated electron/hole bands. The electron/hole carrier density is nearly compensated in MoAs2 (|n e - n h |/n h < 1%). The [Formula: see text] classification for all partially occupied bands are topologically strong (1;001), and therefore robust surface states are expected in these materials. Using the adaptive K-mesh method, no energy degenerate state could be found except the spin degeneracy in the whole Brillouin zone, excluding the possibility of intrinsic Dirac or Weyl points near the Fermi level in the system.
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We report the first nitrogen-containing iron-pnictide superconductor ThFeAsN, which is synthesized by a solid-state reaction in an evacuated container. The compound crystallizes in a ZrCuSiAs-type structure with the space group P4/nmm and lattice parameters a = 4.0367(1) Å and c = 8.5262(2) Å at 300 K. The electrical resistivity and dc magnetic susceptibility measurements indicate superconductivity at 30 K for the nominally undoped ThFeAsN.
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We report bulk superconductivity at 1.0 K in a low-dimensional ternary telluride Ta3Pd3Te14 containing edge-sharing PdTe2 chains along crystallographic b axis, similar to the recently discovered superconductor Ta4Pd3Te16. The electronic heat capacity data show an obvious anomaly at the transition temperature, which indicates bulk superconductivity. The specific-heat jump is ΔC/(γ(n)T(c)) ≈ 1.35, suggesting a weak coupling scenario. By measuring the low-temperature thermal conductivity, we conclude that Ta3Pd3Te14 is very likely a dirty s-wave superconductor. The emergence of superconductivity in Ta3Pd3Te14 with a lower T(c), compared to that of Ta4Pd3Te16, may be attributed to the lower density of states.
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We carried out measurements of the magnetoresistance, magnetic susceptibility and specific heat on crystals of the low-dimensional transition metal telluride Ta4Pd3Te16. Our results indicate that Ta4Pd3Te16 is an anisotropic type-II superconductor in the clean limit with the extracted Ginzburg-Landau parameter KGL = 84. The upper critical field Hc2(T) shows an anomalous temperature dependence at low temperatures and the anisotropy of Hc2(T) is strongly T-dependent, both of which indicate a multiband scenario. The electronic specific heat Cel(T) can be consistently described by a two-gap (s + d waves) model from the base temperature T/Tc ~ 0.12 up to Tc. Our results suggest nodal and multiband superconductivity in Ta4Pd3Te16.
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We have synthesized a novel europium bismuth sulfofluoride, Eu3Bi2S4F4, by solid-state reactions in sealed evacuated quartz ampules. The compound crystallizes in a tetragonal lattice (space group I4/mmm, a = 4.0771(1) Å, c = 32.4330(6) Å, and Z = 2), in which CaF2-type Eu3F4 layers and NaCl-like BiS2 bilayers stack alternately along the crystallographic c axis. There are two crystallographically distinct Eu sites, Eu(1) and Eu(2) at the Wyckoff positions 4e and 2a, respectively. Our bond valence sum calculation, based on the refined structural data, indicates that Eu(1) is essentially divalent, while Eu(2) has an average valence of â¼ +2.64(5). This anomalous Eu valence state is further confirmed and supported, respectively, by Mössbauer and magnetization measurements. The Eu(3+) components donate electrons into the conduction bands that are mainly composed of Bi 6px and 6py states. Consequently, the material itself shows metallic conduction and superconducts at 1.5 K without extrinsic chemical doping.