Geraniol enhances inhibitory inputs to the paraventricular thalamic nucleus and induces sedation in mice.

BACKGROUND: Plant extracts with sedative effects have a long history of clinical use for treating insomnia and epilepsy. Geraniol (GE), a plant-derived acyclic monoterpene, reduces locomotion and prolongs barbiturate-induced anesthesia in rats. However, the mechanisms of GE in sedation remain elusive. PURPOSE: This study aimed to investigate the mechanisms of GE in sedation in mice. METHODS: GE was administered systemically by nebulization and intraperitoneal injection. Open field tests, acute seizure tests, and electroencephalogram (EEG) recordings were performed to examine the sedative effects of GE in mice. The time of loss of the righting reflex and return of the righting reflex were recorded in anesthesia experiments to examine the effect of GE on anesthesia. In vitro c-Fos staining and in vivo fiber photometry recordings were performed to detect the activity change of the paraventricular thalamic nucleus (PVT). Microinjection of GE into PVT and related behavioral tests were performed to confirm that PVT was a critical target for GE. Whole-cell recordings were performed to dissect the effects of GE on PVT neurons via GABAA receptors. Molecular docking was performed to examine the interaction between GE and GABAA receptor subunits. RESULTS: We found that GE reduced locomotion, relieved acute seizures, altered the EEG, and facilitated general anesthesia in mice. Next, we found that GE decreased c-Fos expression and suppressed the calcium activity in PVT. Microinjection of GE into PVT reduced locomotion and facilitated anesthesia. Furthermore, electrophysiology results showed that GE induced dramatic membrane hyperpolarization and suppressed the activity of PVT neurons, mainly by prolonging spontaneous inhibitory postsynaptic currents and inducing tonic inhibitory currents. Molecular docking results indicated that the ß3 subunit might be a potential target for GE. CONCLUSION: By combined using behavioral tests, immunohistochemistry, calcium recording, and electrophysiology, we systematically revealed that GE inhibits PVT and induces sedation in mice. Essential oils have long been considered part of traditional medicine, and they are playing a critical role in aromatherapy. Since GE has a comparatively ideal safety property and multiple delivery methods, GE has great application potential in aromatherapy. Our study also provides a potential candidate for further development of sedatives and anaesthetics.

PBN-PVT projections modulate negative affective states in mice.

Long-lasting negative affections dampen enthusiasm for life, and dealing with negative affective states is essential for individual survival. The parabrachial nucleus (PBN) and thalamic paraventricular nucleus (PVT) are critical for modulating affective states in mice. However, the functional roles of PBN-PVT projections in modulating affective states remain elusive. Here, we show that PBN neurons send dense projection fibers to the PVT and form direct excitatory synapses with PVT neurons. Activation of the PBN-PVT pathway induces robust behaviors associated with negative affective states without affecting nociceptive behaviors. Inhibition of the PBN-PVT pathway reduces aversion-like and fear-like behaviors. Furthermore, the PVT neurons innervated by the PBN are activated by aversive stimulation, and activation of PBN-PVT projections enhances the neuronal activity of PVT neurons in response to the aversive stimulus. Consistently, activation of PVT neurons that received PBN-PVT projections induces anxiety-like behaviors. Thus, our study indicates that PBN-PVT projections modulate negative affective states in mice.

Norepinephrine modulates wakefulness via α1 adrenoceptors in paraventricular thalamic nucleus.

Norepinephrine (NE) neurons in the locus coeruleus (LC) play key roles in modulating sleep and wakefulness. Recent studies have revealed that the paraventricular thalamic nucleus (PVT) is a critical wakefulness-controlling nucleus in mice. However, the effects of NE on PVT neurons remain largely unknown. Here, we investigated the mechanisms of NE modulating wakefulness in the PVT by using viral tracing, behavioral tests, slice electrophysiology, and optogenetics techniques. We found that the PVT-projecting LC neurons had few collateral projections to other brain nuclei. Behavioral tests showed that specific activation of the LC-PVT projections or microinjection of NE into the PVT accelerated emergence from general anesthesia and enhanced locomotion activity. Moreover, brain slice recording results indicated that NE increased the activity of the PVT neurons mainly by increasing the frequency of spontaneous excitatory postsynaptic currents via α1 adrenoceptors. Thus, our results demonstrate that NE modulates wakefulness via α1 adrenoceptors in the PVT.

An Electrochemical Sensor for Determination of Bisphenol A Based on Reduced Graphene/Silver Nanoparticles Composites / 分析化学

Graphene and silver nanoparticles showed good application potentials in electrochemistry due to their unique folded layered structure and good catalytic performance. In this work, reduced graphene oxide-Ag nanoparticles ( rGO/AgNPs ) composite material was prepared in situ by using hydrothermal reduction synthesis method with sodium citrate as reducing agent. The material was then used as modified electrodes to study the electrochemical behaviors of bisphenol A ( BPA) . The results of cyclic voltammetry and square wave voltammetry showed that the fast oxidation-reduction reaction of BPA could occur on the rGO/AgNPs modified glassy carbon electrode and lead to the sensitive determination of BPA. Under the optimal conditions, the oxidation current of BPA was linear to its concentration in the range of 0 . 1-40 . 0 μmol/L and the detection limit was 50 . 7 nmol/L ( S/N=3 ) . The presented method was also used for the determination of BPA in plastic samples with satisfactory results.

Activation of the p38 MAPK/NF-κB pathway contributes to doxorubicin-induced inflammation and cytotoxicity in H9c2 cardiac cells.

A number of studies have demonstrated that inflammation plays a role in doxorubicin (DOX)-induced cardiotoxicity. However, the molecular mechanism by which DOX induces cardiac inflammation has yet to be fully elucidated. The present study aimed to investigate the role of the p38 mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) pathway in DOX-induced inflammation and cytotoxicity. The results of our study demonstrated that the exposure of H9c2 cardiac cells to DOX reduced cell viability and stimulated an inflammatory response, as demonstrated by an increase in the levels of interleukin-1ß (IL-1ß) and IL-6, as well as tumor necrosis factor-α (TNF-α) production. Notably, DOX exposure induced the overexpression of phosphorylated p38 MAPK and phosphorylation of the NF-κB p65 subunit, which was markedly inhibited by SB203580, a specific inhibitor of p38 MAPK. The inhibition of NF-κB by pyrrolidine dithiocarbamate (PDTC), a selective inhibitor of NF-κB, significantly ameliorated DOX-induced inflammation, leading to a decrease in the levels of IL-1ß and IL-6, as well as TNF-α production in H9c2 cells. The pretreatment of H9c2 cells with either SB203580 or PDTC before exposure to DOX significantly attenuated DOX-induced cytotoxicity. In conclusion, our study provides novel data demonstrating that the p38 MAPK/NF-κB pathway is important in the induction of DOX-induced inflammation and cytotoxicity in H9c2 cardiac myocytes.

Effects of fuel additives on the thermal cracking of n-decane from reactive molecular dynamics.

Thermal cracking of n-decane and n-decane in the presence of several fuel additives are studied in order to improve the rate of thermal cracking by using reactive molecular dynamics (MD) simulations employing the ReaxFF reactive force field. From MD simulations, we find the initiation mechanisms of pyrolysis of n-decane are mainly through two pathways: (1) the cleavage of a C-C bond to form smaller hydrocarbon radicals, and (2) the dehydrogenation reaction to form an H radical and the corresponding decyl radical. Another pathway is the H-abstraction reactions by small radicals including H, CH(3), and C(2)H(5). The basic reaction mechanisms are in good agreement with existing chemical kinetic models of thermal decomposition of n-decane. Quantum mechanical calculations of reaction enthalpies demonstrate that the H-abstraction channel is easier compared with the direct C-C or C-H bond-breaking in n-decane. The thermal cracking of n-decane with several additives is further investigated. ReaxFF MD simulations lead to reasonable Arrhenius parameters compared with experimental results based on first-order kinetic analysis. The different chemical structures of the fuel additives greatly affect the apparent activation energy and pre-exponential factors. The presence of diethyl ether (DEE), methyl tert-butyl ether (MTBE), 1-nitropropane (NP), 3,6,9-triethyl-3,6,9-trimethyl-1,2,4,5,7,8-hexaoxonane (TEMPO), triethylamine (TEA), and diacetonediperodixe (DADP) exhibit remarkable promoting effect on the thermal cracking rates, compared with that of pure n-decane, in the following order: NP > TEMPO > DADP > DEE (∼MTBE) > TEA, which coincides with experimental results. These results demonstrate that reactive MD simulations can be used to screen for fuel additives and provide useful information for more comprehensive chemical kinetic model studies at the molecular level.